Effect of genistein on the climbing ability of Parkinson disease model flies

Table of Contents

Abstract Book20th World Congress on Parkinson’s Disease and Related Disorders, Geneva, Switzerland, December 8-11, 2013

HOT TOPICS SESSIONS

Monday, December 9, 2013 HT1-1 – HT1-6 p. 1Tuesday, December 10, 2013 HT2-1 – HT2-6 p. 2Wednesday, December 11, 2013 HT3-1 – HT3-5 p. 4Day 1: Monday, Section 1: Parkinson’s Disease 001 - 166 p. 5Day 1: Monday, Section 2: Imaging 167 - 206 p. 47Day 2: Tuesday, Section 1: Genetics 207 - 251 p. 59Day 2: Tuesday, Section 2: PD Therapy 252 - 369 p. 70Day 2: Tuesday, Section 3: Related Disorders 370 - 429 p. 102Day 3: Wednesday, Section 1: Animal Models 430 - 532 p. 116Day 3: Wednesday, Section 2: Basic Science 533 - 584 p. 144

1.HOT TOPICS SESSIONS ABSTRACTS.indd 11.HOT TOPICS SESSIONS ABSTRACTS.indd 1 10/28/13 5:41 PM10/28/13 5:41 PM

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HOT TOPICS SESSIONS

Monday, December 9, 2013

HT1-1

IDIOPATHIC PARKINSON’S DISEASE – A DISEASE OR A SYNDROME?A.D. Korczyn1,*1Department of Neurology, Tel-Aviv University Medical School, Ramat Aviv 69978, Israel

Many different nosological entities can lead to Parkinsonism. Sometimes, the etiology and mechanisms are known and understood (vascular, neuroleptic, Mendelian genetic, post-infectious etc). Among the neurodegenerative diseases causing Parkinsonism, a large number are termed idiopathic Parkinson’s dis-ease (IPD). Lately, polymorphisms in several genes have been established as being related to IPD. These cases are thought to be caused by a heterogeneous combinations of contributions of several genes and environmental factors.The Mendelian genes causing Parkinson’s disease (PD) can be divided to these related to mitochondrial dysfunction and oxidative stress, proteasome dysfunction and protein mishandling, lysosomal dysfunction, etc. Several other lines of evidence – biochemical, pharmacological etc. support the separation of mechanisms.It is suggested that IPD is actually a clinical syndrome, caused by a hetero-geneous combination of different genetic and environmental factors. Thus, primary disease prevention is impractical. Downstream changes, like apop-tosis, are also unlikely targets for intervention. However, using metabolomics, therapy against the process responsible for the neurodegeneration is feasible, leading to disease course modification.

HT1-2

LATERALITY IN PARKINSON’S DISEASE: UNMET IMPORTANCEP. Riederer1,*1Clinic and Policlinic for Psychiatry and Psychotherapy, University Wurzburg, Wurzburg, Germany

Objectives: Although ‘laterality’ in sporadic Parkinson’s Disease (sPD) is evident from clinical observation and PET-studies, research into this topic is far from being regarded as a ‘hot spot’. This review will try to underline ‘laterality in sPD’ as a key moment to explore its importance for defining ‘causality issues’.Results: As hereditary types of PD are mostly bilateral, environmental trig-gers cause bilateral PD, and all systemically applied toxins to animals result in bilateral Parkinsonism, the hypothesis arises that sPD is due to prenatal, perinatal or early postnatal developmental pathology caused by genetic dis-turbances with predominance affecting one hemisphere in particular. If so, a ‘dosis’ effect (developmental disturbance, mutated gene, environmental toxin concentration) determines the outbreak of sPD. ‘High dosis’ ® early onset PD, ‘low dosis’ ® late onset PD. Consequences are variations in hemispheric motor loop (dys)functions, side specific compensatory mechanisms, symptoms onset and severity, progression and prognosis. Is the right sided onset sPD pheno-type correlated to more depression, anxiety, less creativity but better prognosis while left sided onset is connected with higher frequency of cognitive problems and poorer prognosis? Also treatment strategies could be optimized and drug testing results might be at variance between right and left sided onset sPD.Conclusions: In conclusion, “laterality” in sPD is a “hot spot” worth to be studied in detail.No conflict of interest.

HT1-3

PROBING AMINERGIC MODULATION OF MOOD IN PARKINSON’S DISEASE DEPRESSION: A DIMENSIONAL APPROACHE. Pourcher1,*1Medicine, Laval University, Quebec, Canada

Objectives: Depression in Idiopathic Parkinson’s disease (IPD) is fre-quent, difficult to recognize, under managed and has a profound impact on quality of life. In this study we have chosen to dissect the state of

depressive mood assessed with the Beck Depression Inventory (BDI) at different points in time of pharmacological treatment using a dimensional approach. This study compares the pharmacological treatment’s effective-ness of this approach.Methods: The 21 items BDI were classified in two new categories or factors: hyperkinetic and hypokinetic. The hyperkinetic factor included items related to intrusions of negative feelings and ideas, as well as to behavioral hyperactiv-ity. The hypokinetic factor included items related to loss of drive and mental and physical energy. Analyses were conducted on all PD patients with depres-sion seen at our site in the last 9 years.Results: Analyses using the hypo/hyperkinetic dichotomy support a neuro-biological dissociation of these factors in response to pharmacological inter-vention: hyperkinetic symptoms are responsive to serotonergic drugs while those of the hypokinetic ones are not and may even show deterioration under SSRI’s. In contrast, the hypokinetic symptoms are responsive to dopaminergic drugs and may show deterioration under serotonergic drugs. Furthermore, the two factors seem transiently dissociated on placebo interventions aiming at correcting either mood or motor status.Conclusions: The dimensional approach to depression symptomatology may be of heuristic value in probing aminergic modulation of mood in IPD and establishing new correlations between affective and motor symptoms.No conflict of interest.

HT1-4

NEUROPSYCHOLOGICAL AND IMAGING PROFILE OF PATIENTS WITH PARKINSON’S DISEASE AND FREEZING OF GAITP.K. Pal1,*, M. Jha1, B. Bagepally2, R. Yadav1, J.K. Keshav3, J. Saini21Neurology, National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore, India, 2Neuroimaging & Interventional Radiology, National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore, India, 3Clinical Psychology, National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore, India

Objectives: The objectives of this study were to compare the cognitive profile and gray matter (GM) changes between patients with Parkinson’s disease (PD) with and without freezing of gait (FOG).Methods: Thirty-eight idiopathic PD patients (FOG +ve: 17, FOG −ve: 21) were evaluated clinically and with structured neuropsychological battery. The structural T1W, MRI was acquired under 3T MRI scanner and Voxel Based Morphometric analysis (VBM) was performed using VBM-8 toolbox and re-sults were observed at puncor < 0.001, adjusted for age, sex, total brain volume and PD duration.Results: Clinical characteristics of FOG +ve vs FOG −ve patients were:(a) Age: 56.9 ± 6.6 vs 47.4 ± 9.1 years (p = 0.001)(b) PD duration: 6.0 ± 4.9 vs 5.2 ± 3.5 years(c) Gender (men:women): 11:6 vs 11:10(d) Hoehn & Yahr stage: 1.96 ± 0.53 vs 1.78 ± 0.37FOG +ve patients had significant impairment in memory, attention, executive and visuo-spatial functions.VBM analysis showed significant GM atrophy in FOG +ve patients at right cerebellum (pyramis, declive), left cerebrum (Broadman area (BA) 21 and 22) and right cerebrum (BA 10 and 6).Conclusions: PD patients with FOG showed widespread involvement of cognition localizing to frontal, temporal (especially left) and parietal areas. VBM showed GM atrophy in left temporal and right frontal areas (coinciding with that observed in neuropsychological tests) as well as significant involve-ment of right cerebellum. Thus cerebellar dysfunction may have a role in the genesis of freezing in PD as well as some clinical symptoms of PD (1).Reference1. Wu & Hallett. The cerebellum in Parkinson’s disease. Brain

2013:136;696–709.No conflict of interest.

HT1-5

PARKINSON’S DISEASE IS A SPREADING DISEASE: EVIDENCE FROM THE DRESDEN MOUSE MODEL?H. Reichmann1,*, F. Pan Montojo1

1Neurology, University of Dresden, Dresden, Germany

Objectives: During the last decade Braak and co-workers established that PD is a spreading disease which may well start in the olfactory bulb (hyposmia)

20th World Congress on Parkinson’s Disease and Related Disorders

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and in the autonomic nervous system of the stomach and gut (constipation), before it progresses to the brain.Methods: We used mice in which we administered in low concentrations rote-none via a tubing system to the stomach.Results: Our group replicated these findings in mice which were treated with rotenone administered via a tube system into the stomach/gut. In addi-tion, we could demonstrate that hemi-vagotomy or partial destruction of the sympathetic nervous system delays the occurrence of Lewy bodies in the brain of the mice. Finally, recent work has shown that Lewy bodies develop in transplanted tissue in PD patients, indicating that the pathology crosses over from the recipient brain cells to the donor cells. It can be speculated that pathogenic substances may enter the body of future PD patients via the nose or mouth and exert their effects first on the enteric nervous system of the gut before these effects are transmitted to the brain. It is also possible that the development of PD involves both environmental factors and a ge-netic predisposition.Conclusions: These studies strongly support the hypothesis that PD is a spreading disease.Reference1. F. Pan-Montojo, O. Anichtchik, Y. Dening, L. Knels, S. Pursche, R. Jung,

S. Jackson, G. Gille, M. G. Spillantini, H. Reichmann, R. H. W. Funk (2010): Progression of Parkinson’s Disease Pathology Is Reproduced by Intragastric Administration of Rotenone in Mice. PLoS ONE, Vol. 5, S. 1–10.

No conflict of interest.

HT1-6

FOVEAL REMODELLING IN PDI. Bodis-Wollner*

Objectives: To quantify changes in the inner retinal layer thickness (IRL) measured by spectral-domain optical coherence tomography (SD-OCT) in pa-tients with Parkinson Disease (PD) and healthy controls (HC) and to define the size of the foveal avascular zone in PD. Over the last decade a search for non-invasive markers for the diagnosis, quantification of progression and response to therapy in PD has markedly accelerated. Besides the brain, current interest also focuses on imaging of the retina. This was made possible by the develop-ment of a new imaging modality called Optical Coherence Tomography (OCT).Methods: 21 PD and 12 healthy controls (HC). All had complete ophthalmo-logical examination (Spund et al. 2013). Spectral-domain OCT with foveal scan (RT-Vue100) covering 5.0 × 5.0 mm in 0.25-mm steps. For defining the foveal capillary network and foveal avascular zone (FAZ) we used conventional fluo-rescein angiography Spectral-domain optical coherence tomography (SD-OCT).Results: The perifoveolar IRL is thinned in an annulus between 0.75 and 1.75 mm centered on the foveola (Hajeee et al. 2011) while the outer foveal retina is unaf-fected (30 PD (50 eyes) and 27 control subjects (50 eyes)) (Spund et al. 2013).We quantified the foveal pit with a mathematical equation, a difference of a Gaussian and a polynomial (Ding et al. (2013)) which defines that the tempo-ro-nasal slope is affected in PD.Conclusions: Apparently fovea and capillary architecture is affected in PD.Reference1. Spund, et al. 2013 Remodeling of the Fovea J Neural Transm.

120:745–753.No conflict of interest.

Tuesday, December 10, 2013

HT2-1

MECHANISM OF ADHD TREATMENT WITH STIMULANTSE. Grunblatt1,*, J. Bartl1, R. Schmid1, S. Walitza1

1Child and Adolescent Psychiatry, University Zurich, Zurich, Switzerland

Objectives: It is estimated that around 5% of the children and adolescent world-wide suffer from attention-deficit hyperactivity disorder (ADHD) but also exist in adulthood. To date, the most frequent and successful pharmacologi-cal treatment in ADHD is the use of stimulants, in particular methylphenidate. Methylphenidate is used in the clinic already over 50 years as therapy for ADHD with very high effect size. Although a great deal of information re-garding its effects and side effects was gathered in this period of time, many questions are still open regarding its mechanism of action.Methods: In our laboratory, we are currently investigating in-vitro as well as in neuronal cell culture its mechanism of action using biochemical, genetic and molecular approaches.Results: We could find that methylphenidate influence the activity of various enzymes involved in monoamine metabolisms. In the cell culture models, we could demonstrate how different concentrations influence pro-liferation and differentiation of the neurons, as well as the transcription of transporter, receptors and synaptic proteins important for neurotransmis-sion. Furthermore, we did not only investigate the effect of the racemic form given usually for treatment in ADHD, but also investigate the individual ef-fects of each enantiomer: the d-threo- and l-threo-methylphenidate, since it is postulated that the d-threo-methylphenidate predominantly exerts the effects seen in ADHD.Conclusions: The importance of further investigating the mechanism of ac-tion of methylphenidate lies on the fact that methylphenidate prescriptions seems to increase in the last century, while still the multiple effects of methyl-phenidate has not been fully discovered.No conflict of interest.

HT2-2

ADHD STIMULANT TREATMENT – A RISK FOR TRIGGERING PARKINSON´S DISEASE?M. Gerlach1,*

The psychostimulants amphetamine and methylphenidate have consist-ently shown efficacy and safety the treatment of attention-deficit/hyper-activity disorder (ADHD) when compared with placebo in randomized, controlled trials. Both agents are substrates for both the dopamine and noradrenaline transporters, and are competitive inhibitors of dopamine and noradrenaline uptake in in vitro studies. In addition, amphetamine promotes dopamine efflux by reverse transport through monoamine up-take transporters. A chief concern of psychostimulant medication in the treatment of children and adolescents with ADHD has been the poten-tial adverse effects to the developing brain, specifically as they relate to dopamine brain function. This paper shortly discusses the pharma-cology of this psychostimulants and the potential neurotoxic effects of these psychostimulants to the developing brain in animals, specifically as they relate to dopamine brain function. In addition, the potential clinical significance of these findings for the treatment of ADHD in children and adolescents will be discussed.Document not received.

HT2-3

BASELINE COGNITIVE AND PSYCHIATRIC DATA FROM PPMI STUDYD. Weintraub1,*1Psychiatry, University of Pennsylvania, Philadelphia, USA

Objectives: The objective of this study is to determine the frequency and cor-relates of cognitive impairment and common NPS in a large cohort of early, untreated PD patients and a demographically-comparable group of healthy controls (HCs).Methods: Parkinson Progression Marker Initiative (PPMI) is an international, multi-site, case-control study conducted at 21 academic centers. At base-line participants are recently diagnosed, untreated PD patients or HCs. HCs with cognitive impairment based on a score <26 on the Montreal Cognitive Assessment (MoCA) were excluded, precluding between-group comparisons on cognitive measures. A detailed cognitive and NPS battery is performed on all subjects. We compared the frequency of NPS in patients and HCs, and describe the cognitive status of the PD cohort.Results: Currently, 343 PD patients and 164 HCs (approximately 85% of the planned cohort) have enrolled in PPMI. The mean MoCA score for PD patients was 27.1, and using the recommended MoCA cut-off score <26, 19.2% of PD


Geneva, Switzerland, December 8 – 11, 2013

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patients screened positive for cognitive impairment. Controlling for age and gender, PD patients were about twice as likely to have clinically-significant depressive symptoms (OR = 2.04, p =.04) and more severe state and trait anxiety symptoms (p <.001 for both measures). There were no between-group differences in the likelihood of reporting ICD or related behavior symptoms (OR = 1.25, p =.37).Conclusions: Cognitive impairment and NPS are common manifestations of PD-related disability at the time of diagnosis in the PPMI cohort. In contrast, ICD symptoms are not more common, supporting the probable association between ICD symptoms and dopaminergic therapy in PD.No conflict of interest.

HT2-4

ROLE OF LACTOFERRIN IN PARKINSON’S DISEASEE. Hirsch1,*, E. Rousseau1, P.P. Michel11Experimental Therapeutics of Neurodegenerative Disorders, Institute of Brain and Spinal cord INSERM UMR 975 CNRS UMR 7225, Paris, France

Objectives: Lactoferrin (LF) is an iron-binding glycoprotein with numer-ous biological functions, related in particular, to host defence mechanisms. Previous studies on postmortem human brain tissue have shown that that LF and its receptor are up-regulated in dopamine (DA) neurons that resist to degeneration in Parkinson disease (PD).Methods: To study how this could relate to disease progression, we used midbrain cultures and experimental settings that model the loss of DA neurons in this disorder.Results: Recombinant human LF provided robust protection to vulnerable DA neurons in a culture paradigm where these neurons die spontaneously and selectively as they mature. LF-mediated rescue appeared primarily due to the binding of LF to heparan sulfate proteoglycans on the cell surface of DA neurons and subsequently to partial inactivation of focal adhesion kinase (FAK), a major downstream effector of the integrins. We established that FAK inactivation served to unmask a prosurvival phosphoinositide 3-kinase (PI3K)/AKT-dependent signaling pathway that stimulates calcium shuttling from endoplasmic reticulum to mitochondria. Of note, neuroprotec-tion with LF was also observable in distinct experimental settings where DA cell death results from mitochondrial poisoning caused by the dopaminergic toxin 1-methyl-4-phenylpyridinium or from free radical damage triggered by catalytic iron.Conclusions: Overall, our data suggest that the accumulation of LF in PD brains might be evidence of an attempt by the brain to minimize the conse-quences of neurodegeneration.Acknowledgments: This work was funded by the ANR contract 09-MNPS-019-0, Park Iron and Air Liquide Foundation. The research leading to these results has received funding from program “Investissements d’avenir” ANR-10-IAIHU-06.No conflict of interest.

HT2-5

MINDFULNESS TRAINING IN PARKINSON’S DISEASE LEADS TO MRI GRAY MATTER DENSITY AND NEUROBIOLOGICAL CHANGESB.A. Pickut1, W. Van Hecke2, S. Vanneste3, E. Kerckhofs4, P.M. Parizel5, P.Marien6, P. Cras1

1Neurology, University of Antwerp, Antwerp, Belgium, 2Neurology, icoMetrix, Leuven, Belgium, 3Neuroscience, University of Antwerp, Antwerp, Belgium, 4Physical Therapy, University of Brussels, Brussels, Belgium, 5Radiology, University of Antwerp, Antwerp, Belgium, 6Neurolinguistics, University of Brussels, Brussels, Belgium

Objective: Mindfulness practice has been shown to lead to increases in regional brain gray matter density (GMD) in a non-neurological population (Holzel 2011). We evaluated possible GMD changes and clinical correlates induced by an 8-week mindfulness based intervention (MBI) in people with Parkinson’s disease. Methods: A total of 27 out of 30 PD patients completed a randomized con-trolled longitudinal trial. Fourteen patients participated in an 8-week MBI and 13 patients received usual care (UC). A battery of questionnaires, Unified Parkinson’s Disease Rating Scale (UPDRS) and brain MRI data sets were obtained at baseline and after 8-weeks follow-up. A repeated measures ANOVA was carried out on data obtained from the questionnaires and the UPDRS. MRI voxel based (VBM) analysis was performed using DARTEL from the SPM8 software. Longitudinal gray matter density (GMD) differences were compared between the MBI and UC group. GMD differences were correlated with data obtained from questionnaires and UPDRS. Results were reported at p < 0.001, uncorrected for multiple comparisons. Results: A significant interaction effect after MBI indicated a decrease on the UPDRS motor score, increase on the Parkinson’s Disease Questionnaire (PDQ-39) pain item and increase in the Five Facet Mindfulness Questionnaire observe facet. Correlations of GMD with clinical data were found.

Conclusions: To the best of our knowledge this is the first quantitative analysis of neurobiological effects of MBI in PD correlating clinical measures with structural imaging.Reference1. Holzel, et al. Mindfulness practice leads to increases in regional brain gray

matter density. Psychiatry Res. 2011 Jan 30;191(1):36–43.No conflict of interest

HT2-6

WEIGHT CHANGES IN PARKINSON’S DISEASE AND ITS RELATIONSHIP WITH LONG TERM PROGNOSIS AND DYSKINESIAJ. Sharma1,*1University of Nottingham, Lincoln County Hospital, Lincoln, United Kingdom

Objectives: To study profile of weight change during the course of the disease and its long term implications.Methods: Relevant targeted literature review.Results: A high proportion of PD patients lose weight during disease pro-gression. This may be related to a number of clinical parameters, low en-ergy intake or higher energy utilisation. A significant relationship between body weight, weight change and levodopa related dyskinesia has been re-ported in clinical studies and trials. Patients with low initial body weight and weight losers during the course of the disease are at a higher risk of dyskinesia. There is a linear relationship between levodopa dose per kilogram body weight and the risk of dyskinesia. Higher the levodopa-dose-per kilogram body weight, higher the risk of dyskinesia. Dyskinesia may perpetuate weight loss and initiate dyskinesia cascade. Weight losers, par-ticularly males, are at a higher risk of earlier mortality. In addition weight loss is associated with malnutrition and poor quality of life as assessed on PDQ8. Weight losers may be a different phenotype identifiable with early and severe olfactory loss; patients with more severe olfactory loss are more prone to weight loss and dyskinesia.Conclusions: An early identification of low body weight patients and those at risk of weight loss in PD should lead to measures to prevent long term adverse effects. Weight oriented approach to levodopa therapy may result in less dyskinesia and better quality of life. A dyskinesia risk calculator should enable this practice.No conflict of interest.



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Wednesday, December 11, 2013

HT3-1

HUMAN MIRROR NEURON SYSTEM IS THE ANATOMICAL SUBSTRATE FOR IMITATION APRAXIA IN CORTICOBASAL SYNDROME: [18F]FDG PET AND MRI STUDIESC.S. Lee1,*, H.J. Yoon1, S.M. Lee1, H.J. Yun2, S.C. Yun3, D.J. Doudet4, J.M. Lee2

1Neurology, Asan Medical Center University of Ulsan College of Medicine, Seoul, Korea, 2Biomedical Engineering, Hanyang University, Seoul, Korea, 3Clinical Epidemiology and Biostatistics, Asan Medical Center University of Ulsan College of Medicine, Seoul, Korea, 4Medicine/neurology, University of British Columbia, Vancouver, Canada

Objectives: Corticobasal syndrome (CBS) is a neurodegenerative disorder, most characterized by asymmetric limb apraxia. We investigated anatomical substrates of limb apraxia in patients with CBS.Methods: We studied 24 CBS patients with unilateral limb apraxia and 15 healthy control subjects. Limb apraxia was tested by asking patients to imitate novel gestures. All subjects underwent [18F]FDG PET and 3.0T MRI. For [18F]FDG PET, regional glucose metabolism was expressed as the metabolic ra-tio using primary visual cortex (V1) as reference. In the CBS group, measure-ments of [18F]FDG uptake were compared between the more- and less-affected hemispheres, corresponding to the apraxic and non-apraxic hand respectively. Cortical thickness was obtained from 3.0T MRI using automated surface-based analysis. The inner and outer cortical surfaces were automatically extracted to define cortical thickness. Correlation analysis between measurements of [18F]FDG PET and cortical thickness was performed using z-scores of each variable.Results: Comparisons of regional glucose metabolism between the more- and less-affected hemispheres revealed significant hypometabolism in BA 44(pars opercularis of inferior frontal gyrus) and BA 40(supramarginal gyrus). Similar analysis of cortical thickness showed significant atrophy in the pars opercularis of inferior frontal gyrus (p <.001), supramarginal gyrus, and superi-or temporal gyrus. There were significant correlations between measurements of [18F]FDG PET and cortical thickness in the regions of both hypometabolism and cortical atrophy.Conclusions: Apraxic hemispheres of CBS patients showed significant hypo-metabolism and cortical atrophy in pars opercularis of inferior frontal gyrus and supramarginal gyrus. These findings suggest that anatomical substrates of limb apraxia of imitation to gesture overlap with human mirror neuron system.No conflict of interest.

HT3-2

FUNCTIONAL PLASTICITY IN THE CEREBELLO-CORTICAL PATHWAY IN EXPERIMENTAL PARKINSON’S DISEASEE. Hirsch1,*, I. Ortega-Pérez1, N. Guyon2, C. Lena2

1Experimental Therapeutics of Neurodegenerative Disorders, Institute of Brain and Spinal Cord Hospital de la Salpetriere, Paris, France, 2Institut de Biologie de l’ENS IBENS, Ecole Normale Supérieure INSERM U1024 CNRS UMR8197, Paris, France

Objectives: The cerebellum is a key structure for motor control and there is increasing evidence to suggest that it is involved in a broad spectrum of move-ment disorders. Recent anatomical studies have evidenced a direct interaction between these two subcortical structures, which is likely to have important clinical implications. In Parkinson’s disease, a classical basal ganglia disorder, major functional changes take place in the baso-thalamo-cortical pathways in patients. However, the role of the cerebello-thalamo-cortical pathway has been less studied in this disease.Methods: In this study, we analyzed the neuronal activity of the cerebellar nu-clei, which form the output gateway of the cerebellum, and of the motor cortex, and we examined the influence of the cerebellum on motor cortex activity in a 6-hydroxydopamine (6-OHDA) animal model of Parkinson’s disease.Results: Extracellular recordings of the cerebellar nuclei units revealed a mild decrease in the firing rate of cells in 6-OHDA-lesioned rats. We also observed a reduction in neuronal activity in the motor cortex in these animals. This re-duction was reversed by pharmacological cerebellar inactivation, thus reveal-ing an abnormal inhibitory effect of the cerebellum on motor cortex activity in 6-OHDA-lesioned rats.Conclusions: Altogether, these results demonstrate that the cerebello-thalamo-cortical network is the site of major functional remodelling following the loss of midbrain dopaminergic neurons and strongly suggests an involve-ment of the cerebellum in parkinsonian symptoms.Acknowledgments: This work was supported by an EU FP7 grant REPLACES to E.H, by Agence Nationale de Recherche to C.L. (CeCoMoD ANR-09-MNPS-38, Sensocode ANR-11-BSV4-028) and to D.P. (CereDySTim ANR-12-JSV4-0004).No conflict of interest.

HT3-3

KYNURENINES AND OTHER EXCITOTOXIN ANTAGONISTS IN MOVEMENT DISORDERS: TREATMENT OF MOTOR AND NON MOTOR SYMPTOMSL. Vecsei1,*1Department of Neurology, MTA-SZTE Neuroscience Research Group and University of Szeged, Szeged, Hungary

Objectives: N-methyl-d-aspartate (NMDA) receptors have been implicated as a mediator of neuronal injury associated with many neurological disor-ders including Huntington’s disease (HD) and Parkinson’s disease (PD). The NMDA receptor complex is intimately involved in the regulation of corticostri-atal long-term potentiation, which altered in experimental PD. Kynurenic acid (KYNAC) is an endogenous product of the tryptophan metabolism. KYNAC at high concentrations – as a competitive antagonists of the NMDA recep-tor – acts as a neuroprotectant in different neurological disorders including PD and HD (1). It is interesting that in nanomolar concentrations, KYNAC does not give rise to inhibition, but in fact facilitates the field excitatory post-synaptic potentials. This ‘Janus-face’ effect of KYNAC is a good basis for drug development in PD (1).Methods: It was investigated the effects of KYNAC-analogues in different PD models (6-OHDA and MPTP lesion) and transgenic mouse model of HD.Results: In our preclinical studies we found that specific KYNAC-analogues has beneficial effects in experimental models of PD and HD (N171-82Q).Conclusions: PD receiving dopamine replacement therapy in the form of levodopa develop dyskinesia that becomes a major complicating fac-tor in treatment. These novel compound might have therapeutic prop-erties, as KYNAC-amides may capable preferentially inhibiting NR2B subunit containing NMDA receptors, which predominant in the extrasyn-aptic regions.Reference1. Vecsei, L., Szalardy, L., Fülöp, F., Toldi, J.: Kynurenines in the CNS: recent

advances and new questions. Nature Rev. Drug Discovery 12:64–82, 2013.


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TARGETING BRAIN SIDEROSIS: FROM CONCEPT TO CLINICAL PRACTICED. Devos1,*, C. Moreau2, J.C. Devedjian3, J. Kluza4, C. Laloux5, L. Defebvre6, P. Marchetti4, R. Bordet7, Z.I. Cabantchik8

1Pharmacologie Médicale, Faculté de Médecine de Lille CHRU Lille Université Lille Nord de France, Lille, France, 2Neurology, chru lille Université Lille Nord de France, Lille, France, 3Pharmacology Médicale, chru lille Université Lille Nord de France, Lille, France, 4Unit 837 Equipe 4 Inserm, Université Lille Nord de France, Lille, France, 5Pharmacologie Médicale, Université Lille Nord de France, Lille, France, 6Neurology, chru Lille Université Lille Nord de France, Lille, France, 7Pharmacology Médicale, Faculté de Médecine de Lille CHRU Lille Université Lille Nord de France, Lille, France, 8Della Pergola Chair, Alexander Silberman Institute of Life Sciences Hebrew University, Jérusalem, Israel

Objectives: To explore the pathophysiological role of iron in Parkinson’s dis-ease (PD) by a chelation strategy designed to reducing oxidative damage as-sociated with labile iron that accompanies regional iron deposition, without affecting circulating metals. Cells and animal studies provided proofs of con-cept for its translation to the clinical settings.Methods: We assessed the effect of oxidative insults in mice systemi-cally pre-chelated with deferiprone by following motor functions, striatal dopamine (HPLC and MRI-PET) and brain iron deposition (relaxation-R2*-MRI) aided by measurements of neuronal labile iron and oxidative damage of protein, lipid and DNA. Early-stage PD patients on stabilized dopamine regimens enrolled in a 12-months single-center, double-blind, placebo-controlled-randomized clinical trial with deferiprone (30 mg/kg/day) using a 6-month delayed-start paradigm to assess changes in substantia-nigra iron deposits and UPDRS motor scores as functional indicators of disease.Results: Labile iron and biological damage in oxidation-stressed cells and animals were significantly reduced by Deferiprone, which also improved motor functions while raising striatal-dopamine. Using a 6-month delayed-start para-digm, in 37/40 patients that completed the year study, 19 early-start compared to 18 delayed-start patients responded to chelation significantly earlier and sus-tainably in both substantia-nigra iron deposits and UPDRS motor indicators. Treatment safety was maintained throughout the trial, apart from three revers-ible neutropenia cases.Conclusions: This pilot study describes for the first time a conservative mode of iron chelation that can demonstrably reduce brain iron foci in PD patients and slow-down disease progression without affecting systemic iron parameters.Supported by grants from the French Ministry of Research and HUJI-Jerusalem.No conflict of interest.



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HT3-5

BIOMARKERS FOR PARKINSON’S DISEASE (PD)J. Rabey1,*, S. Mandel21Neurology, Assaf Harofeh Medical Center, Zerifin, Israel, 2Biochemistry, Technion, Haifa, Israel

Objectives: Biomarkers in Parkinson’s disease (PD) are crucial to identify the disease early and monitor the effectiveness of neuroprotective therapies. We aim to assess whether a gene signature detected in blood from early/mild PD patients could support their diagnosis.Methods: The transcriptional expression was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as op-timal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60–0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08–1.61), aldehyde dehydrogenase family 1 sub-family A1 (OR 0.86; 95% CI 0.75–0.99), 19 S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60–0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14–1.70).Results: The five-gene classifier on the de novo PD individuals alone com-posing the early PD cohort (n = 38), resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model. The model was validated in an inde-pendent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100% sensitivity). Notably, the nominal average value of the PP for PD (0.95 (SD = 0.09)) in this cohort was higher than that of the early PD group (0.83 (SD = 0.22)), suggesting a potential for the model to assess disease severity.Conclusions: The findings provide evidence on the ability of a five-gene panel to diagnose early/mild PD, with a possible diagnostic value for detection of asymptomatic PD.No conflict of interest.

DAY 1, MONDAY, DECEMBER 9, 2013

Section 1: Parkinson’s Disease

001

TELEMEDICINE BLURS THE BOUNDARIES IN DIAGNOSTICS OF PARKINSON DISEASEI. Khubetova1,*1Neurosurgery and Neurology, Odessa National Medical University, Odessa, Ukraine

Objectives: Is to provide highly skilled professionals help for patients with Parkinson Disease and other movement disorders with “low cost telemedicine” model.Methods: In 2008 in neurological department of Odessa regional clinical hospital the advisory-diagnostic center of extrapyramidal disorders was founded. We used “low cost telemedicine” model (Skype program) for video consultation of our patients in United Kingdom. We hold two teleconsultation with Prof. A.J. Liss in July–August 2013.Results: In both cases the diagnosis of Parkinson Disease was approved, treatment was corrected.Conclusions: Introduction of telemedicine in clinical practice allows highly trained specialists to help with diagnostic and treatment, to read different view of this clinical problem, assess the effectiveness of chosen treatment, share latest information and analysis of rare clinical cases.No conflict of interest.

002

MARKED INCREASE IN RISK FOR PARKINSON’S DISEASE WITH OLFACTORY DYSFUNCTION IN LRRK2 G2385R CARRIERSM. Cao1,*, C. Piu1

1Neruology, Xuanwu Hospital Capital Medical University, Beijing, China

Objectives: To investigate the olfactory function in Chinese Parkinson’s disease (PD) patients and healthy controls with or without LRRK2 G2385R variant.Methods: PD patients were recruited from Parkinson clinic of Xuanwu Hospital in 2011 and healthy controls were enrolled from the Beijing Longitudinal Study on Aging (BLSA) cohort. Genotyping for the LRRK2 gene was performed on all sub-jects. ‘Five odors olfactory detection arrays’ was applied for olfactory function.Results: One hundred and twenty-two subjects were enrolled in this study, with 46 PD patients (22 LRRK2 G2385R carriers) and 76 healthy controls (38 LRRK2 G2385R carriers). PD group had significantly worse in olfaction detection (OD) and olfaction identification (OI) as compared to the control group (OD: 1.58 ± 1.12 vs. 1.00 ± 1.22, p = 0.005; OI: 2.59 ± 0.59 vs. 2.44 ± 0.65, p = 0.017). Normal sub-jects with severe hyposmia (the olfaction test score >2) might be possibly having the motor phenotype of PD, compared with the ones with normal or mild hypos-mia (84.8 vs. 75%, adjusted p = 0.017, OR = 4.19, 95% CI 1.29–13.57). When the individuals with severe hyposmia were LRRK2 G2385R risk variant carriers, the possibility of having PD motor phenotype might be markedly increased (90.9 vs. 65.8%, adjusted p = 0.004, OR = 39.07, 95% CI 3.24–471.46).Conclusions: The possibility of having PD motor phenotype in non-manifest-ed LRRK2 G2385R variant carriers was ten times higher than that of non-carriers, suggesting that olfactory dysfunction might be a better biomarker for PD in non-manifested LRRK2 G2385R variant carriers.Reference1. Doty, R.L., D.A. Deems, and S. Stellar, Olfactory dysfunction in

parkinsonism: a general deficit unrelated to neurologic signs, disease stage, or disease duration. Neurology, 1988; 38(8):p.1237–44.


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UNBIASED AND MOBILE MOTOR FUNCTION ANALYSIS - SENSHANDV1 SENSORFOOTV1 SYSTEM - IN PD PATIENTS AND HEALTHY SUBJECTS. A WAY FOR PRECLINICAL DIAGNOSIS OF DISEASE?C. Maremmani1, P. Bongioanni2,*, G. Rossi3, N. Tambasco4, G. Meco5, F. Cavallo6, D. Esposito6, E. Rovini6, M. Aquilano6, M.C. Carrozza6, P. Dario6

1Neurology, ASL1 - Carrara Hospital, Carrara, Italy, 2Neuroscience, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy, 3National Research Council, Institute of Clinical Physiology, Pisa, Italy, 4Clinical Neurology, University of Perugia, Perugia, Italy, 5Neuroscience, University of Rome “La Sapienza”, Rome, Italy, 6The BioRobotics Institute, Scuola Superiore Sant’Anna, Pisa, Italy


20th World Congress on Parkinson’s disease and Related Disorders

6

Objectives: We aimed to assess whether our technological system is able to differentiate patients from healthy controls; evaluate quantitatively the tasks of MDS-UPDRS scale; provide measures that correlate with Hoehn-Yahr (H-Y), MDS-UPDRS and Schwab-England scores.Methods: Thirty-three PD patients (68.2 ± 6.5 years; H-Y stage: 2.3 ± 1.0; MDS-UPDRS-III score: 16.7 ± 10.7) and 11 controls (61.1 ± 7.8 years) were included. They underwent to motion analysis through exercises for upper limbs, lower limbs and gait, by SensHandV1 and SensorFootV1 (Figure 1).

Figure 1. SensHandV1 and SensorFootV1 system.

Results: Biomechanical features have been extracted for 69 parameters. Overall, healthy people showed more constant repetitive movements and better performances in comparison to PD patients. A set of 6 very significant (p < 0.01) biomechanical parameters were selected (Table 1).

Table 1. Very significant biomechanical parameters.

1 Opening speed of the hand

2 Number of thumb-index tapping

3 Excursion angle of the ankle during walking

4 Frequency of toe tapping (heel pin)

5 Frequency of heel tapping (forefoot pin)

6 Toe lift angle (tapping heel-tip)

Multivariate discriminant analysis showed a perfect discrimination (100%) between controls’ and patients’ groups (p < 0.0001). Good correlations (0.69 ≤ R ≤ 0.93) between the selected biomechanical parameters and PD patients’ clinical scores were found.Conclusions: Combined analysis of motor pattern allowed a remarkable im-provement in PD patients’ assessment related to both clinical evaluation and discrimination with healthy subjects.SensHandV1 and SensorFootV1 system might be diagnostically very useful at the earliest subclinical stage (patients not yet complaining from motor symp-toms with negative neurological examination).Moreover, our technological system could be used in the follow-up of individu-als at risk for developing PD.No conflict of interest.

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ANALYSIS OF IMMUNOLOGICAL FACTORS, DOPAMINE LEVEL AND OXIDATIVE STRESS AS A PERIPHERAL BLOOD MARKER IN PARKINSON’S DISEASEJ. Gnaanmirthan Pillai1,*, B. Vellingiri2, S. Keshavarao2

1Head of the Institute, Bharathiar University, Coimbatore, India, 2Human Molecular Genetics Laboratory Department of Zoology, Bharathiar University, Coimbatore, India

Objectives: Oxidative stress and generation of reactive oxygen species are believed to be implicated in Parkinson’s disease (PD). Oxidative stress and immunological factors contribute to neuronal dysfunction in PD. Monoamine oxidase type B (MAO-B), which catalyses the breakdown of dopamine in human brain, is said to be involved in the pathophysiology of PD.Methods: The PD patient group comprised of 54 individuals and equal num-bers of control groups were selected. The Hydroxyl radical (OH), glutathione peroxidase (GPx) and dopamine levels in blood, superoxide dismutase (SOD), thiobarbituric-acid-reactive substances (TBARS) and vitamin E (Vit

E) in plasma and also immunologic factors such as interleukin (IL) and tumor necrosis factor (TNF)-α were analyzed in PD and controls of the present study.Results: Compared to healthy controls, PD patients exhibited lower frequen-cies in erythrocyte GPx, plasma Vit E, plasma SOD, IL2, and dopamine, be-sides a significant increase in the levels of hydroxyl radical, plasma TBARS, IL-1β, IL-6 and TNF-α analyzed in the study.Conclusions: The results of the study might provide further support for the interrelationship between the oxidative stress, neurotransmitter and immune system. In addition, identifying the associations between these parameters is a clinically relevant endeavor, and there is a reasonable possibility that iden-tifying more of these associations will assist in identifying susceptibility bio-markers for this challenging disease.Keywords: Parkinson’s disease, interleukin, oxidative stress, dopamineNo conflict of interest.

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PROTEOMIC ANALYSIS TO IDENTIFY NOVEL CANDIDATE DIAGNOSTIC BIOMARKERS IN CSF OF DE NOVO PARKINSON’S DISEASE PATIENTSK.D. van Dijk1,*, D. Chiasserini2, T.V. Pham2, S.R. Piersma2, H.W. Berendse1, C.R. Jimenez2, W.D.J. van de Berg3

1Neurology, VU University Medical Center, Amsterdam, Netherlands, 2OncoProteomics Laboratory of the Department of Medical Oncology, VU University Medical Center, Amsterdam, Netherlands, 3Anatomy and Neurosciences, VU University Medical Center, Amsterdam, Netherlands

Objectives: Clinico-pathological studies have demonstrated that an early clin-ical diagnosis of Parkinson’s disease (PD) can be difficult, as PD symptoms can be subtle and resemble the symptoms of atypical parkinsonian disorders. Biomarkers that improve diagnostic accuracy in the early PD stages are es-sential in the selection of appropriate patients for clinical trials. Cerebrospinal fluid (CSF) is in direct contact with the extracellular fluid surrounding brain cells and therefore holds great promise as a source for biomarker identifica-tion. The aim of the present study was to identify novel diagnostic biomarker candidates for PD in CSF.Methods: We analyzed the CSF proteome of 10 drug-naive PD patients and 10 neurologically healthy controls using a workflow involving immuno-deple-tion of high-abundant proteins, mono-dimensional SDS-PAGE in conjunction with nanoLC-MS/MS-based proteomics and label-free protein quantification. CSF proteomes of PD patients were compared to controls by the number of spectral counts using a beta-binomial statistical model.Results: Ninety-one out of a total of around 1300 identified proteins were differentially expressed in the CSF of PD patients compared to controls. Preliminary analysis indicates that several regulated CSF proteins are asso-ciated with axonal guidance and complement activation. Further analysis to prioritize potential candidates is currently ongoing.Conclusions: The CSF proteome of de novo PD patients provides potential candidate diagnostic biomarkers for PD. Prioritized candidate biomarkers will be validated in an independent cohort of patients using antibody-based methods.No conflict of interest.

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REPRODUCTIVE MARKERS FOR PARKINSON’S DISEASEE. Predtechenskaya1,*1Medicine, Novosibirsk State University, Novosibirsk, Russia

Objectives: Dopamine inhibits neuron receptors of the somatic nervous system (in particular striatopallidal system and motor neuron of the spinal cord). Neuroendocrine system is likewise subject to the dopamine’s in-hibitory influence: Dopamine suppresses the secretion of prolactin in the hypophysis. OBJECTIVE: to study the connection between [A] hyperprol-actinemia induced by reduced dopamine levels in women in reproductive period and [B] the development of Parkinson’s disease in older or elderly women.Methods: Long-term observation, neurological examination focusing on aki-netic–rigid syndromes, and examination of prolactin levels using immunofluo-rescence analysis.

1. In patients with hyperprolactinemia, neurological examinations were con-ducted in the course of several years to detect minimal clinical symptoms of Parkinson’s disease.

2. For older and elderly women with Parkinson’s disease past reproduc-tive history and prolactin levels were analyzed. We excluded symp-tomatic and functional hyperprolactinemia from this study. Long-term observation, neurological examination with a focus on akinetic–rigid

2.Day 1 Monday, Section 1 Parkinson's Disease.indd 62.Day 1 Monday, Section 1 Parkinson's Disease.indd 6 10/28/13 5:42 PM10/28/13 5:42 PM


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syndromes, and examination of prolactin levels using immunofluores-cence analysis.

Results: Group 1: 25 women (23–38 years old) with fertility disorders caused by hyperprolactinemia: 10 women with hypomenstrual syndrome, 16 women with primary infertility, 5 with secondary infertility. Average prol-actin level within the group 1803 mIU/L. Neurological examination revealed minimal manifestations of hypokinetic syndrome (hypomimia, hypopho-nia, general hypokinesia and impairment in running or dancing). Group 2: 25 women (45–65), with Parkinson’s disease. In the past, all women had reproductive disorders: 10 women hypomenstrual syndrome, 10 infertil-ity, 12 premature menopause. Average level of prolactin within the group 1008 mIU/L.Conclusions: Reduced level of dopamine causing hyperprolactinemia and fertility disorders is an early diagnostic marker of Parkinson’s disease.No conflict of interest.

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ASSESSMENT OF TWO POINT TAPPING FREQUENCY VARIATION IN PARKINSONISM. A POTENTIAL ADDITIONAL DIAGNOSTIC TOOL.M. Silva1,*, C.E. Pollock1

1Neurology, Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, United Kingdom

Objectives: The two point tapping test is commonly used in the assessment of patients with parkinsonism. It is recognized that patients with parkinson-ism have slow two point tapping times that fatigue. In idiopathic Parkinson’s disease (IPD) there will typically be frequency asymmetry between both sides.Our hypothesis is that there is a characteristic frequency fluctuation in the two point tapping time that could potentially be used to differentiate IPD from other forms of parkinsonism.The ability to separate these disorders at an early stage would be a significant advance.Methods: We have developed a tapping analyzer and frequency analyzing software to investigate this.Results: Preliminary data on normal controls and individual patients will be shown.Conclusions: The initial data suggests that the analysis of frequency vari-ation in two point finger tapping is worth exploring further and may help to discriminate between IPD and other forms of parkinsonism.Reference1. Muir SR, Jones RD, Andraea JH, Donaldson IM. Measurement and analy-

sis of single and multiple finger tapping in normal and Parkinsonian sub-jects. Parkinsonism and Related Disorders 1995; 1(2):89–96.


008

A PILOT EVALUATION OF THE PURDUE PEGBOARD TEST IN DE NOVO PARKINSON’S DISEASEX. Dan1,*, P. Chan1, J. Ma1, L. Sun1, Z. Gu1

1Neurology and Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China

Objectives: To evaluate the utility of Purdue pegboard test (PPT) in patients with de novo Parkinson’s disease (PD).Methods: We assessed 40 de novo, drug-naive patients with idiopathic uni-lateral parkinsonism and 32 age-similar healthy controls in this preliminary prospective, cross-section study. All participants performed PPT under unitask and dual-task conditions. The correlations of PPT with cognition function and motor symptoms of PD patients as well as the PPT diagnostic accuracy for PD were analyzed.Results: Patients with PD showed reduced pegboard dexterity compared with the controls during the unitask or when adding a serial 3 subtraction concurrent task conditions (Table 1). We found both hands PPT scores had an area under the receiver operating characteristic curve (AUC) of 0.822 (75% sensitivity; 84% specificity). With the addition of the second task, the AUC value reached 0.851(87% sensitivity; 78% specificity). Moreover, the results of executive and visuospatial function as well as the severity of PD patients was correlated with the PPT performance. The stepwise regression analysis demonstrated the PPT scores best reflected the bradykinesia symptoms. While PD patients were separated with pure left or right hand affected groups, all the results remained essentially unchanged.

Table 1. Characteristics and tests results in patients and controls.

Variable PD Control P

N = 40 N = 32

Gender male, n(%) 22(55.0) 15(46.9) 0.636

Age at exam, Mean ± SD, y 58.05 ± 7.81 60.52 ± 8.11 0.194

MMSE, Mean ± SD 28.42 ± 1.60 29.16 ± 9.65 0.026

GDS-30, Mean ± SD 6.06 ± 3.13 4.31 ± 3.85 0.007

TMTB-A 66.40 ± 54.53 59.12 ± 30.66 0.51

Stroop interference 54 ± 12.77 50.78 ± 14.79 0.35

Digit-span(forward) 8.03 ± 0.97 8.20 ± 0.93 0.475

Digit-span(backward) 4.18 ± 1.00 4.70 ± 1.56 0.110

Stereo acuity 6.28 ± 2.52 7.37 ± 2.46 0.078

Single task

Left land 12.49 ± 1.88 14.47 ± 1.36 3.9 × 10−6

Right hand 13 ± 2.14 15.61 ± 1.77 4.9 × 10−7

Both hand 19.90 ± 3.73 24.42 ± 2.98 4.3 × 10−7

Dual tasks

Left hand 10.94 ± 1.91 12.48 ± 2.21 0.002

Right hand 10.54 ± 2.37 13.36 ± 2.13 1.6 × 10−6

Both hand 17.61 ± 3.40 22.83 ± 3.96 7.4 × 10−8

Interference effects

Left hand −0.12 ± 0.13 −0.14 ± 0.13 0.570

Right hand −0.19 ± 0.14 −0.14 ± 0.12 0.167

Both hand −0.11 ± 0.13 −0.06 ± 0.12 0.145

Disease duranon, Mean ± SD, y

1.54 ± 1.06 N/A

Right/left hand affected 24/16 N/A

UPDRS part II 6.38 ± 2.51 N/A

UPDRS part III 10.12 ± 3.44 N/A

UPDRS tatol scores 17.20 ± 5.73 N/A

Bradykinesia 4.00 ± 1.99 N/A

H&Y 1.19 ± 0. 31 N/A

Conclusions: PPT may serve as an auxiliary diagnostic assessment for PD in very early stage and biomarker for the disease progression.No conflict of interest.

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ACETALDEHYDE AND ENDOGENOUS ALCOHOL IN PATHOGENETIC MECHANISMS OF FORMATION OF PARKINSON’S DISEASEA. Malykhin1,*, N. Malykhina1, O. Vasyliieva1

1Emergency Department of Psychiatry and Addiction, Institute of Neurology Psychiatry and Narcology of Academy of Medical Science o, Kharkov, Ukraine

Objectives: To determine originating mechanisms of Parkinson’s disease (PD) considering metabolism of endogenous alcohol, participating in the regu-lation of acetaldehyde and dopamine.Methods: Automatic Noninvasive Express Screening Analyzer ANESA was used, as the main method of examination.Results: In the third Regional Psychiatric Hospital and Neurology Department of the Institute, 160 male-patients were examined during 3 years.Based on analysis of risk factors (RF) of alcohol and food ingestion in all pa-tients (three groups), it has been established that RF have mixed effect on thermal regulation of the body and volume of synthesized endogenous alcohol and acetaldehyde (Table 1).The regulatory system of an organism is based on acetylcholine hydrolysis and metabolism of tyrosine and phenylalanine, glucose and lactic acid, etha-nol and acetaldehyde, calcium and dopamine, which are interacted via molar weights of thrombocyte’s membrane of receptors: PADGEM and Fc immune components, insulin and PRARs, G-proteins and NF-kB



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Conclusions: Thermal regulation is a complex regulatory metabolic and hemodynamic proton-dependent process of interaction between hippocampus and hypothalamus, related to volume of ethyl alcohol and acetaldehyde per body weight unit. Relevant pH values of arterial and venous blood related to thermal regulation and cardio rhythm, determines regulation imbalance in the bradykinin-acetylcholine system, as well as in the dopamine-adrenalin sys-tem. It leads to increasing of acetaldehyde production and changes of dopa-mine metabolism. Those mechanisms are basic for PD development.

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HIGHER SERUM LEVEL OF INFLAMMATORY BIOMARKER NT-PROCNP IN PARKINSON’S DISEASE PATIENTS ON DOPAMINE AGONISTSS. Szlufik1,*, D. Koziorowski1, R. Tomasiuk2, A. Friedman1

1Department of Neurology Faculty of Health Science, Medical University of Warsaw, Warsaw, Poland2Department of Laboratory Diagnostics, Brodnowski Hospital in Warsaw, Warsaw, Poland

Objectives: Recently, there is rapidly growing evidence for the influence of in-flammation on the development and progression of Parkinson’s disease (PD). There are also studies showing possible role of dopamine agonists in the ex-pansion of systemic inflammation. NT-proCNP has been correlated in PD with inflammatory cytokines, especially TNF-α, IL-10. The aim of the study was to as-sess the serum level of NT-proCNP in PD patients, and to evaluate the possibility of correlation between intensity of inflammation and antiparkinsonian treatment.Methods: The study group consisted of 132 patients with idiopathic PD (79 men, 53 women; mean age 59,6 ± 15,1 years) and 42 healthy controls (20 men, 22 women; mean age 58,5 ± 11,5 years). Clinical data regarding to the antiparkinsonian treatment were also assessed. Quantitative determination of human NT-proCNP in serum samples of PD patients and control group was determined with the use of ELISA kits.Results: Serum level of NT-proCNP was significantly higher in PD patients than in the control group (p < 0,05; PD vs. control: mean 3,65 ± 5,5 vs. 1,49 ± 0,73, median 1,81 vs. 1,46). The serum level of NT-proCNP was sig-nificantly correlated with the use of dopamine agonist (ropinirole) (p < 0,001; R = 0,396) as well as with its dosage (p < 0,001; F(4,166) = 13,22).Conclusions: Serum level of NT-proCNP is significantly higher in PD group, especially in patients treated with ropinirole. The higher serum level of NT-proCNP in PD patients treated with ropinirole suggests a potential proinflam-matory characteristic of dopamine agonists.No conflict of interest.

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TAU, PHOSPHO-TAU, β-AMYLOID42 AND α-SYNUCLEIN IN THE CEREB-ROSPINAL FLUID OF PATIENTS WITH PARKINSONISM.A. Bougea1,*, G. Paraskevas1, V.C. Constantinides1, E. Kararizou1, E. Kapaki11Neurology, Eginition Hospital of Athens, Athens, Greece

Objectives: The study of CSF biomarkers in neurodegenerative diseases provides information on the underlying biochemical pathology and may also facilitate their differential diagnosis. The purpose of this study was to identify tau, phospho-tau, β-amyloid42 and α-synuclein levels in the CSF of patients presenting with parkinsonism of neurodegenerative etiology.Methods: The above mentioned biomarkers were measured by ELISA in 28 patients with Parkinson’s disease (PD), 14 patients with multiple system atro-phy (MSA), 30 patients with either progressive supranuclear palsy or cortico-basal degeneration (PSP/CBD) and a control group (CG) of 108 comparable healthy.Results: Tau protein levels were significantly increased in MSA and PSP/CBD patients compared to the control group and PD patients. Phospho-tau and Ab42 levels did not differ among the 4 groups, whereas α-synuclein levels were significantly decreased in PD and PSP/CBD patients compared to the control group and MSA patients.

Conclusions: These results indicate that the combined measurement of CSF levels of tau protein and α-synuclein could facilitate the differential diagnosis between patients with PD, MSA or PSP/CBD.No conflict of interest.

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INTERLEUKIN-6 CONTRIBUTES TO MORTALITY IN PARKINSON’S DISEASE PATIENTS: A 4-YEAR PROSPECTIVE STUDYI. Rektor1,*, M. Dufek2, J. Lokaj3, I. Rektorova4

1Movement Disorders Center Multimodal and Functional Imaging Research Group, Masaryk University CEITEC MU, Brno, Czech Republic, 2Neurology, Masaryk University and Teaching Hospital Ste Anne, Brno, Czech Republic, 3Allergy and Immunology, Masaryk University and Teaching Hospital Ste Anne, Brno, Czech Republic, 4Movement Disorders Center and Applied Neuroscience Research Group, Masaryk University and CEITEC MU, Brno, Czech Republic

Objectives: The association between abnormal serum immunomarkers and mortality in 53 consecutive Parkinson’s disease patients was studied. We recently reported changes in the spectrum of serum immunomarkers mannan-binding lectin (MBL), interleukin (IL)-6, and tumor necrosis factor – alpha (TNF-α) in patients with PD (1). We hypothesized that abnormal plasma cytokine levels may indicate the presence of a cerebral inflammatory process that might contribute to fatal outcomes in PD patients.Methods: The plasma level of cytokines TNF-α, IL-6, and MBL were investi-gated. The baseline serum immunomarkers obtained from patients who died (n = 18) during a 4-year follow-up period were compared with the data of patients who survived (n = 37).Results: The baseline level of IL-6 was significantly higher in the deceased patients than in the survivors. Elevated IL-6 levels and age were major inde-pendent contributors to disease mortality. Differences between other plasma cytokine level abnormalities were not significant.Conclusions: IL-6 elevation may be a marker of increased mortality risk in Parkinson’s disease patients. The decedents were older, with more severe clinical cognitive and vascular impairment than the survivors in our cohort (2). The inflammation may act in association with vascular and other factors and comorbidities in progressive neurodegenerative pathology.References1. Dufek M, et al. Serum inflammatory biomarkers in Parkinson’s disease.

Parkinsonism Relat Disord. 2009; 15(4):318–20.2. Rektor I, et al. Impairment of brain vessels may contribute to mortality in

patients with Parkinson’s disease. Mov Disord. 2012; 27(9):1169–72.No conflict of interest.

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CHARACTERIZATION OF SOME BIOCHEMICAL PARAMETERS AT THE ADVANCED STAGES OF PARKINSON DISEASE.I.V. Milyukhina1,*, M. Tikhomirova2, M.N. Karpenko2

1Department of Physiology Clinic, Institute of Experimental Medicine of the NorthWest Branch of the Russian Academy of Medical Sciences (IEM NWB RAMS), Saint-Petersburg, Russia, 2Department of Physiology, Institute of Experimental Medicine of the NorthWest Branch of the Russian Academy of Medical Sciences (IEM NWB RAMS), Saint-Petersburg, Russia

Objectives: Patients at the advanced stages of Parkinson disease (PD) suffer from non-motor manifestations. Some biochemical parameters can reflect pro-gression of the disease, severity of non-motor symptoms [1]. Identification of the relations between clinical scores, treatments and biochemical parameters in the PD patients.Methods: We measured levels of superoxide dismutase (SOD3), interleukin (IL)-10, tumor necrosis factor-α (TNF-α), uric acid (UA) in blood samples from PD patients (n = 86).Results: UA concentration was inversely related to the rate of change in the UPDRS I score (r = −0.55), UPDRS III score (r = −0.32). Patients having high

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Table 1. Acetaldehyde and endogenous alcohol volume, functional state of the liver depending on the and dynamics of active point temperature indicators.

Groups and temperature values

Acetaldehyde, mg/dl

Ratio of carotid ans abdominal

and temperaturePH*

PH PHPH -PH

a v

a v

+ Cholinesterase, mmol/l

LDH, μmol/l Bilirubin μmol/l

Endogenous alcohol mg/dl

Energy of peptide bond

breaking kJ/sec1 rpynna Σ 168 ± 5C° 0.360 ± 0.150 2.0 < Tcat/abd ≤ 2.05 0.074 ± 0.025 307.02 ± 17.68 2.01 ± 0.17 12.08 ± 0.92 0.0260 1308.662 rpynna Σ 175.5 ± 2C°

0.437 ± 0.170 1.9 ≤ Tcat/abd ≤ 2.00 0.082 ± 0.025 278.03 ± 21.19 2.47 ± 0.19 18.53 ± 1.49 0.0258 1302.55

3 rpynna Σ 178 ± 1.5C°

0.626 ± 0.170 Tcat/abd < 1.9 0.102 ± 0.025 229.61 ± 20.05 3.35 ± 0.27 31.06 ± 2.73 0.0256 1287.42

Arterial-venous pH difference: pHa − pH of arterial blood, pHv − pH of venous blood.



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level of UA were characterized by lower severity of affective and cognition disorders. Direct correlations between the level of TNFα and scores in UPDRS IV and UPDRS II and between increase in the dose of levodopa and the level TNFα were found. In patients with a quick PD progression we report a consid-erable decrease of SOD3 level.Conclusions: The protective effects of the high level of UA are connected with a predominant influence on the cognition/mood. SOD3 level in serum could be a useful biomarker for quick progression of PD. Levodopa has a dose-dependent effect on t IL-10 and TNFα levels also there is a reason to presume the immunomodulatory effect of levodopa. Patients with a high level of TNFα are at the risk of early fluctuations development. Thus, these bio-chemical markers can be helpful in formulation of therapy complications and severity of the non-motor symptoms.Reference1. Schapira A.H. Recent developments in biomarkers in Parkinson disease.

Curr Opin Neurol. 2013 Aug; 26(4):395–400.No conflict of interest.

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THE EARLY ONSET AND SLOW PROGRESSION OF PARKINSON’S DISEASE (PD) CORRELATE TO COPPER STATUS INDEXES OF BLOOD SERUME.Y. Ilyechova1,*, I.V. Milyukhina2, M.N. Karpenko2, A.N. Skvortsov3, V.M. Klimenko2, L.V. Puchkova3

1Department of Molecular Genetics, Institute of Experimental Medicine of the NorthWest Branch of the Russian Academy of Medical Sciences, St.Petersburg, Russia, 2Department of Physiology, Institute of Experimental Medicine of the NorthWest Branch of the Russian Academy of Medical Sciences, St.Petersburg, Russia, 3Department of Biophysics, St.Petersburg State Polytechnical University, St.Petersburg, Russia

Objectives: PD is often associated with low copper status indexes (CSIs: copper and ceruloplasmin concentrations, oxidase activity) of blood serum. In our work we address the nature of this symptom searching for potential targets for PD treatment.Methods: The blood sera of 50 PD patients without regard to gender with severity indexes 1–4 (Hoehn and Yahr scale) were analyzed for copper con-centration (FAAS), ceruloplasmin content (immunoelectrophoresis and immu-noblotting), and oxidase activity (p-phenylenediamine assay).Results: Copper and ceruloplasmin concentrations ranged 400–1200 ug/L and 0.15–0.6 g/L respectively; the normal values being 800–1300 ug/L and 0.25–0.6 g/L. Oxidase activity strongly correlated to ceruloplasmin concen-tration. In 15 patients CSIs comprised ½ of normal values. This is typical for heterozygous carriers of Wilson disease (WD) [1]. All these 15 patients had early onset (before age 45) and slow development of PD. They were born in Eastern Europe, which is the region with the highest frequencies of mutations in Wilson gene (ATP7B, Cu(I)-transporting ATPase) of the former USSR. As is known, in WD patients ATP7B dysfunction results in serum copper, SOD1 and ceruloplasmin deficiencies, while copper, iron, and zinc accumulate in neurons to neurotoxic levels. We obtained the samples of DNA of the patients with nor-mal and low CSIs. The samples are being analyzed for the most widespread mutation H1069Q in ATP7B.Conclusions: Revealing heterozygous WD carriers among the PD patients may permit to treat these cases of PD more specifically.Reference1. Johnson S. Is Parkinson’s disease the heterozygote form of Wilson’s dis-

ease: PD = 1/2 WD? Med Hypotheses. 2001 Feb; 56(2):171–3.No conflict of interest.

015

RISK FACTORS FOR PARKINSON DISEASES. Shaafi1,*1Neurology, Tabriz University of Medical Science, Tabriz, Iran

Objectives: Risk factors for Parkinson diseaseMethods: A systematic review of researches in past 10 years (2003–2013) in published studies (MEDLINE database search on Pubmed and meta-analysis-cochrane collaboration). Review articles, editorials, commentaries, personal ideas, letters that reported no new data were excluded.Results: The family history, stressful occupations, head injury and rural living (exposing to herbicides or pesticides) are strongest risk factors associations with later diagnosis of PD (odds ratio [OR], 3.23; 95% confidence interval [CI], 2.65–3.93 and OR, 4.45; 95% CI, 3.39–5.83 constipation (relative risk [RR], 2.34; 95% CI, 1.55–3.53) each at least doubling the risk of PD. In the system-atic review, additional associations included negative associations also were reported.Conclusions: most individuals will have one or more of the risk factors and never experience any of the symptoms. The one risk factor we all possess is aging, which is a condition that is currently incurable! However, more and more is becoming understood as to how and why these various risk factors

influence likelihood of Parkinson’s. As knowledge grows, so does the possibil-ity of a cure. The most popular risk factors that were studied include.Reference1. 10 years ago (2003–2013) in documented published studies. (MEDLINE

database search on Pub Med and meta-analysis and the Cochrane Collaboration).

016

RISK FACTORS ASSOCIATED WITH PARKINSON DISEASE, AN OBSER-VATIONAL CROSS-SECTIONAL STUDYM. Dumitru1,*, V. Chirita1, R. Chirita1

1Adult Psychiatry, “Socola” Psychiatric Hospital, Iasi, Romania

Objectives: The objective of this study was to examine the prevalence of sleep problems and their associated factors in patients with Parkinson’s dis-ease from a hospital from Romania.Methods: Were included consecutive PD inpatients over a period of 6 months, that responded to the Parkinson’s Disease Sleep Scale (PDSS)1. Factors as-sociated with sleep were also investigated.Results: 44 patients fulfilled the inclusion criteria; the mean Hoehn and Yahr stage was 2.73, and the mean UPDRS part III was 22.6. A score below 5 on one item on the PDSS was observed at 68% of the patients.Conclusions: The current findings call for increased awareness of sleep problems in PD patients, especially focusing on the association with mental health problems, fatigue and RLS.Reference1. Chaudhuri KR. J Neurol Neurosurg Psychiatry 2002.No conflict of interest.

017

INCIDENCE OF PARKINSON’S DISEASE: AGE AND SEX VARIATION IN REPUBLIC OF TATARSTAN, RUSSIAN FEDERATION COMPARED TO RUSSIA AS A WHOLE AND EUROPEM. Jayaraman1,*, Z.A. Zalyalova1, E.I. Bogdanov1

1Department of Neurology and Rehabilitation, Kazan State Medical University Republican Clinical Hospital, Kazan, Russia

Objectives: To estimate the incidence of PD from 2010–2013 and the varia-tion in age and gender and to compare the incidence of PD between Republic of Tatarstan, Russia and Russia as a whole and Europe.Methods: The centre for extrapyramidal disorders, Kazan is where all patients with movement disorders Tatarstan, Russia are treated. All the PD cases in Tatarstan were referred to the Centre. The data were gathered retrospectively from the surveillance database. The diagnosis were made by movement dis-order specialists by PD’s society brain bank criteria and categorized under Hoehn and Yahr scale. The incidence is calculated for the population at risk (>30 years)Results: The distribution of gender and age is shown in Table 1, picture 1, Table 2 and picture 2. The overall gender ratio between male and female is 0.81, The incidence of PD in Russia as a whole was found to be 63.9(2), while in Europe it varies between 8.6- 19(1)

Table 1. Total number of news cases and incidence of PD by variation in gender in republic of Tatarstan in 2010–13.

2010–11 2011–12 2012–13

Cases no

Incidence Cases no

Incidence Cases no

Incidence

Overall 647 28.1 599 25.8 663 28.5

Male 297 29.6 273 27.0 285 28.2

Female 350 29.9 326 24.8 378 28.8

Year

Nos. of cases

2012-13

2011-12

2010-11

0 200 400 600 800 1000 1200 1400

OverallMaleFemale

Picture 1. Total number of cases of Pd in 2011-12 by genter variation.



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Table 2. Total number of cases by variation in age in Republic of Tatarstan in 2010–13.

Total 2010–11 2011–12 2012–13

Age (years)

<30 1 0 0 1

30–39 10 5 5 0

40–49 88 35 23 30

50–59 415 136 137 142

60–69 648 224 190 234

70–79 638 210 209 219

≥80 109 37 35 37

age group<30

0100200300400500600700

30-39 40-49 50-59 60-69 70-79 >80

Nos

. of c

ases

Picture 2. Total number of cases of Pd in 2010-13 by variation in age.

Conclusions: The result of our study shows that there is a steady increase in the incidence of PD after the 5th decade of life both gender, there is no evidence for progressive rise late-life. There is an insignificant increase in incidence among women compared to men. The incidence of PD is markedly low in Tatarstan when compared to Russia as a whole and high in Tatarstan when compared to Europe.References1. Prevalance and incidence of PD in Europe, European

Neuropsychopharmacology 15 (2005) 473–490.2. Parkinsonism in Tatarstan in extrapyramidal centre, Zalyalova ZA 2010.No conflict of interest.

018

THE INCIDENCE OF PARKINSON’S DISEASE ACCORDING TO GENDER, SHAPE AND ONSET OF THE DISEASE OF UZBEK NATIONALITY.R. Matmurodov1,*, M. Raimova1, K. Khalimova1

1Neurology, Tashkent Medical Academy, Tashkent, Uzbekistan

Objectives: To study the occurrence of Parkinson’s disease according to gen-der, shape and onset of the disease Uzbek nationality.Methods: A total of 78 patients (39 men and 39 women) with a mean age of 50,9 ± 5,71 years with PD. All patients underwent clinical and neurological examination, including a detailed assessment of movement disorders using the Unified Parkinson’s Disease Rating ScaleResults: Medium debut of the disease in the total group was 51,93 ± 12,65 years. When akinetic-rigid form of the average age at onset was 47,11 ± 13,13, tremor form of 55,51 ± 11,61 and mixed 53,01 ± 12,48. Akinetic-rigid form occurs in women at a younger age than men (49,36 ± 10,09 and 54,85 ± 9,7, respec-tively, p < 0.05), mixed form was more common in younger men (54,6 ± 8,4 and 58,05 ± 7,6). Debut at the average age of men was 51,8 ± 5,4 years, and females 52,2 ± 6,4. Akinetic-rigid form began in women at a younger age than men (44,6 ± 8,04 and 48,12 ± 7,7, respectively, p < 0.05), mixed form was more common in younger men (50,1 ± 5,3 and 54,68 ± 6,2).Conclusions: Thus, shaking form occurs at older ages, and akinetic - rigid form at younger ages, women have an early onset of the disease is the akinetic - rigid form, and men mixed form of the disease.

019

INCIDENCE AND PATHOLOGY OF SYNUCLEINOPATHIES IN OLMSTED COUNTY, MN FROM 1991- 2005R. Savica1,*, B. Grossardt2, J. Bower2, B. Boeve2, J. Ahlskog2

1Neurology, University of Utah, Salt Lake City, USA, 2Neurology, Mayo Clinic, Rochester, USA

Objectives: The epidemiology of individual synucleinopathies manifesting with parkinsonism has not been well characterized in the general population. Synucleinopathies include: Dementia with Lewy bodies (DLB), Parkinson disease with Dementia (PDD), Parkinson’s disease without dementia (PD), and Multiple System Atrophy (MSA).

Methods: We investigated the incidence of synucleinopathies associated with parkinsonism among the residents of Olmsted County, Minnesota from 1991 through 2005 and compared the incidence of Parkinson Disease (PD) with that of DLB and PDD. We used the medical records-linkage system of the Rochester Epidemiology Project to identify all subjects who received a screening diagnos-tic code related to parkinsonism in Olmsted County, Minnesota, from January 1, 1991, through December 31, 2005. A movement disorders specialist reviewed the complete medical records of each subject who screened positive to deter-mine the type of parkinsonism and the presumed proteinopathy.Results: Among 542 incident cases of parkinsonism, 389 patients were classi-fied as presumed synucleinopathies (71.8%). The incidence rate (per 100.000 person-years) of synucleinopathies was 21.0 overall and increased with age. PD without dementia was documented in 264 cases (48.7%), with an inci-dence of 14.2. In contrast, the incidence per 100.000 was 3.5 for DLB, 2.5 for PDD, and 0.8 for MSA. Findings at brain autopsy confirmed the clinical diagnosis in 53 of 65 patients who underwent autopsy (81.5%).Conclusions: PD without dementia is the most common synucleinopathy and the incidence is almost three fold higher that the incidence of DLB and PDD combined.No conflict of interest.

020

IMPACT OF STATIN USE ON INCIDENCE OF PARKINSON’S DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF OBSERVATIONAL STUDIESK. Undela1,*, K. Gudala2, S. Malla2, D. Bansal2, G. Parthasarathi11Pharmacy Practice, JSS College of Pharmacy JSS University, Mysore, India, 2Pharmacy Practice, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, India

Objectives: The aim of this study was to assess the association between statin use and risk of Parkinson’s Disease (PD) using all observational studies published regarding this subject.Methods: The PubMed database was searched for observational studies of statin use and risk of PD, published up to March 2013. Combined relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using ran-dom-effects model. Subgroup and sensitivity analyses were also performed.Results: A total of 8 (5 case-control and 3 cohort) studies contributed to the analysis. There was heterogeneity and publication bias among the studies. Statin use significantly reduced the risk of PD by 23% (RR 0.77, 95% CI 0.64–0.92; p = 0.005). However, long-term statin use did not significantly affect the risk of PD (RR 0.72, 95% CI 0.45–1.13; p = 0.15). Stratification of studies by age and smoking status, significantly affected the final estimate (age ad-justed RR 0.61, 95% CI 0.42–0.86; p = 0.005, age not adjusted RR 0.93, 95% CI 0.83–1.05; p = 0.23 and smoking adjusted RR 0.60, 95% CI 0.42–0.87; p = 0.007, smoking not adjusted RR 0.92, 95% CI 0.82–1.02; p = 0.10). Furthermore, sensitivity analysis confirmed the stability of results.Conclusions: This study suggests that statin use reduced the risk of PD. Nevertheless, more randomized clinical trials and observational studies are required to confirm this association with underlying biological mechanisms in the future.Reference1. Gao X, et al. Prospective study of statin use and risk of Parkinson disease.

Arch Neurol 2012; 69:380–4.No conflict of interest.

021

THE EPIDEMIOLOGY OF PARKINSON DISEASE AND OTHER TYPES OF PARKINSONISM IN GREEK PATIENTS.A. Bougea1,*, G. Paraskevas1, E. Kapaki11Neurology, Eginition Hospital of Athens, Athens, Greece

Objectives: Current data on the pattern of parkinsonism and Parkinson’s dis-ease in Greeks are sparse. This study aims to investigate their incidence and distribution.Methods: We used the medical records-linkage system of the first Neurology Department of Athens to identify all subjects who received a screening diag-nostic code related to parkinsonism from November 2011, through November 2012 according to specified clinical diagnostic criteria.Results: Among 89 incident cases of parkinsonism: 26 (8,1%) had Parkinson disease (PD), 3 had PD dementia (0,9%), 7 (2,2) had Multiple System Atrophy (MSA) and 11(3,4%) had dementia with Lewy bodies (DLB), 8 (2,5%) corticobasal degeneration (CBD), 5 (1,6%) progressive supranuclear palsy (PSP). One subject had drug-induced parkinsonism (0,3%), 4 had vascular parkinsonism, and 24 remained unspecified (7.5%). Men had a higher incidence than women for all types of parkinsonism. Men also had a risk of developing parkinsonism with dementia twice that of women. Duration of symptoms prior to presentation ranged between 6 months and 16 years. The mean (SD) time interval from the onset of



11

motor symptoms to diagnosis of PD was 3.6 ± 3.4 years. 0,3% had positive family history of PD.Conclusions: This is the first Greek clinic- based study suggests that Lewy body disorders (PD, DLB, MSA) are the most common cause of parkinsonism, and that within that group, Parkinson’s is most common, followed by Lewy body dementias. Further studies are needed to understand how the rate of diagno-ses of Lewy body disorders relates to overall prevalence of these diseases.No conflict of interest.

022

PARKINSON’S DISEASE IN SENEGAL: EPIDEMIOLOGIC, CLINICAL AND THERAPEUTIC ASPECTSN.M. Gaye1,*, S.O.M. Lemine1, L.B. Seck1, O. Cissé1, M. Ba1, A.D. SOW1, M.S. Diop1, N. Diagne1, A. Bass1, K. Touré1, M. Ndiaye1, A.G. Diop1, M.M. Ndiaye1

1Neurological Clinic Service, CHNU Fann, Dakar, Senegal

Objectives: The study aimed to determine the epidemiologic, clinical and therapeutic aspects of patients treated for Parkinson’s disease (PD).Methods: This was a prospective and transversal study conducted on 19 pa-tients aged between 52 and 79 years and treated for PD at the Neurology department of Fann teaching hospital. The data have been collected using a form of a pre-established survey.Results: Sex ratio was 12/7 and the mean age was 65.26 ± years. 68.42% were married. 21.05% were farmers and 63.15% had achieved the primary level education. Notion of consanguinity was found in 42.10% cases and the use of pesticides was noted in 15.78% of our patients. The average age of onset was around 60.52 ± years. Tremor was the first functional sign (68.42%) and this sign was present in 84.21% of patients. Rigidity was found in 94.73% of them. The other signs were represented by motor fluctuations (78.94%), painful syndrome (73.68%), mood disorder (52.63%), hallucinations (42.10%), insomnia (31.57%), falls (10.52%) and orthostatic hypotension (5.26%). Brain CT was available in five patients and was normal in four of them. 36.84% of the patients were receiving (Levodopa + benserazide), (Levodopa + carbi-dopa) or Piribedil and 52.63% in association with Trihexyphenidyl.Conclusions: PD diagnosis is clinical. Frequency of PD signs in our setting are not different from those in western countries. It is important to educate general practitioners and people for early recognition of PD signs for a better management.Reference1. L. Defebvre. Parkinson’s disease and other parkinsonian syndromes.

Médecine Nucléaire 2007; 31:304–313.No conflict of interest.

023

PARKINSON’S DISEASE IN UKRAINE: RETHINKING CLINICAL AND DISABILITY EPIDEMIOLOGY (10 YEARS EXPERIENCE)V. Golyk1,*, A. Ipatov1, N. Gondulenko2

1Neurology and Border States, Ukrainian State Institute of Medical and Social Problems of Disability Ministry, Dnipropetrovsk, Ukraine, 2Cardiology, Ukrainian State Institute of Medical and Social Problems of Disability Ministry, Dnipropetrovsk, Ukraine

Objectives: Parkinson’s disease (PD) is major extrapyramidal disorder world-wide and the main part of parkinsonism syndrome with prevalence rates ranged 108–257 per 100000 inhabitants.Methods: PD (IDC X G20, G21) prevalence and disability incidence rates were detected in Ukraine for 2003–2012 (per 100000, per region). Disability status is set in case of at least grade 2 ICF domain impairment. The systemic mistake in Ukrainian neurology is widespread practice of false positive “vas-cular parkinsonism” diagnostics, followed epidemiological data incorrectness and inadequate neurological healthcare planning (including pharmacological treatment and social support).Results: PD prevalence rates were increased 44,4–48,1–50,5–51,2–54, 1–56,0–58,1–59,6–61,4–63,7 consequently showing local neurologists PD awareness increasing. Surprisingly, primary disability incidence were gradu-ally decreased: 1,9–2,0–1,9–1,5–1,7–1,5–1,4–1,3–1,3–1,4 consequently. Highest prevalence in 2012 were detected in Kyiv city (112,4), Vinnitsa (125,5), L’viv (100,5), Kyiv (95,3) and Cherkassy (93,9) regions where move-ment disorders centers located. Highest primary disability (2012) observed in Zaporizzhya (2,5), Ternopol’ (2,3) regions, Kyiv (2,3) and Sevastopol’ (2,2) cit-ies. Lowest PD prevalence in 2012 detected in Donetsk (34,4), Odessa (34,7) and Dnipropetrovsk (35,4) regions. The same feature observed in terms of primary disability: Donetsk (0,6), Zhytomir (0,7), Volyn’ (0,7), Dnipropetrovsk (0,8) and Sumy (0,8) regions.Conclusions: Revealed data are the subject of further primary educational and awareness corrections.Reference1. Khobzey NK, Mischenko TS, Golyk VA. Disability due to neurological dis-

eases epidemiology peculiarities in Ukraine. International Neurological Journal 2011; 43: 15–9 (in Russian).


024

ETIOLOGY OF PARKINSON’S SYNDROME IN YOUTH AT FANN HOSPITAL, DAKAR, SENEGALP. Sounga Bandzouzi1,*, Y. Fogang1, D.H. Motoula1, Z. Kone1, K. Toure1

1Neurology Fann teaching Hospital, University of Cheikh Anta Diop, Dakar, Senegal

Objectives: The aim of our study was to determine the incidence and etiology of Parkinson’s syndromes in young patients at the University Hospital of FannMethods: We conducted a cross-sectional study from the February 5th, 2012 to July 31st, 2013 on the cases of Parkinson’s syndrome in patients aged less than 50 years, hospitalized in the department of neurology, CHNU Fann in Dakar.Results: We recruited eight patients. The average age was 27.5 years, with a sex ratio of 2.5. The frequency was 0.76%. Five of our patients were male and 3 female. The tremor was the main driver sign followed by akinesia and rigidity. Dyskinesias were present in four of our patients. Two cases of Wilson’s dis-ease were found. Seven patients were on neuroleptic drugs, including 71.43% on antiemetic drugs and 28.57% on haloperidol. The outcome was favorable in 4 patients to stop Cure. Two were put under one anticholinergic under L-dopa and 2 in D-penicillamine. The remaining of the neurological examination was normal and examination to the slot of the other patientsConclusions: The iatrogenic Parkinson’s syndrome, due to neuroleptics ap-pears to be the main cause in young patients in our context, and some cases of hereditary Parkinson’s syndrome are reported favored by a high rate of consanguinityReferences1. Louis ED, Bennett DA. Mild Parkinsonian.2. Richards M, Touchon J, Ledesert B, Ritchie K. Mild extrapyramidal signs

and functional impairment in ageing. Int J Geriatr Psychiatry. 2002 Feb; 17(2):150–3.


025

POSSIBLE CAUSES, SYMPTOMS, SIGNS, PREVENTION AND MANAGEMENT IN PARKINSON’S DISEASE.R. Nansubuga1,*1School, Action to Positive Change on People with Disabilities, Kampala, Uganda

Objectives: The study tested the possible causes, symptoms, signs, preven-tion and management to Parkinson’s disease.Methods: Data was collected from primary and secondary sources. Questionnaires, interviews, records of the institution, reports, internet surfing and published books were used. The research dealt with pa-tients with Parkinson’s disease and their caregivers making the total 25 respondents.Results: It was discovered that Parkinson’s disease also known as idiopathic is a degenerative disorder of the central nervous system. The four cardinal considered motor symptoms in Parkinson’s include tramor, rigidity, slowness of movement and postural instability. These result from dopamine generating cells in the substantial nigra. Others include gait and posture disturbance like festinating speech and swallowing, voice disorders, mask like face expres-sion among others. Parkinson’s disease can also cause neuropsychiatre dis-turbances ranging from mild to severe disturbances like disorders of speech, cognition, mood, behavior and thought. Parkinson’s disease has no specific known cause. A small proportion of cases is attributed to genetic factors. Environmental factors associated with the increased risk of Parkinson’s includ-ing pesticide exposure, head injuries, and drinking well/spring water. Prevention of Parkinson’s includes increased consumption of caffeine. Although tobacco smocking reduces life expectancy and quality of life, but the risk of Parkinson’s reduces by a third compared to non-smokers. Parkinson’s disease has no cure but medication, surgery and multi disciplinary management provides relief.Conclusions: In Uganda a myth goes that people with Parkinson’s have had a relationship with an in-law which is a taboo. Parkinson’s mostly affects peo-ple who are above 50. In conclusion therefore the cause of Parkinson’s dis-ease remains unknown.Reference1. Institutional records.No conflict of interest.

026

CHARACTERISTICS OF PATIENTS WITH PARKINSONISM SEEN OVER 3 YEARS IN A PRIVATE NEUROLOGY PRACTICE IN NAIROBI, KENYAJ. Mokaya1,*, D.R. Hooker2

1School of Nursing, Nairobi University, Nairobi, Kenya, 2Neurology, Agha Khan University Hospital, Nairobi, Kenya

Objectives: To characterize patients with Parkinsonism



12

Methods: A review of case notes of patients with Parkinsonism seen over 3 years from 2009 to 2012 in a private neurology practice with a movement disorders bias at the Agha Khan University Hospital in Nairobi KenyaResults: 74 patients with parkinsonism seen over 3 years.50 patients (67.6%) had Parkinson’s disease, while 8 patients (10.8%) each had demen-tia with Lewy bodies, progressive supranuclear palsy and multiple system atrophy.41(55.4%) of patients were male, mean age 70 years, mean age of onset 63 years and 36.5% of patients self-referrals, with 51.4% present-ing within 3 years of symptoms onset.52.7%of subjects presented at age of <65 years.58.1% of patients experienced falls, 43.2% had cognitive impair-ment, and 52.7% had depression.50% of patients had neuroimaging.25.7% on a dopamine agonist, 16.2%on a MAO-B inhibitor, and 2.7% on ama-tandine.77% of patients remained on follow-up, with 60.8% reporting some improvement or stability in symptoms.55.4% of study subjects remained inde-pendent in activities of daily livingConclusions: Parkinsonism is a significant burden in neurological practice in Kenya. Many of the patients had relatively young onset presentation. Most of the patients were on levodopa or dopamine agonists. We hope this small study stimulates interest in advocacy for clinical work and research in move-ment disorders in this part of the worldReference1. Professional guide to Parkinson’s disease.No conflict of interest.

027

PREDICTION OF PARKINSON’S DISEASE GLOBAL SEVERITY AFTER A 4-YEAR FOLLOW-UPJ.M. Triviño1, M. Forjaz2, C. Rodriguez-Blazquez3, A. Ayala4, J.M. Rojo5, P. Martinez-Martin6,*1Preventive Medicine and Quality Management, General University Hospital Gregorio Marañon, Madrid, Spain, 2National School of Public Health, Instituto de Salud Carlos III, Madrid, Spain, 3National Center of Epidemiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain, 4National School of Public Health, Carlos III Institute of Health, Madrid, Spain, 5Department of Statistics Centre of Human and Social Sciences, Spanish Council for Scientific Research, Madrid, Spain, 6Alzheimer Centre Reina Sofia Foundation and CIBERNED, Carlos III Institute of Health, Madrid, Spain

Objectives: The Clinical Impression for Severity Index for Parkinson’s Disease (CISI-PD) provides information about the global severity in PD. In cross-sec-tional studies, CISI-PD scores were related to motor examination, disease duration and depression. Goal: To predict PD global severity at 4 years, based on clinical information obtained at baseline.Methods: 205 PD patients were followed yearly through 4 years. Measures: SCOPA scales (motor, autonomic, sleep, cognition, psychosocial, and psychiatric complications), CISI-PD; Hospital Anxiety and Depression Scale (HADS); and EQ-5D-index. We used a multilevel regression model to predict the PD global severity at 2, 3, and 4 years, controlling for the baseline severity level as well other clinical variables, after checking for collinearity. The model goodness-of-fit was tested using paired-samples t-tests, Spearman correlations and intra-class correlation coefficients (ICC).Results: At baseline, age was 63.71 ± 10.71 and disease duration 7.67 ± 5.65 years. Most patients were men (52.7%), in Hoehn and Yahr stage I-II (77.7%). The following indicators, at baseline, were significant predictors of PD severity: EQ-5D-index, HADS, and SCOPA-COG, controlling for baseline CISI-PD and disease duration. The model showed an adequate goodness-of-fit (r = 0.682–0.783, ICC = 0.650–0.743), and a non-significant difference between observed and expected values.Conclusions: The severity of PD is related to the patient’s previous cognitive level, quality of life, and anxiety and depression. These results could help clinicians to identify groups of patients that might suffer deterioration in the PD evolution. More studies are needed with longer follow-up times.No conflict of interest.

028

LOCALIZATION VS. DISTRIBUTED REPRESENTATION IN PD: FOCAL ALTERATIONS IN GLOBAL EFFICIENCY OF FMRI CONNECTIVITY PATTERNS ARE ASSOCIATED WITH DISEASE PROGRESSION AND CLINICAL SYMPTOMATOLOGYS. Tan1,*, A. Nguyen1, H.W. Ming1, A. Liu2, N. Baradaran3, S. Galley3, J. Wang2, M.J. McKeown4

1Pacific Parkinson’s Research Centre, University of British Columbia, Vancouver, Canada, 2Department of Electrical and Computer Engineering, University of British Columbia, Vancouver, Canada, 3Pacific Parkinson’s Research, University of British Columbia, Vancouver, Canada, 4Pacific Parkinson’s Research Centre Department of Electrical and Computer Engineering Department of Medicine (Neurology), University of British Columbia, Vancouver, Canada

Objectives: Traditional approaches in clinical neurology have emphasized changes in activation at discrete loci in the brain (‘localization’). Recently, network approaches to degenerative diseases such as PD have been empha-sized. For example, global efficiency (GE), which refers to the overall capacity for parallel information transfer and integrated processing, is decreased in PD (Skidmore et al., 2011).Here we utilized a method that lies between extremes of localization and net-work analysis to examine the influences of individual regions within PD fMRI connectivity.Methods: Twenty subjects (10 PD, 10 controls) performed a partial visually-guided fMRI tracking task. Anatomically-defined Regions o`f Interest (ROI) – visual, motor and Default Mode Network -- were segmented. We assessed the changes in GE of the connectivity network when each node was individually computationally ‘lesioned’. We determined if any ROIs resulted in consistent ∆GE across subjects after ‘lesioning’. In PD subjects, regression identified the relationship between clinical scores (UPDRS, bradykinesia, tremor and rigidity scores) with ∆GE.Results: In PD subjects, ∆GE in 16/52 ROIs were negatively or posi-tively correlated with disease progression; In a subset of these regions, GE was also significantly different between PD subjects and controls (Table 1).

Table 1. Regions of interest with significant changes in connectivity (re-gression analysis with ∆GE values) with progression of clinical scores (UPDRS, tremor, rigidity, and bradykinesia).

Clinical parameters

Brain region with POSIRIVE(+) correction

Brain region with NEGATIVE(–) correction

UPDRS (United Parkinson’s disease rating scale)

Left superior parietal* Left thalamus proper

Left somatosensory

Left temporal pole

Right cerebellum cortex Right putamen*

Right somatosensory* Right lateral occipital*

Right inferior temporal*

Right caudal middle frontal gyrus

Tremor Left inferior parietal Left thalamus proper

Left superior temporal* Left ventral premotor

Left prefrontal cortex*

Left somatosensory

Left temporal pole

Right cerebellum cortex Right lateral occipital*

Right temporal pole Right inferior temporal*

Right inferior parietal

Right caudal middle frontal gyrus

Rigidity Left cerebellum Left thalamus proper

Left ventral premotor Left lateral occipital


Right somatosensory* Right inferior temporal*

Right temporal pole

Cerebellum vermis

Bradykinesia Left precuneus Left thalamus proper

Left cerebellum Left somatosensory

Left putamen Left temporal pole


Right caudate* Right inferior temporal*

Right somatosensory* Right putamen*

Cerebellum vermis Right caudal middle frontal gyrus

Brain region italicized reoccur in all four clinical parameters (UPDRS, tremor, rigid-ity, and bradykinesia).*Region with clinically significant changes in ∆GE values between age-matched normal control and subjects with PD.



13

Conclusions: With progression of the disease, recruitment or isolation of cer-tain “hubs” have disproportionate influence on PD symptomatology.Reference1. Skidmore F, Korenkevych D, Liu Y, He G, Bullmore E, Pardalos PM (2011).

Connectivity brain networks based on wavelet correlation analysis in Parkinson fMRI data. Neuroscience letters 499:47–51.


029

THE BURDEN OF PARKINSON’S DISEASE IN NOMADIC POPULATION: MONGOLIAN STUDYT. Sosorburam1,*, B. Baatar2

1Intensive Care, Union hospital, Wuhan, China, 2Neurology, University General Hospital, Ulanbator, Mongolia

Objectives: One of the most common neurologic illness that elders expe-rience in developing world, Parkinson’s disease (PD) is demanding greater need of taking neurological care at primary level where majority of the patients struggle. The aim of this study was to explore the challenges people with PD facing among the nomadic population with no previous data.Methods: A questionnaire interviews was conducted to look into challenges that PD patients are struggling. The study continued for 2 years from 2010 and interviewed 56 patients in the 3 different provinces.Results: Out of 56 patients, 35 were males. The age was 48 ± 4 years. 62% had concomitant psychiatric diseases. 58% was on medication and all of them were using levodopa. 19% never had on medication, and about 20% was treated for short term and stopped. 64% were never attended follow-up checkup at local clinic. 71% were tried traditional medicines and applied local healer prior to see physicians.Conclusions: Lack of financial resources and nomadic life style make it very difficult and challenging to tackle this problem. Interestingly some patients still thought that the symptoms of disease are spiritual power and God’s gift. Majority of the patients are seen by general practitioners at local clinics who have little knowledge about neurological illnesses. The study found that under-diagnosis of PD is common due to lack of diagnostic knowledge and no long term availability of medication, patient education is lacking severely. Multidisciplinary actions and fur-ther studies should address these issues, including other neurological disordersMongolian National Health Data.No conflict of interest.

030

COMPARISON BETWEEN EARLY AND LATE ONSET PARKINSON’S DISEASE: A PROFILE OF 1000 PATIENTS FROM INDIAA. Sivan1,*, R. Yadav2, P. Pal21Neurology, EMS Memorial Hospital and Research Center, Perithalmanna, India, 2Neurology, Nimhans, Bangalore, India

Objectives: To compare the clinical profiles of patients with Parkinson’s dis-ease (PD) attending movement disorder clinic in a tertiary care center in India, according to the age of onset (AOO) of motor symptoms.Methods: Retrospective chart review of clinical characteristics of PD patients (n = 1000), seen by the Department of Neurology of the National Institute of Mental Health and Neurosciences in the last decade (2001–2010).Results: The mean AOO of motor symptoms of PD was 52.2 ± 11.5 years, women [50.8 ± 10.4 years] had younger AAO than males [52.6 ± 12.1] (p = 0.03). Late onset PD (LOPD, onset >40 years) comprised of 83.6 % (n = 836), young onset PD (YOPD, 40–21 years) was 15.6 % (n = 156) and 0.8 % (n = 8) were Juvenile onset (≤20 years). Duration of illness was longer in YOPD (58.4 ± 62.5 months) compared to LOPD (37.0 ± 36.9). (p = 0.02). Alcohol use was significantly low in YOPD, 12 (7.3%) compared to LOPD, 106 (12.7%) (p = 0.04). There was no significant difference in gender, family history, smoking, comorbid illness, motor or non-motor features or disease se-verity, between the two groups. When the group with AOO ≤45 years (n = 286) was compared to those >45 years (n = 714), the duration of PD (p = 0.001), hemiparkinsonian phenotype, dyskinesias (p = 0.002) and anxiety (p = 0.03), were more prevalent in AOO ≤45 group. Smoking (p = 0.03), hypertension and diabetes were more common in AOO >45 years groupConclusions: In India the age of onset of PD, especially in women, is much earlier compared to Western countries. Different genetic factors may be respon-sible and may have implications in the long-term management and prognosisNo conflict of interest.

031

DETERMINANTS OF HEALTH-RELATED QUALITY OF LIFE IN ESTONIAN PATIENTS WITH PARKINSON’S DISEASEL. Kadastik-Eerme1,*, M. Rosenthal1, P. Taba1

1Neurology and Neurosurgery, University of Tartu, Tartu, Estonia

Objectives: To identify the determinants of health-related quality of life (HRQol) in patients with idiopathic Parkinson’s disease (PD)Methods: A total of 268 patients (105 men, 163 women) were evaluated using the following instruments: the Parkinson’s Disease Quality of Life Questionnaire (PDQ39), the Hoehn and Yahr Scale (HY), the Schwab and England Activities of Daily Living Scale (SE-ADL), Mini Mental State Examination (MMSE), the Movement Disorders Unified Parkinson’s Disease Rating Scale (MDS_UPDRS) and the Becks Depression Inventory (BDI).Results: HRQol in PD patients deteriorated significantly with higher scores of MDS_UPDRS part I (non-motor symptoms), presence of depression, advanced disease stage, lower score of SE-ADL, higher scores of MDS_UPDRS part III (motor symptoms), longer duration of disease, and lower score of MMSE. All non-motor symptoms worsened significantly HRQol, except the features of dopamine dysregulation syndrome. In the multiple regression model, poorer overall HRQoL was predicted by higher HY stage, depression and presence of non-motor symptoms. These factors explain 56% (adjusted R² 0.56) of variance of PDQ-39 SI, with HY being the strongest determinant of HRQol.Conclusions: Disease severity was found to be the most important and inde-pendent factor of poor HRQoL. Also depression and other non-motor symp-toms are associated with impaired HRQol, therefore should be recognized and treated appropriately.No conflict of interest.

032

REASONS FOR HOSPITALIZATION IN PARKINSON’S DISEASE.K.V. Kotenko1,*, I.G. Smolentseva2, N.A. Amososva2, O.V. Krivonos2, L.P. Chupina3, O.A. Maslyuk2

1Administration, Federal Medical Biophysical Center, Moscow, Russia, 2Federal Neurological Center of Movement Disorders and Mental Health, Federal Medical Biophysical Center, Moscow, Russia, 3Department of Neurology, Federal Medical Biophysical Center, Moscow, Russia

Objectives: Considering senior age, comorbid conditions and course of Parkinson’s disease (PD) reasons for hospitalization may be different.Methods: The concurrent 3-year study included 136 patients with Parkinson’s disease who were hospitalized in different departments of medical institutions, including 77 men and 59 women, at average age of 63,16 ± 10,4 years, aver-age disease duration of 5,8 ± 4,4 years, and average stage by Hoehn–Yahr of 2,5 ± 0,6. 50 patients (36.8 %) had stage 1–2 by Hoehn–Yahr, 67 (49.3 %) patients - stage 3 by Hoehn–Yahr and 19(13.9 %) patients had stage 4–5.Results: The study was 3 years. 136 patients with PD were hospitalized in dif-ferent departments, of which 24.1 % of patients – every year. The reasons for hospitalization were directly or indirectly. 84.5 % of the patients were hospital-ized to neurological department more often for reasons related to PD.50 % pa-tient with early stage were hospitalized for management of treatment and right diagnosis. 68.4 % of the patients were hospitalized in the non- neurological departments (traumatology, therapeutic, oncology, urology, and unit stroke). Of these, one third of patients, had reasons for hospitalization that were in-directly associated with PD (e.g., trauma, as a result of falls due to postural instability and freezing).Conclusions: Consequently, the main reasons for hospitalization were associated with clinical progression of PD.Reference1. Data of hospital register of Closed Administrative-Territorial Formations of

FMBA.No conflict of interest.

033

COMPARISON OF FUNCTIONAL STATUS AND CLINICAL CHARACTERIS-TICS OF INDIVIDUALS WITH AND WITHOUT PARKINSON’S DISEASE AT THE TIME OF NURSING HOME ADMISSIONC. Zadikoff1,*, K. Sail2, E. Merikle2, T. Niecko3, T. O’Shea4, C. Allen4, B. Zarowitz4

1Department of Neurology, Northwestern University, Chicago, USA, 2Health Economics and Outcomes Research, AbbVie, Chicago, USA, 3Health Economics, Niecko Health Economics LLC, Naples, USA, 4Clinical Services, Omnicare Inc, Livonia, USA

Objectives: Parkinson’s Disease (PD) is a chronic progressive neurodegen-erative disorder often leading to nursing home (NH) admission in the more advanced stages of the disease. The study objective was to assess differ-ences in the functional status and clinical characteristics of individuals with and without PD at the time of NH admission.Methods: 4,671 U.S. NH residents with a clinical diagnosis of PD were identified among the Minimum Data Set resident admission assessments conducted between October 1, 2009 and September 30, 2010. These were compared cross-sectionally to a 1:1 age and gender matched group of resi-dents without PD.



14

Results: Residents with PD were significantly more physically disabled at admission than residents without PD, as measured by their ability to per-form activities of daily living and tests for balance (p < 0.01). A significantly higher proportion of residents with PD had experienced falls in the 30 days prior to NH admission compared to residents without PD (42% vs. 34%, p = 0.001). Additionally, the frequency of non-motor symptoms such as de-pression, dementia, cognitive impairment, incontinence (bowel and bladder) and dysphagia was significantly higher for residents with PD (p < 0.01). Higher proportion of residents without PD had conditions including renal fail-ure, diabetes, congestive heart failure and cancer than residents with PD at admission.Conclusions: Results demonstrate that NH admission of patients with PD is significantly associated with the symptoms of motor and non-motor difficul-ties that accompany the more advanced stages of the disease. Treatment options for advanced PD offering better symptom control may delay admis-sion to a NH.

034

AUDIT ON MOVEMENT DISORDER CLINIC – HOW SHOULD WE FOLLOW UP?S. Ghosh1,*1Geriatric Medicine, Lincoln County Hospital, Lincoln, United Kingdom

Objectives: Parkinson’s disease (PD) can lead to extensive disability, which affects the patients as well as family and carers. NHS, UK spends £5993/patient/year. The Primary aim of this audit was to find out whether we are adhering the NICE guideline (CG35) - “People diagnosed with PD should be seen at regular intervals of 6–12 months to review their diagnosis” The audit criteria was 100% patients with PD should be reviewed at 6–12 months inter-vals in the PD Clinic. Secondary aim of this audit was to look at the common motor and non-motor symptoms, commonly prescribed medicines from clinic, number of medicines needed to control the disease with side effects, whether 6–12 monthly review was adequate or not and to identify group of PD patients needed more frequent follow up.Methods: We audited for 50 patients prospectively over 3 months period at-tended our “Movement Disorder Clinic”. Data collected during clinic consulta-tion using self- designed template.Results: Primary: 96% of PD patients were followed up in the PD clinic against the target of 100%. Secondary: 34% patients were followed up 6–12 monthly.• 54% patients required more frequent follow up requiring 2 weeks to

4 months solely on clinical ground.• 62% patient’s symptoms controlled with maximum two drugs.• 14% patients showed dyskinesia as side effect of treatment.

Change of Medication in Clinic

Number of drugs needed to control the disease

30%32%

6%

6% LD/CarbiLD/Carbi/EntaDopa AgonistAmanta

COMT-IMAO-B

ClonazepamBblockerOthers

First start Dose Reduced Dose Increased Further Addition

One Med

Two Meds

Three Meds

>Four Meds

Conclusions: We followed up most PD patients as recommended in NICE guidelinePD patients followed up more frequently than 6–12 months for clinical reasonsReference1. www.nice.org.uk/cg035.No conflict of interest.

035

KNOWLEDGE AMONG SENIOR MEDICAL STUDENTS ON DIAGNOSIS AND MANAGEMENT OF PARKINSONS DISEASE: VIEWS FROM KENYA AND UGANDAP. Yonga1,*1Internal Medicine, Moi Teaching and Referral Hospital, Eldoret, Kenya

Objectives: With an ever-growing aging population worldwide, Parkinson’s disease has gained significant attention in the developed world and minimal attention in the developing world. The main objective of this study was to as-sess the knowledge of senior medical students in Kenya and Uganda on the diagnosis and management of Parkinson’s disease.Methods: Prospective, cross-sectional study where 350 senior medical stu-dents were sampled from two medical schools in Kenya and Uganda, and recruited. Data on their demographic characteristics, and knowledge on rec-ognizing the clinical features, diagnosis, and management of Parkinson’s dis-ease were captured using researcher-administered questionnaires, and data entry and analysis performed using Epi-data 3.1 and SPSS 20 respectively.Results: 85% of the students knew the clinical features of Parkinson’s dis-ease whereas 5% of the students reported using neuroimaging as part of the diagnostic criteria in ruling out parkinsonian-like disorders. 3% of the stu-dents noted the importance of neuropathology during autopsy as a diagnostic marker, and 70% of the students were aware of levodopa being used in the management of Parkinson’s disease.Conclusions: There are significant gaps as far as diagnosis and manage-ment is concerned and focus should be paid to the teaching of movement disorders in medical school at undergraduate level.Reference1. Hughes AJ, Daniel SE, Kilford L. Accuracy of clinical diagnosis of idiopath-

ic Parkinson’s disease: a clinicopathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992; 55:181–184.


036

IMPACT OF DISEASE SEVERITY, MOTOR AND NON-MOTOR SYMPTOM BURDEN ON HEALTH RELATED QUALITY OF LIFE AMONG PATIENTS WITH PARKINSON’S DISEASEK. Sail1,*, E. Merikle1, T. Niecko2, J. Jackson3, A. Espay4

1Health Economics and Outcomes Research, AbbVie, Chicago, USA, 2Health Economics, Niecko Health Economics LLC, Naples, USA, 3Disease Specific Programme, Adelphi Real World, Macclesfield, United Kingdom, 4Neurology and Rehabilitation Medicine, University of Cincinnati, Cincinnati, USA

Objectives: Parkinson’s Disease (PD) is a chronic neurodegenerative pro-gressive disease characterized by motor and non-motor symptoms differ-entially impacting patients’ health-related quality of life (HRQL). The study objective was to assess the impact of disease severity, motor and non-motor symptom burden on HRQL among patients with PD.Methods: A multinational cross-sectional real world survey of neurologists and their consulting patients with PD was conducted between November 2011 and January 2012. Patients were invited to complete a survey regarding: motor and non-motor symptom burden, disease-specific HRQL (Parkinson’s Disease Questionnaire, PDQ-39) and global HRQL (EuroQol 5-Dimension-5-Level, EQ-5D). Clinical information such as Hoehn and Yahr (HY) scoring (mild to moderate [HY = 1–2.5], moderate to severe [HY = 3–5]), off-time and dyskinesia were provided through physician reported data.Results: 1,237 patients with PD on oral medications were included (mean time since PD diagnosis:3.6 ± 10 years, range:0–25 years). A significantly higher proportion of patients with moderate to severe PD experienced trouble due to dyskinesia (36% versus 8%) and off-time (60% versus 19%) than pa-tients with mild to moderate PD. The motor and non-motor symptom burden was significantly higher in patients with moderate to severe PD (p < 0.0001). PDQ-39, EQ-5D utility and visual analogue scores were significantly worse across disease severity (p < 0.0001). Linear regression models found disease severity, off-time, motor and non-motor symptom burden scores to be signifi-cant predictors of HRQL.Conclusions: Results highlight the role of PD severity, motor and non-motor symptom burden as important determinants of HRQL. Treatment strategies offering better motor and non-motor symptom control may improve HRQL among patients with advanced PD.



15

037

QUALITY OF LIFE IN PARKINSON’S DISEASE IN SHANGHAI: A PROSPECTIVE 3-YEAR STUDYZ. Liu1,*, X. Ren1, M. Zhou1, J.I.N.G. Gan1, Y.I.N.G. Wan1, L. Lu1, J. Wu1, H. He1, Y. Wei11Neurology, Xinhua Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, Shanghai, China

Objectives: Follow up quality of life of Parkinson’s disease patients for 3 years, and investigate the change of it and its predictors.Methods: At baseline, collect patients’ information and clinical characteristic. Assess patients with UPDRS, Hoehn–Yahr stage, HAMA, HRSD, MMSE. Assess the quality of life of patients using PDQ-39 ques-tionnaire specific for PD patients. These questionnaires were finished again after 3 years.Results: PDQ-39 scores at 3-year follow up increase significantly compared with the baseline (baseline 26.62 ± 18.39 vs. follow-up time 45.10 ± 20.63, P = 0.000); Deterioration of quality of life consistent with disease progres-sion (P < 0.01). Multiple regression analysis showed that the main factor affected the patients’ quality of life was patients’ depression (OR = 1.216, P < 0.01).Conclusions: PD has an increasing impact on quality of life as the disease progresses. During 3-year follow-up, higher severity of depressive symptoms were found to be important and independent predictor of poor QoL.References1. Tsang KL, Chi I, Ho SL, et al. Translation and validation of the standard

Chinese version of PDQ-39: a quality-of-life measure for patients with Parkinson’s disease. Mov Disord, 2002; 17(5):1036–1040.

2. Luo N, Tan LC, Li SC, et a1. Validity and reliability of Chinese (Singapore) Version of the Parkinson’s disease Questionnaire (PDQ-39). Qual Life Res, 2005; 14:273–279.

3. Schrag A, Jahanshahi, Quinn N. What contributes to quality of life in patients with Parkinson’s disease? Neurol Neurosurg Psychiatry, 2000; 69:308–312.

4. Forsaa EB, Larsen JP, Wentzel-Larsen T, et al. Predictors and course of health-related quality of life in Parkinson’s disease. Mov Disord. 2008; 23(10):1420–1427.


038

FACTORS CONTRIBUTING TO CAREGIVERS’ STRESS AND BURDEN IN PARKINSON’S DISEASED. Santos-García1,*, T. de Deus1, J. Abella1, A. Aneiros1, M. Llaneza1, I. Expósito1, M. Macías1, R. de la Fuente-fernández1

1Neurology, Hospital A. Marcide Complejo Hospitalario Universitario de Ferrol (CHUF), Ferrol, Spain

Objectives: To analyze the main determinants of burden and stress in car-egivers of Spanish Parkinson’s disease (PD) patients.Methods: One hundred and fifty non-demented PD patients (57.3% males; 70.9 ± 8.6 years old) were included in this cross-sectional, monocenter, evaluation study. Caregivers (n = 136; 70.6% females; 60.7 ± 15.1 years old) were assessed using the Zarit Caregiver Burden Interview (ZCBI) and Caregiver Strain Index (CSI). Multiple linear regression methods were used to evaluate factors contributing to caregivers’ stress and burden: 1) PD motor dysfunction (ON-state Hoehn and Yahr/Unified Parkinson’s Disease Rating Scale [UPDRS] part III and motor complications [UPDRS part IV]); 2) Mood (Beck Depression Inventory [BDI]); 3) Non motor symptoms (Non-Motor Symptoms Scale [NMSS]); 4) Disability (Schwab and England Activities of Daily Living Scale [ADLS]); 5) Socio-demographic and other disease-related variables.Results: ZCBI and CSI mean scores were 16 ± 13.9 and 2.1 ± 2.3 re-spectively. High correlation was found between ZCBI and CSI (r = 0.819; p < 0.0001). 7.3% of caregivers presented moderate to severe burden (ZCBI > 40) and 4.7% had high levels of stress (CSI ≥ 7). Moderate to strong correlations were observed between Hoehn and Yahr, UPDRS-III, UPDRS-IV, BDI, NMSS and ADLS and ZCBI and CSI (p < 0.0001). Linear regression methods showed that ADLS, followed by BDI, had the strongest influence on ZCBI and CSI.Conclusions: Disability (ADLS) and mood (BDI) of PD patients are the main factors contributing to burden and stress in caregivers.Reference1. Martinez-Martin P, Rodriguez-Blazquez C, Forjaz MJ. Quality of life and

burden in caregivers for patients with Parkinson’s disease: concepts, assessment and related factors. Expert Rev Pharmacoecon Outcomes Res. 2012 Apr; 12(2):221–30.


039

PRETESTING AN ELECTRONIC VERSION OF THE PDQ-39D. Morley1,*, S. Dummett1, L. Kelly1, J. Dawson1, C. Jenkinson1

1Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom

Objectives: To pretest an electronic version of the PDQ-39, the most widely used and validated self-report instrument for the assessment of health-related quality of life in people with Parkinson’s disease (PwP).Methods: The PDQ-39 was transferred to an electronic platform using estab-lished survey software in a format replicating as closely as possible the style of the originally validated paper-based version. Six computer literate PwP, with a range of ages and disease duration, subsequently took part in cognitive interviews in order to assess the acceptability of the electronic version of the PDQ-39 (e-PDQ).Results: Participants generally found the e-PDQ to be user-friendly and straightforward to complete, although minor adjustments were incorporated over the course of the interview process. Most found a survey completion tracker bar to be a useful tool, as respondents appreciated knowing how far through the questionnaire they were at any given time. The incorporation of a ‘back’ button was popular as this provided the option of returning to check or look at previous answers. There was a general consensus that it is preferable to have fewer items on one screen to avoid having to continually scroll down.Conclusions: Results suggest that migration of the PDQ-39 to electronic format is acceptable to PwP, although further minor adjustments may be re-quired. The e-PDQ will now be subject to a large scale survey in order to vali-date its psychometric properties and to assess the feasibility of implementing forced or non-response options during completion.

040

ELECTROMYOGRAPHIC FEATURES IN THE EARLY STAGES OF PARKINSON’S DISEASEN. Titova1,*, E. Katunina1, G. Avakyan1

1Neurology and Neurosurgery Department, Pirogov Russian National Research Medical University (RNRMU), Moscow, Russia

Objectives: The purpose of the study was to reveal electrophysiological fea-tures in the early stages of PD by means of electromyography (EMG) and electroneuromyography (ENMG).Methods: The study included examination of 100 de novo patients (Hoehn and Yahr stages I-II), 59 patients with tremor, and 41 patients with akinetic-rigid dominant PD. The average age at disease onset was 63,3 ± 8,1 years. The average disease duration was 16,04 ± 2 months. All examined patients and 35 healthy subjects underwent EMG (mm. op-ponens pollicis, peroneus longus) and ENMG (nn. medianus, peroneus, tibialis).Results: Early manifestation of neuromotor apparatus dysfunction in PD in-cluded changes in the pattern of electromyographic curves, increase in the mo-tor nerve conduction velocity, and M-wave modification (reduction of latency and increase in amplitude) as well as an increase in the mean normalized H-reflex amplitude. The increase in tremor was associated with an increase in the amplitude of EMG activity at rest and M-response. Increased severity of akinetic-rigid symptoms was associated with a decrease in the amplitude of the EMG curve at maximum muscle tension, pulse conduction parameters of the motor fibers of peripheral nerves, and the amplitude of the M-response.Conclusions: In order to objectivize motor dysfunctions in patients with sus-pected PD, it is recommended to complement clinical examination with dy-namic observation using the proposed widespread neurophysiological tests available in routine clinical practice (EMG, ENMG).No conflict of interest.

041

CEREBELLAR THETA-BURST STIMULATION FOR THE EVALUATION OF THE PATHOPHYSIOLOGY AND THE THERAPEUTIC POTENTIAL FOR REST TREMOR IN PARKINSON’S DISEASEM.A. Stephan1,*, F. Vingerhoets1, D. Benninger1

1Department of Neurology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

Objectives: To investigate whether functional activation or inhibition of the cerebellum by transcranial magnetic stimulation modulates rest tremor in Parkinson’s disease.Rest tremor in PD responds often incompletely to conventional therapy. Its pathogenesis remains largely unknown and therapeutic alternatives are needed. Functional imaging, neurophysiological, and structural studies point to an involvement of the cerebellum and the cerebello-thalamo-cortical pathway in the generation of parkinsonian tremor. Given that Theta-Burst



16

Stimulation (TBS) activates or inhibits the cerebellum, a modulation of rest tremor by cerebellar stimulation may indicate its contribution to the generation of rest tremor.Methods: In a randomized, double-blind, sham-controlled, cross-over study design, 15 PD patients with rest tremor undergo single sessions of continuous TBS (cTBS, inhibitory), intermittent (iTBS, excitatory) and sham stimulation of both cerebellar hemispheres. Assessment of rest tremor, motor function and neurophysiology are performed before and after each intervention.Results: Preliminary results of 8 PD patients indicate a possible modulation of rest tremor by stimulation of the cerebellum (delta cTBS-Sham: 0.68 Hz, delta iTBS-Sham 0.14 Hz), which needs to be confirmed. This observation is congruent with lesional studies and in line with the presumed modulatory role of the cerebellum as recently postulated in the “switch-dimmer” model of Parkinson rest tremor.Conclusions: This study may provide further insights into the pathophysiol-ogy of rest tremor in PD and a rationale for a future therapeutic trial.No conflict of interest.

042

FRACTAL ANALYSIS OF SURFACE EMG IN PARKINSON’S DISEASE PATIENTSM. Ljubisavljevic1,*, M. Cukic2

1Physiology, United Arab Emirates University, Al-Ain, United Arab Emirates, 2Department for Computing and Control Engineering Faculty of Technical Sciences, University Novi Sad, Novi Sad, Serbia

Objectives: The main aim of the study was to gauge the characteristics of the neural activity underlying voluntary muscle activation in Parkinson’s disease (PD) patients.Methods: We used fractal dimension (FD), to explore the ‘complexity’ of sur-face EMG (SEMG) signal from the affected right side abductor pollicis brevis muscle, during weak and strong voluntary contraction, in PD patients when on and off – dopaminergic medication. The results were compared with a sub-group of drug-naïve PD patients and with an age-matched control subjects. FD was calculated using the Higuchi Fractal dimension algorithm.Results: FD was significantly lower in PD patients when compared to control subjects, while there was no difference in FD when on or off medication. FD was higher in a subgroup of drug-naïve compared to chronically treated PD patients. The intensity of muscle contraction (weak vs. strong) did not af-fect FD in chronic PD patients, while stronger contraction decreased FD in control subjects and in some drug-naïve patients.Conclusions: The results indicate increased self-similarity of the SEMG sig-nal, reflecting lower complexity of the neural activity in chronic PD patients. The results may also suggest presence of somewhat preserved neural mech-anisms underlying voluntary activation in early PD (drug-naïve patients) and that FD may be sensitive in detecting disease related changes. Given the small population of drug-naïve patients, the results encourage further explora-tion of non-linear SEMG methods (FD) perhaps as a quick and non-invasive screening biomarkers in PD and other movement disorders.No conflict of interest.

043

CLINICAL APPLICATIONS OF MOTOR EVOKED POTENTIALS IN PARKINSONISMT.W. Kim1,*, Y.H. Kim1, J.W. Cho2, J. Park1, W.H. Chang1

1Physical and Rehabilitation Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea, 2Neurology, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea

Objectives: Transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEP) have been widely used in various fields of neuroscience. The objective of this study is to investigate the clinical significance of upper and lower extremity MEP in Parkinsonism patients.Methods: A total of 20 patients (14 men; mean age 70.5 ± 9.1 years) partici-pated in this study. Six patients were diagnosed as Parkinson’s disease and 14 patients were with Parkinson plus syndrome. To assess the corticospinal excit-ability of upper and lower extremity motor cortex, all participants received sin-gle-pulse transcranial magnetic stimulation (TMS) session using a TMS system (Magstim Rapid2® stimulator: Magstim Ltd, UK) and a double cone coil. The resting motor threshold (RMT), peak-to-peak amplitude and latency of the MEP were calculated in upper and lower extremity, respectively. Unified Parkinson’s Disease Rating Scale (UPDRS), and timed 10 m walk test were also applied.Results: RMT of upper and lower extremity MEP was significantly correlated with UPDRS score in Parkinsonism patients, respectively (r = −0.462 and

−0.478, p < 0.05). Also, the amplitude of upper extremity MEP showed a sig-nificant correlation with gait speed (r = 0.633, p < 0.05).Conclusions: In this study, we found that some parameters of upper and lower extremity MEP were significantly correlated with the functional status of patients with Parkinsonism. These parameters may need attention to be con-sidered as quantitative methods of testing the motor function in Parkinsonism patients (Supported by Samsung Medical Center grant [#CRO112051] and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (20110014021)).

044

PARKINSON’S DISEASE: RELATIONSHIP BETWEEN NON-MOTOR SYMPTOMS AND MOTOR PHENOTYPEF. Ba1,*, M. Obaid1, M. Wieler1, R. Camicioli1, W.R.W. Martin1

1Movement Disorder Program Neurology, University of Alberta, Edmonton, Canada

Objectives: Parkinson’s disease (PD) is a neurodegenerative disorder that causes motor and non-motor symptoms (NMS). The NMS often precede the onset of motor symptoms. Motor phenotypes have been divided into tremor dominant (TD), and postural instability gait difficulty (PIGD) subtypes. We hypothesized that the PIGD phenotype would be more likely to have NMS compared to the TD phenotype.Methods: Sequential patients with PD attending the Movement Disorders Program at University of Alberta were administered the NMS Questionnaire along with the Unified PD Rating Scale (UPDRS). We conducted a retrospec-tive chart review to assess the relationship between NMS and PD motor phe-notypes. Secondary outcomes examined were the relationships between NMS and age of onset, gender, UPDRS part 3, disease duration, and cognitive status. TD and PIGD subtypes were determined from motor scores and as described.The relationship between each parameter was analyzed using linear regres-sion models with P < 0.01 considered significant. In patients receiving PD medication, dosage was adjusted to levodopa dose equivalents. Patients not receiving PD medication were analyzed separately.Results: A total of 249 patients were studied. Gender and age of onset did not correlate with NMS; there was a correlation with disease duration. Overall, the TD subtype showed no correlation with NMS. PIGD and its clinical compo-nents (falling/freezing/gaiting difficulties/postural instability) were significantly correlated to NMS.Conclusions: The observations indicate that NMS profile varies according to motor phenotype. The PIGD subtype correlates with a worse NMS score than does the TD subtype.No conflict of interest.

045

GENDER DIFFERENCES IN NON-MOTOR SYMPTOMS IN EARLY, DRUG NAÏVE PARKINSON’S DISEASEM. Moccia1,*, M. Picillo1, M. Amboni2, R. Erro3, K. Longo2, C. Vitale2, R. Allocca1, G. Orefice1, M.T. Pellecchia4, P. Barone4

1Department of Neurosciences, University of Naples Federico II, Naples, Italy, 2Center for Parkinson’s Disease and Movement Disorders, IDC Hermitage Capodimonte, Naples, Italy, 3Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology UCL Queen Square, London, United Kingdom, 4Center for Neurodegenerative Diseases, University of Salerno, Salerno, Italy

Objectives: To assess gender differences in NMS frequency in a large sample of early, drug-naïve PD patients compared with age-matched healthy controls.Methods: Two hundred early, drug-naïve PD patients and sixty age-matched healthy controls were included in the study. Frequency of NMS was evaluated by means of NMS Questionnaire. The difference in gender distribution of NMS was evaluated with the X2 exact test; multiple comparisons were corrected with Benjamini–Hockberg method.Results: Male PD patients complained of problems having sex and taste/smell-ing difficulties significantly more frequently than female PD patients. Furthermore, men with PD complained more frequently of dribbling, sadness/blues, loss of in-terest, anxiety, acting during dreams, and taste/smelling difficulties as compared to healthy control men, while female PD patients reported more frequently loss of interest and anxiety as compared with healthy control women.Conclusions: This study shows specific sex-related patterns of NMS in drug-naïve PD. In contrast with previous data, female PD patients did not present higher prevalence of mood symptoms as compared to male PD patients. Comparison with healthy controls showed that some NMS classically present in premotor and early stage of disease (i.e. acting during dreams, taste/smell-ing difficulties) are more frequent in male than in female patients.



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References1. Chaudhuri KR, Healy DG, Schapira AH, et al. Non-motor symptoms of

Parkinson’s disease: diagnosis and managment.Lancet Neurol 2006; 5:235–245.

2. Martinez-Martin P, Falup Pecurariu C, Odin P, et al. Gender-related dif-ferences in the burden of non-motor symptoms in Parkinson’s disease. J Neurol 2012; 259:1639–1647.

3. Chaudhuri KR, Martinez-Martin P, Schapira AHV, et al. An international multicentre pilot study of the first comprehensive self-completed non-mo-tor symptoms questionnaire for Parkinson’s disease: the NMSQuest study. Mov Disord 2006; 21:916–923.


046

PREVALENCE OF NON-MOTOR SYMPTOMS OF PARKINSON’S DISEASE: A SYSTEMATIC REVIEW WITH META-ANALYSISG. Pagano1,*, M. Tagliati21Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy, 2Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, USA

Objectives: Non-motor symptoms (NMS) of Parkinson’s disease (PD) are a key determinant of health, quality of life and societal cost of PD. Despite their impact, they are not well recognized and their prevalence varies widely among studies. The aim of this study is to systematically identify NMS prevalence as reported by studies in large populations of PD patients.Methods: MEDLINE, Web of Science, CENTRAL and Scopus databases were searched until August 2013 and two independent reviewers selected the papers. Cumulative plots of prevalence estimates weighted by sam-ple size were created with random effect analysis and the influence of selected key variables, including gender, motor subtypes (tremor-pre-dominant vs. akinetic-rigid) and age at onset (<50 vs. ≥50 years) was examined.Results: From 15726 references identified and screened, 71 were assessed for eligibility and 24 articles, presenting prevalence rates of NMSs based on NMSQuest or NMSS, were included for a total of 6,378 patients. Multiple pub-lications from the same database were excluded. Nocturia (59.7%), urinary urgency (54.6%), depression (51.7%), constipation (48.5%), anxiety (46.9%), forgetfulness (45.5%) and insomnia (44.7%) were among the most prevalent NMSs, with highly significant statistical heterogeneity. Based on combined prevalence estimates, we found no significant effect of gender, motor subtype or age at onset.Conclusions: Our study confirms a significant clinical heterogeneity among different studies, which could be explained by differences in disease severity. Despite this variability, some NMSs appears to be more prevalent than other in PD patients and could provide direction for future standards of care and hypothesis-driven research.No conflict of interest.

047

NON-MOTOR SYMPTOMS AND PARKINSON’S DISEASE SUBTYPES: PREVALENCE, MANIFESTATIONS AND HEALTH RELATED QUALITY OF LIFEP. Lolekha1,*, K. Kulkuntrakorn1

1Internal Medicine, Thammasat University, Pathumthani, Thailand

Objectives: Parkinson’s disease (PD) has a highly clinical heterogeneity and various subtypes. The prevalence of non-motor symptoms (NMS) in each sub-type is unknown. The aim of this study was to identify the prevalence and pat-tern of NMS in each subtype and its impact on quality of life.Methods: A total of 81 PD patients from Thammasat University hospital were included. Patients were classified into four subtypes: early onset (EOPD; <55 years old) vs. late onset (LOPD; ≥55 years old) and tremor dominant (TD) vs. non-tremor-dominant (NTD) subtype. NMS and quality of life were assessed using the Non-Motor Symptom Questionnaires (NMSQuest), and Parkinson’s Disease Questionnaire-8 (PDQ8).Results: Patients reported an average of 13 NMS (range: 3–23). The sleep/fa-tigue domain was the most prevalent NMS in TD, EOPD and LOPD, whereas gastrointestinal domain was more prevalent in NTD. NMSQuest and PDQ8 scores were significantly higher in NTD patients than in TD patients, while no difference was found between EOPD vs. LOPD (Table). Significant correla-tions were observed between NMSQuest score and Hoehn and Yahr stage (r = 0.37, P < 0.01), UPDRS III (r = 0.42, P < 0.01), Schwab and England ADL Scale (r = −0.49, P < 0.01), and PDQ8 (r = 0.63, P < 0.01).Conclusions: NMS are common and have an impact on quality of life of PD patients. Advance disease stage, poor motor function, decreased ADL func-tion, and NTD subtype are associated with higher number of NMS.No conflict of interest.

048

NON-MOTOR FEATURES ASSOCIATED WITH APOE EPSILON4 ALLELE IN A SAMPLE OF BULGARIAN PATIENTS WITH LATE-ONSET PARKINSON’S DISEASER. Pavlova1, S. Mehrabian1, M. Petrova1, S. Skelina1, K. Mihova1, A. Jordanova1, V. Mitev1, L. Traykov1,*1Neurology, University Hospital Alexandrovska, Sofia, Bulgaria

Objectives: Non-motor symptoms (NMS) in Parkinson’s disease (PD) are authonomic, cognitive, neuropsychiatric, sensory changes and sleep dis-turbances. The aim of the study is to evaluate the role of Apolipoprotein E (APOE) epsilon4 allele on the NMS in a sample of Bulgarian patients with late-onset Parkinson’s disease (LOPD, age at onset >55 years).Methods: 19 LOPD patients with APOE epsilon3/epsilon4 genotype and 60 LOPD patients with APOE epsilon3/epsilon3 genotype were matched by their demographic data. NMS of both groups were evaluated by ‘PD NMS Questionnaire’.

047

Table Demographic and clinical variables of total subtypes.

Total number (n) Total (81) TD (29) NTD (52) p-Value EOPD (23) LOPD (58) p-Value

Age (years) 68.4 ± l2.5 66.8 ± 13.9 69.3 ± 11.7 0.399 52.8 ± 5.6 74.6 ± 8.4 <0.01

Duration (years) 4.7 ± 4.4 4.6 ± 5.1 4.7 ± 3.9 0.87 4.9 ± 4.2 4.6 ± 4.5 0.78

S&E ADL 76.4 ± 16.0 85.2 ± 15.5 71.5 ± 14.2 <0.01 80.9 ± 18.3 74.7 ± 14.8 0.12

UPDRS III 22.4 ± 10.7 18.6 ± 11.8 22.4 ± 9.6 0.02 22.8 ± 13.2 22.2 ± 9.8 0.82

H&Y stage 2.3 ± 0.8 1.7 ± 0.8 2.6 ± 0.7 <0.01 2.1 ± 0.8 2.3 ± 0.8 0.39

NMS quest 12.7 ± 5.18 11.2 ± 5.2 13.6 ± 5.0 0.05 12.9 ± 5.0 12.7 ± 5.3 0.87

PDQ-8 9.2 ± 6.0 6.1 ± 4.9 11.0 ± 5.8 <0.01 9.6 ± 5.9 9.1 ± 6.1 0.70

Most prevalent NMS domains (%)

Sleep/fatigue (95.1) Sleep/fatigue (96.2) Gastrointestinal tract (94. 1)

Sleep/fatigue (91.3) Sleep/fatigue (96.6)

Urinary tract (90.0) Gastrointestinal tract (89.7)

Sleep/fatigue (93.1) Cardiovascular (86.4)

Urinary tract (94.8)

Gastrointestinal tract (85.0)

Apathy/attention/memory (82.8)

Urinary tract (90.2) Apathy/attention/memory (81.8)

Gastrointestinal tract (87.9)

S&E ADL: Schwab & England Activities of Daily Living, UPDRS: Unified Parkinson’s Disease Rating Scale, H&Y: Hoehn & Yahr, NMS Quest: Non-Motor Symptom Questionnaires, PDQ: Parkinson’s Disease Questionnaires.



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Results: The LOPD patients who carried an APOE epsilon4 allele showed higher tendency of expression of gastrointestinal discomfort (p = 0.003), body weight change (p = 0.005), day-time sleepiness (p = 0.005) and hallucinations (p = 0.000).Conclusions: Data obtained by PD NMS questionnaire suggested a modify-ing role of the APOE epsilon4 allele on the severity of the pathologic process in authonomic and limbic structures, in LOPD patients.No conflict of interest.

049

FATIGUE IN PARKINSON’S DISEASEM. Moarcas1, R. Chiperi1, O. Falup-Pecurariu2, R. Alexandru3, B. Carlan3, C. Falup-Pecurariu3,*1Department of Neurology, Emergency County University Hospital, Brasov, Romania, 2Department of Pediatrics, Faculty of Medicine Transilvania University, Brasov, Romania, 3Department of Neurology, Faculty of Medicine Transilvania University, Brasov, Romania

Objectives: Fatigue is an important non-motor symptom in Parkinson’s dis-ease (PD). The aim of this study is to evaluate the prevalence and types of fatigue in PD patients.Methods: Prospective study on 53 patients with PD. We used the follow-ing assessment instruments: Hoehn and Yahr staging, UPDRS, Parkinson Fatigue Scale, Beck Depression Inventory (BDI), EQ-5D. A specific fatigue questionnaire was designed.Results: there were 37 men (69,81%), with the mean age of 64,21 ± 16,87 years. We assessed general fatigue, with its components - physical and mental fa-tigue. 34 patients (64,15%) reported fatigue. There was a correlation between fatigue intensity and depression, respectively disease severity. Disease du-ration and presence of motor complications were not correlated with fatigue. Reduced activity was encountered more in the fatigue group.Conclusions: fatigue is a frequent symptom reported by PD patients. In all fatigued patients there is need for a careful assessment of depression.No conflict of interest.

050

AN INVESTIGATION ON FATIGUE IN PARKINSON’S DISEASE: CLINICAL FEATURES AND POTENTIAL BIOMARKERSL.J. Zuo1, S.Y. Yu1, C.J. Cao1, F. Wang1, Y. Hu1, Z.J. Chen1, X.Y. Huang1, L. Sun1, Z. Liu1, W. Zhang1,*1Neurology, Beijing Tiantan Hospital, Beijing, China

Objectives: To investigate clinical features and biomarkers in Parkinson’s dis-ease (PD) patients with fatigue.Methods: (1) 315 PD patients were evaluated by fatigue severity scale, fa-tigue scale-14, scales of motor and non-motor symptoms; (2) Levels of iron and its metabolism-related proteins, Aβ1–42 oligomer, neuroinflammatory fac-tors and neurotransmitters in CSF were detected; (3) Correlation was ana-lyzed between fatigue and above factors.Results: (1) Fatigue was positively correlated with anxiety, depression and cognition decline (Table 1); (2) Fatigue was related to abnormal iron metabo-lism (Table 2) and Aβ1–42 decline (Table 3), indicating excessive depositions of iron and Aβ1–42 in brain; (3) Fatigue was correlated with TNF-α, H2O2 and NO levels negatively, and correlated with sTNF-αR level positively, which in-creased TNF-α level in serum (Table 4); (5) Fatigue was negatively correlated with 5-HT and Ach levels (Table 5).Conclusions: Depression and anxiety were the risk factors of fatigue. Fatigue might predict PD with cognition decline. Iron and its metabolism-related pro-teins (ferritin, transferrin and lactoferrin), Aβ1–42, neuroinflammatory factors (TNF-α, H2O2 and NO) and neurotransmitters (5-HT and Ach) in CSF might be potential biomarkers of fatigue in PD.No conflict of interest.

051

DOES INFLAMMATION PLAY ROLE IN THE PATHOGENESIS OF FATIGUE SYNDROME IN PARKINSON’S DISEASE?V. Datieva1,*, O. Levin1

1Neurology, Russian Medical Academy of Postgraduate Education, Moscow, Russia

Objectives: Neuroinflammation plays a key role in the pathophysiology of Parkinson’s disease (PD). Fatigue syndrome (FS) often accompanies inflammation. Research on the nature and management of FS has been chal-lenging. The role of inflammation in the origin of FS is being debated. The present study has been designed to examine peripheral biomarkers of inflam-mation in relation to FS in patients with PD.

Methods: 40 PD patients without dementia. Mean age was 63,8 ± 7,7. Mean disease duration was 5,5 ± 3,79. Mean Hoehn and Yahr stage was 2,6 ± 0,84 Patients were divided into two groups according to the presence (PD-F group, n = 20) or absence (PD-NF group, n = 20) of fatigue. Presence of FS was defined as score >3,3 on the Parkinson Fatigue Scale (PFS). Patients were ordered UPDRS – MDS. C-reactive protein (CRP) and tumor necrosis factor-α (TNFα) were used as biomarkers of inflammation in pe-ripheral blood.Results: Mean CRP level in PD-F group was 1,54 ± 1,04; and 1,6 ± 1,01 in PD-NF group. Mean TNFα level was 6,72 ± 0,83 in PD-F group; and 6,5 ± 0,83 in PD-NF group. Mean UPDRS-MDS score was 84,4 ± 21,5 in PD-F group and 72,4 ± 35,9 in PD-NF group. No correlation was seen between UPDRS-MDS score, PFS performance and level of biomarkers of inflammation. None of the 40 patients showed pathological level of these biomarkers in blood.Conclusions: We didn’t find link between FS severity and level of CRP and TNFα in peripheral blood. This fact can imply that other then inflammation fac-tors contribute to FS severity, or other biomarkers should be detectedReference1. Appel S. Inflammation in Parkinson’s disease: Cause or consequence?

Movement Disorders 2012; 27.No conflict of interest.

052

MEASURES OF AUTONOMIC DYSFUNCTION IN PARKINSON’S DISEASES. Schreglmann1,*, L. Epprecht2, O. Götze3, L. Zimmerli4, C.R. Baumann1, D. Waldvogel11Department of Neurology, University Hospital of Zurich, Zurich, Switzerland, 2Department of Neurosurgery, KantonsSpital St.Gallen, St.Gallen, Switzerland, 3Department of Internal Medicine, University Hospital Würzburg, Würzburg, Germany, 4Department of Internal Medicine, University Hospital of Zurich, Zurich, Switzerland

Objectives: Symptoms of autonomic dysfunction are increasingly recognized as part of the clinical spectrum in Parkinson’s disease (PD), often causing considerable distress. This cross-sectional study aimed at comparing the au-tonomic nervous system (ANS) function of the upper gastrointestinal (GI) and cardiovascular system in early PD patients (Hoehn and Yahr 2) to sex- and aged-matched controls (Ctrl).Methods: Subjective (questionnaires) and objective (gastric emptying breath test, Schellong test, central blood pressure, and 7 days blood pressure meas-urement) measures of ANS function were assessed in 16 PD patients and 11 Ctrl subjects without history of gastrointestinal disease, diabetes mellitus and antihypertensive treatment. All medication interfering with GI motility or blood-pressure-regulation incl. dopaminergic agents were stopped at least the elimination half-life of the drug before testing.Results: Groups were well matched for age (PD 66.3 ± 8.5 vs. Ctrl 61.7 ± 7.1), sex (10/6 vs. 7/4) and BMI (25.4 ± vs. 24.1). Measures for gastric emptying and subjective GI function reported in questionnaires were similar in both groups. However patients reported significantly more subjective orthostatic hypoten-sion (OH) symptoms than Ctrl subjects (8.9 ± 6.2 vs. 1.8 ± 3.0, p = 0.001), although Schellong test and 7 days blood pressure measurements did only mildly differ between groups.Conclusions: Excluding the influence of GI and cardiovascular comorbidity as well as medication, our data suggest only a mild degree of autonomic dys-function in early stages of PD. The degree of subjective OH symptom severity was not reflected in objective measurements.No conflict of interest.

053

AUTONOMIC DISORDERS IN PARKINSONIAN PATIENTS HOLDING G2019S OF LRRK2 MUTATION IN TUNISIAI. Lakhdar1,*, S. Ben Sassi1, H. Nahdi1, R. Amouri1, F. Hentati11Neurology, National Institute Mongi Ben Hmida of Neurology, Tunis, Tunisia

Objectives: Determine the existence and the severity of the autonomic disor-ders in Parkinson’s disease associated to LRRK2 compared to idiopathic PD.Methods: 181 patients with PD related to the LRRK2 G2019S mutation were included and compared with 178 patients with idiopathic PD. The motor scores (MDS-UPDRS, Hoehn and Yahr, Schwab and England) and cognitive scales MMS, MoCA and BREF, scale of depression GDS sleepiness Epworth and dysautonomia score SCOPA- AUT were used.Results: In the LRRK2 group of autonomic disorders were observed in 40.9% of patients with severe disease in 11.2% of cases. They were dominated by urinary disorders, sexual disorders and disorders of ther-moregulation. Only 9.9% of our patients were treated. We did not find any significant difference in the frequency and severity of autonomic reached between the two groups, with the exception of a lower severity of gastro-intestinal symptoms in patients with LRRK2 and more severe disorders thermoregulation in the same group of patients, compared to the group



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with an idiopathic PD. The severity of this autonomic impairment was cor-related with the severity of motor, cognitive, depression, sleep disorders and L-dopa dose used.Conclusions: The presence and severity of autonomic disorders seems over-all the same in patients with the G2019S mutation and patients with idiopathic PD, except gastrointestinal and thermoregulatory disorders. Despite the high prevalence of these disorders and the severity of their impact on the quality of lives of the patient and the course of the disease, they are largely under treated comparing to motor symptoms.Reference1. Verbaan D, et al. Patient-reported autonomic symptoms in Parkinson dis-

ease. Neurology 2007; 69:333–341.No conflict of interest.

054

GASTROINTESTINAL SYSTEM DYSFUNCTION IN PARKINSON’S DISEASEE. Okuyucu1,*, A.Y. Sertpolat1, M. Guntel1, T. Duman1, I. Melek1

1Neurology, Mustafa Kemal University, Antakya, Turkey

Objectives: GIS disorders can appear in any stage of disease in almost all Parkinson’s patients and may contribute to the load of disease. The estimated rate of symptoms of gastrointestinal system dysfunction affecting quality of life negatively in Parkinson’s patients is more than 70–80%. The aim of this study was to evaluate the relation between non-invasive gastrointestinal dysfunction scale tests and the severity of disease and also the relation between activities of daily living scale and the severity of disease.Methods: The consecutive patients of Mustafa Kemal University Neurology Clinics with PD diagnosis participated in study. The patients who has DM, thyroid disorder, gastrointestinal system disorder, secondary Parkinsonism or are using drugs affecting gastrointestinal system were not involved.Results: In Parkinson’s patients there was no correlation between gastro-intestinal system dysfunction scales and the severity of disease (p > 0.005). We detected statistically significant moderate degree negative correlation be-tween the severity of disease and Schwab-England Activities of Daily Living Scale (p < 0.0001).Conclusions: We concluded that gastrointestinal system dysfunction which has an important impact on mortality and quality of life is very common in Parkinson’s Disease. We observed that an assessment with the usage of sial-orrhea clinical scale, simple dysphagia scale, and Rome II scale for gastroin-testinal system dysfunction; UPDRS and H&Y scale for severity of disease; and Schwab-England Activities of Daily Living Scale for patients’ quality of life can give valuable information.Reference1. Dewey RB, Jr. Autonomic dysfunction in Parkinson’s disease. Neurol Clin.

2004; 22(3 Suppl):S127–39. Epub 2004/10/27.No conflict of interest.

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GASTROINTESTINAL DYSFUNCTIONS IN PARKINSON’S DISEASE AND OTHER PARKINSONIAN DISORDERSJ. Lee1,*, C.M. Shin2, H. Park1, J.M. Kim3, H.R. Kim1, T.J. Kim1

1Neurology, Seoul National University Boramae Medical Center, Seoul, Korea,2Gastroenterology, Seoul National University Bundang Hospital, Sungnam, Korea,3Neurology, Seoul National University Bundang Hospital, Sungnam, KoreaObjectives: To investigate the frequencies of gastrointestinal (GI) symptoms and their clinical correlates in patients with Parkinson’s disease (PD) and Parkinson-plus syndromes.Methods: A total 456 consecutive patients were screened for GI symp-toms over a defined period using a structured questionnaire; the Simplified Nutritional Appetite Questionnaire, Sialorrhea Clinical Scale for PD, Swallowing Disturbance Questionnaire, Gastroesophageal Reflux Disease (GERD) Questionnaire, and Korean Bowel Disease Questionnaire-7. Clinical informations of age, sex, duration of the disease, Hoehn and Yahr stage, the Unified PD rating scale (UPDRS), and daily anti-parkinsonian medications were collected.Results: The frequencies of GI symptoms were 30.7%, 18.7%, 14.4%, 19.2%, 10.0% and 64.5% in PD for weight loss, reduced appetite, drooling, dyspha-gia, GERD and constipation versus 34.7%, 32.8%, 21.9%, 25.0%, 5.7% and 70.2% in other parkinsonian syndromes. Weight loss was related to the UPDRS part 1 and 2 scores whereas reduced appetite was associated with age rather than the severity of parkinsonian symptoms. GERD were signifi-cantly correlated with daily drug dosages. Constipation was the most com-mon GI symptom, which was significantly associated with akinesia and axial symptom scores. The severity of dysphagia and drooling was correlated with HY stage, dyskinesia and freezing in PD group.

Conclusions: GI dysfunction is comparably common both in Parkinson-plus syndromes and PD. Constipation is commonest from early stages whereas dys-phagia and drooling are more frequent in advanced stages. GERD is more likely to be associated with medications rather than disease progression. Further large studies including drug-naïve patients are warranted to confirm this finding.Reference1. Pfeiffer RF. Lancet Neurol 2003; 2:107–16.No conflict of interest.

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PAIN IN PARKINSON’S DISEASE: A FREQUENT BUT UNDERTREATED SYMPTOMC. Falup-Pecurariu1,*, M. Moarcas2

1Department of Neurology, Faculty of Medicine Transilvania University, Brasov, Romania, 2Department of Neurology, Emergency University County Hospital, Brasov, Romania

Objectives: Pain is a frequently encountered symptom in clinical practice and one of the important non-motor symptoms in Parkinson’s disease (PD). The aim of this study is assessing the prevalence and types of pain in PD patients, the use of pain medication.Methods: Prospective study on 71 patients with PD. We used the following assessment instruments: Hoehn and Yahr staging, SCOPA Motor, Brief Pain Inventory, Beck Depression Inventory (BDI). For pain history and evaluation we used a specific questionnaire.Results: There were 41 men (57,74%), mean age 66,43 ± 19,23 years [limit 44–87 years]. Forty two patients (59,15%) reported pain. 27 of them (62,28%) reported back pain as main type of pain, followed by headache. 32/42 patients (76,19%) received medication for pain, while 10/42 (23,8%) did not receive pain medication. Pain intensity was correlated with disease severity, duration of the disease, and score of BDI.Conclusions: Pain is a symptom often reported by PD patients. However, a significant percentage of them did not receive pain medication.No conflict of interest.

057

DIFFICULTY OF CLASSIFYING PAIN IN PARKINSON’S DISEASES. Mrabet1,*, N. Ben Ali1, M. Kechaou1, S. Belal11Neurology, Charles Nicolle Hospital, Tunis, Tunisia

Objectives: Pain may be a symptom of Parkinson’s disease (PD) or occur during its motor fluctuation stages.The purpose of our study is to character-ize the painful presentations in PD, their relationship with the evolution of the disease and their replies to dopaminergic therapy. Also, we determinate the impact of pain on quality of life of the patients.Methods: We reviewed painful syndromes in 90 patients followed for PD in the Department of neurology of Charles Nicolle hospital. An interview, a clinical examination and a neuropsychological assessment were conducted. Some investigations (sonography, spinal scan, electromyography…) have been requested.Results: The pain was observed in 44% of our patients and at all stages of the disease. All types were identified: osteo-muscular (17%), radicular (34%), articular (25%), dystonic (10%) and neuropathic (11,5%). Akathisia was the less frequent (2.5%).The average age was 63 years. The female predomi-nance was obvious. The majority reported an improvement after dopaminergic therapy with varying degrees. The impact of the painful symptoms on quality of life is evident. The pain worsens the motor disability and seems to generate a higher risk of depression and anxiety in our patients.Conclusions: A significant percentage of pain occurs during the inaugural stage of the disease. The atypical presentation often ill-defined and some-what suggestive of PD leads to misdiagnosis and unnecessary investigations. Recognition of parkinsonian pain at an early stage could justify the use of neuroprotective therapy currently under evaluation.References1. Fil A, et al. Parkinson Relat Dis. 2013.2. Dufrène C. Douleurs (Paris). 2013.3. Brefel-Courbon C, et al. Neurologie. 2010.No conflict of interest.

058

THE ROLE OF THE SUBTHALAMIC NUCLEUS ON EMPATHY TO PAIN: A NEUROPHYSIOLOGICAL STUDY.F.L. Godinho1, M. Magnin2, M.S. Rocha3, N.E. Marinho3,*, C.M. Godinho3, O.J. Moraes1, A.M. Cravo4

1Neurosurgery, Hospital Santa Marcelina, Sao Paulo, Brazil, 2Neurosurgery, Universidade de Lyon, Lyon, France, 3Neurology, Hospital Santa Marcelina, Sao Paulo, Brazil, 4Psychology, Universidade Federal do ABC, Sao Paulo, Brazil



20

Objectives: To study the electrophysiological responses of the subthalamic nucleus (STN) during empathy to pain.Methods: We enrolled 11 patients who underwent surgery for Parkinson’s Disease. Empathy to pain was experimentally evoked by presenting a bank of videos designed for research. In half of the videos, actors overtly ex-pressed “pseudo” painful sensation, while the other half contained neutral expression. The block-design paradigm was performed during intraoperative semi-microelectrode recordings. Each block contained 3 videos of 1.8 sec each and same category. Patients were instructed to estimate how much pain people in videos were feeling using a 0–9 scale. Scores were provided through a finger gesture 5 seconds after the last video. Data were epoched from −1.5 to 6.5 s relative to the first of three videos in each block. Time-frequency analysis was performed. Data were averaged for the period from 0 to 5.8 s relative to the first video of the block onset. Power increase/decrease relative to the baseline was expressed in decibels (dB). We used paired t-tests to compare power increase/decrease in pain and control blocks at the group level.Results: Pain videos scores were significantly higher than control F(1.00,11.00) = 352.918, p = 0.000. We found a significant difference be-tween pain and control conditions in frequencies around 6 to 8 Hz - teta band (t = 2.2, p < 0.05). A non-significant tendency was also observed for Beta oscillations.

45

PainControl

40

35

30

25

20

15

10

5

-2.0 -1.5 -1.0 1.0 1.5 2.0-0.5 0.50Spectral Power (dB)

Freq

uenc

y (H

z)

Conclusions: Teta oscillations may underpin the involvement of the STN in the empathy to pain. This suggests the need for more comprehensive evaluation of mind’s properties when the STN is eligible for neuromodulation approaches.No conflict of interest.

059

PAIN IN PARKINSON’S DISEASE AND ITS RELATION TO NEGATIVE AFFECTG. Engels1,*, E.J.A. Scherder1

1Clinical Neuropsychology, VU University, Amsterdam, Netherlands

Objectives: To investigate how pain and negative affect (mood) are related in Parkinson’s disease (PD).Methods: Fourty-one patients with PD, and twenty-one persons without PD participated in this study. Intensity of pain was assessed with a colored ana-logue scale (CAS) for pain intensity and the Faces Pain Scale (FPS). Pain affect was measured with CAS for suffering of pain and the Number of Words Chosen Affective (NWCA). Mood was assessed with Beck’s Depression Inventory and subscales ‘Depression’ and ‘Anxiety’ of the Symptoms Checklist 90 (SCL-90).Results: Compared to a control group, patients exhibited more intensity of pain (CAS intensity (t(60) = 1.999; p =.050) and FPS (t(60) = 1.889; p =.064)). Also, pain affect was higher in PD (CAS for suffering (t(60) = 2.114; p =.039) and NWCA (t(60) = 4.097; p =.000)). BDI and subscales of the SCL-90 were added in the domain ‘Mood’ (Crohnbach’s α =.927). Symptoms of de-pression and anxiety were more present in PD patients (t(57.926) = 4.455 p =.000). Moreover, having higher scores on the domain ‘Mood’ was

predictive for all measures of pain: CAS intensity (R2 =.091, F(1,57) = 5.71, p =.020), CAS suffering (R2 =.188, F(1,57) = 13.20, p =.001), NWCA (R2 =.455, F(1,57) = 47.62, p =.000) and FPS (R2 =.190, F(1,57) = 13.35, p =.001).Conclusions: Even though pain and negative affect (mood) have been re-lated in healthy persons before, few studies have investigated this relation in PD. This is surprising, since both depression and pain are important non-motor symptoms and predictive for quality of life.No conflict of interest.

060

PAIN AND QUALITY OF LIFE OF PATIENTS WITH PARKINSON’S DISEASEV. Romanenko1,*, Y. Romanenko2

1Department of Neurology, Lugansk City Hospital #11, Lugansk, Ukraine, 2Department of Neurology, Lugansk City Hospital #4, Lugansk, Ukraine

Objectives: Pain is a very common, but often neglected syndrome that affects quality of life (QoL) of patients with Parkinson’s disease (PD). The objective of this work was to determine frequency of different pain syndromes and its impact on QoL of patients with PD.Methods: Twenty five patients (16 men and 9 women) aged from 43 to 78 with PD and pain in cervical area have been studied. Clinical and neurological examination, EEG, MRI, ultrasonic examination of great vessels of the neck along with application of UPDRS, Hoehn and Yahr Scale, MMSE, ADL Scale, SF-36 Questionnaire and Visual Analog Scale (VAS) have been performed. All patients received replacement and symptomatic therapy.Results: Twelve patients were found to have myofascial, radicular or verte-brogenous components of neck pain. Pain intensity in this group varied from 4 to 8 (5,83 on average) points on VAS, in comparison to 3 to 6 points in second group (4,23 on average). In 10 days after treatment (NSAIDs and myorelax-ants) intensity of pain significantly decreased by 2,5 points in first group, in comparison to 1,31 points in second group.Conclusions: Adequate differential diagnosis and mechanism-oriented man-agement of pain improves QoL in patients with PD.No conflict of interest.

061

VALIDATION OF A FIRST NOVEL PARKINSON’S DISEASE PAIN SCALE (PD PAIN SCALE): INTERIM ANALYSIS OF A MULTICENTRE PILOT STUDYA. Rizos1,*, P. Martinez-Martin2, S. Pal3, C. Carroll4, D. Martino5, D. Paviour6, B. Kessel7, M. Silverdale8, L. Gallagher1, A. Todorova9, A. Sauerbier9, A. Martin9, M. Parry10, S. Bassi1, J. Tuazon1, E. Ekins1, P. Odin11, A. Antonini12, K. Ray-Chaudhuri9, o.b. of EUROPAR1

1Neuroscience, King’s College Hospital, London, United Kingdom, 2Alzheimer Disease Research Unit and CIBERNED, Carlos III Institute of Health Alzheimer Centre Reina Sofia Foundation, Madrid, Spain, 3Neurology, Forth Valley Royal Hospital, Scotland, United Kingdom, 4Neurology, Derriford Hospital, Plymouth, United Kingdom, 5Neurology, Queen Mary’s Hospital, Kent, United Kingdom, 6Neurology, St Georges Hospital, London, United Kingdom, 7Geriatric Department, Princess Royal University Hospital, Orpington, United Kingdom, 8Neurology, Greater Manchester Neuroscience Centre, Manchester, United Kingdom, 9Neurology, King’s College Hospital, London, United Kingdom, 10Neurology, University Hospital Lewisham, London, United Kingdom, 11Neurology, University of Lund, Lund, Sweden, 12Neurology, University of Padua, Venice, Italy

Objectives: To validate an “easy to use” novel clinical Parkinson’s specific pain scale using internationally accepted methods.Background: Pain is one of the most under-explored and poorly character-ized non-motor symptom of Parkinson’s and a key determinant of quality of life. Yet there are currently no validated Parkinson’s specific bedside scales to characterize the various types of pain in PD for focused treatment, epidemio-logical studies and clinical trials.Methods: In this cross-sectional, open, multicenter pilot study, we report data from use of a specific PD-Pain-Scale developed from patient responses to a questionnaire. The scale will be tested for clinimetric evaluation of acceptabil-ity, internal consistency, reliability, construct validity and precision in 150 PD and 75 age and gender matched, healthy controls. Test-retest reliability, tested after 2 weeks (average), is reported in 50 patients. Co-morbidity, motor and non-motor symptoms and quality of life are also assessed.Results: So far, 89 patients (mean age 64.1 ± 11.5 years, duration of disease 6.4 ± 5.4 years, 47.2% male) and 58 controls have been studied. Patient data only are reported here with no missing data, floor or ceiling effect, and ac-ceptable skewness. Internal consistency was acceptable, inter-rater-reliability and test-retest highly satisfactory. Correlations between domains are weak-moderate, with other measures of PD or mood disorder moderate-high, with HRQoL high. (Table 1)



21

Table 1.

Item Measure ResultQuality of data and acceptability

Computable data (missing data)

100% (0%) Fully satisfactory

Floor effect/ceiling effect

1.12/2.25% Fully satisfactory (<10)

Range (total score) 1–78 Complete range not covered (0–168)

Range (domains) 12–32 All but one cov-ered complete range

Range (items) 0–12 All but one covered com-plete range

Skewness 1.15 Marginally higher than standard (1.0)

Internal consistency

Cronbach’s α 0.73 Higher than threshold (0.70)

Inter-item Correlation 0.002–0.68 Partially within standard (0.20–0.70)

Item homogeneity (all items)

0.13 Lower than min. standard (0.30)

Corrected item total correlation (domains)

0.30–0.53 (0.07–0.24)

Ail (but one) within standard (>0.30)

Reliability (inter-class correlation coefficient)

Inter-rater reliability: ICC for total score

0.99 Excellent (>0.70)

Test-retest: ICC for total score

0.85 Satisfactory (>0.70)

Construct validity

Correlation with “Pain” items EQ-5D, PDQ-8 NMSS

0.30–0.47 Moderate

Other measures of PD (SCOPA-motor, NMSS, CISI-PD)

0.45–0.63 Moderate to high

Mood disorder (HADS)

0.46–0.53 Moderate to high

Item Measure ResultHRQoL (EQ-5D. PDQ-8)

0.54–0.63 High

Discriminative (known-groups) validity classified by EQ-5D (pain item) and QUICK (fluctua-tion pain)

p < 0.001 Significant

Precision Standard error of measurement

7.53 Satisfactory (<1/2 SD at baseline)

Conclusions: Interim results suggest that the PD Pain Scale is a valid and potentially useful specific tool for assessment of pain in PD.No conflict of interest.

062

CONTRIBUTION OF MUSCULOSKELETAL DISORDERS TO CHRONIC LUMBAGO IN PARKINSON’S DISEASEM. Shiraishi1,*, N. Sasaki1, F. Maki1, H. Akiyma1

1Neurology, St. Marianna University School of Medicine, Kawasaki, Japan

Objectives: To clarify the impact of comorbid musculoskeletal disorders on chronic lumbago in Parkinson’s disease (PD).Methods: Data was retrospectively analyzed from 52 PD patients treated by our outpatient for more than 1 year (mean age, 63 ± 4 years; mean duration from onset, 6.3 ± 0.8 years. Chronic lumbago (>3 months’ duration) was identi-fied by structured interview. Patient characteristics, comorbid musculoskeletal disorders, and serum biomarkers of musculoskeletal disorders including os-teocalcin, 1 alpha-hydroxyvitamin D3 (1alpha(OH)D3), tartrate-resistant acid phosphatase (TRACP)-5b and N-terminal telopeptide (NTX), were compared between PD patients with or without chronic lumbago. Factors associated with chronic lumbago were examined by logistic regression analysis.Results: Twenty-one PD patients (40.3%) had chronic lumbago. Severe camptocormia and scoliosis were the most common musculoskeletal disor-ders in this group (47.6% of PD patients afflicted by lumbago, followed by os-teoporosis (14.3%), compression fracture (4.8%), and other disorders (4.7%). In contrast, only one patient without chronic lumbago had severe campto-cormia (3.3%). There was no significant difference in PD duration, frequency of falls, or Hoehn–Yahr stage between PD patients with and without chronic lumbago. Serum 1alpha(OH)D3, but not serum TRACP-5b, osteocalcin, or NTX, was significantly higher in PD patients with chronic lumbago than in those without (p = 0.036). Multivariate logistic regression analysis identified the independent predictors of chronic lumbago in PD patients as compression fracture (odds ratio [OR] = 87.8, 95%CI 4.2–1825), chronic pain other than

Initials: DOB:Domain 4: Nocturnal Pain

Domain 5: Oro-facial Pain

Domain 6: Discolouration; oedema/swelling

Domain 5 TOTAL SCORE:




Domain 3: Fluctuation-related Pain

Domain 3: Chronic Pain

Domain 3: Musculoskeletal Pain



TOTAL SCORE (all domains):

Comments:

Domain 7: Redicular Pain


Severity Frequency Frequencyx Severity

Severity

Severity

Frequency

Frequency

Frequencyx Severity

Patient ID No:

This scale is designed to define and accurately describe the different types and the pattern of painthat your patient may have experienced during the last month due to his/her Parkinson’s diseaseor related medication.

Each symptom should be scored with respect to

0 =None,1 = mild (symptoms present but sauses little distress or disturbance to patient),2 = moderate (some distress or disturbance to patient),3 = Severe (major source of distress or disturbance to patient).

0 =Never,1 = Rarely (<1/wk),2 = Often (1/wk),3 = Frequent (several times per week),4 = Very Frequent (daily or all the time).

1. Does the patient experience pain around their joints? (including arthritic pain)

2. Does the patient experience pain deep within the body? (A generalised constant, dull, aching pain - central pain)

3. Does the patient experience pain related to an internal organ? (For example, pain around the liver, stomach or bowels-visceral pain)

4. Does the patient experience dyskinetic pain? (pain related to abnormal involuntary movements)

5. Does the patient experience “off” period dystonia in a specific region? (in the area of dystonia)

6. Does the patient experience generalised “off” period pain? (pain in whole body or areas distant to dystonia)

7. Does the patient experience pain related to jerking leg movements during the night (PLM) or an unpleasant burning sensation in the legs which improves with movement (RLS)?

8. Does the patient experience pain related to difficulity turning in bed at night?

9. Does the patient experience pain when chewing?

10. Does the patient have pain due to grinding their teeth during the night?

11. Does the patient have burning mouth syndrome?

14. Does the patient experience a shooting pain/ pins and needles down the limbs?

13. Does the patient experience generalised lower abdominal pain?

12. Does the patient experience a burning pain in their limbs? (often associated with swelling or dopaminergic treatment)

Version: V1 1 Date: 01.10.2012 Version: V1 2 Date: 01.10.2012

(0 - 3) (0 - 4)

PD PAIN SCALE PD PAIN SCALE

(0 - 3) (0 - 4)

061



22

lumbago (OR = 30.5, 95%CI 1.7–560), and elevated serum 1alpha(OH)D3 level (OR = 0.92, 95%CI 0.86–0.98).Conclusions: Many PD patients may experience chronic pain associated with bone remodeling.ReferenceNègre-Pagès L, Mov Disord. 2008No conflict of interest.

063

FREQUENCY OF THE PAIN AND SLEEP PROBLEMS AT PATIENTS WITH PARKINSON’S DISEASE AND INFLUENCE OF DEEP BRAIN STIMULATION ON THEMV. Vuletic1,*1Neurology, University Hospital Dubrava, Zagreb, Croatia

Objectives: Pain and sleep problems are often neglected and under-recog-nized and affect significantly quality of life and disability. Our aim was to see the frequency of them at Parkinson’s disease (PD) patients and influence of the Deep brain stimulation (DBS) on them.Methods: We conducted investigation with appropriate NM self-completed questionnaires, Visual Analogue Scale and McGill questionnaire and anam-nesis’ data. The study involved randomly selected 200 PD patients and 20 PD patients that had treated with DBS last year. For patients with DBS we did the investigation before DBS and 1 year after operation. In addition we try to see factors that were connected with pain and sleep problems.Results: The pain prevalence was 68%. Depression was present in 45% of pa-tients and constipation in 40% of patients, sleep disturbances in 30% and cogni-tive disturbances in 20% of patients. After deep brain stimulation we observed significant decreased in frequency concerning sleep problems (from 45 % to 10% of patients) and pain (from 70% to 25%) (p < 0,05). We found that both symptoms were associated with depression and pain, also, with present dyskinesias.Conclusions: There is rather high frequency of the pain and sleep problems at PD patients and they should have to be assessed regularly in our clinical practice. DBS helps in relieving of the pain and sleep problems.No conflict of interest.

064

SLEEP DISTURBANCES IN ESSENTIAL TREMOR AND PARKINSON’S DISEASE: A POLYSOMNOGRAPHIC STUDYB. Ozen Barut1,*, N.F. Tasçilar1, A. Varol11School of Medicine, Bülent Ecevit University, Zonguldak, Turkey

Objectives: Sleep problems are a common non-motor complication of Parkinson’s disease. As well as patients with ET share a number of motor and non-motor features of PD. To clarify any potential relationships between these disorders, we evaluated and compared the sleep problems in patients with ET and PD using assessment scales and polysomnographic (PSG) testing.Methods: Sleep problems are a common non-motor complication of Parkinson’s disease. As well as patients with ET share a number of motor and non-motor features of PD. To clarify any potential relationships between these disorders, we evaluated and compared the sleep problems in patients with ET and PD using assessment scales and polysomnographic (PSG) testing.Results: The results of our study have shown that patients with PD were more likely than were those with ET to have a history of REM sleep behavior disorders (RBD) (p = 0,001) and excessive daytime sleepiness (p ≤ 0.05). Additionally, PSG data revealed that ET patients had lower mean SpO2 val-ues (p ≤ 0.05) and REM without atonia (RWA) (p = 0.032) than did patients with PD.Conclusions: This is the first study to use PSG to compare ET and PD, and the results may assist with the differential diagnosis of these diseases.No conflict of interest.

065

THE PREVALENCE OF SLEEP DISORDERS IN THE EARLY STAGES OF PARKINSON’S DISEASEE. Gubanova1, N. Fedorova1,*, T. Kulua1

1Medicine, Russian Medical Academy of Postgraduate Education, Moscow, Russia

Objectives: Parkinson’s disease (PD) - one of the most frequent neurodegenera-tive diseases. It manifests as a wide symptoms including dyssomnia. To deter-mine the frequency and severity of sleep disorders on PD patients in early stages.Methods: 80 patients with PD on the early stages were included (male:female = 30:50). Middle stage of the disease – 1,5 ± 0,5 at H&Y scale. The average age was 59,5 ± 23,5 years. The mixed form of PD predominated over others (75%). We used Hoehn and Yahr scale modified by Lindvall to as-sess PD severity (Hoehn M., Yahr M., 1967, O. Lindvall, 1989); assess affective

disorders - Hamilton Rating Scale (M. Hamilton, 1959, 1999); to assess the quality of life - a questionnaire PDQ-39 (Peto V. et al., 1995). Evaluation of sleep disorders - Pittsburgh Sleep Scale (PSQI, Buysee DJ et al., 1989) and Epworth Sleepiness Scale (ESS, Johns MW, 1993).Results: Sleep disorders were observed in 75% of patients. Insomnia disorders in 44% of patients: presomnia – 42.5%, intrasomnia – 55%, postsomnia – 40%. Hypersomnia – 34%. Pathological behavior in REM-sleep phase – in 45.7% of patients. Affective disorders - 80%. There was a negative correlation (r = -0,597) of quality of life with sleep disorders and a positive correlation of affective disorders (anxiety and depression) (r = 0,587) and (r = 0,642).Conclusions: Sleep disorders in the early stages of the disease significantly deteriorate the quality of life and daily activities of patients with PD.Reference1. Johns M.W. Daytime sleepiness, snoring and obstructive sleep apnea.

The Epworth Sleepiness Scale.//Chest 1993; 103:30–36.No conflict of interest.

066

ESTIMATION OF SLEEP RELATED DISORDERS (SRDS) IN PARKINSON’S DISEASE- A HOSPITAL BASED STUDYP. Ghosh1,*, A.K. Bhattacharyya2, K.B. Bhattacharya3, A. Ghosh4, I. Ghosh5

1Neurology, Vivekananda Institute of Medical Sciences, Kolkata, India, 2Neurology, Mata Gujri Memorial Medical College, Kishanganj, India, 3Neurology, Bangur Institute of Neurosciences, Kolkata, India, 4Internal Medicine and Neurology, Mata Gujri Memorial Medical College, Kishanganj, India, 5Internal Medicine, Nil Ratan Sircar Medical College, Kolkata, India

Objectives: To estimate the proportion of sleep-related disorders (SRDs) in pa-tients of Idiopathic Parkinson’s Disease (PD) and to find out the proportion of symp-toms present before the diagnosis was established (i.e. pre-motor symptoms).Methods: A cross sectional hospital based study was carried out on 63 patients of Idiopathic PD attending the neurology clinic of 2 hospitals in Kolkata and Kishanganj, India during December 2010 and December 2012 for assessment of sleep related disorders. Positive responders were asked to fill up pre-designed standardized questionnaires on RLS rating scale, Parkinson’s Disease Sleep Scale (for Insomnia) and Epworth Sleepiness Scale (for EDS). Polysomnography and audio-visual recording was done for abnormal movements (for RBD). They were also asked if these symptoms preceded the diagnosis of PD.Results: Out of 63 patients, 19 (30%) has REM sleep Behavior Disorder (RBD), 16 (26%) has Restless Leg Syndrome (RLS) [Mild 8, Moderate 5 and Severe 3], 27 has Insomnia, 29 has Excessive day time somnolence (EDS) [Mild 23 (ESS score 10–15) and severe 6 (ESS score 16–24)], 25 has vivid dreams. 13 (68%) patients with RBD, 10 (63%) patients with RLS, 20 (74%) patients with Insomnia, 20 (69%) patients with EDS and 11 (44%) patients with Vivid dreams complained specifically of these symptoms being present prior to the establishment of PD.Conclusions: SRDs are present in large proportion of PD patients and are common pre-motor symptoms.No conflict of interest.

067

CLINICAL SIGNIFICANCE OF REM SLEEP BEHAVIOR DISORDER IN PARKINSON’S DISEASE.E.A. Lyashenko1,*1Neurology Department, Russian Medical Academy of Postgraduate Studies, Moscow, Russia

Objectives: REM sleep behavior disorder (RBD) is a parasomnia in which normal muscle atonia of REM sleep is lost. RBD are often associated with Parkinson’s disease (PD) and some other neurodegenerative diseases and can precede its development for more than 10 years. The study aimed to compare the characteristics of patients with PD with RBD versus those without RBD.Methods: Consecutive patients with PD were evaluated with detailed clini-cal history and examination. PD patients underwent polysomnography (PSG) to diagnose the presence of RBD. Clinical scores included RBD screening questionnaire (RBDSQ), UPDRS, H&Y, Schwab and England (S&E) scale, Parkinson’s disease Sleep Scale (PDSS), Epworth Sleep Scale (ESS), non-motor symptoms scale (NMSS), the hospital anxiety and depression scale (HADS), Beck Depression Inventory (BDI), Short Cognitive Performance Test (SCT) and Montreal Cognitive Assessment (MoCA). Measures of disease se-verity, quantitative motor indices, motor subtypes, therapy complications, and autonomic, affective and cognitive dysfunction were assessed and compared using regression analysis, adjusting for disease duration, age, and sex.Results: PD patients with RBD were older, had more likely non-tremor subtype of PD, with a higher frequency of freezing and falls (p < 0.05). Patients with RBD more often had a depression, cognitive and autonomic disorders (p < 0.05).Conclusions: Our results support previous findings that patients with PD who have RBD tend to have specific motor and non-motor manifestations. This could mean that RBD may be a marker of a definite subtype of PD and more complex and aggressive neurodegenerative process.No conflict of interest.



23

068

CLINICAL FEATURES AND POTENTIAL MECHANISM OF PARKINSON’S DISEASE PATIENTS WITH PROBABLE RBDY. Hu1, S.Y. Yu1, L.J. Zuo1, F. Wang1, Z.J. Chen1, C.J. Cao1, W. Zhang1,*1Neurology, Beijing Tiantan Hospital, Beijing, China

Objectives: To investigate clinical features and potential mechanism in Parkinson’s disease (PD) patients with probable rapid eye movement sleep behavior disorders (P-RBD).Methods: 170 PD patients were evaluated by RBD screening question-naire (RBDSQ) and scales for motor and non-motor symptoms. Levels of α-synuclein oligomer and neuroinflammatory factors in CSF from 19 P-RBD patients, 52 NP-RBD patients and 31 normal subjects were detected.Results: (1) 47 of 170 (27.64%) PD patients had P-RBD (RBDSQ ≥ 6 points); P-RBD group had significantly longer duration than NP-RBD group. There was no difference in gender, educational level, age, age of onset, side of onset, clinical subtypes and levodopa equivalent dose between the two groups; (2) The number of wearing-off in P-RBD group was dramatically more than that in NP-RBD group. The total number of NMS in P-RBD group was remark-ably more than that in NP-RBD group. Depression, anxiety, sleep disorders, autonomic dysfunctions and fatigue in P-RBD group were severer than that in NP-RBD group; (3) CSF levels of IL-1β, TNF-α and NO in NP-RBD group were prominently higher than that in normal subjects. CSF levels of α-sunuclein, IL-1β and NO in P-RBD group were significantly higher than that in NP-RBD group. In P-RBD group, α-synuclein level was positively correlated with IL-1β and NO levels.Conclusions: PD patients had high incidence of PRBD. PD-PRBD patients had severe wearing-off and NMS. Neuroinflammation induced by excessive α-synuclein deposition in brain might be a potential mechanism of PD-RBD.No conflict of interest.

069

REVISITING THE IMPACT OF REM SLEEP BEHAVIOR DISORDER ON PROGRESSION OF PARKINSON’S DISEASEM. Sommerauer1,*, P.O. Valko1, E. Werth1, R. Poryazova1, S. Hauser1, C.R. Baumann1

1Neurology, University Hospital Zurich, Zurich, Switzerland

Objectives: Estimation of progression in Parkinson’s disease (PD) is essen-tial to guide clinical decisions and to enable patients to plan and manage their life with PD. Rapid eye movement (REM) sleep behavior disorder (RBD) and REM sleep without atonia (RWA) are recognized as early harbingers of neu-rodegeneration and may precede motor symptoms by years. However, their impact on motor progression remains elusive.Methods: We retrospectively analyzed polysomnographic and clinical data of 59 PD patients, dividing them into patients with RBD (n = 15), RWA (n = 22) and those with normal muscle atonia (n = 22). We compared the three groups with regard to motor progression, defined as changes in Unified Parkinson’s Disease Rating Scale (UPDRS) III values per year and selected PD specific characteristics.Results: Motor disability at first visit and time interval between first and last visits were similar between groups. We observed a significantly faster motor progression in PD patients with RBD and RWA than in those with preserved REM sleep atonia.Conclusions: Our findings suggest that brainstem abnormalities responsible for loss of muscle atonia during REM sleep might represent a marker of faster motor progression in PD.Reference1. Lavault S, Leu-Semenescu S, Tezenas du Montcel S, et al. Does clini-

cal rapid eye movement behavior disorder predict worse outcomes in Parkinson’s disease? Journal of Neurology 2010; 257:1154–1159.


070

POLYSOMNOGRAPHIC STUDIES IN PATIENTS WITH IDIOPATHIC PARKINSON’S DISEASE AND SLEEP DISTURBANCES.Y. Ouahmane1,*, J. Mounach1, A. Satte1, A. Zerhouni1, H. Ouhabi11Neurophysiologie, Hôpital Militaire Mohamed V, Rabat, Morocco

Objectives: To describe sleep disturbances, and polysomnographic param-eters in a cohort of patients with idiopathic Parkinson’s disease who have sleep disturbances.Methods: 9 patients; 6 men and 3 women aged 64 ± 4.5 years, having an idiopathic Parkinson’s disease with moderate severity (Hoehn and Yahr 2.26 ± 0.8) who increased from 1 to 9 years. They complained sleep disor-ders. A preliminary evaluation showed the absence of major psychiatric or cognitive impairment (MMS > 24). The study consist to analyze the character-istics of sleep disorders, the evaluation of daytime sleepiness according to the Epworth scale. And the analyze of polysomnographic parameters of one night.

Results: Moderate to severe insomnia according to the scale of Morin (EM) was found in 33% of cases. Sleep disorder breathing were present in 33% of patients. Periodic limb movements occurred in 22%. REM behavior disorders (RBD) were present in 22%. And 11% of patients complained an excessive daytime sleepiness confirmed by the Epworth scale. Polysomnography study confirmed these disorders; 33% of patients have total sleep time (TTS) less than five hours, and 33% have sleep efficiency below 68%. In general, the TTS was 318.3 ± 96.6 min. The main determinants of TTS were: EM, duration of the Parkinson and severe motor impairment.Conclusions: These results shows different types of sleep disorders in this cohort of patients with Parkinson’s disease of moderate severity. The inverse relationship between disease duration and TTS suggest the influence of the neurodegenerative process of sleep mechanisms. However, the level of day-time alertness does not seem compromised by Parkinson diseaseNo conflict of interest.

071

SLEEP AND EXECUTIVE FUNCTIONS: A VIRTUAL AND NEURO-PSYCHOLOGICAL STUDY IN PARKINSON’S DISEASE AND SLEEP APNEA SYNDROMEG. Albani1,*, P. Cipresso2, E. Pedroli2, G. Riva2, L. Priano1, A. Mauro1

1Neurology and Neurorehabilitation, Istituto Auxologico Italiano IRCCS, Verbania, Italy, 2Psychology, Catholic University of Milan, Milan, Italy

Objectives: Aim of this study was to evaluate the impact of sleep disturbances on decision making in non demented PD patients compared with OSAS, by using a virtual immersion in a supermarket.Methods: We used a Virtual Reality version of the Multiple Errand Test (VMET) in order to evaluate decision making ability in 12 PD not-demented patients, 12 OSAS patients and 14 controls. The MET is an assessment of executive functions in daily life and consists to perform tasks according predefined rules, so that there are items to be bought and informations to be obtained. (www.neurovr.org). All three groups of patients performed a video polysonnographyc study within a week after the VMET evaluation and a dedicated neuropsycho-logical battery including FAB, Corsi, MMSE, Panda, Digit span forward and backward, Raven, Rey, Trail making test Token test.Results: In control subjects, neuropsychological tests resulted correlated with findings of VMET. By comparing with controls, while OSAS patients showed no significant differences, PD patients showed significant lower performances in the virtual strategies. Much more, the defective strategy in a virtual supermarket was significantly correlated with polysonnographyc abnormalities.Conclusions: In our study patients with OSAS showed a normal decision making in the virtual test. On the other side, our data suggest that in PD, the alteration of some executive functions may be correlated much more with the abnormal microstructure of sleep, than the deprivation of sleep “per se”. Neurodegenerative process may involve common anatomofunctional pathways regulating REM and N-REM sleep structure and some executive functions.No conflict of interest.

072

IRON AND ITS METABOLISMIN PARKINSON’S DISEASE PATIENTS WITH SLEEP DISORDERSS. Yu1, L. Sun1, Z. Liu1, X. Huang1, L. Zuo1, C. Cao1, X. Wang2, W. Zhang1,*1Department of Neurology, Beijing Tiantan Hospital, Beijing, China, 2Department of Physiology, Capital Medical University, Beijing, China

Objectives: To investigate iron and its metabolism in Parkinson’s disease (PD) patients with sleep disorders (SD).Methods: (1) 95 PD patients with Pittsburgh Sleep Quality Index (PSQI) ≥ 5 and PSQI < 5 points were recruited into PD with SD (PD-SD) and with no SD (PD-NSD) groups; (2) 95 blood and 38 cerebral spinal fluid samples (CSF) were collected and the levels of iron and its metabolism-relating proteins including ferritin, transferrin and lactoferrin were detected (3). The levels of above factors were analyzed between the two groups.Results: (1) Iron level in CSF in PD-SD group was dramatically higher than PD-NSD group, implying an excessive iron deposition in brain; (2) Levels of transferrin and lactoferrin in CSF were obviously higher in PD-SD group than PD-NSD group, suggesting that abnormal iron metabolism in brain induced iron deposition in brain; (3) Iron level in serum in PD-SD group wasn’t differ-ent with PD-NSD group, indicating that elevated brain iron wasn’t resulted from systemic iron elevation; (4) Transferrin level in serum was significantly decreased, reflecting that the enhanced brain iron wasn’t due to the translo-cation of transferrin from peripheral to central system, a process that highly contributed to the iron increase in brain.Conclusions: Abnormal iron metabolism in brain might cause excessive iron deposition and be related to PD-SD. Hence, inhibition of iron deposition might be a target for PD-SD therapy.



24

073

THE CHANGES OF NEUROINFLAMMATORY FACTORS IN PARKINSON’S DISEASE PATIENTS WITH SLEEP DISORDERSS. Yu1, L. Sun1, Z. Liu1, X. Huang1, L. Zuo1, C. Cao1, X. Wang2, W. Zhang1,*1Department of Neurology, Beijing Tiantan Hospital, Beijing, China, 2Department of Physiology, Capital Medical University, Beijing, China

Objectives: To investigate the changes of neuroinflammatory factors in Parkinson’s disease (PD) patients with sleep disorders (SD).Methods: (1) 95PD patients with Pittsburgh Sleep Quality Index (PSQI) ≥ 5 and PSQI < 5 points were recruited into PD with SD (PD-SD) and with no SD (PD-NSD) groups; (2) 95 blood and 38 cerebral spinal fluid (CSF) samples were collected and the levels of neuroinflammatory factors, including pros-taglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), hydrogen peroxide (H2O2) and nitric oxide (NO) were detected; (3) The levels of above factors were compared between the two groups.Results: (1) In PD-SD group, PGE2 level was significantly elevated in CSF but not in serum compared with PD-NSD group, indicating a potential role of neuroinflammation in PD-SD reflected by the enhanced brain PGE2 level; (2) TNF-αlevel in CSF in PD-SD group was strikingly declined compared with PD-NSD group, however, TNF-αlevel in serum in PD-SD group wasn’t promi-nently different compared with PD-NSD group, demonstrating that the decline of brain TNF-αlevel might lead to PD-SD because of the less sleep-promoting effect exerted by the declined brain TNF-α; (3) Other neuroinflammatory fac-tors, including IL-1β, H2O2 and NO in CSF and serum were not remarkably changed.

Table 1. Levels of neuroinflammatory factors in serum and CSF of PD patients.

Serum PD-SD group PD-NSD group P-values

(64 cases) (31 cases)

PGE0 (pg/ml) 3.145 (4.437–14.021)

5.619 (3.763–10.770)

X:

TNF-α 63.317 (49.430–63.023)

64.334 (52,313–74.446)

X:

IL-1 β (pg/ml) 3.430 (3.471–74.171)

12042 (6.154–165.730)

X:

H2O2 (mmol/l) 23.332 (23.933–35.316)

23.025 (24.593–30.312)

X:

NO (mmol/l) 44.351 ±23.426 52.784±29.106 X:

CSF PD-SD group PD-NSD group P-value

(12 cases) (26 cases)

PGE0 (pg/ml) 5.142 (4.643 ~ 5.767)

6.074 (4.363 ~ 11.273)

0.022*

TNF-α 515.1476 (482.967 ~ 636.290)

45.700 (32.809 ~ 479.859)

0.001**

IL-1 β (pg/ml) 9.026 (6.296 ~ 76.186)

27 702 (8.576 ~ 165.393)

NS

H2O2 (mmol/l) 1.973 (1.349 ~ 2.368)

1.973 (1.432 ~ 2.106)

NS

NO (mmol/l) 56.705 ± 20.705 53.793 ± 23.746 NS

NS: not significant, P>0.05; *: P<0.05, **: P<0.01

Conclusions: Neuroinflammatory factors displayed different profile in PD-SD patients with PGE2 enhanced, TNF-α reduced and IL-1β, H2O2 and NO unchanged.No conflict of interest.

074

CEREBROLYSIN DOWNREGULATES NEURONAL AND INDUCIBLE NITRIC OXIDE SYNTHASE EXPRESSION AND INDUCES NEUROPROTECTION IN A MOUSE MODEL OF PARKINSON’S DISEASEH. Sharma1,*, R. Castellani2, R. Patnaik3, A. Sharma4, H. Moessler5, D. Muresanu6

1Surgical Sciences Anesthesiology and Intensive Care Medicine, Uppsala University Hospital, Uppsala, Sweden, 2Division of Neuropathology, University of Maryland School of Medicine, Baltimore MD, USA, 3School of Biomedical

Engineering, Indian Institute of Technology Banaras Hindu University, Varanasi UP, India, 4Deptartment Surgical Sciences Anesthesiology and Intensive Care Medicine, University Hospital Uppsala University, Uppsala, Sweden, 5Neuropharmacology, Ever Neuro Pharma, Oberburgau, Austria, 6Clinical Neurosciences, University Hospital University of Medicine and Pharmacy, cluj-Napoca, Romania

Objectives: Parkinson’s Diseases (PD) is altered nitric oxide synthase (NOS) metabolism. An increased production of neuronal NOS (nNOS) or inducible NOS (iNOS) occurs in the animal models of PD. Thus, down-regulation of NOS may have some neuroprotective effects in PD. Since oxidative stress in PD is responsible for nitric oxide (NO) production and cellular injury, in this investigation influence of cerebrolysin, a potent neuro-protective agent with marked antioxidant activity was examined in a mouse PD model.Methods: The PD like symptoms were induced by 4 methamphetamine (METH, 10 mg/kg, i.p.) or 1-metyl-4-fenyl-1, 2, 3, 6-tetrahydropyridin, (MPTP, 20 mg/kg, i.p.) injections daily within two h intervals for 5 days. This dose and time schedule on eighth day produces PD like symptoms in striatum (ST) and substantia niagra (SN). In groups cerebrolysin or saline was given (3 to 5 ml/kg, i.v.) in identical manner for 1 week. In these rats, immunohistochemical analyses were made to detect nNOS, iNOS, activa-tion of microglia and astrocytes together with neuronal injuries using Nissl staining.Results: Our results showed pronounced activation of microglia, astrocytes and neuronal damages together with overexpression of nNOS and iNOS in the ST and in SN in MPTP or METH treated mice. Cerebrolysin significantly attenuated neuronal damage, astrocytic and microglial activation and down-regulated the nNOS and iNOS in a dose dependent manner.Conclusions: These observations are the first to show that the NO has a potential role in PD pathology and chronic cerebrolysin induced marked neu-roprotection in mice indicating its neurotherapeutic role in PD.No conflict of interest.

075

A LONG-TERM PROSPECTIVE FOLLOW-UP STUDY OF INCIDENT RLS IN THE COURSE OF CHRONIC DOPAMINERGIC THERAPY IN DE NOVO PD PATIENTSS. Calzetti1,*, M. Angelini1, A. Negrotti1, E. Marchesi1, M. Goldoni21Department of Neuroscience, Azienda Ospedaliero Universitaria, Parma, Italy, 2Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy

Objectives: The aim of this prospective study is to assess the incidence rate of RLS in patients with previously untreated PD.Methods: RLS was diagnosed according the IRLSSG criteria by face-to-face interviewResults: Fifteen out of 106 PD patients (67 male and 39 female) developed RLS following the starting of DAergic therapy resulting in an overall incidence rate of 47 per 1000 case/person/year and of 37 per 1000 case/person/year after the exclusion of possible ‘secondary’ forms of the disorder (n = 3), which are both are higher than those reported in German general population (14 per 1000 case/person/year). In PD patients an incidence rate of overall RLS sig-nificantly higher than that reported in the above mentioned population was found in the age ranges 55–64 years and 55–64 and 65–74 years pooled together (70 and 50.5 versus 18 and 17 per 1000 case/person per year, re-spectively, p < 0.02 and <0.05). Ten out of 12 patients (83.3%) developed RLS within 24 months from the starting of DAergic medication (median latency 7.5 months).Conclusions: These findings confirm the co-morbidity between PD and RLS supporting the view that sustained DAergic therapy could represent the critical condition inducing an increased occurrence of RLS in PD through chronic stimulation of hypersensitive post-synaptic DA receptors in the spi-nal cord in patients in which the neurodegenerative process has involved the A11 hypothalamic area, site of origin of the DAergic diencephalo-spinal pathway.Reference1. Szentkiralyi A, Fendrich K, Hoffman W, Happe S, Berger K (2011). Sleep

Med 12: 815–820.No conflict of interest.

076

AN INVESTIGATION ON THE CHANGES OF NEUROTRANSMITTERS AND IRON METABOLISM IN PARKINSON’S DISEASE PATIENTS WITH RESTLESS LEGS SYNDROMEZ. Chen1, W. Zhang1,*, S. Yu1, L. Zuo1, C. Cao1, Y. Hu1, F. Wang1

1Department of Neurology, Beijing Tiantan Hospital, Beijing, China



25

Objectives: To investigate the changes of neurotransmitters and iron metabolism in Parkinson’s disease (PD) patients with restless legs syn-drome (RLS).Methods: (1) 112 PD patients were divided into RLS group (40 cases) and non-RLS (nRLS) group (72 cases) according to the International Restless Legs Syndrome Rating Scale (IRLS); (2) Blood and cerebral spinal fluid (CSF) (17 cases in PD-RLS group and 34 cases in PD-nRLS group) were collected and the levels of neurotransmitters including dopamine (DA), acetylcholine (Ach), norepinephrine (NE) and serotonin (5-HT), iron and its metabolism-related proteins containing ferritin (Fer) and transferrin (Tf) were detected.Results: (1) The levels of DA and 5-HT in CSF were significantly descended in PD- RLS group, the same as the levels of DA, 5-HT, NE and Ach in serum (Table 1);

Table 1. Comparison of the levels of neurotransmitters in CSF and serum between PD-RLS group and PD-nRLS group.

Cases DA (pg/ml)

5-HT (pg/ml)

NE (pg/ml)

Ach (pg/ml)

CSF PD-RLS

group

Mean 17 0.0046 0.0070 0.5115 0.0043

SD 0.0011 0.0039 0.0897 0.0012

PD-nRLS group

Mean 34 0.0057 0.0128 0.5247 0.0037

SD 0.0006 0.0056 0.0855 0.0006

P value

0.003** 0.001** 0.673 0.256

Serum PD-RLS

group

Mean 40 0.0039 0.2881 0.1374 0.0153

SD 0.0016 0.1164 0.0586 0.0054

PD-nRLS group

Mean 72 0.0048 0.3851 0.2035 0.0193

SD 0.0011 0.1634 0.0867 0.0061

P value

0.024* 0.004** 0.021* 0.035*

*: P<0.05, **: P<0.01.(2) Abnormal iron metabolism was found in PD-RLS patients by the decreased lev-els of iron and Fer and the increased Tf level in CSF, and reduced levels of iron and Fer in serum (Table 2);

Table 2. Comparison of the levels of iron and its metabolism-related protein in CSF and serum between PD-RLS group and PD-nRLS group.

Cases Iron (nmol/L)

Fer (ng/ml)

Tf (nmol/L)

CSF PD-RLS group

Mean 17 0.5044 9.350 0.1345

SD 0.2552 4.976 0.0354

PD-nRLS group

Mean 34 0.8101 13.261 0.1070

SD 0.2298 4.229 0.0274

P value 0.002** 0.015* 0.013*

Serum PD-RLS group

Mean 40 2.1413 12.288 0.1062

SD 0.9931 5.613 0.0211

PD-nRLS group

Mean 72 2.6351 14.612 0.1036

SD 0.8384 4.924 0.0175

P value 0.025* 0.0032** 0.546

*: P < 0.05, **: P < 0.01.(3) There was a negative correlation between the severity of RLS and the levels of DA, Fer and Tf in CSF (Table 3).

Table 3. Correlation between the severity of RLS and the levels of neu-rotransmitters and iron and its metabolism-related proteins in CSF of PD-RLS patients.

Partial correlation P value

DA −0.956 0.000**

5-HT 0.932 0.000**

NE 0.004 0.990

Ach −0.464 0.354

Iron 0.887 0.000**

Fer −0.875 0.000**

Tf −0.957 0.000**

**: P < 0.01.

Conclusions: The impaired multiple neurotransmitter systems and the abnor-mal iron metabolism might be the potential mechanisms of PD-RLS.No conflict of interest.

077

OLFACTORY NEURODEGENERATIVE PATHOLOGY IN LEWY BODY DISEASEJ. Attems1,*, L. Walker1, K.A. Jellinger2

1Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom, 2Institute of Clinical Neurobiology, Vienna, Vienna, Austria

Objectives: Olfactory dysfunction is a common and early symptom of many neurodegenerative diseases including Lewy body diseases (LBD) and Alzheimer’s disease (AD). In mild cognitive impairment (MCI) olfactory dys-function heralds the progression to dementia. Olfactory dysfunction is associ-ated with the deposition of α-synuclein and hyperphosphorylated tau (tau) in the olfactory bulb (OB).Methods: Our study cohort consisted of 536 post mortem brains (mean age: 81.3 years, SE ± 0.46; 57% male). According to neuropathologically confirmed diagnoses 33.6% had AD, 8.7% LBD (i.e. Parkinson’s disease with/ without dementia, dementia with Lewy bodies), 5.4% vascular demen-tia (VaD) and 9.8% other neurodegenerative diseases (controls: 42.3%). In all cases the OB was stained with antibodies against α-synuclein and tau. The severity of OB α-synuclein and tau pathology was assessed semiquantitatively.Results: In the OB α-synuclein and tau correlated with Lewy body Braak stages and neurofibrillary tangle Braak stages, respectively. Likewise, OB pathologies correlated with the presence of clinical dementia. However, the correlation between OB α-synuclein pathology and clinical dementia failed to remain statistically significant when controlling for concomitant OB tau pathol-ogy; the latter was seen in 85.7% of LBD cases while only 34.4% of AD cases showed OB α-synuclein pathology.Conclusions: Our data show that OB tau pathology is frequently seen and associated with clinical dementia in LBD patients. Hence, we suggest that in a considerable proportion of LBD patients olfactory dysfunction is biomarker for both cerebral α-synuclein and tau pathology.No conflict of interest.

078

COULD OLFACTORY DYSFUNCTION GENUINELY BE A DISCRIMINATING SIGN BETWEEN ELDERLY WITH PARKINSON’S DISEASE AND HEALTHY CONTROLS?C. Foguem1,*, B. Schaal1, J.C. Nwatchok2, M. Kack2, G. Brand1

1Center for Food and Taste Sciences (Csga), Umr 6265 Cnrs – Umr 1324 Inra – Burgundy’s University, Dijon, France, 2Department of Acute Geriatric, Auban Moët Hospital, Epernay, France

Objectives: Olfactory dysfunction is a prodromal and prevalent non-mo-tor symptom of Parkinson’s disease (PD) and an appealing biomarker for PD because of the high prevalence (>90%) among young PD patients or at the beginning of the disease [1]. The aim of this study is to evalu-ate the deficits in odor detection in Elderly with PD and suggests that trigeminal sensibility dysfunction is less severe that olfactive sensibility in elderly over 70 years old with PD and would contribute to the diagnostic accuracy.Methods: Olfactory detection threshold tests using two odors: Phenyl Ethylic Alcohol (PEA) [activating mainly olfactive (CN I) system] and N- butanol (BUT) [activating both olfactive and trigeminal (CN V) systems] for odors threshold were performed on thirty patients aged over 70 years old with PD and carefully



26

matched controls. Neuropsychologic evaluations were done as well as stage of PD estimations.Results: Patients with PD had impaired olfaction detection ability (mean PEA threshold: 16.7; mean BUT threshold: 13.04) compared with controls (mean PEA threshold: 18.28; mean BUT threshold: 14.2), independent of age and the type of PD. The PEA and BUT thresholds were correlated for patients with PD (p < 0.02) and for controls (p < 0.008).Conclusions: Our patients with PD over 70 years old have a moderate olfac-tory deficit than controls, but not statistically significant. This could be partly due to decline of olfactory threshold sensitivity in healthy control due to olfac-tory senescence.Reference1. Doty RL, et al. Neurology 1988; 38:1237–1244.No conflict of interest.

079

THE STUDY OF OLFACTION IN PATIENTS WITH PARKINSON’S DISEASE LIVING IN THE TOMSK REGION, RUSSIAO. Izhboldina1,*, I. Zhukova1, M. Nikitina1, N. Zhukova1, V. Alifirova1

1Department of Neurology and Neurosurgery, Siberian State Medical University, Tomsk, Russia

Objectives: To investigate the smell patients with Parkinson’s dis-ease (PD) seen at the Movement Disorders Center of “Siberian Medical University”.Methods: The study involved 43 Tomsk patients with PD: 18 men (42%) and 25 women (58%), aged 37 to 81 years (mean age 65,5 ± 9,1).The study was to assess the smell: the olfactory boundary, the ability to discriminate between odors and identification (choice of some alternatives).Results: Prior to the study, only 25,6% did not report reduced sense of smell. During of assessing olfactory disorders were found in 100% of the subjects. In 78,1% of patients smell violation appeared an average of 8,7 ± 11,0 years before the first motor symptoms. The olfactory boundary was dramatically in-creased in 65,1%. The most of patients (95,3%) had significantly disorders of smell discrimination. Identification of odors had only 23,3% of patients. Anosmia was detected in 4,7% of the patients. One patient has olfactory hallucinations.Conclusions: All patients with clinical confirmed PD had impaired olfactory function, developed in the majority, before the first clinical symptoms of disease. Therefore, early detection of smell disorders is necessary for the early diagnosis of the disease.No conflict of interest.

080

OLFACTORY SULCUS DEPTH AS A PREDICTOR OF IMPAIRED OLFACTION, WEIGHT CHANGE, DYSKINESIA AND QUALITY OF LIFE IN PARKINSON’S DISEASE PATIENTS.J. Sharma1,*, C. Butcher2, J. Turton3

1Medicine, Lincoln County Hospital Nottingham University, Lincoln, United Kingdom, 2Radiology, Kings Mill hospital Nottingham University, Mansfield, United Kingdom, 3Medicine, Kings Mill hospital Nottingham University, Mansfield, United Kingdom

Objectives: Olfactory sulcus (OS) can be measured in patients with Parkinson’s disease on MRI scans. Does OS depth relate to the degree of olfactory loss, predict changes in weight, dyskinesia and quality of life?Methods: Forty nine patients were studied for measurement of OS depth on MRI scan, olfaction with UPSIT 40 item test, quality of life with PDQ8 and measurement of current and sequential body weight.Results: Right sulcus (ROS) was significantly larger than the left, 5.9 ± 1.5 mm vs. 5.2 ± 1.5, p = 0.001; Rest of the results are described for ROS and aver-age OS measurements. There was a significant difference in the ROS be-tween anosmic (6.4 ± 1.6) vs. hyposmic group (5.3 ± 1.2 mm), p = 0.01 and significant negative correlation between ROS and UPSIT values, r = −.285, p = 0.047; significant negative correlation between current body weight and ROS, r = −0.264, p = 0.03; weight losers (14 patients) had larger ROS than non-weight losers (35 patients) -(6.6 ± 1.5 mm vs. 5.6 ± 1.6 mm), p = 0.06, Larger ROS patients had lost weight during the previous 4 years from 85 to 77 kg; there was significant positive correlation with the ROS (r = 0.392, p = 0.005) and average sulcus (r = 0.390, p = 0.006) for PDQ8 scores. Dyskinetic patients had significantly larger ROS than the non-dyskinetic pa-tients – 6.6 ± 1.5 vs. 5.6 ± 1.6 mm, p = 0.05. Regression analysis revealed that the most significant variable for dyskinesia was the average sulcus measure-ment - β coefficient –0.307, std error 0.043, p = 0.032; other variables were not significant.Conclusions: OS measurement seems to have a predictive value for impair-ment of olfaction, weight change, dyskinesia and quality of life in Parkinson’s disease patients.No conflict of interest.

081

MAXIMUM HEART RATE IN IDIOPATHIC PARKINSON’S DISEASEA. O’Callaghan1,*, D. Jakovljevic2, M. Trenell2, R. Walker1

1Department of Medicine, Northumbria Healthcare NHS Foundation Trust, North Shields, United Kingdom, 2MoveLab – Physical Activity and Exercise Research, Newcastle University, Newcastle upon Tyne, United Kingdom

Objectives: Exercise based research studies and programes frequently use target heart rate zones based on estimates of predicted maximum heart rate (HRmax) derived from age. The objective of this study was to measure the HRmax at VO2peak, during a cardiopulmonary exercise test (CPET), in a rep-resentative population with idiopathic Parkinson’s disease (IPD) and compare the values to predicted.Methods: 31 individuals with IPD (13F, 18M, mean age 67), under the care of Northumbria PD service, had CPETs with maximal ramp protocol on an elec-tromagnetically controlled recumbent bicycle ergometer. HRmax at VO2peak was recorded and compared to predicted values as calculated using 3 differ-ent univariate prediction equations (1).Results: Mean percent predicted HRmax achieved using the 3 different pre-diction equations were 72.9%, 75.5% and 78.9% (range 54.2%–101.4%). Only 1 participant achieved predicted HRmax. 4 participants were taking beta-blocking medication. The mean difference between achieved maximum and resting heart rate was 45.Conclusions: This study shows this population have difficulty achieving pre-dicted HRmax based on 3 prediction equations and the mean difference between resting and maximum achieved heart rate is small. This has implications for the use of estimated target heart rate zones in this population and alternative out-come measures may need to be considered, for example ratings of perceived exertion.Reference1. Robergs RA, Landwher R. The Surprising History of the “HRmax = 220-age”

equation. Journal of Exercise Physiologyonline. 2002; 5:1–10.

082

ELECTROCARDIOGRAPHIC ARTEFACT IN IDIOPATHIC PARKINSON’S DISEASEA. O’Callaghan1,*, R. Walker1

1Department of Medicine, Northumbria Healthcare NHS Foundation Trust, North Shields, United Kingdom

Objectives: Electrocardiographic (ECG) artefact is not uncommon and it is vital that this is differentiated from true pathology to avoid unnecessary inves-tigation and treatment. The objective of this study was to identify the preva-lence and type of ECG artefact in a representative population with idiopathic Parkinson’s disease (IPD).Methods: 93 individuals with IPD (27F, 66M, mean age 69), under Northumbria PD service, had 12-lead electrocardiograms (ECGs). ECG rhythm, any visual degradation of limb lead signal quality, and artefact type were recorded.Results: 89 ECGs showed sinus rhythm (SR), 3 atrial fibrillation (AF), 1 paced. Up to 64.5% (60) of 93 ECGs had degrees of signal quality degrada-tion in one or more limb leads (aVR, aVL, aVF, I, II, III) on visual inspection. 6 (6.5%) had artefact similar in morphology to atrial flutter, particularly marked and difficult to differentiate from true pathology in 3 (3.2%).Conclusions: Previous case reports noted the effect of tremor on ECG mimick-ing atrial and ventricular arrhythmias. This study highlights the frequency of this. The original ECGs in the series were performed with the limb leads on the limbs as per routine. By moving the limb leads to more proximal positions, in some onto the torso, medial to the deltoids and onto the abdomen (positions similar to those for constant ECG monitoring) the signal quality and artefact significantly improved, aiding interpretation. We suggest individuals with IPD and apparently abnormal ECG, have this repeated with the limb leads in a proximal position.No conflict of interest.

083

INTER-OBSERVER AGREEMENT OF A CARDIAC VISUALISATION CLASSIFICATION USING MIBG SCANS IN MOVEMENT DISORDERS: REPRODUCIBLE AND RELIABLE.A. Sauerbier1,*, N. Mulholland2, N. Dimitrov1, R. Chakravartty3, G. Vivian3, B. Corcoran3, J. Jarosz4, Y. Wang5, K.R. Chaudhuri61Neurology, King’s College Hospital, London, United Kingdom, 2Nuclear Imaging, King’s College Hospital, London, United Kingdom, 3Nuclear Imaging, King’s College Hospital, London, United Kingdom, 4Neuroradiology, King’s College Hospital, London, United Kingdom, 5Division of Health and Social Care Research, King’s College London, London, United Kingdom, 6Neurology, King’s College Hospital, London, United Kingdom

Objectives: Cardiac MIBG Scan is not widely used in clinical practice related to Movement Disorders. Variability in reporting is considered a problem.



27

Methods: We report on inter-observer agreement variability of 3 reviewers (a Nuclear physician, a research fellow of Movement disorders and a clini-cal trainee) of interpretation of Cardiac MIBG used in clinical practice at the Centre of Excellence Movement Disorders clinic since 2005. We classified the MIBG images of 38 patients to 3 types (1 = no visualization of the heart, 2 = borderline visualization of the heart, 3 = clear visualization of the heart).Results: 38 MIBG Scans were studied and uptakes at 15 min and 3 hours were considered. We found a substantial inter-observer agreement among the clinical trainee and the research fellow (Kappa = 0.79, p < 0.001), the clinical trainee and the Nuclear physician (Kappa = 0.69, p < 0.001) as well as between the research fellow and the Nuclear physician (Kappa = 0.65, p < 0.001).Conclusions: Cardiac MIBG Scan is a reproducible and easily characterized imaging tool that should be used in clinical practice using the cardiac visualiza-tion classification.No conflict of interest.

084

FIRST-DEGREE ATRIOVENTRICULAR BLOCK IN IDIOPATHIC PARKIN-SON’S DISEASEA. O’Callaghan1,*, R. Walker1

1Department of Medicine, Northumbria Healthcare NHS Foundation Trust, North Shields, United Kingdom

Objectives: First-degree atrioventricular (AV) block, originally thought be-nign in prognosis, was subsequently demonstrated to be associated with increased risks of atrial fibrillation (AF), pacemaker implantation, and all-cause mortality (1). The objective of this study was to determine the preva-lence of first-degree AV block in a representative population with idiopathic Parkinson’s disease (IPD).Methods: 93 individuals with IPD (27F, 66M, mean age 69), under the care of Northumbria PD service, had 12 lead electrocardiographs (ECGs). ECG rhythm and PR interval were evaluated.Results: 89 ECGs showed sinus rhythm (SR), 3 AF, 1 paced. Of 89 SR, 12 (13.5%) had first-degree AV block (PR>200 milliseconds). 4 of the 12 were on calcium channel and/or beta-blockers (increase AV node refractory period) and 2 of these 4 had ischaemic heart disease (IHD). The remaining 8 (9.0%) had no known IHD or above medication use.Conclusions: Previous, not disease specific, research has shown prevalence of first-degree AV block of between 2.5% (population based surveys) and 7.0% (urban hospital group) (2). Considering the high percentage of our IPD population with first-degree heart block we suggest regular ECG, medication review and larger studies.References1. Cheng S, et al. Long-term outcomes in individuals with prolonged PR

interval or first-degree atrioventricular block. JAMA : the journal of the American Medical Association. 2009; 301(24):2571–7.

2. Upshaw CB, Jr. Comparison of the prevalence of first-degree atrioven-tricular block in African-American and in Caucasian patients: an electro-cardiographic study III. Journal of the National Medical Association. 2004; 96(6):756–60.


085

LOW CALCITRIOL LEVEL MIGHT BE ASSOCIATED WITH ORTHOSTATIC HYPOTENSION IN PARKINSON’S DISEASEJ. Yoon1, W. Jang2,*1Emergency Medicine, Dong-In Hospital, Gangneung, Korea, 2Neurology, Gangneung Asan Hospital, Gangneung, Korea

Objectives: Considering that the pathophysiology of orthostatic hypotension in PD is thought to be associated with the impairment of sympathetic neurons due to the neurodegenerative process, we investigated that the association between calcitriol level and presence of orthostatic hypotension in PD patients and correlation with severity.Methods: We studied 55 patients with PD diagnosed by the eligible criteria which is classified into two groups: PD with orthostatic hypotension, PD with-out orthostatic hypotension. Then we compared difference of calcitriol level between two groupsResults: Calcitriol level was significantly lower in PD with orthostatic group than that in PD without orthostatic group.(20.47 ± 6.79 versus 35.50 ± 9.32, p < 0.01) Calcitriol level also showed negative correlation with change of each blood pressure, average OHQ, OHDAS scoreConclusions: Calcitriol might be strongly associated with presence of orthostatic hypotension in PD patients and this may be potential therapeutic target.References1. Bonuccelli U LCDDP, et al.: Orthostatic hypotension in de novo Parkinson

disease. Archives of Neurology 2003, 60:1400–1404.

2. Tamez H, Kalim S, Thadhani RI: Does vitamin D modulate blood pressure? Current Opinion in Nephrology and Hypertension 2013, 22:204–209

3. Smith M, Fletcher-Turner A, Yurek D, Cass W: Calcitriol Protection against Dopamine Loss Induced by Intracerebroventricular Administration of 6-Hydroxydopamine. Neurochem Res 2006, 31:533–539.

4. Newmark HL, Newmark J: Vitamin D and Parkinson’s disease – A hypoth-esis. Movement Disorders 2007, 22:461–468.


086

PARKINSON DISEASE INCREASES ASLEEP BLOOD PRESSURE AND DECREASES AMBULATORY BLOOD PRESSURE VARIABILITYH. Kanegusuku1,*, C. Silva-Batista1, T. Peçanha1, N.D. Silva Jr1, A.C.C. Queiroz1, L.A.R. Costa1, M.T. Mello2, M.E.P. Pimentel3, C. Ugrinowitsch1, C.L.M. Forjaz1

1School of Physical Education and Sport, University of São Paulo, Sao Paulo, Brazil, 2Center for Psychobiology and Exercise Studies, Federal University of São Paulo, Sao Paulo, Brazil, 3Institute of Psychology, University of São Paulo, Sao Paulo, Brazil

Objectives: This study aimed to investigate the impact of PD on ambulatory BP level and variability.Methods: 21 normotensive subjects with PD (14 male, 64 ± 2 years, 118 ± 2/77 ± 2 mmHg, 25.2 ± 0.6 kg.m−2, 7.55 ± 0.48 disease duration) and 21 aged matched normotensive subjects without PD (8 male, 64 ± 1 years, 121 ± 1/79 ± 1 mmHg, 25.2 ± 0.8 kg.m−2) underwent an ambulatory BP moni-toring during 24 hours. Ambulatory data were analyzed by averages of 24-h, awake and asleep periods, as well as by the average of awake and asleep weighted standard deviations (SDdn). Data were analyzed with two-sample t-test and are presented as mean ± SE.Results: PD subjects presented averages of 24-h and awake systolic and diastolic BP similar to the subjects without PD (120 ± 2/74 ± 2 vs. 119 ± 2/72 ± 1 mmHg; 122 ± 2/76 ± 2 vs. 123 ± 2/76 ± 1 mmHg, respectively, p < 0.05). However, subjects with PD presented higher asleep systolic and di-astolic BP (117 ± 3/70 ± 2 vs. 109 ± 2/64 ± 1 mmHg, p < 0.05) as well a higher systolic and diastolic SDdn (10.6 ± 0.8/8.2 ± 0.5 vs. 8.2 ± 0.3/7.1 ± 0.3 mmHg, p < 0.05).Conclusions: Subjects with PD demonstrate harmful alterations on am-bulatory BP, including a higher asleep BP and ambulatory BP variability. These results suggest that these subjects might present higher cardiovas-cular risk.Financial support: CNPQ, CAPES, FAPESP, CEPE-UNIFESP and CEPID-SONO.No conflict of interest.

087

QUANTITAIVE SENSORY AND AUTONOMIC FUNCTION EVALUATION IN PARKINSONIAN SYNDROMESR.M. Kandadai1,*, M.K.V. Chunduri1, R. Borgohain1, A. Jabeen1, M.A. Kannikannan1

1Neurology, Nizam’s Institute of Medical Sciences, Hyderabad, India

Objectives: To identify autonomic and quantitative sensory abnormalities in idiopathic PD (PD) and atypical parkinsonian patients and correlate them with disease duration and severity.Methods: Thirty-nine patients attending a movement disorders clinic in South with diagnosis of PD, progressive supranuclear palsy (PSP) and multi-ple systems atrophy (MSA-P) were included in the study. Patients with other causes of autonomic dysfunction were excluded. Detailed history, neuro-logical examination, electroneuromyogram, autonomic function testing (AFT) and computer assisted sensory examination (CASE IV) studies were evalu-ated in all.Results: Among 39 patients, males were 33 (84.6%); PD were 15 (38.4%), PSP 12 (30.7%), MSA 12 (30.7%). Mean age for patients with PSP, IPD and MSA were 62 ± 5.2, 59.8 ± 9.5 and 56.6 ± 5.3 years, respectively. Mean duration of disease was 3.2 ± 2.2 years with significantly longer du-ration in IPD (p = 0.003). AFT abnormalities were seen in 75% of MSA, 46% of PD and 33.3% of PSP patients. Significantly more MSA patients had abnormalities in sympathetic skin response (p = 0.0119) and BP fall on standing (p = 0.003) when compared to IPD and PSP groups. 30:15 ratio was significantly lower in PD compared to PSP patients (p = 0.024).No pa-tient had peripheral nerve disease either clinically or electrophysiologically. PD (53.3%) and MSA-P (41.6%) had significantly higher abnormalities on CASE-IV compared to PSP patients (8.1%). On comparison of QST and AFT abnormalities, there was significant correlation with Pearson correla-tion coefficient of 0.42.Conclusions: AFT and QST abnormalities were more common in MSA and PD compared to PSP with a significant correlation between the two abnormalities.No conflict of interest.



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088

A SYSTEM FOR ANALYSIS OF TREMOR IN PARKINSON’S DISEASE PATIENTSM. Stawarz1,*, S. Kwiek2, M. Boczarska-Jedynak3, R. Sordyl2, K. Kubicki4, M. Humieniuk2, L. Przeklasa2, A. Przybyszewski5, K. Wojciechowski6, A. Polanski61Automatic Control Electronics And Computer Science Institute of Computer Science, Silesian University of Technology, Gliwice, Poland, 2Departament of Neurosurgery, Medical University of Silesia Central University Hospital, Katowice, Poland, 3Department of Neurorehabilitation Department of Neurology, Medical University of Silesia Central University Hospital, Katowice, Poland, 4Departament of Neurosurgery Department of Neurorehabilitation, Medical University of Silesia Central University Hospital, Katowice, Poland, 5Dept Neurology, University of Massachusetts Medical School, Worcester, USA, 6Computer Science, Polish-Japanese Institute of Information Technology, Bytom, Poland

Objectives: Analysis of resting tremor in PD Patients with implanted DBS dur-ing four experimental sessions (Table 1), among two frequency ranges 4–6 and 3–7 Hz.Methods: Data were collected from seven PD patients (in standing position), using the 3D motion capture system (Vicon). Based on the trajectory of mark-ers located on hands, the maximum and average tremor amplitude and the AUC of amplitude spectrum were calculated.Results: Results show a positive correlation between the intensity of tremor and subjective evaluation with UPDRS score. Both the DBS and medica-tion have a positive effect on reducing resting tremor in PD patients. The improvement is significantly higher for the treatment with only DBS. Results confirm that the parkinsonian resting tremor occur at frequency 4–6 Hz. No statistically significant differences were found in comparison with 3–7 Hz ranges.

Table 1. Sessions during experiment.

Session Stimulation Medication

S1 OFF OFF

S2 ON OFF

S3 OFF ON

S4 ON ON

Conclusions: Detailed analysis of the reduction of tremor under the influ-ence of treatment is essential for a correct evaluation of therapeutic effect, and thus the further treatment planning. The proposed system for the assessment of tremor in PD patients based on kinematic data seems to be a promising method that allows for precise measurement and objective evaluation of the degree of severity.This work has been partly supported by The Polish National Science Center (NN518289240) and by the European Union from the European Social Fund (UDAPOKL.04.01.01-00-106/09-00 M. Stawarz)No conflict of interest.

089

UTILITY OF ASSESSMENT OF MOTOR AND PROCESS SKILLS (AMPS) IN PARKINSON’S DISEASEJ. Alegre-Ayala1, L. Vela Desojo2,*, R. Cano-De-La-Cuerda1, Y. Macias Macias2

1Physical Therapy Occupational Therapy Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, Alcorcon, Spain, 2Neurology, Hospital U Fundación Alcorcón, Alcorcon, Spain

Objectives: To determine the degree of loss of occupational performance skills in a group of patients with Parkinson’s disease (PD) analyzing its rela-tionships to the severity of illness, duration of illness, functional status and the presence of dyskinesias and motor fluctuations.Methods: This is a cross-sectional, descriptive study. We included forty-nine patients with PD. Patients were evaluated with the Assessment of Motor and Process Skills (AMPS). The severity of illness was measured by the Hoehn and Yahr (HY) and Section III of the UPDRS and functional status with the Schwab and England Scale.Results: There were statistically significant differences between all HY stages scores in motor skills and in process skills only between stages II and IV. Strong correlations were observed between the scores of motor skills and HY scale (r = −0.77, P < 0.001) and section III of the UPDRS (r = −0.70, P < 0.001), and moderate correlations with process skills. There were mod-erate correlations between motor skills and Schwab and England scale (r = 0.64, P < 0.001) and a strong correlation with process skills (r = 0.73, P < 0.001). Regarding the duration of illness was only weak correlations with

motor skills. There was no association with the presence of dyskinesias and motor fluctuations.Conclusions: The study findings indicate that AMPS could be a useful tool to allow monitoring the evolution of the PD through the performance of activities of daily living.Reference1. Sturkenboom IH, Graff MJ, Borm GF, Veenhuizen Y, Bloem BR, Munneke

M, et al. The impact of occupational therapy in Parkinson’s disease: a randomized controlled feasibility study. Clin Rehab 2013; 27 (2): 99–112


090

ANALYSIS OF IN-AIR MOVEMENT IN HANDWRITING: A NOVEL MARKER FOR PARKINSON’S DISEASEI. Rektorova1,*, P. Drotar2, J. Mekyska2, Z. Smekal2, L. Masarova1, M. Faundez-Zanuy3

1Department of Neurology School of Medicine Masaryk University St. Anne’s Hospital, Applied Neuroscience Research Group CEITEC MU, Brno, Czech Republic, 2Department of Telecommunications, Brno University of Technology, Brno, Czech Republic, 3Escola Universitaria Politecnica de Mataro, Tecnocampus, Mataro, Spain

Objectives: Micrographia is a common feature of Parkinson’s disease (PD). Handwriting a text consists of on-surface and in-air movements. We used a digitizing tablet to assess both in-air and on-surface kinematic variables dur-ing the handwriting and studied the extent to which any set of the obtained measurements is useful in discriminating PD from HC.Methods: In-air and on-surface kinematic variables during the handwriting of a sentence were assessed in 37 PD patients on medication and 38 age- and gender-matched healthy controls (HC) using a digitizing tablet. By applying feature selection algorithms and support vector machine learning methods we studied to which extent any set of the obtained measurements is useful in discriminating PD from HC.Results: We demonstrated that assessing the in-air/ on-surface hand move-ments led to accurate classifications in 84% and 78% of subjects, respectively. Combining both modalities only improved the accuracy by 1% over the evalu-ation of in-air features alone.Conclusions: Assessment of in-air movements during handwriting has a ma-jor impact on disease classification accuracy. Future studies should explore the sensitivity, specificity, and underlying pathophysiological mechanisms of this novel marker.Supported by project NT13499 “Speech, its impairment and cognitive perfor-mance in Parkinson’s disease”, CZ.1.07/2.3.00/20.0094.No conflict of interest.

091

SACCAD’S CHANGES IN PATIENTS WITH PARKINSON’S DISEASER. Bogdanov1,*, P. Ratmanova2, A. Litvinova2, D. Napalkov2, S. Kotov1, L. Turbina1

1Neurology, Moscow Regional Scientific Research Clinical Institute n.a. M.F. Vladimirskiy, Moscow, Russia, 2Faculty of biology, M.V. Lomonosov Moscow State University, Moscow, Russia

Objectives: Reflexive and voluntary saccades were studied in 30 pa-tients with early-stage Parkinson’s disease (PD) and 30 age-matched con-trol subjects. None of PD patients were receiving any anti-parkinsonian treatment.Methods: Reflexive saccades were initiated by the sudden appearance of a visual stimulus. Voluntary saccades generated by internal goals during constant visual stimuli presentation. Eye movements were recorded using electrooculography and a video based eye tracker.Results: PD patients exhibited different eye movement characteristics to control subjects making. The mean latency of reflexive saccades was significantly longer in the patients. Moreover, PD patients produced a lot of multistep saccades. The changes in saccadic eye movement charac-teristics were more pronounced on the side of the clinical symptoms in patients with stage I (by Hoehn and Yahr’s scale). In the voluntary sac-cade task patients and control subjects also showed different results. PD patients had longer initiation time in the beginning of each trial, longer fixation time between voluntary saccades and made less eye movements during the task.After 4 weeks of dopamine agonist therapy the state of PD patients was improved. At the same time the characteristics of reflexive saccades were changed: the mean saccade latency and the percentage of the multistep saccades significantly decreased. The percentage of multistep saccades cor-related with the neurological status of a patient (r = 0.7, p < 0.05).Conclusions: our results show that saccadic eye movement exploring may be used as a promising technique for PD diagnostics and control of medica-tion treatment.No conflict of interest.



29

092

COMPUTARIZED DYNAMIC POSTUROGRAPHY IN PATIENTS WITH PARKINSON’S DISEASE IN STAGE 2 OF THE HOEHN AND YAHR SCALE.M. Ramiro Gonzalez1, L. Vela Desojo2,*, J.C. Miangolarra Page3, Y. Macias Macias2, L. Castillo Moreno2, U. Joseph4, S. Collado Vazquez5, C. Martin Llorente2

1Servicio: Medicina Preventiva y Salud Pública, Hospital U Gregorio Marañón, Madrid, Spain, 2Neurology, Hospital U Fundación Alcorcón, Madrid, Spain, 3Medicina Física y Rehabilitación, Hospital U Fuenlabrada, Madrid, Spain, 4Fisioterapia., Universidad Autonoma, Madrid, Spain, 5Medicina Física y Rehabilitación, Universidad Rey Juan Carlos, Madrid, Spain

Objectives: It was traditionally accepted that postural instability in patients with Parkinson’s disease appeared in advance stages of the illness. However, present scientific evidence affirms that this postural change is present in early stages. The aim of this study was to analyze through computerized dynamic posturography (CDP) if patients with early-stage Parkinson’s disease have postural disturbances.Methods: Case-study with a reference control group. Forty-three subjects with Parkinson’s disease in stage 2 of the Hoehn and Yahr scale were in-cluded. The reference group was made up of 42 subjects without Parkinson’s disease. Results from the Unilateral Stance (US) and Limits of Stability (LOS) of the CDP were compared and analyzed between the groups.Results: The mean US duration of the group with Parkinson’s disease in all the tests was shorter than the reference group, with statistical significance for the left foot with closed eyes and for the right foot with open eyes (p < 0.05). Patients’s LOS were narrower than the reference group in all directions (p < 0.01).Conclusions: Patients with Parkinson’s disease in stage 2 of the Hoehn and Yahr scale show postural instability measured by the US and LOS of the CDP.References1. Chastan N, Debono B, Maltête D, Weber J. Discordance Between

Measured Postural Instability and Absence of Clinical Symptoms in Parkinson’s Disease Patients in the Early Stages of the Disease. Movement Disorders. 2008; 23(3):366–372.

2. Postural instability and cognitive dysfunction in early Parkinson’s disease. Lee JM, Koh SB, Chae SW, Seo WK, Kwon do Y, Kim JH, Oh K, Baik JS, Park KW. Can J Neurol Sci. 2012; 39:473–82.


093

ASSESSMENT OF SYMPTOMS AND DISABILITY OF UPPER LIMB IN PARKINSON’S DISEASEC. Falup-Pecurariu1,*, M. Moarcas2

1Department of Neurology, Faculty of Medicine Transilvania University, Brasov, Romania, 2Department of Neurology, Emergency University County Hospital, Brasov, Romania

Objectives: Musculoskeletal problems are frequent in Parkinson’s disease (PD). They can influence the disability status of PD patients and affect their quality of life.The aim of this study is to determine the symptoms and disability in the upper limb in PD patients.Methods: prospective study on 28 consecutive PD patients (19 males 67,85%, mean age 64,32 ± 12,54 years). The following instruments were used: Hoehn and Yahr staging, SCOPA Motor, Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, Beck Depression Inventory (BDI), PDQ-39. Other markers of function and pain were used as well. The DASH is a self-assess-ment Outcome Measure which consists of 30-items. It evaluates the symp-toms in upper limb and physical function.Results: both proximal and distal symptoms were assessed with DASH questionnaire. Disability was correlated with pain degree and reduced quality of life.Conclusions: upper limb symptoms influence the disability of PD patients.No conflict of interest.

094

SWALLOWING IMPAIRMENT AND PULMONARY DYSFUNCTION IN PARKINSON’S DISEASE: THE SILENT THREATSL. Monteiro1,*, A. Souza-Machado1, P. Pinho1, M. Sampaio1, A. Nobrega1, A. Melo1

1Neurosciences Department, Universidade Federal Da Bahia, Salvador Bahia, Brazil

Objectives: The objective was to investigate if there is an association be-tween pulmonary impairment and swallowing dysfunction in PD patients.Methods: A cross-sectional study with comparison group was conducted among PD patients that met the eligibility criteria. Subjects enrolled were submitted to demographic questionnaires and performed spirometric and

videofluorographic assessments. The spirometric parameters of forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), peak ex-piratory flow (PEF), forced middle expiratory flow rate (FEF 25–75%) and FEV1/FVC ratio were measured. Swallowing outcomes were clinical com-plaints as assessed by the section II of the UPDRS (question 7), and vide-ofluoroscopic variables such as presence of vallecula and pyriform fossa residues (VPFR) and pharyngeal transit time (PTT). Significance level was considered at 95%.Results: Among thirty PD patients, 40% presented with swallowing com-plaints. However, 22% of the clinically asymptomatic patients presented airway food penetration on videofluoroscopy. In 20% of PD patients the ma-terial entered the airways and in 7% there was contact with the vocal folds. However, there was an efficient cleaning with residue deglutition in almost all patients. No P/A was detected among controls (n = 35). Respiratory pa-rameters were below normal predicted values in PD patients when compared to healthy controls. In addition, PD patients with swallowing complaints pre-sented significantly lower FVC and PEF values, when compared to clinically asymptomatic patients and controls.Conclusions: These data suggest an association between pulmonary dysfunction and swallowing impairment in PD patients.Reference1. Kalf JG, de Swart BJ, Bloem BR, Munneke M: Prevalence of oropharynge-

al dysphagia in Parkinson’s disease: A meta-analysis. Parkinsonism Relat Disord 2011.


095

CHARACTERISING NEUROPHYSIOLOGICAL MECHANISMS UNDER-LYING DYSPHAGIA IN PARKINSON’S DISEASE: A TRANSCRANIAL MAGNETIC STIMULATION STUDY DURING ‘ON’ AND ‘OFF’ LEVODOPAE. Michou1,*, J. Dick2, M. Kellet2, J.O.H.N. Rothwell3, S. Hamdy1

1Gastrointestinal Sciences, University of Manchester, Manchester, United Kingdom, 2Manchester Neurosciences Unit, Salford Royal NHS, Manchester, United Kingdom, 3Institute of Neurology, UCL, London, United Kingdom

Objectives: Dysphagia in Parkinson’s disease (PD) patients, persisting despite dopaminergic medication, affects nutritional and drug intake with reduced quality-of-life (QOL) (1). Here we explore the possible neurophysi-ological mechanisms contributing to dysphagia in PD ‘on’ and ‘off’ Levodopa with transcranial magnetic stimulation (TMS).Methods: Following reviewing with qualitative questionnaires for dysphagia and QOL a cohort patients, 26 verified PD patients (65 ± 9 yoa, 10 male) completed the protocol. After 12 hours ‘off’ L-dopa, patients underwent cortical TMS mapping of swallowing (pharyngeal) musculature, craniobulbar (trigemi-nal) TMS stimulation, and videofluoroscopy (VFS) of swallowing. The study was repeated following re-intake of L-dopa. Factorial and non-parametric sta-tistical tests were applied.Results: VFS identified swallowing impairments both ‘on’ and ‘off’ Levodopa in 10 patients (SI), while 6 patients showed swallowing impair-ments only ‘On L-dopa’(SIon), with the remainder 10 subjects showing no swallowing impairments during both states (NSI). Aspiration-penetration scores worsened on dopamine-replete state only for SIon. In Levodopa-replete state, both SIon and NSI had significantly different pharyngeal corti-cal excitability compared to SI. The brainstem reflexes for the SIon group were significantly different to the NSI group only ‘off’ medication. For the SIon group, the decrease in craniobulbar excitability compared to the off-state was significant.Conclusions: Different patterns of cortical and brainstem activity, reflecting different mechanisms of compensation with L-dopa intake, can differentiate dysphagic PD groups. Physiology was negatively affected by L-dopa in groups presenting concurrent inhibition of brainstem reflexes amplitudes. Our novel brain stimulation data provides the platform for research on rehabilitation for dysphagia in PD.Reference1. Michou and Hamdy, Exp Rev Neurother 2010No conflict of interest.

096

ORAL HEALTH IN PARKINSON’S DISEASE PATIENTSM.A.E. van Stiphout1,*, C. de Baat2, W.M. van der Boon3

1Research, Stichting Mondzorg en Parkinson, Rotterdam, Netherlands, 2Gerodontology, UMC St. Radboud Nijmegen, Nijmegen, Netherlands, 3Research, Stichting Mondzorg en Parkinson, Oegstgeest, Netherlands

Objectives: Adequate oral health is important in order to prevent or at least minimize oral pain, infections, and functional problems. However, little is known about the actual oral health situation of Parkinson’s disease patients. Probably, the oral health of persons suffering from Parkinson’s disease is worse than the oral health of comparable healthy persons. Oral health self care may be



30

impaired by Parkinson’s disease symptoms, such as rigidity and tremor. Other factors, e.g. side effects of medications or dysphagia, possibly contribute to changes in oral health. The objective of this study was to collect information about the oral health of Parkinson’s disease patients internationally.Methods: A study of the literature available on this topic was conducted.Results: It was concluded that the oral health of Parkinson’s disease patients does not receive much attention. The literature provides no oral health data of Parkinson’s disease patients in The Netherlands and only a few interna-tional publications are dealing with this topic. The literature on oral health in Parkinson’s disease patients shows a negative tendency and suggest that oral health in Parkinson’s disease patients is poor.Conclusions: More information is required. In order to provide a reliable over-view of the oral health of Parkinson’s disease patients in the Netherlands, a case-control study will be conducted. This information is needed to be able to provide adequate oral health care to Parkinson’s disease patients.No conflict of interest.

097

FACTORS RELATED TO VOICE HANDICAP IN PARKINSON DISEASEM.K. Sunwoo1, J.Y. Hong1, J.E. Lee1, P.H. Lee1, Y. Sohn1,*1Neurology, Yonsei University College of Medicine, Seoul, Korea

Objectives: Dysphonia frequently appears at any stage of Parkinson disease (PD), 1 but its mechanism has yet to be clear. This study investigated possible clinical factors related to PD dysphonia.Methods: Dysphonia severity (voice handicap) was assessed in 137 non-de-mented PD patients using Voice Handicap Index (VHI)-102. A cut-off value of 12 VHI-10 score was used to define the presence of dysphonia. Parkinsonian severity and depression were measured by using UPDRS-motor score and Geriatric Depression Scale (GDS).Results: Dysphonia was observed in 50 patients (36.5%). The patients with dys-phonia showed higher UPDRS-motor and GDS scores than those without dys-phonia. The comparison of Receiver Operating Characteristic curves revealed that GDS was more significantly related to the presence of dysphonia than PD severity. If we selected non-depressed patients (GDS score less than 7), logistic regression analysis revealed that UPDRS-motor score was no longer a significant factor.Conclusions: The present results support that dysphonia is a frequent symp-tom accompanied in PD, and demonstrate that depression is more closely related with voice handicap in PD patients than symptom severity.References1. Pinto S, Ozsancak C, Tripoliti E, Thobois S, Limousin Dowsey P, Auzou

P. Treatments for dysarthria in Parkinson’s disease. Lancet Neurol 2004; 3:547–556.

2. Rosen A, Lee AS, Osborne J, Zullo T, Murry T. Development and validation of the voice handicap index-10. Laryngoscope. 2004; 114:1549–1556.


098

ANALYSIS OF VOICE QUALITY AND RELATIONSHIP WITH GENDER, AGE, DURATION AND DISEASE SEVERITY IN PARKINSON DISEASE PATIENTSE. Jancic1,*, Z. Aleric2, V. Bauer2

1Neurology, General Hospital Karlovac, Karlovac, Croatia, 2Otorhinolaryngology, General Hospital Karlovac, Karlovac, Croatia

Objectives: The aim of this study is to evaluate and to compare the subjective perception of the voice quality in patients with Parkinson disease (PD) and to explore the correlation between voice quality and gender, age, duration and severity of the disease.Methods: Cross-sectional study was done on 23 randomly selected PD patients compared with 23 control participants. An assessment of disability caused by voice disorders was scored according to the Voice Handicap Index (VHI). Patient’s perceptual voice analysis was scored using Gradus Roughness Breathiness Asthenia Strain (GRBAS) scale by three experienced voice therapists. The Unified Parkinson’s Disease Rating Scale (UPDRS) is used for determination of disease severity.Results: The mean VHI was higher in patients group (22,65 ± 20,84–5,13 ± 5,01 p = 0,002). Sixty one percent report voice problems. According to the GRBAS scale, differences between two groups were significant for all five components. All scores were higher in male patients. We found signifi-cant positive correlation between VHI and G component of GRBAS (r = 0,63), between G and S component of GRBAS scale and duration of the disease (r = 0,51 and 0,59), and between VHI and UPDRS (r = 0,51). There was no correlation between voice quality and age.Conclusions: Significant number of our PD patients report voice problems which are also detectable with auditory perception. Voice problems are in rela-tion with male gender, disease severity and duration but not with ageNo conflict of interest.

099

SPEECH RHYTHM IN PERSONS WITH IDIOPATHIC PARKINSON DISEASEA. Rao1,*, S. Narayanan2

1Speech and Hearing, All India Institute of Speech and Hearing, Mysore, India, 2Speech-Language Pathology, All India Institute of Speech and Hearing, Mysore, India

Objectives: To investigate the speech rhythm of Kannada speaking persons with idiopathic PD on a reading task.Methods: Twelve Kannada speaking individuals with idiopathic PD in the age range of 60–85 years with mild-moderate dysarthria and twelve neurotypical individuals matched on age, gender, socio-economic status, language, dialect and knowledge of other languages were considered for the study. Speech rhythm was assessed using a reading task. Five unrelated sentences in Kannada were used as the stimulus. The reading samples were collected us-ing Cool Edit Pro 2.1 and were edited and acoustically analyzed using PRAAT software. Normalized pairwise variability index (nPVI) was calculated by aver-aging the duration measured of the vocalic and intervocalic segments. nPVI was computed using the Microsoft Office Excel Program.Results: The results revealed that the nPVI values for the vocalic and intervo-calic segments were higher for clinical group than the control group. A signifi-cant difference was found in the nPVI values between both the groups. This could be attributed to the greater clustering that was seen in their productions, prolonged phonemes and a variable rate of speech.Conclusions: It can be concluded from the results of the study that the speech rhythm was affected in persons with idiopathic PD.Reference1. Lowe, J. (1994). Lewy bodies. In D.P. Calne (Ed.) Neurodegenerative dis-

eases, (pp. 51–69). Saunders: Philadelphia.No conflict of interest.

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NARRATIVE DISCOURSE IN PERSONS WITH PARKINSON’S DISEASES. Narayanan1,*, A. Rao2, M. Reddy2

1Department of Speech-Language Pathology, All India Institute of Speech and Hearing, Mysore, India, 2Deparment of Speech and Hearing, All India Institute of Speech and Hearing, Mysore, India

Objectives: To investigate the narrative discourse skills in Kannada speak-ing persons with idiopathic Parkinson’s disease (PD) and to investigate the variation in discourse characteristics, if any, across the different stages of the disease (early and middle stage).Methods: Two groups comprising of twelve Kannada (a south Indian Dravidian language) speaking individuals with idiopathic PD in the age range of 60–85 years and twelve neurotypical individuals matched on age, gender, socio-economic status, language, dialect and knowledge of other languages were considered for the study. To assess the narrative skills, the participants were provided with a series of eight pictures to narrate a story for a minimum of 2–3 min. The samples were collected using Cool Edit Pro 2.1 and were transcribed. The transcribed samples were divided into communication units. The communication units were analyzed in terms of the quantity and informa-tiveness of output and the syntactic aspects.Results: The results revealed that there was a significant difference between the two groups on most of the communication units including the number of syntactic units, mean length of utterance, percentage of simple and compound sentences, percentage of correct informative units and informative utterances. Between the early and middle stage of idiopathic PD, a significant difference was found only in the percentage of complex sentences.Conclusions: Based on the results it can be concluded that the narrative skills were affected in persons with idiopathic PD, although differences be-tween the two stages were not evident.No conflict of interest.

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ACOUSTIC SPACE AS MEASURE OF DYSARTHRIA: 40 CASES OF PARKINSON’S DISEASED. Misra1,*, M. Behari2, V. Narang1

1Centre for Linguistics, Jawaharlal Nehru University, Delhi, India, 2Department of Neurology, All India Institute of Medical Sciences, Delhi, India

Objectives: To measure the Acoustic Space (AS) of dysarthric speech in cases of PD, and determine whether difference in AS can act as an assess-ment tool of different stages of neuromotor degeneration in PD.Methods: Inclusion criteria: 55 subjects, with 24–30 score in MMSE; 1.5–4 H&Y score in UPDRS, 40(20 M + 20 F) selected; 40 age and gender matched control subjects; 80 subjects divided into 10 groups (5M + 5F). Words chosen with vowels i, e, a, o and u in the same CVC position. Software used: Goldwave, PRAAT.



31

Results: AS gets reduced in PD cases with an average of 72% and 74% reduction for males and females respectively. As the results below show, this indicates progressive neuromotor degeneration in PD. Minimal deficit with H&Y score of 1.5: speech generally comprehensible by AS reduced to 40%. H&Y score 2: further decline of 10%, H&Y score 2.5: further decline of 3%, H&Y score 3: further decline of 5% AS in male and female. H&Y score 4: shows the other extreme with a maximal deficit of 84% in male and 86% in female. AS is reduced to 16% in male and 14% in female.

50 Area of Acoustic space for male and Female45

39 40

29 302628

2520

1814

H & Y3H & Y2.5H & Y2H & Y1.5 H & Y4

40

35

30

25

20

15

10

5

0M F

Conclusions: Acoustic space can thus be used as an indicator of early onset of PD with marked deficit of 60% and further reduction corresponding to H7Y2, 2.5 and 3, culminating in cases of H&Y 4.Reference1. Darley, F, et al (1975). Motor speech disorders. Philadelphia: W. B.

Saunders, Co.No conflict of interest.

102

MONITORING PARKINSON RELATED GAIT DISORDERS WITH EIGENGAITSM. Leonardo1,*, R. Fischer2, H. Oliveira1, L. Silva3, A. Perkusich4

1COPIN, Universidade Federal de Campina Grande, Campina Grande, Brazil, 2UFAL, Universidade Federal de Alagoas, Maceió, Brazil, 3IC, Universidade Federal de Alagoas, Maceió, Brazil, 4COPELE, Universidade Federal de Campina Grande, Campina Grande, Brazil

Objectives: Non-obtrusively monitoring of Parkinson symptoms integrated in a patient’s daily routine can be an important tool in chronic disease management.In this work we propose a method to monitor Parkinson related gait disor-ders (PRGD) by comparing signals from force sensors in the patient’s shoes against known Parkinson patterns.Monitoring PRGD during the patient’s daily routine allows for a faster respond to changes in the symptoms and thus a better medication management.Methods: In adaptation of a well established method for facial recognition (ei-genfaces) we use eigengaits to distinguish between personal gait characteris-tics and patterns that indicate PRGD. Our system was built using data from the Parkinson Disease Database, which includes 60 patients with idiopathic PD, and 60 healthy control subjects. A total of 120 normalized gait cycles were used to calculate an orthogonal base of eigengaits. Projecting the labeled data from the database into the eigengait space we could identify two clusters, i.e. healthy sub-jects and subjects with PRGD. A patient’s personal gait pattern is represented as a point in this eigengait space. Changes in the patient’s gait pattern will result in a moving of this point. In case the point moves towards the direction of the subjects with PRGD, the system detects an increase of PRGD symptoms with the patient.Results: To test the accuracy of the eigengaits methods with cross-validation, we applied it to classify the data in the database, resulting in 81,66% correctly detected subjects.Conclusions: Eigengaits could be useful to monitor PRGD Symptoms changes.Reference1. Gait in Parkinson’s Disease - http://physionet.org/physiobank/database/

gaitpdb/No conflict of interest.

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FACTORS RELATED TO FROZEN GAIT IN PARKINSON’S DISEASES. Perez Lloret1,*, P. Negre-Pages2, L.D. Schelosky3, P. Derkinderen4, F. Tison5, A. Destée6, O. Rascol11Pharmacology Department, Paul Sabatier University, Toulouse, France, 2LN Pharma, LN Pharma, Toulouse, France, 3Neurology Department, Kantonsspital Münsterlingen, Münsterlingen, Switzerland, 4Department of Neurology, Hôpital Laënnec CHU Nantes, Nantes, France, 5Department

of Neurology, CHU Pellegrin Bordeaux, Bordeaux, France, 6Department of Neurology, CHU Lille, Lille, France

Objectives: Freezing of gait (FoG) is a poorly known disabling feature affect-ing many patients with Parkinson’s disease (PD). The objective of this study was to determine the prevalence, assess its impact on Quality of Life (QoL) and describe factors related to FoG in a large group of PD patients and to assess the change in FoG scores from OFF to ON in patients with motor fluctuations.Methods: 683 PD patients were evaluated. Patients with FoG were identified as those with a UPDRS Item 14 ≥ 1 in the ON condition. All patients were assessed in a standardized manner [demographics, treatments, Unified PD Rating Scale (UPDRS), Hospital Anxiety and Depression Scale and QoL scales (SF36, PDQ39).Results: FoG was reported by 257/672 PD patients (38%) and Quality of life was significantly worse in patients with FoG. FoG correlated with longer PD duration, higher UPDRS II + III score, the presence of apathy (UPDRS item 4), higher levodopa equivalent daily dose and more frequent exposure to antimuscarinics (logistic regression). FoG improved from OFF to ON in 148/172 (87%) patients with motor fluctuations (>50% improvement in 40%), while there was no change in 15%. Greater improvement in ON was observed in younger patients, those with smaller UPDRS II + III scores, entacapone therapy and not exposed to antimuscarinics.Conclusions: FoG worsened quality of life in PD patients. The presence of FoG correlated with PD severity, cognitive deficit and antimuscarinics ex-posure. Dopaminergic therapy improved FoG in most patients with motor fluctuations, especially in younger ones, with less severe disease and no antimuscarinics.No conflict of interest.

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FREEZING OF GAIT IN PARKINSON’S DISEASE PATIENTS: NEW METHOD FOR DETAILED ANALYSIS FROM INERTIAL SENSORSM. Djuric-Jovicic1,*, S. Radovanovic2, V. Kostic3, M. Popovic4

1Innovation Center, Electrotechnical faculty University of Belgrade, Belgrade, Serbia, 2Dept of Neurophysiology, Institute for Medical Research University of Belgrade, Belgrade, Serbia, 3Clinic for Neurology, School of Medicine University of Belgrade, Belgrade, Serbia, 4Signals and Systems Division, Electrotechnical faculty University of Belgrade, Belgrade, Serbia

Objectives: Postural impairments and gait disorders in Parkinson’s disease affect stability, impaired postural adjustment and evoke poor responses to per-turbation. Some patients can suffer from episodic features such as freezing of gait (FOG). Objective gait assessment and monitoring progress of the disease can give clinicians and therapist important information about changes in gait pattern and potential deviations, in order to prevent concomitant falls. We pro-pose the method for identification of freezing episodes and gait disturbances for patients with PD. The wireless inertial sensor system can be used to pro-vide follow-up of the treatment effects or progress of the disease.Methods: The system is simple for mounting, comfortable, simple for record-ing, reliable and provides high-quality sensor data. Twelve patients were recorded and tested. Software calculates gait parameters that could be es-timated. User friendly visual tool provides information about changes in gait, either in a form of spectrogram or by observing spatio-temporal parameters. Based on these parameters, the algorithm performs classification of strides and identification of FOG types.Results: Stride classification is merged with an algorithm for stride recon-struction, resulting in useful graphical tool that allows clinicians to inspect and analyze subject’s movements.Conclusions: The described gait assessment system can be used for detec-tion and categorization of gait disturbances by applying rule-based classifica-tion based on stride length, stride time, and frequency of the shank segment movements. The method provides graphical interface easy to interpret and provides clinicians and therapists with valuable information regarding the tem-poral changes in gait.No conflict of interest.

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GERMAN TRANSLATION AND VALIDATION OF THE „FREEZING OF GAIT QUESTIONNAIRE” IN PATIENTS WITH PARKINSON’S DISEASEA. Vogler1,*, J. Janssens2, K. Meyer2, S. Bohlhalter3, T. Vanbellingen3

1Health department, Bern University of applied sciences, Bern, Switzerland, 2Neurorehabilitation, Klinik Bethesda Tschugg, Bern, Switzerland, 3Department of Internal Medicine, Neurology and Neurorehabilitation Centre, Luzern, Switzerland

Objectives: Freezing of Gait (FOG) is a frequently observed and disturbing symptom in patients with Parkinson’s disease (PD), leading to reduced qual-ity of life (QoL) 1. The Freezing of Gait Questionnaire (FOG-Q) is the only questionnaire to reliably detect FOG in patients with PD. So far a German validated version of the FOG-Q is lacking. The aim of this study is to develop a German translated version of the FOG-Q, which will be valid to assess FOG in patients with PD.



32

Methods: The German translation of the FOG-Q was carried out by means of a forward-backward-translation. For the validation of the questionnaire German native speaking patients with PD (H&Y II–IV) were assessed with the FOG-Q, the Movement Disorder society – Unified Parkinson’s Disease Rating Scale I-III (MDS-UPDRS) and the Parkinson Disease Questionnaire 39 (PDQ 39). The internal structure of the FOG-Q was measured by using prin-cipal component analysis and Cronbach’s alpha. Convergent and divergent validity was assessed by means of correlation analyses between the FOG-Q and the subscales of the MDS-UPDRS and the PDQ-39.Results: Preliminary results indicate a good internal structure (Cronbach’s al-pha = 0.74) of the German FOG-Q. The lack of correlation between the FOG-Q and the MDS-UPDRS I demonstrates good divergent validity. Moderate cor-relations between the FOG-Q and the PDQ-39 were found.Conclusions: Our results suggest that the German FOG-Q is a valid ques-tionnaire to assess FOG in German native speaking patients with PD.Reference1. Giladi N, et al. Validation of the freezing of gait questionnaire in patients

with Parkinson’s disease. Mov Disord. 2009 Apr 15; 24(5):655–61.No conflict of interest.

106

TANDEM STAND TEST, TANDEM 180 PIVOT, TANDEM WALK TEST AND BIOFEEDBACK ANALYSIS AS DIAGNOSTIC TOOLS IN BALANCE AND POSTURAL STABILITY EVALUATION OF PARKINSON’S DISEASE PATIENTSM. Kloda1, S. Szlufik2,*, D. Koziorowski2, I. Potrzebowska2, J. Dutkiewicz2, A. Friedman2

1Department of Neurology Faculty of Health Science Medical University of Warsaw, Department of Rehabilitation II Faculty of Medicine Medical University of Warsaw, Warsaw, Poland, 2Department of Neurology Faculty of Health Science, Medical University of Warsaw, Warsaw, PolandObjectives: Balance disorder seems to be one of the mostly disabling fac-tors in Parkinson’s disease (PD) patients. There are various clinical tests and balance scales used to assess postural stability and the risk of falling in these patients, but most of them are time consuming and sometimes need sophisticated medical equipment. Therefore the aim of our study is to present the evaluation of balance disorders in PD patients using Tandem Stand Test (TST), Tandem 180° Pivot Test (TPT) and Tandem Walk Test (TWT), and bio-feedback analysis.Methods: The study group consisted of 41 patients with idiopathic PD (15F, 26M; mean age 57,5 years) and 41 healthy volunteers (38F, 3M, mean age 59,3). Balance assessment was evaluated using TST, TPT, TWT, and postural stability was evaluated with TecnoBody medical equipment. The patients were assessed in “ON” and “OFF” phase.Results: All tests were significantly different in PD patients compared to con-trol group (p < 0,01). The balance and postural instability were correlated with UPDRS in “ON” phase (Rb = 0,39; Rps = 0,35; p < 0,05) and “OFF” phase (Rb = 0,39; p < 0,05; Rps = 0,30; p > 0,05).Conclusions: TST, TPT and TWT seem to be potentially good and simple clinical markers of balance disorders in PD patients and they correlate with postural stability disorders in these patients.No conflict of interest.

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MOTOR SYMPTOMS ASSOCIATED WITH APOE EPSILON4 ALLELE IN A SAMPLE OF BULGARIAN PATIENTS WITH LATE-ONSET PARKINSON’S DISEASER. Pavlova1, S. Mehrabian1, M. Petrova1, S. Skelina1, K. Mihova2, A. Jordanova2, V. Mitev2, L. Traykov1,*1Neurology, University Hospital Alexandrovska, Sofia, Bulgaria, 2Molecular Medicine Centre Department of Medical Chemistry and Biochemistry, Medical University, Sofia, Bulgaria

Objectives: Motor symptoms (MS) in Parkinson’s disease (PD) are classi-cally referred as dopaminergic, although for some of them (tremor, speech, postural control) non-dopaminergic mechanisms (serotoninergic, adrenergic, cholinergic) are considered.The aim of the current study was to evaluate the role of APOE epsilon4 allele on the MS in a sample of Bulgarian patients with late-onset Parkinson’s dis-ease (LOPD, age at onset >55 years).Methods: 16 LOPD patients with APOE epsilon3/epsilon4 genotype were compared to 30 LOPD patients with APOE epsilon3/epsilon3 genotype, matched by age, sex, years of education and disease duration. MS were evaluated by UPDRS.Results: The LOPD patients carrying an APOE epsilon4 allele had higher UPDRS scores (p = 0,045), severely affected speech (p = 0,030), hand move-ments (p = 0,002), rapid alternating movements (p = 0.032) and postural sta-bility (p = 0,045). Higher expression of wearing off (p = 0.027) and freezing

fenomena were observed, with no difference to ‘peak of dose’ levodopa-in-duced dyskinesias (LIDs) (p = 0,167).Conclusions: Our results suggested a modifying role of the APOE epsilon4 allele on the severity of the MS in LOPD, with affection of dopaminergic and non-dopaminergic transmitter systems.No conflict of interest.

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THE DIGITIZING TABLET IN DIFFERENTIATION OF TREMOR FREQUENCY IN PARKINSON’S DISEASE AND ESSENTIAL TREMORS. Szlufik1,*, D. Koziorowski1, J. Dutkiewicz1, A. Friedman1, E. Slubowska2

1Department of Neurology Faculty of Health Science, Medical University of Warsaw, Warsaw, Poland, 2Institute of Metrology and Biomedical Engineering, Warsaw University of Technology, Warsaw, Poland

Objectives: Archimedes spiral is commonly used to estimate the frequency of tremor in patients with various movement disorders. There are fewer stud-ies describing the use of circle movements’ frequency analysis evaluated on digitizing tablet. Therefore the aim of the study was to create a digitizing tablet with circle tremor analysis, as a potential marker in differentiation of tremor in movement disorders.Methods: The data were collected from 70 Parkinson’s disease (PD) patients, 43 essential tremor (ET) patients and 70 healthy volunteers, using the computer system for diagnostic analysis of human hand writing. The system recorded the x and y-coordinates of the electronic pen moving across the digitizer surface. For each measurement point, the system calculated the differences between the centre of the theoretical circle printed on the pattern and the actual x-y pen position. These deviations were analyzed by spectral methods, and then the integrals in selected frequency ranges of the tremor were calculated.Results: The analysis of tremor frequency was able to differentiate PD, ET and control group (p < 0,05). The extent of peak frequency was correlated within the study groups: 5–7 Hz in PD, 3–5 Hz in ET and non-specific in control group. In PD patients the quantitative analysis also revealed higher peak level in UPDRS “OFF” phase than in “ON” phase (p < 0,05).Conclusions: Digitizing tablet with circle tremor analysis can be potentially an useful tool in interpreting and differentiating PD, ET and other movement disorders.No conflict of interest.

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PARKINSONISM AND PERIPHERAL NEUROPATHY ARE INTER-RELATEDN. Haldar1,*, N. Haldar2, M. Prasad2, S. Das3

1Internal Medicine, B.P. Koirala Institute of Health Sciences, Dharan, Nepal, 2Neurology, Siliguri Neuro Centre, Siliguri, India, 3Neurology, Burdwan Medical College, Burdwan, India

Objectives: Parkinsonism is a result of neuronal damage of uncertain etiology in a special group of neurons within the basal ganglia of the brain producing Dopamine. Aging leads to neuronal damage in a linear manner in all cell type. Parkinsonism is premature or faster damage of one group of cells. Aging also leads to damage of peripheral nerves leading to senile peripheral neuropathy. We tried to find any relation, if present, between basal ganglia neuronal cells and peripheral nerves in our study.Methods: We studied 100 randomly selected Parkinsonism patients and sub-jected them to nerve conduction study to see their peripheral nerve conduction status. Patients were selected on OPD basis. For comparison we also stud-ied the nerve conduction velocity of their spouses who are non-Parkinsonian. Cases were selected randomly to avoid sex and age bias. Sensory and motor conduction study were done in details.Results: Out of the 100 Parkinsonian patients as per electrophysiologic cri-teria, 60 had definite peripheral neuropathy while 22 patients had borderline conduction problems. Out of 100 control spouses, only 13 had peripheral neu-ropathy and 35 had borderline conduction defect. The different is significant.Conclusions: It was noted from our study that peripheral nerves are equally damaged as basal ganglia cells in Parkinsonism. So it may be inferred that the Dopamine secreting cells in basal ganglia have some relation with peripheral nerves.No conflict of interest.

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A SYSTEMATIC REVIEW AND META-ANALYSIS OF FRACTURE RISK IN PARKINSON’S DISEASEK.M. Torsney1,*, A.J. Noyce2, K.M. Dorothy2, J.P. Bestwick3, R. Dobson4, A.J. Lees2

1West Middlesex Hospital, Imperial College London, London, United Kingdom, 2Reta Lila Weston Institute of Neurological Studies, University College London, London, United Kingdom, 3Wolfson Institute of Preventive Medicine, Queen



33

Mary University of London, London, United Kingdom, 4Blizard Institute for Cell and Molecular Science Centre for Neuroscience and Trauma, Queen Mary University of London, London, United Kingdom

Objectives: Patients with Parkinson’s disease (PD) have poor bone mineral density and are at increased risk of falls.1 Single studies demonstrate that frac-tures are common in PD, with the hip most commonly injured. The aim of this study was to further explore the relationship between PD and fracture risk.Methods: The study was carried out as part of a wider systematic review and meta-analysis of bone health and fracture risk in PD. A thorough literature search was performed on 4th September 2012 using three indexed databases. Strict inclusion and exclusion criteria were followed. Data from relevant stud-ies were extracted and tabulated. Formal quality assessment was undertaken and nine articles were included in the final analysis. Risk estimates were pooled to give an overall effect size and 95% confidence interval (CI).Results: The combined effect size for the nine studies was 2.31 (95% CI 1.84 to 2.91). When studies were grouped according to their statistical methodol-ogy, three studies had a combined hazard ratio of 2.10 (95% CI 1.55 to 2.86), four studies had a combined odds ratio of 4.01 (95% CI 1.77 to 9.04), and two studies had a combined relative risk of 2.10 (95% CI 1.57 to 2.81).Conclusions: This systematic review and meta-analysis has shown that Parkinson’s patients are more than twice as likely to fracture bones than indi-viduals without PD. Contributory factors include postural instability, autonomic dysfunction, cognitive impairment and decreased bone mineral density.1

Reference1. Dobson R, Yarnall A, Noyce AJ, et al. Pract Neurol 2013; 13:70–79.No conflict of interest.

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THE OCCURRENCE OF CROHN’S DISEASE IN PARKINSON’S DISEASES.E. Curry1, K.D. Kennelly1, S. Fujioka1,*, P. Tacik1, A.J. Strongosky1, I. Tsuneya2, Z.K. Wszolek3

1Neurology, Mayo Clinic, Jacksonville Florida, USA, 2Pharmacology and Experimental Therapeutics and Neurology, Boston University School of Medicine, Boston, USA, 3Neurology, Mayo Clinic, Jacksonville, USA

Objectives: LRRK2 gene is the most common causative gene for familial Parkinson’s disease (PD) [1]. Certain LRRK2 gene polymorphisms have been linked to an increased risk of Crohn’s disease [2]. Therefore, we explored the occurrence of Crohn’s disease in PD patients.Methods: The medical histories of 1,146 patients with PD were reviewed. Of these, 876 PD patients had donated their blood samples for our molecular ge-netic studies. We searched for any history (present or past) of Crohn’s disease in these patients.Results: Only 2 PD patients were found who also had the diagnosis of Crohn’s disease. This is consistent with the expected number of cases in this sample size [3].Conclusions: Our results do not suggest any correlation between the two diseases. We plan to investigate our PD patients with further molecular ge-netic studies. AJS and ZKW are supported by the NIH/NINDS P50NS072187. PT is supported by the Max Kade Foundation. IT and ZKW are supported by the Michael J. Fox Foundation for Parkinson’s Research. ZKW has a financial interest in a technology (LRRK2 gene) referenced in this abstract.References1. Correia Guedes L, et al. Worldwide frequency of G2019S LRRK2 mutation

in Parkinson’s disease: a systematic review. Parkinsonism Relat Disord 2010; 16:237–42.

2. Van Limbergen J, et al. The genetics of Crohn’s disease. Annu Rev Genomics Hum Genet 2009; 10:89–116.

3. Kappelman MD, et al. Recent trends in the prevalence of Crohn’s disease and ulcerative colitis in a commercially insured US population. Dig Dis Sci 2013; 58:519–25.

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RHEUMATIC DISEASES AND IDIOPATHIC PARKINSON’S DISEASE: DIFFERENTIAL DIAGNOSIS, COMPLICATION OR COMORBID CONDITIONSS. Mrabet1,*, N. Ben Ali1, M. Kechaou1, S. Belal11Neurology, Charles Nicolle Hospital, Tunis, Tunisia

Objectives: Our study consists in examining the prevalence of rheumatologic manifestations in a cohort study of patients with PD and establishing the rela-tionship between the two conditionsMethods: We conducted a retrospective study for a cohort of 150 Tunisian patients followed for PD in the Department of neurology in Charles Nicolle hospital. Rheumatologic history was specified using an interview and a con-sultation in Rheumatology. We studied the incidence rates of rheumatologic diseases in our cohort, the date of their occurrence compared to the neuro-logic symptomatology and various predisposing factors

Results: Among the 150 patients followed for PD, thirty of them have rheuma-tologic manifestations. The prevalence is 20 %. The mean age is 57 years. The sex ratio is about 1. These manifestations are concomitant with the beginning of the PD in nine cases (30%): back pain is the most reported protests. Otherwise, they precede the disease in 12 patients (40%) and appear during the evolution in 9 patients (30%). Rheumatologic diseases reported are various inflammatory and degenerative. This association raises the possibility of a shared etiopatho-logical basis. Faced with persistent joint pain, looking for extra pyramidal hyperto-nia and akinesia can help uncover early PD. However, we cannot draw a specific rheumatologic table to alert the rheumatologist to the neurological disorderConclusions: Osteoarticular manifestations in PD worsen functional disability of patients. Several arguments are supportive of a causal link between these two conditions. However, additional studies are needed to substantiate this association.References1. F. Etchepare, et al. Revue du Rhumatisme. 2006.2. V. Etchepare, et al. Revue du Rhumatisme. 2010.No conflict of interest.

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PREVALENCE OF CANCERS IN PARKINSON’S DISEASEK.D. Kennelly1, S.E. Curry1, S. Fujioka1,*, P. Tacik1, A.J. Strongosky1, M.G. Heckman2, Z.K. Wszolek1

1Neurology, Mayo Clinic, Jacksonville Florida, USA, 2Biostatistics, Mayo Clinic, Jacksonville Florida, USA

Objectives: To estimate the proportion of Parkinson’s disease (PD) patients who have various types of cancer.Methods: A total of 869 patients with PD were included in this retrospective study. The majority of patients (N = 564,64.9%) were male, and all patients were unrelated. The information collected was current or personal history of various types of cancer, including colon cancer, leukemia, lymphoma, prostate cancer, breast cancer, bladder cancer, pancreatic cancer, melanoma, ovar-ian cancer, non-melanoma skin cancer, lung cancer, brain cancer, stomach cancer, bile duct cancer, uterine/cervical/gynecological cancer, esophageal/gastric cancer, liver cancer, thyroid/ear/nose/throat cancer, bone cancer, and kidney cancer. The proportion of patients with each type of cancer was esti-mated along with a 95% confidence interval (CI).Results: The most common type of cancer in these patients was breast can-cer (9.2% in women, 95% CI: 6.2%–13.0%), followed by non-melanoma skin cancer (8.6%, 95% CI: 6.8%–10.7%), prostate cancer (8.2% in men, 95% CI: 6.4%–10.2%), melanoma (2.5%, 95% CI: 1.6%–3.8%), colon cancer (2.0%, 95% CI: 1.1%–3.1%), and bladder cancer (1.3%, 95% CI: 0.6%–2.3%). All other types of cancer were observed with a prevalence of 1.0% or lower.Conclusions: It is likely that the prevalence of several types of cancer ob-served in our PD series was higher than the estimated prevalence of those cancers in general population. To confirm this hypothesis, we are conducting a case-control study.Acknowledgment PT is supported by Max Kade Foundation. AJS and ZKW are supported by the NINDS P50NS072187.No conflict of interest.

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PREVALENCE OF HYPO- AND HYPERDOPAMINERGIC BEHAVIORS IN PD PATIENTS AND IMPACT ON QUALITY OF LIFEF. Durif1,*, J.L. Houeto2, B. Pereira1, I. Rieu1, I. De Chazeron1, K. Dujardin3, P. Krack4

1Neurology, CHU Clermont-Ferrand, Clermont-Ferrand, France, 2Neurology, CHU Poitiers, Poitiers, France, 3Neurology, CHU Lille, Lille, France, 4Neurology, CHU Grenoble, Grenoble, France

Objectives: To assess the prevalence of behavioral disorders in PD and their impact on quality of life.Methods: 136 (62% male) patients were assessed with the Ardouin scale and PDQ-39. The Ardouin scale is a new instrument that uses a structured, stand-ardized interview to detect and quantify all the hypo- and hyperdopaminergic symptoms, and the non-motor fluctuations (NMF) in PD.Results: 97% of PD patients had at least one symptom listed from the Ardouin scale. The prevalence of depressive mood was 42.3%, apathy 31.2%, anxi-ety 45.0%, compulsive shopping 15.0%, pathological gambling 10.0%, hy-persexuality 16.9%, eating behavior 36.5%, dopaminergic addiction 2.7%. Hypodopaminergic disorders (depression, anxiety, irritability, apathy, hyper-emotivity) were correlated to the following dimensions of the PDQ-39 (emo-tional well-being, r = 0.55, p < 0.01; stigma, r = 0.23, p < 0.05; social support, r = 0.25, p < 0.05; cognition, r = 0.29, p < 0.01 and bodily discomfort, r = 0.22, p < 0.05). NMF were correlated to dimensions mobility, r = 0.25, p < 0.05; ac-tivities of daily living, r = 0.27, p < 0.01; emotional well-being, r = 0.23, p < 0.05; stigma, r = 0.31, p < 0.01 and communication, r = 0.24, p < 0.05. No correlation



34

was observed between PDQ-39 and hyperdopaminergic symptoms (behavio-ral addictions, dopaminergic addiction, nocturnal hyperactivity…).Conclusions: This study shows the high frequency of behavioral disorders in PD and the main impact of hypodopaminergic symptoms and NMF on quality of life in PDReference1. Ardouin C, et al. [Assessment of hyper- and hypo-dopaminergic behaviors

in Parkinson’s disease]. Rev Neurol (Paris) 2009; 165:845–856.No conflict of interest.

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THE MOST IMPORTANT NEUROPSYCHIATRIC SYMPTOMS IN PATIENTS WITH PARKINSON DISEASE WITHOUT DEMENTIA.M. Nodel1,*, N.N. Yakhno1, M.A. Koulikov2

1Neurology, I.M.Sechenov The First Moscow State Medical University, Moscow, Russia, 2Neurology, Institute of Higher Nervous Activity and Neurophysiology of RAS, Moscow, Russia

Objectives: The neuropsychiatric symptoms (NS) affecting the majority of patients with Parkinson’s disease (PD). NS are important determinants of health-related quality of life (Hr-QoL). Currently, there is insufficient information regarding what are the most important neuropsychiatric symp-toms in patients with PD without dementia. To better recognize the compara-tive impact the motor and NS on Hr-QoL in patients with PD without dementia.Methods: 148 PD patients (mean age: 58,3 ± 4,02 years; mean duration of PD: 5,92 ± 2,36 years, H-Y stages 1–3) were enrolled in the study. Clinical assessments were carried out using the UPDRS («Motor function»), Beck de-pression inventory (BDI), PD Sleep Scale (PDSS), Epworth Sleepiness Scale, Parkinson fatigue scale (PFS-16), Lille Apathy Rating Scale (LARS), Spielberg trait anxiety test (STAT), Scales for Outcomes of Parkinson’s disease-cogni-tion (SCOPA-COG), Parkinson’s Disease Questionnaire (PDQ-39). The symp-toms severity was assessed on scales with PDQ-39 scores, using Spearman rank correlation and stepwise multiple regression analysis.Results: BDI, PFS-16, PDSS, but not UPDRS score scores were significant predictors of Hr-QoL (beta = 0.26, 0.25, 0.23, respectively).Conclusions: This study demonstrates that a depression, fatigue and sleep problems are major correlates of poor Hr-QoL in PD patients without dementia.References1. D.A. Gallagher, A.J. Lees, A. Schrag. What are the most important non-

motor symptoms in patients with Parkinson’s disease and are we missing them? Mov. Dis. 2010;25:2493–2500.

2. D. Aarsland, L. Marsh, A. Shrag. Neuropsychiatric symptoms in Parkinson’s disease. Mov. Dis. 2009; 24:1–11.

3. Mc Kinlay A., Grace R.C., Dalrymple-Alford J.C., et.al. A profile of neu-ropsychiatric problems and their relationship to quality of life for Parkinsons disease. //Park. and Relat. disord 2008; 14:37–42.


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NEUROPSYCHIATRIC DISTURBANCES IN EARLY VS. LATE STAGES OF PARKINSON’S DISEASET. Smiljkovic1,*, M. Svetel2, V. Nikolic1, A. Gavrilovic1, P. Smiljkovic3

1Department of Neurology, Clinical Hospital Center “ ”vezdara” Dental School of Medicine University of Belgrade, Belgrade, Serbia, 2Clinic for Neurology, Clinical Center of Serbia Medical Faculty University of Belgrade, Belgrade, Serbia, 3Clinic for Neurology, Clinical Center of Serbia Medical Faculty University of Belgrade, Belgrade, Serbia

Objectives: To estimate the prevalence and characteristics of neuropsychiat-ric symptoms in patients in early versus late stages of PD.Methods: The cross-sectional study of the profile of neuropsychiatric symp-toms was conducted on 179 consecutive patients. They all fulfilled Brain bank criteria for PD. Ninety five patients were in early stages of the disease (I and II stage by Hoehn and Yahr) while eighty four patients were in late stages (III and IV stage). Original questionnaire was performed to obtain demo-graphic, disease, and treatment data. Standardized scales such as UPDRS, MMSE, and H-Y were used. Hamilton depression rating scale (HDRS) and NPI were performed for psychiatric disturbances.Results: At least one of psychiatric symptoms exhibited 88,42% of patients in early stages and 94% of patients in late stages. On three or more symp-toms complained 46,3% of patients in early stages and 82% of patients in late stages. Mean total NPI score, as well as each mean NPI item scores, were significantly higher in late stages especially for hallucinations, depression, anxiety, irritability and sleep problems.Patients in late stages were older, with longer PD duration, higher total daily levodopa dose, as well as UPDRS scores. MMSE score was lower than in patients in early stages.Conclusions: Neuropsychiatric alterations are common features in all stages of PD, but their frequency and severity are more expressed in late stages of PD.No conflict of interest.

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AN INVESTIGATION ON APATHY IN PARKINSON’S DISEASE: CLINICAL FEATURES AND POTENTIAL MECHANISMF. Wang1,*, S.Y. Yu1, L.J. Zuo1, C.J. Chao1, Y. Hu1, Z.J. Chen1, X.Y. Huang1, L. Sun1, Z. Liu1, W. Zhang1

1Neurology, Beijing Tiantan Hospital, Beijing, China

Objectives: To investigate the clinical features and potential mechanism in Parkinson’s disease (PD) patients with apathy.Methods: 142 PD patients were evaluated by Modified Apathy Estimate Scale (MAES), scales for motor symptoms (MS), non-motor symptoms (NMS), ac-tivity of daily living (ADL) and quality of life (QOL). The levels of α-synuclein oligomer, iron, neuroinflammatory factors and neurotransmitters in CSF were detected.Results: (1) 62 cases (42.25%) of PD patients had apathy; (2) In apathy group, disease duration was longer, and the scores of UPDRS III, HAMA, PSQI, SCOPA-AUT and FSS were prominently higher than non-apathy group; (3) The scores of UPDRS II and PDQL39 in apathy group were significantly changed; (4) Compared to the non-apathy group, α-synucleinoligomer level in CSF was significantly elevated; (5) NE level in CSF in the apathy group was dramatically lower than that in non-apathy group; (6) The score of MAES was positively correlated with the levels of α-synuclein oligomer, iron, OH and TNF-α in CSF.

Table 1. Camparison of motor symptoms, non-motor symptoms and the levels of α-synuclein oligomer and NE in CSF between apathy group and non-apathy group.

Apathy group Non-apathy group

P value

Motor symptoms (mean ± SD)

UPDRS III 29.25 ± 15.73 20.63 ± 15.01 0.000**

H-Y stage 2.10 ± 0.95 1.91 ± 0.75 0.118

Non-motor symptoms [media (quartile)]

Numbers of NMS 11.00 (6.00 ~ 15.00)

5.00 (3.00 ~ 9.00)

0.000**

UPDRS I 3 (2 ~ 4) 3 (2 ~ 4) 0.004**

PSQI 8.00 (5.00 ~ 10.00)

5.00 (3.00 ~ 9.00)

0.020*

SCOPA-AUT 37.00 (31.50 ~ 42.50)

34.00 (29.00 ~ 37.00)

0.015*

FSS 11.00 (8.00 ~ 13.00)

7.00 (4 00 ~ 10.00)

0.000**

HAMA 10.50 (4.00 ~ 19.25)

7.00 (3.00 ~ 14.00)

0.041*

HAMD 10.00 (5.00 ~ 18.00)

9.00 (4.00 ~ 16.25)

0.162

MMSE 28.00 (25.00 ~ 30.00)

28.00 (26.00 ~ 30.00)

0.739

MoCA 23.00 (15.75 ~ 26.00)

25.00 (20.00 ~ 27.00)

0.165

ESS 5.00 (2.75 ~ 8.00)

5.00 (2.00 ~ 8.0) 0.380

RBD 2.00 (1.00 ~ 5.00)

2.00 (0.00 ~ 5.00)

0.741

RLSRS 0.00 (0.00 ~ 19.00)

0.00 (0.00 ~ 10.00)

0.069

ADL and QOL (score, mean ± SD)

UPDRS II (ADL) 13.61 ± 7.13 10.02 ± 6.69 0.006**

PDQI-39 (QOL) 133.15 ± 27.654 146.52 ± 27.89 0.012*

α-Synuclein in CSF 36.95 ± 14.03 21.98 ± 19.71 0.003**

NE in CSF 0.40 ± 0.15 0.53 ± 0.09 0.025*

*P < 0.05, **P < 0.01.



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Table 2. Correlation between the score of MAES and the levels of α-synuclein oligomer, iron and neuroinflammatory factors in CSF of PD patients.

Partial correlation P value

α-Synuclein 0.218 0.006**

Iron 0.090 0.017*

TNF-α 0.027 0.005**

OH 0.032 0.048*

H2O2 0.213 0.434

NO 0.068 0.075

PGE2 0.169 0.283

IL-lβ 0.043 0.173

IL-6 4.342 0.536

γ-INF −0.019 0.981

*: P < 0.05, **: P < 0.01.

Conclusions: PD patients have high incidences of apathy; PD patients with apathy have longer duration, severer MS and NMS and compromised ADL and QOL. Excessive depositions of α-synuclein oligomer and iron might cause apathy through producing neuroinflammatory factors and reducing NE level in apathy-relevant regions, which might be the potential mechanism of apathy in PD patients.No conflict of interest.

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DEPRESSION AND APATHY IN PARKINSON DISEASEM.M. Dumitru1,*, V. Chirita1, R. Chirita1

1Adult psychiatry, “Socola” Psychiatric Hospital, Iasi, Romania

Objectives: The objectives of this study were to examine the prevalence and demographic and clinical correlates of depression and apathy in a hospitalized population with Parkinson disease (PD).Methods: 40 patients were included in this cross-sectional study and were investigated psychiatric with Starkstein Apathy scale (AS)1, HAMD scale and MMSE, motor scoring with Hoehn and Yahr staging (HY) and UPDRS.Results: Patients were classified into four groups: patients with apathy and depression 37.5%, apathy without depression 22.5%, depression without apathy 5%, and neither depression, nor apathy 35%. Depression and apathy were present at 42.5% and respectively 60% of patients.Conclusions: Depression and apathy may occur separately in Parkinson dis-ease, although both are common in these patients.Reference1. Starkstein SE, J Neuropsychiatry Clin Neurosci. 1992.No conflict of interest.

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THE IMPACT OF DEPRESSION ON COGNITIVE FUNCTION AND HEALTH RELATED QUALITY OF LIFE OF PATIENTS WITH PARKINSON’S DISEASEP. Lolekha1,*, K. Kulkuntrakorn1

1Internal Medicine, Thammasat University, Pathumthani, Thailand

Objectives: To describe the prevalence of depression in Parkinson’s disease (PD) patients and evaluate the relationship between depression, cognitive function and quality of life in PD patients.Methods: A total of 81 PD patients from Thammasat University hospital were included. Depression was screened using the Geriatric Depression Scale-15 (GDS-15). Mild cognitive impairment, dementia and quality of life were assessed using the Montreal Cognitive Assessment (MoCA), Thai Mental Stage Examination (TMSE) and Parkinson’s Disease Questionnaire-8 (PDQ8).Results: Forty two patients (52.5%) were screening positive for depression (GDS-15 ≥ 5). Among the screen positive patients, 7 patients (16.7%) were considered as having severe depression (GDS-15 ≥ 10). The mean GDS-15 score was 5.08 ± 3.33 (range 0–15). Mild cognitive impairment (MoCA ≤ 24) and dementia (TMSE ≤ 23) was observed in 82.4% and 23.07% respectively. Average MoCA and TMSE score was significantly lower in the depressed group than the non-depressed group (17.20 ± 5.59 vs. 19.71 ± 4.22, p = 0.03; 23.74 ± 4.80 vs. 26.88 ± 2.45, p = 0.02). Significant correlation were observed between MoCA (r = −0.33, p < 0.01), TMSE (r = −0.47, p < 0.01), PDQ-8 (r = 0.49, p < 0.01) and GDS-15.

Conclusions: Depression is a common psychiatric comorbidity in PD patients and has a significant impact on cognitive function and quality of life. Recognition and proper treatment of depression could improve not only de-pressive symptoms but also cognitive function and quality of life of PD patients.No conflict of interest.

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HEAVY METALS IN BLOOD AND URINE AND ITS RELATION TO DEPRESSIVE SYMPTOMS IN PARKINSON’S DISEASE PATIENTST. Fukushima1,*, X. Tan2, Y. Luo3, P. Wang3, J. Song3, H. Kanda1, T. Hayakawa1, T. Kumagai1, T. Kakamu1, M. Tsuji1, T. Hidaka1, Y. Mori11Hygiene and Preventive Medicine, Fukushima Medical University, Fukushima, Japan, 2School of Public Health, Wuhan University, Wuhan, China, 3Neurology, Xiangfan No.1 Hospital, Xiangfan, China

Objectives: Some heavy metals are suspected to be pathogenic to both Parkinson’s disease (PD) and depression. Common background may exist in them. The blood and urine levels of manganese, iron, copper and zinc, and serum vitamin E and vitamin B12 in the PD patients with depression, the PD patients without depression and the controls in the general population were compared.Methods: Subjects comprised PD patients with depression, PD patients without depression and controls recruited from the outpatient clinic in China. Morning blood and urine samples were used to measure concentrations of metals and vitamins.Results: Whole-blood manganese was significantly higher in the PD patients without depression than in both the PD patients with depression and the con-trols. Serum iron was significantly higher in the PD patients without depression than in the controls. Urine iron was also significantly higher in the PD patients without depression than in the controls. Serum copper was significantly lower in the PD patients with depression than in both the PD patients without depres-sion and the controls.Conclusions: Excessive intake of iron and accumulation of manganese seemed to be involved in the etiology of non-depressive PD.References1. Fukushima T, et al. Relationship between blood levels of heavy metals and

Parkinson’s disease in China. Neuroepidemiology, 34: 18–24, 2010.2. Fukushima T, et al. Serum vitamins and heavy metals in blood and urine,

and the correlations among them in Parkinson’s disease patients in China. Neuroepidemiology, 36: 240–244, 2011.

3. Fukushima T, et al. Nutritional effects on depressive symptoms in Parkinson’s disease patients. e-SPEN Journal, 7: e64-e68, 2012.


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DOES DEPRESSION OR EXECUTIVE DYSFUNCTION PREDICT APATHY IN PATIENTS WITH PARKINSON’S DISEASE (PD)?A. Meyer1,*, R. Zimmermann1, H. Bousleiman2, U. Gschwandtner1, F. Hatz1, C. Schindler2, P. Fuhr1

1Neurology, Hospital of the University of Basel, Basel, Switzerland, 2Swiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland

Objectives: To examine the hypotheses that apathy in PD is correlated with executive dysfunction and/or with depression.Methods: 51 patients (19f) with PD completed the Apathy Evaluation Scale (AES) and Beck Depression Inventory (BDI) and were tested for performance in executive functions (Fluency Tasks, Wisconsin Card Sorting Test (WCST), 5-Point-Test, Trail Making Test (TMT) Stroop test), attention and working memory.Results: Stepwise regressions dropped the variables for depression, disease stage, education, working memory, levodopa equivalent dose and severity of motor symptoms from the model explaining apathy. Relevant cognitive vari-ables in the resulting model (p < 0.01; R2 = 0.38) were the 5-Point-Test (execu-tive functions; b = −0.35; p = 0.06) and the TMT part A (Attention; b = −0.34; p = 0.07). Furthermore, higher levels of apathy were related to age (b = −0.06; p = 0.03), gender (b = −6.36; p = 0.01) and their interaction (b = 0.11; p < 0.01).Conclusions: Apathy in PD is predicted by executive dysfunction. Non-verbal flu-ency tasks are the most important variables predicting apathy. Furthermore, apathy is influenced by age and gender. In women age is negatively correlated with apa-thy. No significant correlation between apathy and depression was found. If a PD patient is diagnosed with dysexecutive syndrome the question of apathy arises.No conflict of interest.

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IL-6 AND AFFECTIVE DISTURBANCES IN PARKINSON’S DISEASET. Torgan1,*, T. Baidina1, N. Demchuk1

1Neurology, Perm State Academy of Medicine, Perm, Russia



36

Objectives: A comparison of concentrations of interleukin-6 (IL-6) in the se-rum of patients with PD and its association with anxiety and depression.Methods: The concentration of IL-6 was determined in 65 patients with PD, 18 healthy control persons of the same age. Duration of illness was 4 (2–5) years. Stage of disease on a scale Hoen–Yahr was 2.5 (2–2.5). Affective disturbances was assessed using the Hospital Anxiety and Depression Scale (HADS)Results: The concentration of IL-6 in patients with PD was 2 times higher than that of the control group (respectively 0.6; 0.2–1.2 pg/ml and 0.3; 0,0–0,8 pg/ml). A comparative analysis showed that the level of IL-6 was significantly higher (p = 0,050) in patients with depression (0.9, 0, 3–2, 2 pg/ml) and without it (0.4, 0, 0–0 8 pg/ml). There were no differences in cytokine concentrations in patients with anxiety 0,9 (0,3–1,9) pg/ml, without it – 0,5 (0,0–0,9) pg/ml. There was a significant correlation between level of IL-6 and the manifestation of depression.Conclusions: The increased concentration of IL-6 in patients with PD is associated with the severity and the presence of depressi on.No conflict of interest.

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DIFFERENCES IN PSYCHOMETRIC PROFILE ACCORDING TO PARKINSON’S DISEASE PHENOTYPEM. Alexeev1,*, G. Pavlic2, I. Moldovanu2, N. Diaconu3

1Intensive Care, Scientific and Practical Center of Emergency Medicine, Chisinau, Moldova, 2Neurology, Institute of Neurology and Neurosurgery, Chisinau, Moldova, 3Cardiology, Institute of Cardiology, Chisinau, Moldova

Objectives: To assess differences in neuropsychiatric symptoms in Moldavian Parkinson disease patients according to phenotype.Methods: We have included 140 consecutive PD patients, all assessed with Beck depression inventory and Spielberger Trait Anxiety Inventory, other col-lected variables being gender, age, treatment duration, age at motor onset, PD phenotype and H&Y staging. The patients were classified into a tremor predominant phenotype (30, group 1), akinetic-rigid (55, group 2) and mixed one (55, group 3).Results: The mean patients’ age was 58.42 ± 7.8 years, 79 men (56.4%), with an average Hoehn and Yahr stage 1.95, UPDRS part III off score 25.3 ± 12.7, mean disease duration was 4.07 (0.5–16 years). All the motor scores presented more severe values in the akinetic-rigid group. The average score of depres-sion was significantly higher in akinetic-rigid type of PD vs. tremor predominant vs. mixed one (6.90 ± 1.19 for tremor group vs. 9.58 ± 0.63 for akinetic-rigid one vs. 6.94 ± 0.59 for mixed group, (p1–2 < 0.05, p1–3 > 0.05, p2–3 < 0.01). Both reactive and trait anxiety score were also higher in the akinetic-rigid group. No correlations were observed between anxiety and disease duration or motor score, but between anxiety and depression and health related quality of life.Conclusions: Akinetic-rigid phenotype of PD has a more severe expression of anxiety and depressive symptoms both in the frequency and intensity, add-ing to clinical heterogeneity of this particular disorder.References1. Dissanayaka N, et al. Anxiety disorders in Parkinson’s Disease: preva-

lence and risk factors. Mov Disord 2010, Vol 25, 7: 838–845.2. Schrag A, Jahanshahi M, Quinn N. What contributes to depression in

Parkinson’s disease? Psychological Medicine, 2001, 31, 65–73.No conflict of interest.

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FACTORS AND PREDICTORS OF ANXIETY IN PARKINSON’S DISEASE: A FACTOR ANALYSIS AND MULTIPLE REGRESSION ANALYSIS OF THE BECK ANXIETY INVENTORYS. Rutten1,*, I. Ghielen2, C. Vriend2, H.W. Berendse3, J.H. Smit1, Y.D. Van der Werf2, O.A. Van den Heuvel11Psychiatry, VU University Medical Center, Amsterdam, Netherlands, 2Anatomy and Neurosciences, VU University Medical Center, Amsterdam, Netherlands, 3Neurology, VU University Medical Center, Amsterdam, Netherlands

Objectives: Anxiety disorders in patients with Parkinson’s disease (PD) often have an atypical presentation. Moreover, diagnosis is hampered by sympto-matic overlap with other PD-related disorders. This study aims to reach a bet-ter understanding of anxiety in PD and to assess the relationship between anxiety, depression, autonomic and motor symptoms.Methods: In 265 patients with idiopathic PD, data on demographics, medica-tion use, anxiety (Beck Anxiety Inventory: BAI), depression (Beck Depression Inventory: BDI), autonomic (SCOPA-AUT) and motor symptoms (UPDRS-III) was collected. Dimensionality of the BAI was assessed with principal compo-nent analysis. Multiple regression analysis was used to identify predictors of anxiety in PD.Results: In the factor analysis of the BAI, the scree plot indicated five factors, all with an eigenvalue >1. These factors (or subscales) were inter-preted as “affective”, “thermoregulation”, “hypotension”, “hyperventilation”

and “tremble”, explaining 61,3% of variance. Multiple regression analysis demonstrated that BDI-score, age, gender, use of dopaminergic medica-tion and autonomic dysfunctions were significant predictors of the BAI-score. The model explained 59,1% of variance (F = 4.289, p = 0.0001). These analyses were also conducted on all subscales of the BAI except the ‘tremble’ subscale as it consisted of only two items. Table 1 displays their predictors.

Table 1. Hierarchical multiple regression on subscales of the BAI in re-sponse to depression, age, gender, use of dopaminergic medication and severity of motor symptoms and autonomic dysfunction. N = 2621.

Subscaie BAI Variables with signifi-cant predictive value

Model statistics

Affective BDI, use of dopaminer-gic medication

R2 = 0.477, F = 2.393, p = 0.038

Thermoregulation BDI, age, SCOPA-AUT R2 = 0.228, F = 5.419, p < 0.001

Hypotension BDI, SCOPA-AUT, UPDRS-III

R2 = 0.497, F = 8.153, p < 0.001

Hyperventilation BDI, gender, SCOPA-AUT

R2 = 0.324, F = 3.359, p = 0.006

Ad 1: Three additional subjects were removed from these analyses due to missing values on the BDI, SCOPA-AUT and/or UPDRS-III.

Conclusions: The BAI reflects one affective dimension of anxiety in PD, and various somatic dimensions. The latter are partially predicted by autonomic and motor symptoms.No conflict of interest.

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GENDER DIFFERENCES IN ANXIETY AND DEPRESSION AMONG THE CAREGIVERS OF PATIENTS WITH PARKINSON’S DISEASES. Mina1,*, R. Verma1, K.S. Anand2

1Psychiatry, Lady Hardinge Medical College, New Delhi, India, 2Department of Neurology, PGIMER Dr RML Hospital, New Delhi, India

Objectives: To evaluate gender differences related to anxiety and depression in caregivers of patients with Parkinson’s disease (PD).Methods: This cross-sectional study was carried out in an out-patient set-ting in the Movement Disorder Clinic of a tertiary care hospital. One hundred and one caregivers of consecutive PD patients were assessed using the Hospital Anxiety and Depression Scale (HADS). Descriptive analysis was done to find in between group differences for the male and female caregiv-ers and Pearson’s correlation coefficient was calculated to find the associa-tion between the scores on HADS and any socio-demographic or clinical parameter.Results: Female caregivers had significantly higher scores than males on the HADS – Total and Depression subscale (p = 0.002 and p = 0.017, respec-tively) while there was no significant difference on HADS Anxiety subscale scores (p = 0.47). HADS scores significantly increased with increasing PD se-verity levels among both genders. There was a significant correlation between the number of family members with chronic illness and HADS-Total scores in male caregivers.Conclusions: It is crucial to screen caregivers of patients with PD for pres-ence of anxiety and depression. This approach will help timely identification and proper management of these individuals. It is important to promote meas-ures to soften the impact that the patient has on the caregiver, and that, at the same time, improves the quality of life of the patient.References1. Fernandez HH, et al. Predictors of depressive symptoms among spouse

caregivers in Parkinson’s disease. Mov Disord 2001; 16(6):1123–5.2. Schrag A, et al. Caregiver-burden in Parkinson’s disease is closely associ-

ated with psychiatric symptoms, falls, and disability. Parkinsonism Relat Disord 2006 Jan; 12(1):35–41.


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DEPRESSION, ANXIETY AND DEMENTIA: HIDDEN SIDE OF PARKINSON’S DISEASES. Mrabet1,*, N. Ben Ali1, M. Kechaou1, S. Belal11Neurology, Charles Nicolle Hospital, Tunis, Tunisia



37

Objectives: Our study aims to determine the prevalence of depression, anxi-ety and dementia in a hospital cohort of patients followed for Parkinson’s dis-ease (PD) and to clarify their clinical and scalable features.Methods: The analysis was conducted on 45 patients followed for PD in the department of neurology in Charles Nicolle hospital. It was performed in all patients a clinical examination, neuropsychological exploration and brain imaging.Results: In our cohort, the rate of depression is estimated at 62%: major depressive episodes are about 28%. Depression precedes the onset of mo-tors symptoms even by several years or occurs during the evolution of the disease. Anxiety is less common, corresponding to 6% of the population. Impaired cognitive functions are found in 46% of patients with various as-pects of cognitive decline: mild cognitive impairment (6%), lighter (17%), moderate (2%), and severe dementia (4%). Depression and anxiety can improve under dopaminergic therapy, particularly when they occur during phases of low mobility. Parkinsonian dementia occurs several years after the onset of the disease, and includes leading difficulty in retrieving information, accompanied by disorders related to the planning and carrying out actions, as well as a deficit visual and spatial representation rather than memory impairmentConclusions: The neurologist must be aware about non motor symptoms oc-curring in parkinsonian patient, especially depression and anxiety, to optimize the management at any stage of the diseaseReferences1. Aarsland D, et al. Prevalence and characteristics of dementia in

Parkinson’s disease. Arch Neurol. 2003; 60:387–92.2. Weintraub D, et al. Impulse control disorders in Parkinson disease. Arch

Neurol. 2010; 67:589–95.No conflict of interest.

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SOME EEG FEATURES IN EARLY-STAGE PARKINSON’S DISEASE PATIENTSY. Obukhov1,*, M. Korolev1, K. Obukhov1, O. Sushkova1, O. Sushkova1, R. Nigmatullina2, Z. Zaljalova3, A. Karabanov4, A. Gabova5, G. Kuznetsova5, M. Ugrumov6

1Biomedical Engineering, Kotel’nikov Institute of Radio Engineering and Electronics of RAS, Moscow, Russia, 2Physiology, Kazan State Medical University, Kazan, Russia, 3Neurology, Kazan State Medical University, Kazan, Russia, 4Clinical Department, Neurological Research Centre of RAMS, Moscow, Russia, 5Neurophysiology, Institute of Higher Nervous Activity and Neurophysiology of RAS, Moscow, Russia, 6Hormonal Regulation, Koltzov Institute of Developmental Biology of RAS, Moscow, Russia

Objectives: Time-frequency EEG features of early-stages in Parkinson dis-ease (PD) were investigated.Methods: 54 untreated PD patients of the 1st stage of Hoehn-Yahr scale were examined. EEG (scheme 10 × 20) and measured by accelerometers tremor of both hands were registered. Quantitative estimation of EEG wavelet spectro-grams was performed. It is based on analysis of wavelet spectrograms local extreme time-frequency distribution (Obukhov et al., 2013).Results: Four main differences in EEG of PD patients were found in com-parison to healthy volunteers. 1) Some slowing of EEG dominant frequency band was observed. Slowing of EEG dominant frequency band confirmed the data of the previous authors 2) Reliable disordering for the EEG wavelet spectrograms local extreme distribution in frequency range higher than ~6 Hz was shown. These data were observed for the first time in this work. 3) More powerful theta rhythm in contra lateral hemisphere was found in the case of one-sided tremor. The frequency synchronization of EEG theta rhythm and tremor was shown. 4) Increase of EEG extreme in beta frequency range was revealed especially in the frontal, central and parietal brain areas. This phe-nomenon can be a result of changes in excitation and inhibition processes in striatum during the early stage of PD.Conclusions: Reliable differences in EEG of early-stages PD patients in com-parison to healthy volunteers were revealed. They can be considered as early clinical markers of PD.Reference1. Obukhov, et al. Method of early stage Parkinson’s disease electroenceph-

alography diagnosis// RF patent. – 2484766, 20.06.2013.No conflict of interest.

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CORTICAL ATROPHY IN PARKINSON’S DISEASE WITH AND WITHOUT MILD COGNITIVE IMPAIRMENTB. Segura1, H.C. Baggio1,*, M.J. Marti1, F. Valldeoriola1, Y. Compta1, E. Tolosa1, A.I. Garcia-Diaz1, P. Vendrell1, N. Bargallo1, C. Junque1

1Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain

Objectives: Cognitive deficits are frequent manifestations of Parkinson’s dis-ease (PD), and the presence of mild cognitive impairment (MCI) is known to increase the risk of subsequent dementia. Our aim was to evaluate the pres-ence of cortical degeneration as measured by cortical thinning according with the presence of MCI in PD patients using structural MRI.Methods: Thirty-four healthy controls (HC) and 90 non-demented PD patients received high-resolution structural MRI scans. MCI was determined if Z scores for at least two tests in the three most-affected cognitive domains in PD (atten-tion/executive, memory and visuospatial/visuoperceptual) fell below 1.5 points the expected score for age, sex and education. FreeSurfer was used to as-sess cortical thickness and perform group comparisons.Results: Forty patients (44%) of PD patients were classified as having MCI. Group comparisons, correcting for age and education, revealed that, com-pared with controls, PD patients showed cortical thinning in posterior, pre-dominantly parieto-temporal regions. Compared with non-MCI patients, MCI patients had reduced thickness in frontal and occipital areas. Global mean cortical thickness was significantly reduced in the collapsed PD patient group and in the MCI PD subgroup compared with HC.Conclusions: Our findings show that PD is accompanied by global cortical atrophy that predominates in posterior regions and, in patients with cognitive impairment, also involves frontal areas.No conflict of interest.

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HEART RATE VARIABILITY AND COGNITIVE PERFORMANCEL. Giblin1,*, L. De Leon1, L. Smith1, R. Clifton-Bligh2, C. Zaslawski1, S. Lal11Neuroscience Research Unit School of Medical and Molecular Biosciences, The University of Technology Sydney, Sydney, Australia, 2Cancer Genetics Unit Kolling Institute, The Royal North Shore Hospital, Sydney, Australia

Objectives: Parkinson’s disease affects approximately 2% of those over 65 years, and is predicted to increase. Approximately 50–80% of Parkinson’s disease patients eventually experience Parkinson’s disease dementia, affecting cognitive domains such as recognition and word-find-ing. Literature suggests changes in autonomic activity may occur prior to detectable cognitive symptoms. Few studies assess autonomic nervous system activities (as measured by heart rate variability (HRV)) for predict-ing cognitive impairment. The present study aimed to address this gap in the literature by identifying relationships between HRV and cognition between sexes and over a range of ages (18–35 years, 36–50 years, and 51–65 years).Methods: HRV was derived using 3-lead electrocardiogram recordings (10 minutes baseline and 10 minutes active cognitive task) (n = 191). Two psychometric assessment tools were administered (Mini-Mental State Examination and Cognistat).Results: Different cognitive domains were linked to HRV parameters in the 3 age and sex groups. For example, in females 18–35 years, low frequency (sympathetic drive) during baseline was inversely related to calculation skill (r = −0.3359; p = 0.034). In males, 51–65 years, total HRV activity dur-ing baseline was inversely linked to memory performance (r = −0.4976; p = 0.036).Conclusions: Findings suggest HRV is linked to performance in different cognitive domains for different age groups and between sexes. These and future findings may determine those at higher risk of cognitive impairment, prior to detectable cognitive symptoms seen in Parkinson’s disease dementia. Intervention strategies can be applied sooner in life to delay cognitive decline progression.No conflict of interest.

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INCREASED PERIPHERAL LEVELS OF SOLUBLE TUMOR NECROSIS FACTOR RECEPTORS ARE ASSOCIATED WITH POORER COGNITIVE PERFORMANCE IN PARKINSON’S DISEASEN.P. Rocha1,*, A.L. Teixeira2, P.L. Scalzo3, I.G. Barbosa2, M.S. Sousa4, I.B. Morato2, E.L.M. Vieira2, P.P. Christo4, H.J. Reis1

1Laboratório de Neurofarmacologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, 2Laboratório Interdisciplinar de Investigação Médica, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, 3Laboratório de Neurobiologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, 4Departamento de Neurologia e Neurocirugia, Santa Casa de Belo Horizonte Hospital, Belo Horizonte, Brazil

Objectives: The pathogenesis of the progressive loss of dopaminergic neu-rons in Parkinson’s disease (PD) remains elusive. Accumulating evidence sug-gest the involvement of immune and/or inflammatory mechanisms. Non-motor symptoms experienced by PD patients - particularly cognitive impairment - are frequent and disabling. Inflammation has been associated to cognitive decline in a range of neuropsychiatry disorders. This study aimed to compare



38

the plasma levels of soluble tumor necrosis factor receptors (sTNFR)1 and sTNFR2 of individuals with PD with a group of controls matched by age, gen-der and educational level. We also investigated the association between these plasma markers and cognitive performance.Methods: Forty PD patients and twenty-five controls were subjected to cognitive examination, which included the Mini-Mental State Examination (MMSE) and the Frontal Assessment Battery (FAB). Plasma levels of sTNFR1 and sTNFR2 were measured by Enzyme-Linked Immunosorbent Assay (ELISA).Results: PD patients presented higher sTNFR1 and sTNFR2 plasma levels than control individuals. PD patients presented a poorer performance on the MMSE and programming task of FAB in comparison with controls. Among PD patients, higher sTNFR1 and sTNFR2 levels were associated with lower cog-nitive tests scores. After multiple linear regression sTNFR1 level and educa-tional level remained as significant predictors for FAB scores.Conclusions: Our data suggest that PD is associated with a pro-inflammatory profile and sTNFRs are putative biomarkers of cognitive performance in PD. Especially higher sTNFR1 level predicted poorer executive functioning in PD patients.No conflict of interest.

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ALTERED PERCEPTION OF SPATIAL FREQUENCY BUT NOT CONTRAST IN LEFT-ONSET PARKINSON’S DISEASED. Norton1,*, A. Cronin-Golomb1

1Psychology, Boston University, Boston, USA

Objectives: Patients with Parkinson’s disease (PD) with symptom onset on the left side of the body (LPD) show mild left-sided visuospatial neglect, whereas patients with right-onset (RPD) do not. The mechanisms underly-ing these observations are unknown. Two hypotheses are that left-space in LPD is either compressed or reduced in salience. We tested these hypotheses psychophysically.Methods: Participants were 21 non-demented patients with PD – 11 LPD, 10 RPD – and 9 normal control adults (NC). The spatial compression hy-pothesis was tested by showing two sinusoidal gratings, side by side. A comparison grating was held at a constant spatial frequency (SF), while the other grating’s SF was varied across trials following a staircase procedure. Participants estimated the point at which they perceived the two gratings to be equal in SF. The reduced salience hypothesis was tested in a similar way, but manipulating the contrast of the test grating rather than its spatial frequency.Results: Across SFs, LPD perceived the gratings to be equal in SF when the one on the left was thinner than the one on the right (i.e., opposite the direction hypothesized), a pattern significantly different than NC (p =.02), who showed a slight bias in the opposite direction. RPD and NC did not differ. For contrast discrimination across hemifields, there were no group differences.Conclusions: While perception of space does not appear to be “compressed” in the left hemifield for LPD, it does appear to be altered in a way that is inde-pendent of the overall salience of stimuli on that side.Reference1. Lee, et al. (2001) Vision Res, 41, 2677–86.No conflict of interest.

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COGNITIVE-LINGUISTIC ABILITIES IN PERSONS WITH PARKINSON DISEASES. Manjunath1,*, S. Narayanan2

1Speech and Hearing, All India Institute of Speech And Hearing, Mysore, India, 2Speech language Pathology, All India Institute of Speech And Hearing, Mysore, India

Objectives: To investigate the performance of Kannada speaking persons with idiopathic PD on a set of cognitive-linguistic tasksMethods: The clinical group comprised of nineteen persons (13 males and 6 females) with idiopathic PD with native language Kannada (a Dravidian Indian Language) between the age range of 60–80 years. The control group consisted of twenty one, age, gender, socio economic status and language matched neurotypical persons. The adapted and standardized version of the Cognitive and Linguistic Quick Test Kannada (CLQT-K, Vandana and Shyamala, 2011) was used to assess the cognitive-linguistic abilities of all the participants. CLQT-K assesses five cognitive processes i.e. attention, memory, executive function, visuospatial skills and language through ten dif-ferent tasks, namely, Personal facts, Symbol cancellation, Confrontation nam-ing, Clock drawing, Story retelling, Symbol trial, Generative naming, Design memory, Mazes and Design generation. The clinical group underwent a series of screening procedures after which CLQT-K was administered. After scoring each task for both the groups, the data was subjected to statistical analysis

Results: The results revealed poorer performance of the clinical group in comparison with the control group. A significant difference was found across five tasks i.e., symbol cancellation, clock drawing, story retelling, design mem-ory and design generation.Conclusions: There was a decline in all the cognitive-linguistic tasks in per-sons with idiopathic PD. The results throw light on the possible inclusion of the cognitive-linguistic tasks in the assessment and treatment protocol of persons with PDReference1. Murdoch, B. E. (2010). Acquired speech and language disorders: A neuro-

anatomical and functional approach. 2nd edition, Wiley-Blackwell, UK.No conflict of interest.

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DIFFERENTIAL ROLES OF DORSAL STRIATUM AND ANTERIOR CINGULATE CORTEX IN SPATIAL LEARNING AND MEMORY IN MICET. Pooters1,*, I. Gantois1, B. Vermaercke1, L. Arckens2, R. D’Hooge1

1Department of Psychology and educational Sciences, KU Leuven, Leuven, Belgium, 2Department of Biology, KU Leuven, Leuven, Belgium

Objectives: Cognitive symptoms of Parkinson’s disease (e.g., impaired executive functions, behavioral inflexibility) remain largely intractable with available treatment. The striatum has been suggested to contribute to these cognitive deficits. However, the specific role of striatal subareas and cortico-striatal pathways in cognitive (dys) functioning remains unclear. Therefore, we presently studied the roles of the dorsal striatum and anterior cingulate cortex (aCC) in spatial learning and memory.Methods: Mice with lesions in dorsomedial (DMS) and dorsolateral striatum (DLS), and in aCC were trained for 15 days in the hidden-platform version of the Morris water maze, followed by 3 days of reversal training to assess behavioral flexibility.Results: Compared to sham controls, animals with DMS damage were impaired during acquisition training, displaying delayed spatial learning, in-creased thigmotaxis, and increased search distance to the platform. Animals with lesions in DLS and aCC were impaired in reversal performance, show-ing delayed learning and increased distance to the platform. Search strategy analysis indicated that the observed deficits coincided with a decrease in the ability to switch flexibly between search strategies.Conclusions: Our results indicate a differential role of dorsal striatal sub-areas and aCC in spatial learning and memory, suggesting that specific cortico-striatal connections are involved in the acquisition of goal-directed behaviors. It also shows that behavioral flexibility, a cognitive function im-paired in patients with Parkinson’s disease, is impaired in animals with striatal or aCC lesions. The present results contribute to understand further the cognitive pathogenesis of Parkinson’s disease and other basal ganglia diseases.No conflict of interest.

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COMPENSATORY FRONTO-PARIETAL HYPERACTIVATION DURING SET-SHIFTING IN UNMEDICATED PATIENTS WITH PARKINSON’S DISEASEN.J.H.M. Gerrits1,*, Y.D. van der Werf1, K.M.W. Verhoef1, D.J. Veltman2, H.J. Groenewegen1, H.W. Berendse3, O.A. van den Heuvel11Anatomy and Neurosciences, VU University Medical Center, Amsterdam, Netherlands, 2Psychiatry, VU University Medical Center, Amsterdam, Netherlands, 3Neurology, VU University Medical Center, Amsterdam, Netherlands

Objectives: Patients with Parkinson’s disease (PD) often suffer from impair-ments in executive functions, such as mental rigidity, which can be measured as impaired set-shifting. Previous studies have shown that set-shifting deficits in PD patients result from a hypo-excitation of the caudate nucleus and lat-eral prefrontal cortices. These studies, however, included patients who used dopaminergic medication and employed set-shifting paradigms in which task performance also depended on other cognitive mechanisms (e.g. matching-to-sample). To circumvent these potential confounding factors, we tested PD patients that were not yet using dopaminergic medication and developed a new set-shifting paradigm.Methods: Eighteen patients and thirty-five matched healthy controls per-formed the set-shifting task, while measuring their task-related neural activa-tion with functional MRI.Results: Behaviorally, PD patients, compared with healthy controls, made more errors on repeat, but not set-shift trials. There were no group differences in switch costs or normalized switch costs. PD patients, com-pared with healthy controls, showed increased task-related activation of the inferior parietal cortex (IPC) and pre-supplementary motor area (preSMA), and a decreased activation of the right ventrolateral prefrontal cortex (VLPFC) at set-shift trials. Normalized switch costs, in addition,



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correlated in patients, but not in controls, with activation of the right pre-frontal cortex.Conclusions: The data suggest that, despite decreased task-related activa-tion of the right VLPFC, these early-stage unmedicated PD patients do not yet suffer from set-shifting deficits due to compensatory hyperactivation in the IPC and preSMA.No conflict of interest.

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COGNITIVE DISORDERS IN PARKINSON’S DISEASE PATIENTSS. Tomic1, M. Vladetic1, K. Solic2, S. Misevic1, S. Butkovic Soldo1,*1Department of Neurology, University Hospital Center Osijek, Osijek, Croatia, 2Department of Biophysics Medical Statistics and Medical Informatics, Medical School University of “J. J. Strossmayer in Osijek”, Osijek, Croatia

Objectives: Cognitive disorder and dementia are among most common non-motor impairments in Parkinson disease patients. In our study we try to inves-tigate appearance and type of cognitive impairment in patients with idiopathic PD.Methods: Previously demented and depressed patients with PD were ex-cluded using Mini Mental State Examination Test (MMSE) and Geriatric Depression Scale (GDS). To evaluate severity of motor symptoms we used Unified Parkinson Disease Rating Scale (UPDRS) Part III and to analyze cognitive functions in PD and control group we used: Dementia Rating Scale (DRS), Raven progressive colored matrices (RPCM) and Mill Hill Vocabulary (MCV) test.Results: Significant difference was observed in results of Mill Hill Vocabulary test (p < 0.05) between PD and control groups. In subscales for construction and initiation/perseveration (DRS test) PD group had more often results bel-low the cut of score in regard to control group (p < 0.05). No correlation was observed between the results of neuropsychological tests and UPDRS Part III in the group of PD patients. There are no connection between cognitive disorder and severity of motor impairment or type of PD in regard to dominant symptoms (rigid vs. tremorous).Conclusions: In PD group we find, beside dysexecutive syndrome and impaired visuo-constructive ability, also limited ability to identify synonyms in comparison to control group.References1. Kulisevs. ky J, Pagonabarraga J. Cognitive Impairment in Parkinson’s

Disease: Tools for Diagnosis and Assessment. Mov Disord. 2009; 24(8):1103–1110.

2. Rodríguez-Ferreiro J, Cuetos F, Herrera E, Menéndez M, Ribacoba R. Cognitive impairment in Parkinson’s disease without dementia. Mov Disord. 2010; 25(13):2136–2141.


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DETECTING COGNITIVE DEFICITS WITH NO MANIFEST SYMPTOMS: THE USEFULNESS OF COGNITIVE PROCESSING SPEED IN EARLY STAGES.J. Subirana-Mirete1,*, O. Bruna Rabassa1, C. Virgili Tejedor1

1Graduate School of Psychology Blanquerna, Ramon Llull University, Barcelona, Spain

Objectives: The aim of this communication is introducing the importance of the inclusion of cognitive processing speed (CPS) in neuropsychological as-sessments for MCI, PD or AD as the slowdown of the CPS is present in multi-ple diseases of the CNS among which we can include cognitive impairments of diverse aetheologies. In the assessment of cognitive domains we usually use time-controlled neuropsychological tasks. These timings are often con-sidered for the final conclusions of the overall cognitive status of the patients. However, we do not take into consideration that maybe only the CPS is slowed and there’s no affectation in the other cognitive domains but only slowed ca-pacity of the system.Methods: To enhance those assessments some tests have been recently de-veloped and adapted in order to be able to differentiate among the cognitive difficulties presented over evaluation on everyday clinical practice. We will be presenting several studies that have been conducted to quantitatively evalu-ate the slowing of CPS in different stages of aging and cognitive impairment, including MCI and early stages of AD and PD.Results: Decreased speed of processing has been found to contribute to compromised functional status. We will be presenting some guidelines again which an individual could be assessed; the ability to assess separately the dif-ferent cognitive areas and the CPS can be of great help to assess and monitor the evolution of different conditions.

Conclusions: CPS should be considered in everyday assessments as maybe some conditions attributed to specific diseases are only the reflect of the slow-ness in CPS due to the aging process.No conflict of interest.

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COGNITION IN EARLY PARKINSON’S DISEASE AND THE EFFECT OF LATERALITY OF MOTOR SYMPTOMSR. Yadav1,*, S.G. Adwani1, S.R. Chandra1, K. Kumar J2, P.K. Pal11Neurology, National Institute of Mental health and Neurosciences, Bangalore, India, 2Clinical Psychology, National Institute of Mental Health and Neurosciences, Bangalore, India

Objectives: Cognitive dysfunction in Parkinson’s disease (PD) is seen in ex-ecutive, memory and visuospatial domains. The present study was conducted to know the cognitive profile of patients with early PD and to assess the effect of laterality of motor symptoms on cognition.Methods: The patients with PD were prospectively recruited from de-partment of Neurology of National Institute of Mental Health and Neurosciences (NIMHANS) in Bangalore, India from October 2011 to December 2012, diagnosed as per Queen square criteria and after sat-isfying other inclusion parameters. The patients were evaluated using various standard scales and a neuropsychological battery devised at NIMHANS was used.Results: Fifty patients (right onset (RPD): left onset (LPD)- 1:1)) and 50 age, gender and education matched controls were enrolled in the study. The mean age of patients was 50.4 ± 8.2 years. The mean age, age of onset, years of education and duration of PD in patients with RPD was 52.24 ± 7.96 years; 49.72 ± 8.4 years; 12.32 ± 2.9 years; 2.31 ± 1.28 years and in LPD was 48.44 ± 8.07 years; 46.04 ± 8.22 years; 12.52 ± 3.22 years and 2.58 ± 1.48 years. The patients performed poorly on the memory task, executive functions, atten-tion and psychomotor speed as compared to controls (p < 0.05). No difference in the neuropsychological scores was seen between RPD and LPD versus controls and also between RPD and LPD groups (p > 0.05).Conclusions: Memory, executive functions and attention impairment is com-mon in the early stage of PD. Side of onset of symptoms do not influence cognition in early PD.References1. Tomer, et al. 1993.2. Cubo, et al. 2010.No conflict of interest.

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ASSESSMENT OF COGNITIVE PROFILE IN NON-DEMENTED PARKINSON’S DISEASE PATIENTST. Puussaar1, M. Ennok1, P. Taba2,*1Institute of Psychology, University of Tartu, Tartu, Estonia, 2Department of Neurology, University of Tartu, Tartu, Estonia

Objectives: There is growing evidence that non-demented Parkinson’s disease (PD) patients have significant cognitive deficits, but results about the degree and pattern of impairments have varied across the studies. The purpose of this study was to specify the cognitive profile in non-demented PD patients by using a comprehensive neuropsychological test battery.Methods: Research participants were 16 non-demented PD patients and 16 age and education matched control subjects. The following cognitive domains were assessed: 1) simple concentration; 2) attention flexibility; 3) processing speed; 4) working memory; 5) learning; 6) delayed recall; 7) visuospatial skills; 8) executive functions; 9) reasoning; 10) semantic knowl-edge. Relationships between test performances and research participants’ characteristics were also examined.Results: The results showed no statistically significant group differences in any of the 10 cognitive domains assessed, and the corresponding ef-fect sizes ranged from minimal to medium (d =.00 -.58). Education level and/or age were statistically significant predictors in 9 cognitive domains. Longer educational history and younger age were related to better test performance. The patient group only predicted to have significantly lower semantic knowledge than the control group. In addition, younger age of PD onset and longer duration of disease were significantly correlated to lower working-memory.Conclusions: This study provides a confirmation that the incidence of cogni-tive impairment varies substantially in non-demented PD patients. The study also directs attention to the necessity to explore the relationships between non-demented PD patients’ cognitive abilities and different demographical and disease characteristics more thoroughly.No conflict of interest.



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COGNITIVE FUNCTION OF PARKINSON’S DISEASE -EXAMINATION ACCORDING TO WECHSLER ADULT INTELLIGENCE SCALE?Y. Kobayashi1,*, A. Kumon1, M. Saruwatari1, E. Horiuchi1, T. Yokoyama1, K. Hasegawa1

1Neurology, National Sagamihara Hospital, Kanagaawa, Japan

Objectives: We examined 96 cases (70.3 ± 7.3 years old) of PD patients using a Japanese version of the Wechsler Adult Intelligence Scale, 3rd Edition (WAIS-III) to evaluate cognitive function PD.Methods: To investigate cognitive function of Parkinson’s disease (PD)Results: The average score of VIQ and PIQ were compared; as a result, PIQ is a significant lower than VIQ. And four secondary indices; Verbal Comprehension (VC), Working Memory (WM), Perceptual Organization (PO), and Processing Speed (PS) the average score of was compared for duration of illness. A result of analyzing the significant difference was seen in PS, and the significant tendency was seen in PO and WM.Conclusions: The result of PIQ is a significant lower is supported Hasegawa’s study (1997). Even more PO, WM and PS score of PD is the significant lower as a result of duration of illness is longer. That in this study, with the duration of illness, the social function and physical function of PD is lower was suggested.Reference1. Chieko Hasegawa, et al. (1997). The cognitive assessment in Parkinson’s

disease patients - Examination According to Wechsler Adult Intelligence Scale-R-, Rehabilitation Medicine, 34(12), pp.939


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EVALUATION OF MILD COGNITIVE IMPAIRMENT IN JAPANESE PARKINSON’S DISEASE PATIENTSY. Tajiri1,*, M. Hamada1, S. Yamasaki1, S. Nakashita1, T. Adachi1, K. Wada1, K. Nakashima1

1Division of Neurology Department of Brain and Neurosciences, Faculty of Medicine Tottori University, Tottori-ken, Japan

Objectives: To detect mild cognitive impairment of Parkinson’s disease (PD-MCI), the Movement Disorder Society (MDS) recommends two levels of neuropsychological tests: Level 1 and Level 2. Our aim was to determine the utility of these tests in Japanese PD patients.Methods: We assessed the cognitive function of 53 idiopathic PD patients. The diagnosis of PD was made based on the UK Brain Bank Criteria. We applied the Japanese version of the Montreal Cognitive Assessment (MoCA-J) as a Level 1 test and five cognitive domain tests as Level 2: Trail Making, Letter Number Sequencing, Tower of London, Verbal fluency, Similarities, Boston Naming, Auditory Verbal Learning, Logical Memory, Benton’s Judgment of Line Orientation and Clock Copying. The diagnoses of PD-MCI and PD with dementia (PDD) were made according to the diagnostic criteria for PD-MCI and PDD presented by MDS.Results: Of the 53 patients, 13 PD patients were diagnosed as PDD. Twenty-three patients were diagnosed as MCI using a cut-off value of 26/25 on the MoCA-J. Twenty patients were diagnosed as MCI on the Level 2. A discrep-ancy in diagnosis existed between the Level 1 and Level 2. Three patients who were diagnosed as normal cognition on the MoCA-J were classified as MCI on the Level 2. Six patients who were diagnosed as MCI on MoCA-J were classi-fied as normal cognition on the Level 2.Conclusions: The MDS PD-MCI diagnostic criteria are considered to be in-sufficient to accurately evaluate PD-MCI in Japanese PD patients.No conflict of interest.

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THE PERFORMANCE OF MONTREAL COGNITIVE ASSESSMENT AND APOE PHENOTYPES IN JAPANESE PATIENTS WITH PARKINSON’S DISEASET. Shinoda1,*, T. Maeda1, M. Yamamoto2, M. Saito1, R. Muraoka1

1Neurology, Institute for Brain and Blood Vessels, Akita, Japan, 2Neurology, Takamatsu Neurology Clinic, Takamatsu, Japan

Objectives: The Montreal cognitive assessment (MoCA) is a useful tool for screening mild cognitive impairment for the patients with Parkinson’s disease (PD). In Alzheimer’s disease, apolipoprotein E (apoE) e4 allele is known as a genetic risk factor, but an association between apoE and PD has been incon-clusive. This study aims to clarify the relationship between the performance of MoCA and apoE phenotypes in Japanese patients with PD.Methods: In PD enrolled in two medical facilities, serum apoE pheno-types, MoCA and the mini-mental state examination (MMSE) were investi-gated. Patients were divided into 3 groups according to apoE phenotypes,

as following groups: A) ApoE4 homozygous, B) ApoE4 heterozygous and C) ApoE4 negative. MoCA and MMSE scores were statistically compared among 3 groups.Results: 145 PD patients were enrolled (61 male and 84 female, mean age 67.7). Their total scores of MoCA and MMSE were 23.1 ± 4.6 and 28.2 ± 2.9. The numbers of the patients for each group were as follows: group A) 4, group B) 36, and group C) 105. About 30% of the patients were E4 carriers. The total scores of MoCA were group A) 17.3 ± 5.7, group B) 23.3 ± 4.9 and group C) 23.2 ± 4.3. The score of group A was significantly lower than those of group B and group C (p < 0.05).Conclusions: In this study, ApoE4 homozygous PD patients showed cog-nitive dysfunctions evaluated with MoCA. This result suggested that MoCA could detect mild or more severe cognitive impairments relating with ApoE4 genotype in PD.No conflict of interest.

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MILD COGNITIVE IMPAIRMENT AND RESTING-STATE FUNCTIONAL CONNECTIVITY CHANGES IN PARKINSON’S DISEASEH.C. Baggio1,*, B. Segura1, R. Sala-Llonch1, M.J. Marti1, F. Valldeoriola1, Y. Compta1, E. Tolosa1, N. Bargallo1, P. Vendrell1, C. Junque1

1Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain

Objectives: Cognitive deficits are frequent in Parkinson’s disease (PD), and the presence of mild cognitive impairment (MCI) is known to increase dementia risk. Resting-state functional MRI (fMRI) can be used to detect interregional correlations in blood-oxygen-level dependent signal fluctuations, which have proven to be useful in the study of neurodegenerative diseases. We aimed to evaluate the presence and spatial distribution of resting-state functional connectivity changes associated with the presence of MCI in PD patients using fMRI.Methods: Thirty-six healthy controls (HC) and 66 non-demented PD patients underwent resting-state fMRI. Subjects’ brain connectivity matrices were calculated after parcelation into 90 regions of interest. MCI was determined if Z scores for at least two tests in the three most-affected cognitive domains in PD (attention/executive, memory and visuospatial/visuoperceptual) fell below 1.5 points the expected score for age, sex and education.Results: Twenty-three (25%) PD patients fulfilled criteria for MCI. Compared with HC, PD patients had widespread reductions in interregional correla-tion strength. MCI patients had long-range connectivity reductions and shorter-range increases compared with HC. Comparisons between MCI and non-MCI patients, controlling for depression, medication and UPDRS-III, showed connectivity reductions in MCI patients mainly involving the frontal and occipital lobes.Conclusions: Our findings show that the presence of MCI in PD is accom-panied by long-range reductions in resting state functional connectivity, giving support to the potential of fMRI in detecting changes underlying cognitive defi-cits in this disease.No conflict of interest.

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DOUBLE DISSOCIATION IN HABIT AND RECOLLECTION: EVIDENCES FROM PARKINSON DISEASE AND AMNESIC-MILD COGNITIVE IMPAIRMENTE. Guerdoux1,*, A. Rossignol2, S. Bayard3

1Department of Medicine Subject and Society Sciences Sport Sciences, Laboratory Epsylon EA 4556 Dynamics of Human Abilities and Health Behaviors University, Montpellier, France, 2Neurology, Montpellier University Hospital, Montpellier, France, 3Neurology, Montpellier University Hospital Gui-de-Chauliac, Montpellier, France

Objectives: We aim to (1) determinate the contribution of habit and rec-ollection to episodic memory performance in Parkinson Disease (PD); and (2) investigate the role of the striatum and the medial temporal lobe by comparing patients with PD and amnesic-Mild Cognitive Impairment (MCI-a).Methods: Forty-five participants were separated into 3 groups matched on age, sex, socio-cultural level, level of anxiety and depression: (1) a control group, (2) a PD patients group without dementia, (3) a MCI-a patients group. They all performed the Epreuve de Glissement de Mémoire –EGM (Guerdoux et al., 2012), a French memory task that provides the habit and recollection contributions within a single episodic memory task.Results: A double dissociation was observed at the EGM: the PD patients showed a significant decrease in habit (p <.04) while the MCI-a patients exhibited a recollection deficit (p <.01).Conclusions: PD patients may suffer from a retrieval deficit due to a striatum dysfunction whereas MCI-a patients may exhibit a recollection impairment



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linked to the medial temporal lobe. The “retrieval deficit hypothesis” should be discussed according to the “encoding deficit” but also to the processes specificity (Brønnick et al., 2011).References1. Brønnick K, Alves G, Aarsland D, Tysnes OB, Larsen JP. (2001). Verbal

memory in drug-naive, newly diagnosed Parkinson’s disease. The retrieval deficit hypothesis revisited. Neuropsychology. 2011, 25(1):114–24.

2. Guerdoux E, Dressaire D, Martin S, Adam S, Brouillet D. Habit and recol-lection in healthy aging, mild cognitive impairment, and Alzheimer’s dis-ease. Neuropsychology, 26(4):517–33.


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MILD COGNITIVE IMPAIRMENT AND DEMENTIA IN PATIENTS WITH PARKINSONISMI. Barbov1,*, S. Lazarova1, I. Petrov1

1Cerebrovascular disease, University Clinic for Neurology, Skopje, Macedonia

Objectives: The causes and characteristics of Mild Cognitive Impairment (MCI) in patients with different forms of parkinsonism are still not well identi-fied. The purpose of this work is to evaluate the cognitive capacities in a cohort of parkinsonism patients and to identify the clinical determinants of cognitive decline and dementia.Methods: A total of 100 consecutive patients were admitted to our Clinic for Neurology in a period of 2 years, 55 man an 45 women at the age of 42–79 years with different forms of parkinsonism. We made neuropsychological battery that included a screening tests (the Mini Mental State Examination - MMSE) and a comprehensive battery administrated to those who had a low score in MMSE. Dementia was defined according to the DSM IV and ICD 10 criteria.Results: 28% of patients have MCI and 18% have dementia. Vascular parkin-sonism is more frequent associated with cognitive impairment.Conclusions: MCI and dementia most frequently appears in patients with vascular parkinsonism (with bilateral multiple infarctions and in patients with cortical reduced changes and white matter changes detected on CT or MRI).Reference1. Aarsland, D., Anderson, K., Larsen, J. P., et al (2001a) Risk of dementia in

Parkinson’s disease – a community-based, prospective study. Neurology, 56, 730–736.


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PATIENTS WITH PARKINSON’S DISEASE AND MILD COGNITIVE IMPAIR MENT HAVE AN INCREASED CORTICAL DEGRADATION COMPARED TO COGNITIVELY HEALTHY PATIENTS, IN A LONGITUDINAL STUDYA. Hanganu1, C. Bedetti2, C. Degroot1, B. Mejia-Constain1, A.L. Lafontaine3, S. Chouinard4, M.A. Bruneau1, O. Monchi5,*1Centre de Recherche Institut Universitaire de Gériatrie de Montréal, Université de Montréal, Montreal, Canada, 2Psychologie, Centre d’Études Avancées en Médicine du Sommeils Hôpital du Sacré Coeur de Montréal, Montreal, Canada, 3Movement Disorders Unit, McGill University Health Center, Montreal, Canada, 4Unité des troubles du mouvement André Barbeau, Centre Hospitalier de l’Université de Montréal, Montreal, Canada, 5Department of Radiology, University of Montreal, Montreal, Canada

Objectives: In order to reveal whether mild cognitive impairment (MCI) in Parkinson’s disease (PD) influences the evolution of cortical morphol-ogy and subcortical volumetry, we performed a longitudinal study in PD patients who had MCI and in those who were cognitively intact, to assess changes in cortical thickness and in volumes of subcortical structures over time.Methods: Our study included 18 healthy controls and 33 PD patients at the early stages of the disease. Each group was studied twice 20 months apart. At each time point they underwent an MRI session and a comprehensive neuropsychological assessment based on which patients were divided in two groups at time 1: MCI positive (N = 17) and MCI negative (N = 15). The analysis was based on MPRAGE 3T images, using FreeSurfer 5.3 image analysis suite. Images underwent a standard pre-processing and the analyz-ing longitudinal stream procedure. Statistical analyses for cortical thickness were performed using the longitudinal two-stage model and the rate of change of cortical thickness (mm/year) was computed.Results: The most significant changes in the PD-MCI group were revealed by an increased rate of thinning of the cortical grey matter in the temporal and occipital lobes and the supplementary motor area as well as a significant decrease in volume of the amygdala and nucleus accumbens.Conclusions: Our data suggest that the early presence of MCI in PD patients is indicative of faster grey matter degradation.No conflict of interest.

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THE QUALITY OF ACTIVITIES OF DAILY LIVING PERFORMANCE IN PATIENTS WITH DIFFERENT FORMS OF DEMENTIAJ. Jansa1,*, M. Gregoric Kramberger1, M. Trost1, Z. Pirtosek1

1Division of Neurology, University Medical Centre, Ljubljana, Slovenia

Objectives: Activities of daily living (ADL) performance is an important factor for persons with dementia. Several ADL evaluation tools are available. We introduced Assessment of Motor and Process Skills (AMPS) that provides information about the quality of ADL motor and ADL process skills. We studied ADL profile in patients with Alzheimer’s dementia (AD), Lewy body dementia (LBD) and Parkinson’s disease dementia (PDD).Methods: 48 patients participated in the study: 17 with AD and average age of 74 ± 4,3; 18 with PDD and average age of 72 ± 2,4; 13 with DLB and average age of 72 ± 3,9. They were assessed with AMPS. It has no ceiling or floor effect. AMPS is associated with criterion-referenced cutoff measures, indicat-ing the lower limit for competent ADL.Results: Average ADL motor and process scores were below the cutoff indi-cating that patients have problems with independent, safe and efficient ADL performance. The greatest impairment of performance of motor skills was found in PPD, followed by LBD and AD groups. Differences among groups were statistically significant (p = 0,05; p = 0,01). The greatest impairment of process skills was found in LBD, followed by PDD and AD groups. Differences among groups were not statistically significant.Conclusions: AMPS has shown the variability of ADL performance among the different dementia groups. This difference was more obvious in the perfor-mance of motor skills than in the performance of process skills.Reference1. Fisher AG. AMPS Mannuall, 7 ed. Three Star Press, 2009.No conflict of interest.

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NEUROPSYCHOLOGICAL PREDICTION OF DEMENTIA IN PARKINSON’S DISEASE: A REVIEW AND METAANALYSIS OF LONGITUDINAL STUDIESE. Lyros1,*, K. Fassbender1, S. Kalampokini11Neurology, Saarland University, Homburg, Germany

Objectives: Dementia occurs in a reasonably high proportion of PD patients as the disease progresses. We aimed to identify which cognitive domain per-formance is more sensitive to predict later occurrence of dementia.Methods: We conducted a Pubmed literature search using the terms “Parkinson’s disease, dementia, cognitive decline, longitudinal, neuropsy-chological, risk factors, prediction”. We only included longitudinal prospec-tive studies assessing dementia as a primary outcome, as these are less subject to bias. Analyses were performed with Comprehensive Metaanalysis Version 2. Due to heterogeneity among studies a random-effects model was adopted.Results: 11 eligible studies were included with a total of 774 non-demented PD patients at baseline. A total of 256 became demented or showed significant cognitive decline over time (range of follow-up 1–10 years). Preliminary analy-ses showed among various neuropsychological parameters significant results for performance on semantic and phonemic fluency, as well as delayed verbal memory. Marginal effects were also revealed for the total immediate recall and visuospatial/constructive functions.Conclusions: Tests of verbal fluency and delayed verbal memory appear to be significant predictors of future occurrence of dementia in Parkinson’s dis-ease. They may be favored for routine neuropsychological screening of PD individuals or for selecting vulnerable patients to be included in clinical trials of preventing therapies.No conflict of interest.

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PREDICTING DEMENTIA IN PARKINSON’S DISEASE BY COMBINING NEUROPHYSIOLOGICAL AND COGNITIVE MARKERSK. Olde Dubbelink1,*, A. Hillebrand2, J.W.R. Twisk3, J.B. Deijen4, D. Stoffers1, B.A. Schmand5, C.J. Stam2, H.W. Berendse1

1Neurology, VU University Medical Center, Amsterdam, Netherlands, 2Clinical Neurophysiology, VU University Medical Center, Amsterdam, Netherlands, 3Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, Netherlands, 4Clinical Neuropsychology, VU University, Amsterdam, Netherlands, 5Psychology, University of Amsterdam, Amsterdam, Netherlands

Objectives: To assess the ability of neurophysiological markers in conjunction with cognitive assessment to improve prediction of progression to dementia in Parkinson’s disease (PD).



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Methods: Baseline cognitive assessments and magnetoencephalo-graphic recordings from 63 prospectively included non-demented PD patients were analyzed in relation to PD-related dementia (PDD) conver-sion over a 7-year period. We computed Cox proportional hazard models to assess the risk of converting to dementia conveyed by cognitive and neurophysiological markers in individual as well as combined risk factor analyses.Results: Nineteen patients (30.2%) developed dementia. Baseline cog-nitive performance and neurophysiological markers each individually predicted conversion to PDD. Of the cognitive test battery, performance on a posterior (pattern recognition memory score < median; Hazard Ratio (HR) 6.80; p =.001) and a fronto-executive (spatial span score < median; HR 4.41; p =.006) task most strongly predicted dementia conversion. Of the neurophysiological markers, beta power < median was the strongest PDD predictor (HR 5.21; p =.004), followed by peak frequency < median (HR 3.97; p =.016) and theta power > median (HR 2.82; p =.037). In com-bination, baseline cognitive performance and neurophysiological meas-ures had even stronger predictive value, the combination of impaired fronto-executive task performance and low beta power being associated with the highest dementia risk (both risk factors versus none: HR 27.3; p <.001).Conclusions: Combining neurophysiological markers with cognitive as-sessment can substantially improve dementia risk profiling in PD, providing potential benefits for clinical care as well as for the future development of therapeutic strategies.No conflict of interest.

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ADDENBROOKE’S COGNITIVE EXAMINATION-REVISED (ACE-R) AND MONTREAL COGNITIVE ASSESSMENT (MOCA): DIAGNOSIS OF PARKINSON’S DISEASE DEMENTIA IN BRAZILM.S. Rocha1, N.E. Marinho1,*, R.G. Kuark1, E.S. Tres1, M.O. Oliveira1, S.M. Brucki11Neurology, Hospital Santa Marcelina, Sao Paulo, Brazil

Objectives: To evaluate two screening cognitive scales, Addenbrooke’s Cognitive Examination-revised (ACE-R) and Montreal Cognitive Assessment (MoCA), for cognitive assessment of Parkinson’s disease patients.Methods: A neuropsychologist, blinded to ACE-R and MoCA results, adminis-trated full neuropsychological battery for PD dementia (PDD) diagnosis. Two independent neurologists administered MoCA and ACE-R scales. PD patients had also motor evaluation using Unified Parkinson’s Disease Rating Scale (UPDRS), Hoehn and Yahr stage (HY), and Schwab and England (SE) daily activities scale.Results: 65 PD patients with a mean age of 64.1 years, mean disease duration of 8.1 years and mean schooling time of 5.9 years were studied. Mean total UPDRS score was 68.5 and mean HY stage was 2.4. Twenty-four patients (36.9%) fulfilled criteria for PDD. Mini-Mental examination score varied from 11 to 29 (mean: 24,3). Mean ACE-R scale scores were: 55.4 for PDD patients, 76.1 for PD without dementia (PDN), and 80.7 for controls. Mean scores on MoCA scale were: 14.9 for PDD patients, 21.6 for PDN patients and 23.5 for controls. Area under ROC was 0.91 [95%CI: 0.82–0.98 – p < 0.001] for ACE-R and 0.87 (95%CI: 0.78–0.97 – p < 0.001) for MoCA. Best cutoff value for ACE-R was 70 points (Sensitivity = 75,6%; Specificity = 95,8%) and 20 points for MoCA (sensitivity = 78.1%; specific-ity = 87.5%). There was no significant difference between areas under ROC from both scales (p = 0.481).Conclusions: ACE-R and MoCA appear to be valid tools for dementia evalu-ation in PD. ACE-R scale displayed better specificity than MoCA scale, for similar sensitivity.Reference1. Mioshi, E, et al. Int J Geriatr Psychiatry 21:1078–1085, 2006.No conflict of interest.

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THE ASSESSMENT OF APRAXIA IN DEMENTED PATIENTS WITH ALZHEIMER’S DISEASE AND PARKINSONS DISEASE.E. Tamme1, M. Ennok1, U. Linnamagi1, P. Taba1,*1Department of Neurology and Neurosurgery, Tartu University Clinics, Tartu, Estonia

Objectives: Motor actions can be disturbed due to deficits in translating the motor movement patterns to actual motion acts (ideomotor apraxia, IMA) or due to impairment in semantic knowledge system, when patients fail to evoke object-related or sequential activities (ideational apraxia, IDA). Aim of this study is to assess the nature and severity of apraxia in patients with

Alzheimer’s disease (AD) and dementia in Parkinson’s disease (PDD) in com-parison with healthy elderly controls.Methods: The sample was 15 patients with AD (mean age 75.0 years; mean education 10.2 years) and 15 patients with PDD (mean age 80.9 years; mean education 10.0 years). Their results were compared with group of healthy controls (N = 30, mean age 76.3; mean education 11.5 years). IMA was assessed with a test of imitating meaningless hand positions with right, left and both hands. IDA was assessed with two tests: 1) subjects were asked to copy a sequences of hand movements (combin-ing 3 different positions: palm, side, fist); 2) subjects were asked to pan-tomime intransitive gestures (i.e. salute) or transitive gestures (i.e. using a key).Results: Both patient groups received significantly poorer results in all apraxia tests (Kruskal-Wallis ANOVA, p <.01). Results of AD and PDD patients were similar in all tests but when comparing both groups with controls separately AD patients faired better in imitating gestures.Conclusions: Apraxia can be observed in various dementia conditions in using tests of IMA and IDA. Motor skills and proficiency is more influenced by the severity of dementia. It should be taken into consideration in assessing dementia patients.No conflict of interest.

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PARKINSON’S DISEASE DEMENTIA AND LEWY BODY DEMENTIA, ARE THEY DIFFERENT? (A LITERATURE REVIEW OF COGNITIVE AND NEUROIMAGING STUDIES)A. Hashish1,*, C. Selai2, A. Cavanna3

1Neurology, Ministry of Health, Mansoura, Egypt, 2University College London, Institute of Neurology, London, Egypt, 3Birmingham University, Department of Neuroscience, Birmingham, United Kingdom

Objectives: we reviewed and critiqued the available literatures to under-stand the relationship boundaries between PDD and DLB related to cogni-tive profile and imaging, and determine which features best differentiate DLB and PDDMethods: A systematic literature search was performed in (PubMed, MetaLib, Central, Cochrane library, MetaLib and TRIP database) according to prede-fined criteria following the Centre for Reviews and Dissemination (CRD) guide-lines, 2008. Unpublished and on-going studies and feedbacks from known experts in the field were done through personal communications. Conference lectures and talks were also considered. Manual library search of dementia textbooks was performed.Results: Initial search yielded total of 292 articles, of which 215 were in PubMed, 36 in PMC, one in Cochrane review database 17 in MetaLib (EMBASE and BIOSIS) and 23 in TRIP database. Then duplicate articles were excluded. The remaining 94 articles were screened manually screened by their abstracts and irrelevant articles were excluded, this left 22 articles eligible for this review.Conclusions: In cognitive domains, DLB patients show poorer performance than PDD especially in memory domain. Structural imaging found more pro-nounced cortical atrophy in DLB than PDD. DLB and PDD can be differentiated by different amyloid load in C-PiB PET scan. Majority of DLB patients had significantly raised amyloid load with C-PiB PET scan whereas PDD patients did not.No conflict of interest.

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CEREBROSPINAL FLUID BIOMARKERS IN CLINICAL DIAGNOSIS OF LEWY BODY SPECTRUM DISORDERS. Nakashita1,*, K. Tanaka1, Y. Tajiri1, M. Yamakawa1, K. Wada-Isoe1, K. Nakashima1

1Brain and Neurosciences, Faculty of Medicine Tottori University, Yonago, Japan

Objectives: Dementia of Lewy bodies (DLB) is the second most common form of neurodegenerative dementia following Alzheimer’s disease (AD). DLB patients also have parkinsonian motor sign. There are some difficul-ties to distinguish DLB from Parkinson’s disease (PD) and PD with dementia (PDD). In this study, we explored the features of Lewy body spectrum dis-orders (LBSD) in cerebrospinal fluid (CSF) measurements of AD-like CSF patterns.Methods: CSF samples from 112 subjects with PD, 26 subjects with PDD, 26 subjects with DLB, 47 subjects with AD, and of 34 subjects with control (CTL) were used to measure the CSF level of Amyloid-β1–42 (Aβ1–42) and phosphoryl-ated tau (p-tau) by ELISA kit.Results: The mean CSF Aβ1–42 level of the CTL subjects was significantly higher than those of DLB and AD, and that of the PD patients was significantly



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higher than those of PDD, DLB, and AD (P < 0.05). The mean CSF p-tau level of the AD patients was significantly higher than those of other patients (P < 0.001).Conclusions: In our study, potential biomarkers for the diagnosis of AD and LBSD have been shown in the measurement of CSF levels Aβ1–42 and p-tau.No conflict of interest.

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PLASMA CERAMIDES ARE ELEVATED IN PERSONS WITH AUTOPSY-CONFIRMED LEWY BODY OR ALZHEIMER’S DISEASE PATHOLOGY AND CORRELATE WITH LEWY BODY DEMENTIA SEVERITYM.M. Mielke1,*, R. Savica2, T. Ferman3, M. Murray4, K. Kantarci5, N.R. Graff-Radford6, G. Smith7, J. Parisi8, D. Dickson4, R. Petersen9, B. Boeve9

1Department of Health Sciences Research, Mayo Clinic, Rochester MN, USA, 2Department of Neurology, University of Utah, Salt Lake City UT, USA, 3Department of Psychology, Mayo Clinic, Jacksonville FL, USA, 4Department of Neuroscience, Mayo Clinic, Jacksonville FL, USA, 5Department of Radiology, Mayo Clinic, Rochester MN, USA, 6Department of Neurology, Mayo Clinic, Jacksonville FL, USA, 7Department of Psychology, Mayo Clinic, Rochester MN, USA, 8Departments of Pathology and Laboratory Medicine, Mayo Clinic, Rochester MN, USA, 9Department of Neurology, Mayo Clinic, Rochester MN, USA

Objectives: To examine whether plasma ceramides and fatty acids are associated with autopsy-confirmed Lewy Body and Alzheimer pathology and dementia severity.Methods: Using the Mayo Clinic Alzheimer Disease Research Center Brain Bank, we identified 4 autopsy groups with available plasma at the last study visit: cognitively normal with normal aging pathology (Control; n = 21), dementia with neocortical Lewy bodies (High likelihood LBD; n = 12); de-mentia with Alzheimer’s pathology (no Lewy bodies and Braak stage 6; n = 18), and dementia with both neocortical Lewy bodies and Alzheimer pathology (n = 14). Groups were matched on sex and age at blood draw and death. Lipids were measured using ESI/MS/MS. Non-parametric tests were used to assess group comparisons. Spearman rank correlation exam-ined the relationship between the plasma lipids and the Global Deterioration Scale (GDS) within each group.Results: There were significant group differences for ceramides C16:0 (p = 0.016), C18:1 (p = 0.014), C20:0 (p = 0.011), and C24:1 (p = 0.026). Specifically, while these lipids did not differ between the High Likelihood LBD and Alzheimer pathology groups, both had higher levels than Controls. Among those with High Likelihood LBD only, ceramides C18:1 (r = 0.536, p = 0.048), C18:0 (r = 0.552, p = 0.041), C20:0 (r = 0.536, p = 0.048) and sphingosine-1-phosphate (r = −0.577, p = 0.031) correlated with the GDS. None of the plasma fatty acids varied by group or where associated with disease severity.Conclusions: These results suggest that plasma ceramides are elevated in individuals with either Lewy body or Alzheimer pathology and are promising bi-omarkers. Ongoing research is examining whether plasma glucosylceramides levels will differentiate these pathologic groups.No conflict of interest.

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TWO AUTOPSY CASES OF MINIMUM NIGRAL DEGENERATION IN PSYCHIATRIC HOSPITAL: IMPLICATION OF EARLY STAGES OF DEMENTIA WITH LEWY BODIESH. Fujishiro1,*, C. Habuchi1, S. Iritani1, H. Sekiguchi1, Y. Torii1, K. Umeda1, M. Miyata2, M. Yoshida3, N. Ozaki1, K. Fujita2

1Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan, 2Department of Psychiatry, Okehazama Hospital Fujita Mental Care Center, Toyoake, Japan, 3Department of Pathology, Institute for Medical Science of Ageing Aichi Medical University, Nagakute, Japan

Objectives: The discrepancies between clinical and pathological diagnoses are due to the fact that the full disease progression of dementia with Lewy bod-ies (DLB) remains unclear, especially during the early stage. We attempted to identify the clinicopathological correlations.Methods: We reported on two psychiatric patients who had autopsy-proven limbic-type DLB.Results: The first case was a 78-year-old Japanese man. At the age of 77, he became hypochondriacal and paranoid following the death of his wife. Because he became violent and threatened others, he was admitted to a psychiatric hospital. Sixteen days after admission, he died of acute pneumonia. The second case was a 75-year-old Japanese man. At the age of 71, he developed delirium when he was treated with a steroid for ANCA-associated vasculitis during admission in the internal medicine ward. Because his abnormal behavior continued, he was transferred to a psy-chiatric hospital at the age of 72. At the age of 75, he died of renal failure.

Neither of the patients exhibited visual hallucinations. Neuropathological investigation revealed limbic-type DLB with concurrent minimum Alzheimer pathology, which corresponds to high-likelihood DLB pathology. Both patients had minimum nigral degeneration, which is consistent with the absence of parkinsonism.Conclusions: These autopsy cases may indicate a pattern in the early devel-opment of DLB pathology. DLB exhibits various symptomatic phenotypes in clinical settings, especially in the early stage of the disease.References1. Fujishiro H, et al. J Neuropathol Exp Neurol 67:649–56, 2008.2. Fujishiro H, et al. Neurosci Lett 486:19–23, 2010.3. Frigerio R, et al. Neurobiol Aging 32: 857–863, 2011.No conflict of interest.

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CEREBRAL MICROBLEEDS IN DEMENTIA WITH LEWY BODIEST. Makotrova1,*, O. Levin1, A. Arablinskiy2

1Neurology, Russian Medical Academia of Postgraduate Education, Moscow, Russia, 2Neurology, Clinical Hospital of S.P.Botrkin, Moscow, Russia

Objectives: To identify the location and number of cerebral microbleeds (CMB) in dementia with Lewy bodies (DLB) and to estimate the influence CMB on cognitive decline.Methods: We examined 33 patients with DLB ((mean age 73.5 years, 20 (67%) male) and 51 patients with Alzheimer’s disease (AD) with cognitive de-cline. MRI was performed by 1.5 Tesla MR tomography. CMB were estimated in T2*GRE. Patients with DLB (16 (49%)) had hyperintensity in 2 reflecting vascular leukoencephalopathy which were estimated by Fazekas scale. Neuropsychological testing was carried out by MoCA, ACE-R, Clock Drawing Test, verbal fluency test, visual memory test (SCT).Results: CMB in DLB were found in 13 (39%) patients. The total number of CMB were 70,40 (57%) - subcortical. Patients with cortical CMB had less memory score (3 ± 2) by ACE then patients with deep CMB. Deep CMB were found in 10 cases with of severe vascular leukoencephalopathy. Most cortical CMB were observed in AD - 340 (96%). Patients with AD and CMB had signifi-cantly lower score of ACE-R (less than 3.7) then in DLB (p < 0.01). Significant differences in MoCA had been not detected.Conclusions: We have no found cortical CMB in patients with DLB by MRI 1.5 Tesla. The absence cortical CMB in patients with DLB might be the ad-ditional criteria of diagnosis DLB. This observing allows proposing that pres-ence cortical CMB in patients with clinically diagnosed DLB to point out to the coexistence DLB with AD.Reference1. Werring D. Cerebral Microbleeds: Detection, Mechanisms, and Clinical

Challenges: Executive Summary Future Neurol. 2011; 6(5):1–25.No conflict of interest.

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CLINICO-PATHOLOGICAL PHENOTYPES OF MIXED AD/LBDL. Walker1,*, A.J. Thomas1, J. Attems1

1Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom

Objectives: Cases that neuropathologically fulfill criteria for both Alzheimer’s disease (AD) and Lewy body disease (LBD – Dementia with Lewy bodies (DLB) or Parkinson’s disease dementia (PDD)) are classified as mixed AD/LBD. Using semi-quantitative scoring, no differences were detected between cases that presented clinically with AD or LBD. We investigated whether a quantitative approach could reveal differences in the amounts of AD and LBD pathology in mixed AD/LBD cases.Methods: 18 mixed AD/LBD cases, which presented clinically as AD (n = 8), DLB (n = 8) or PDD (n = 2) were stained for antibodies against for tau, β amy-loid and α-synuclein and percentage burden of each pathology was quantified in neocortical, limbic and brainstem regions.Results: Differences in the degree of pathology between clinically AD and LBD in various regions were detected quantitatively, as a significant increase in the amount of tau pathology was observed in the hippocampus (p < 0.05), striatum (p < 0.01) and locus coeruleus (p < 0.01) in clinically AD compared to LBD patients, respectively. When compared against the PDD phenotype, clinically AD cases have greater burden of tau pathology in the majority of areas analyzed. Of note, we found an increase of α-synuclein in the cingulate of clinically PDD cases compared to clinically AD casesConclusions: Our findings suggest that cases neuropathologically diagnosed as mixed AD/LBD can be separated into different clinicopathological pheno-types when quantitative neuropathological methods are applied. However, the question whether the clinical diagnosis reflects the primary disease, which may be confounded by concomitant pathologies, warrants further investigation.No conflict of interest.



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PARKINSON’S DISEASE-ASSOCIATED PSYCHOSIS: A CROSS-SECTIONAL STUDY BASED ON THE NINDS-NIMH CRITERIA WORK GROUP.N.E. Marinho1,*, R.G. Kuark1, F.L. Godinho1, A.T. Neves1, M.S. Rocha1

1Neurology, Hospital Santa Marcelina, Sao Paulo, Brazil

Objectives: To assess consecutive and unselected outpatients with PD for the existence of psychotic symptoms, covering the whole spectrum of PD as-sociated psychosis (PDAP) symptoms, following the NINDS-NIMH criteria for PDAP.Methods: All PD patients included met the UK Brain Bank criteria for PD. Demographic and clinical variables were recorded. The patients answered a structured questionnaire composed of ten qualitative items on hallucinations, delusions and minor phenomena (sense of presence and illusions).Results: The characteristics of the 65 patients are summarized in Table 1. Twenty-four patients (36.9%) had either hallucinations or delusions, thus ful-filling the usual definition of PDAP, while 36 patients (55.4%) fulfilled the NINDS-NIMH criteria for PDAP. Twenty-one patients (32.3%) had at least one type of hallucination, 29 patients (44.6%) described sense of presence, and 25 patients (38.5%) illusions. Psychotic symptoms correlated with the presence of dementia (rs = 0.29, P < 0.02), with Pfeffer instrumental scale (rs = 0.44, P < 0.05), and SCOPA-PC (rs = 0.59, P < 0.0001). Hallucinations correlated with disease duration (rs = 0,29, P < 0.05) and levodopa ther-apy duration (rs = 0,27, P < 0.05). The NINDS-NIMH criteria for PDAP did not correlated with age at onset, levodopa equivalents and rate of disease progression.

Table 1

Age (years) 63.9 (10.7)

Gender (M/F) 37/28

Age at onset (years) 55.1 (9.8)

Duration of PD (years) 8.7 (4.7)

Schooling duration (years) 5.0 (3.65)

Hoehn and Yahr stage (in “off” state) 3.0 (0.8)

UPDRS total score 74 (30.2)

Schwab and England scale score 70 (19.2)

Progession disease rale (UPDRS 1–3/PD duration) 10.3 (5.4)

PDQ-39 scale 59.9 (20.5)

ACE-R dementia scale 69.5 (14.1)

MoCA dementia stale 20 (5.6)

MMSE 25 (3.3)

Pfefter functional activity questionnaire 2.0 (4.8)

Neuropsychiatric inventory 12 (11.9)

SCOFA-sleep 12 (7.8)

SCOFA-psychosis 3 (3.4)

Daily levodopa-equivalent dose (mg) 465 (119)

Duration of levodopa therapy (years) 7.3 (4.6)

Conclusions: The frequency of PDAP should be revisited using the new NINDS-NIMH criteria. Minor phenomena and non-visual hallucinations are an important part of the PDAP spectrum, which has commonly been restricted to visual hallucinations and delusions.Reference1. Ravina B, et al. Movement Disorders 22(8):1061–1068, 2007.No conflict of interest.

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AN INVESTIGATION ON THE RELATIONSHIP BETWEEN HALLUCINATION AND OTHER NON-MOTOR SYMPTOMS IN PATIENTS WITH PARKINSON’S DISEASEZ. Chen1, W. Zhang1,*, S. Yu1, C. Cao1, L. Zuo1, F. Wang1, Y. Hu1


Objectives: To investigate the relationship between hallucination and other non-motor symptoms in patients with Parkinson’s disease (PD).

Methods: 105 PD patients with disease duration within 10 years were di-vided into hallucination group (12 cases) and non-hallucination group ac-cording to the second item of Neuropsychiatric Inventory. A comparison study was conducted by using series of PD related non-motor symptoms scales.Results: (1) Hoehn–Yahr staging was significantly higher in hallucination group than that in non-hallucination group, but there was no difference in gen-der, age, disease duration and levodopa equivalent doses between the two groups (P > 0.05);(2) The incidences of depression, anxiety, fatigue, sleep disorders and RBD were all significantly higher in hallucination group than that in non- hallucination group (P < 0.05); the scores of Montreal Cognitive Assessment, Hamilton Depression Scale, Hamilton Anxiety Scale, Fatigue Scale, Pittsburgh Sleep Quality Index and the number of autonomic dysfunctions assessed by The Scale for Outcomes in PD for Autonomic Symptoms were all significantly dif-ferent between the two groups (P < 0.05) (Table 1);

Table 1. Comparison of the scores of PD related non-motor symptoms scales between PD-hallucination group and PD-non-hallucination group.

PD-hallucination group

PD-non-hallucination group

P value

Montreal cognitive assessment

20.5 (11.5, 26.0) 24.0 (19.0, 26.0) 0.033*

Hamilton depression scale

23.0 (15.5, 29.0) 10.0 (5.0, 16.5) 0.000**

Hamilton anxiety scale 17.5 (12.0, 25.5) 7.0 (3.5, 15.0) 0.001**

Fatigue scale 10.0 (9.0, 13.0) 8.0 (6.0, 11.0) 0.032*

Pittsburgh sleep quality index

10.0 (7.5, 15.0) 6.0 (4.0, 9.0) 0.003**

Number of autonomic dysfunctions

14.0 (9.0, 17.0) 8.0 (5.0, 11.0) 0.009**

*: P < 0.05, **: P < 0.01.

(3) Hoehn–Yahr Staging and the score of Hamilton Depression Scale were the risk factors of PD with hallucinations with the OR value of 2.996 and 1.096, respectively.Conclusions: The incidence of hallucination in PD with disease duration within 10 years is 11.4%, and hallucination is closely correlated with Hoehn–Yahr Staging and other non-motor symptoms, including cognitive impairment, mood disorders, fatigue, sleep disorders and autonomic dysfunction.No conflict of interest.

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NEUROPATHOLOGY OF PARKINSONISM IN PURE ALZHEIMER’S DISEASEP.R. Burkhard1, C. Bouras2, F.R. Herrmann3, E. Kövari21Neurology, University Hospitals of Geneva, Geneva, Switzerland, 2Mental Health and Psychiatry, University Hospitals of Geneva, Geneva, Switzerland, 3Internal Medicine and Geriatrics, University Hospitals of Geneva, Geneva, SwitzerlandObjectives: About one third of Alzheimer’s disease (AD) patients develop some parkinsonian features yet half of them do not have Lewy-body pathology at autopsy. The aim of this study was to clarify the neuropathological substrate of parkinsonism in AD.Methods: We compared the nigrostriatal pathway at the presynaptic and postsynaptic sides, in 2 groups of AD patients: one with overt clinical par-kinsonism, the other without parkinsonism. We measured neuronal and neurofibrillary tangles (NFTs) densities in the substantia nigra pars com-pacta (SN) and in the putamen of 22 AD patients, 11 with and 11 without parkinsonism.Results: Our study showed that parkinsonism associated with AD was related to a significant loss of neurons both in the SN and in the putamen, suggesting pre-and postsynaptic alterations of the nigrostriatal pathway. Neuronal tau deposition was a less important factor as density of NFTs correlated with parkinsonism only in the SN but not in the putamen.Conclusions: We propose that a subgroup of pure AD patients develop parkinsonian symptoms as a result of neuronal loss in the basal ganglia, indicating a prominent subcortical involvement, which appears unrelated to the Braak stage of AD.



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References1. Attems J, Quass M, Jellinger KA (2007). Tau and α-synuclein brain-

stem pathology in Alzheimer disease:relation with extrapyramidal signs. ActaNeuropathol 113, 53–62.

2. Burns JM, Galvin JE, Roe CM, MorrisJC, McKeel DW (2005). The pathol-ogy of the substantia nigra in Alzheimer diseasewith extrapyramidal signs. Neurology 64, 1397–1403.


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DOPAMINE DYSREGULATION SYNDROME, IMPULSIVITY AND IMPULSE CONTROL DISORDERS IN IDIOPATHIC PARKINSON DISEASE- CROSS SECTIONAL ANALYSIS FROM TURKEYM. Ozerden1,*, N. Karagoz Sakalli1, A. Soysal11Department of 3rd Neurology, Bakirkoy Research and Training Hospital for Psychiatry Neurology and Neurosurgery, Istanbul, Turkey

Objectives: Impulse control disorders (ICDs) are mainly triggered by do-paminergic therapy in Parkinson’s disease (PD) (1). We aimed to identify the frequency and phenomenology of ICDs and dopamine dysregulation syndrome (DDS) in our PD population, and we also aimed to assess factors associated with ICD in PD.Methods: 40 PD patients and age-matched 41 volunteering healthy people without dementia were examined for ICD and impulsivity. The presence of DDS was also evaluated in PD patients. The Barratt Impulsiveness Scale (BIS-11A), the Minnesota Impulsive Disorders Interview (MIDI), and DDS diagnostic criteria proposed by Giovannoni et al. were applied.Results: ICD was more frequent in PD patient group (p = 0.012). ICD were more common in patients treated with a dopamine agonist (DA) than in patients not taking DA (p = 0.02). Hypersexuality were more common in younger age PD patients. On the other hand duration of the disease, sex and LEDD (L-dopa equivalent daily dosages) were not related to the existence of ICD. DDS was more common in the patients with higher LEDD (p < 0.0001). There was no significant difference between two groups in the terms of impulsivity.Conclusions: The results was correlated with the literature suggesting ICD are mainly triggered by dopaminergic therapy in PD patients despite the socio-cultural structure of turkey. A detailed behavioral assessment after starting dopaminergic therapy is recommended to protect the patient and care givers from these side effects.Reference1. Dopamine and impulse control disorders in Parkinson’s disease American

neurological association movement disorders 2010 august 15, 25–11; 1660–1669.

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IMPULSE CONTROL DISORDERS IN PARKINSON’S DISEASE: A CASE-CONTROL STUDYA. Sivan1,*, P. Pal2, Y.C.J. Reddy3, R. Yadav4

1Neurology, EMS Memorial Hospital And Research Center, Perithalmanna, India, 2Neurology, NIMHANS, Bangalore, India, 3Psychiatry, Nimhans, Bangalore, India, 4Neurology, Nimhans, Bangalore, India

Objectives: To ascertain the point prevalence of 8 Impulse control disorders (ICDs) in PD patients and determine their associations with clinical char-acteristics. ICDs, a set of behaviors presumed to be related to aberrant or excessive dopaminergic stimulation, are being increasingly recognized in Parkinson’s disease (PD).Methods: One hundred and fifty consecutive patients with idiopathic PD were recruited from the Neurology Department of the National Institute of Mental Health and Neurosciences, Bangalore, a tertiary care centre in India. The following questionnaires/scales were applied: (1) Questionnaire for ICDs In Parkinson’s Disease (QUIP), (2) Scales for Outcome in PD-Psychiatric com-plications (SCOPA-PC), (3) Questionnaire for OCD -MINI PLUS 5- Jan 2002, and (4) Short Form-12 (SF 12).Results: An ICD was identified in 19.3% of patients, which included: overmed-ication (14.0%), hypersexuality (12.7%), gambling (2.7%), punding (2.7%), compulsive buying (2%), walkabouts (1.3%) and binge-eating disorder (0.5%). Two ICDs were present in 10.7% and three in 2.7%. ICDs were more common in patients treated with higher doses of levodopa. The prevalence of ICDs was similar for pramipexole and ropinirole. Additional variables independently as-sociated with ICDs were higher doses of levodopa and younger age at onset of motor symptoms (≤45 years)Conclusions: A high prevalence of ICD was found in patients with PD and included seven clinically significant ICDs. A combination of ICDs was common than a single ICD, indicating common risk factors and pathophysiology. ICDs were associated with significant co morbidities such as depressionNo conflict of interest.

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IMPULSE CONTROL DISORDES (TCI) IN PATIENTS WITH EARLY-ONSET PARKINSON’S DISEASE. A CASE-CONTROL MULTICENTER STUDYL. Vela Desojo1,*, J.C. Martínez Castrillo2, P. García Ruiz3, I. Ibot4, I. Posada5, C. Ruiz Huete6, C. Borrue7, F. Vivancos Castellano4, R. Marinescu8, M. Mata9, Y. Macias Macias1, M. Kurtis10, J. del Val3, L. Lopez11, E. Lopez Valdes12, A. Rojo13

1Neurology, Hospital U Fundación Alcorcón, Madrid, Spain, 2Neurology, Hospital U Ramón y Cajal, Madrid, Spain, 3Neurology, Fundación Jiménez Diaz, Madrid, Spain, 4Neurology, Hospital U La Paz, Madrid, Spain, 5Neurology, Hospital U 12 de Octubre, Madrid, Spain, 6Neurology, Hospital Nuestra Sra del Rosario, Madrid, Spain, 7Neurology, Hospital Infanta Sofía, Madrid, Spain, 8Neurology, Hospital U de Getafe, Madrid, Spain, 9Neurology, Hospital U Puerta de Hierro, Madrid, Spain, 10Neurology, Hospital Ruber Internacional, Madrid, Spain, 11Neurology, Hospital U de la Princesa, Madrid, Spain, 12Neurology, Hospital Clinico San Carlos, Madrid, Spain, 13Neurology, Hospital U Principe de Asturias, Madrid, Spain

Objectives: To determine the frequency of impulse control disorders (ICD) in a cohort of early-onset Parkinson’s disease (EOPD) patients and in controls. To analyze the association of ICD with dopamine drugs intake and dopamine agonists (DA) dosis.Methods: This is a cross-sectional, case-control multicentric study carried out in some Hospitals of the Community of Madrid, Spain. Patients were recruited from the outpatient movement disorders clinics. ICD was assessed by the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP). Severity of the disease through the unified Parkinson’s disease rating scale (UPDRS) part III and the Hoehn and Yahr stage, Beck inventory depres-sion score, quality of live and other demographic and clinical variables were included in the statistical analysis.Results: 88 EOPD patients (54 man) and 88 controls were included. Patients were 47 (9) years old and had 5 (2–11) years of evolution of Parkinson. 48 patients (56.5%) and 26 controls (31%) had ICD (p = 0.02). Mean number of ICD in patients was 1.29 (1.62) and 0.51 (0.8) in controls (p = 0.001). ICD was more frequent in patients under dopamine agonists (p = 0.014). Higher dose of AD LEDD was associated with more ICD (p = 0.033).Conclusions: ICD is more prevalent in EOPD patients than in controls in Madrid. ICD was associated with the intake of DA. Higher total dose of DA LEDD were associated with more ICDReference1. Weintraub D, Hoops S, Shea J, Lyons K, Pahwa R, Driver-Dunkley, et al.

Validation of the questionnaire for Impulsive-Compulsive Disorders in Parkinson’s disease. Mov Disord 2009 Jul 30; 24(10):1461–7.


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INCREASED FREQUENCY OF COMPULSIVE GAMBLING AMONG PARKINSON’S DISEASE PATIENTS WITH EXCESSIVE DAYTIME SLEEPINESSM. Chondrogiorgi1,*, S. Konitsiotis1

1Department of Neurology, Medical School University of Ioannina, Ioannina, Greece

Objectives: The relationship between impulsivity and sleep disorders in Parkinson’s disease (PD) remains unclear. Our purpose was to investigate the possible link between excessive daytime sleepiness (EDS) and pathologi-cal gambling in PD along with the contribution of dopaminergic treatment on these disorders.Methods: Clinical and pharmacological data were acquired from 17 PD pa-tients with EDS and 17 non-EDS PD patients. The level of daytime somno-lence was rated with the Epworth Sleepiness Scale (ESS). The subjects were also asked for pathological gambling defined as inability to resist impulses to gamble, resulting to severe personal or social consequences. Levodopa equivalent doses (LEDs) were calculated according to equivalencies pro-posed by Tomlinson CL, et al [1]. The chi-square test and Student’s t-test were used to test for differences between the groups with categorical and con-tinuous variables respectively. Statistical analysis was performed with SPSS software (version 20.0).Results: The total dopaminergic load was significantly higher in the EDS-group (p < 0.05). The dose of levodopa and dopamine agonists as separate variables differed insignificantly between the groups as well as the duration of PD. Significantly more PD patients with EDS compared to those without EDS referred pathological gambling (p = 0.03).Conclusions: A relationship between EDS and pathological gambling in PD could be suggested. The increased dopaminergic load probably represents the inner link between these disorders.Reference1. Tomlinson CL, et al. Systematic Review of Levodopa Dose Equivalency

Reporting in Parkinson’s Disease. Mov Disord 2010; 25(15):2649–85.No conflict of interest.



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INCREASED FREQUENCY OF IMPULSE CONTROL SYMPTOMS IN PATIENTS WITH PARKINSON’S DISEASE AND REM SLEEP BEHAVIOR DISORDERM. Fantini1,*, L. Macedo2, M. Zibetti3, T. Vidal2, B. Pereira4, A.R. Marques1, P. Derost1, B. Debilly1, M. Ulla1, N. Vitello1, A. Cicolin3, L. Lopiano3, F. Durif1

1Neurology, CHU Clermont-Ferrand, Clermont-Ferrand, France, 2CMRR, CHU Clermont-Ferrand, Clermont-Ferrand, France, 3Dept. of Neurosciences, A.O. Città della Salute e della Scienza di Torino, Turin, Italy, 4Délégation Recherche Clinique and Innovation, CHU Clermont-Ferrand, Clermont-Ferrand, France

Objectives: To assess the frequency of impulse control disorders (ICDs) symptoms in patients with Parkinson’s disease (PD) with and without REM sleep behavior disorder (RBD).Methods: Two hundred and twenty patients with idiopathic PD (132 M, mean age:66.6 ± 11.0 years; mean Hoehn and Yahr score:1.9 ± 0.7, mean Levodopa Equivalent Daily Dose (LEDD):731.8 ± 448.6 mg) filled out the RBD-Single question, the RBD Screening Questionnaire (RBDSQ) and the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease’s (QUIP)- Short Form.1

Results: Probable RBD (pRBD) was found in 99/220 (45%) patients. One or more ICDs or related behaviors were found in 60/99(60.6%) of patients PD-pRBD and in 46/121 (38.0%) PD-noRBD (p = 0.001). PD-pRBD showed a higher QUIP score (1.5 ± 1.7 vs. 0.8 ± 1.3; p = 0.009) and a higher number of ICD symptoms (1.5 ± 1.7 vs. 0.9 ± 1.3; p = 0.001) compared to PD-noRBD. A positive correlation between RBDSQ and QUIP scores was observed in the whole group (R = 0.269; p < 0.001). The frequencies of ICD symptoms in PD-pRBD compared to PD-noRBD were as follows: compulsive gambling (9.1% vs. 3.3%; p = 0.07), hypersexuality (11.1% vs. 6.6%; p = 0.23), compulsive shopping (14.4% vs. 4.1%, p = 0.008) compulsive eating (18.2% vs. 14.0%, p = 0.39), hobbyism (24.2% vs. 13.2, p = 0.03), punding (19.2% vs. 10.7%, p = 0.09), walkabout (6.1% vs. 7.4%, p = 0.67), dopamine dysregulation syndrome (18.2% vs. 5.0%, p = 0.002). A logistic regression model account-ing for Institution, sex, age, PD duration, PD severity and LEDD, indicated that PD-pRBD have a two-fold risk to develop any ICDs (RR:2.1; p = 0.003) and a three-fold risk to develop compulsive shopping (RR:3.15; p = 0.03 and Dopamine Dysregulation syndrome (RR:3.15; p = 0.017) compared to PD without pRBD.Conclusions: RBD is associated to an increased risk to develop ICD symp-toms in PD, even after adjusting for age, severity, duration of PD and do-paminergic treatment. Further studies are needed to clarify the mechanism underlying this association.Reference1. WeIntraub, et al. Mov Dis 2009.No conflict of interest.

165

IMPULSE CONTROL BEHAVIOURS IN PATIENTS WITH PARKINSON’S DISEASE IN THE MALAYSIAN POPULATIONS. Azmin1,*, E.L. Tan1, H. Zakaria2, N.J. Nik Ruziyanei2, A. Mohd Nawi3, N.F. Pakarulrazy4, N.A. Abdul Murad4, K.H. Ling5, M.I. Norlinah6

1Department of Medicine, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia, 2Department of Psychiatry, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia, 3Department of Public Health, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia, 4UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia, 5Clinical Genetics Unit Department of Obstetrics and Gynecology, Universiti Putra Malaysia, Serdang, Malaysia, 6Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia

Objectives: Impulse control behaviors are repetitive and excessive activities that may be subsyndromal and not fulfill the criteria for impulse control disor-der. These activities may negatively impact on the daily lives of sufferers. We conducted a study to investigate the prevalence of impulse control behaviours and its associated features in Parkinson’s disease in the Asian population.Methods: This was a prospective cross-sectional study conducted on con-secutive patients attending neurology clinic. Inclusion criteria include idi-opathic Parkinson’s disease patients with Hoehn and Yahr stage I-IV and on stable dopaminergic medication for at least 3 months. Eighty patients were screened for impulse control behaviours using the Questionnaire for Impulsive-Compulsive Disorder for Parkinson’s disease (QUIP). Patients screened positive, with controls, were then referred for formal psychiatric assessment.Results: Prevalence of impulse control behaviours among our cohort was 11.3%; the features significantly associated with it were higher education

(p = 0.022), advanced stage of disease (p = 0.026) and higher levodopa dosage (p = 0.01). The commonest impulse control behavior in our cohort is shown in Figure 1. Following formal psychiatric assessment, QUIP was shown to have a negative predictive and positive predictive value for impulse control disorders of 100% and 50%, respectively.

pund

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1.25% 1.25%

Figure 1.

Conclusions: Our findings appear to suggest that there is an association between impulse control behavior and higher levodopa dosage. QUIP is an effective screening tool for impulse control disorders in Parkinson’s disease patients in Malaysia.Reference1. Weintraub D, et al. Impulse control disorders in Parkinson disease: a

cross-sectional study of 3090 patients. Arch Neurol 2010; 67(5):589–95.No conflict of interest.

166

IMPULSE CONTROL DISORDER IN PARKINSONIAN PATIENTS UNDER DOPAMINE AGONIST THERAPY. A MULTICENTER STUDYP. Garcia-Ruiz1,*, J.C. Martinez Castrillo2, A. Alonso Canovas2, A. Herranz Barcenas3, L. Vela Desojo4, P. Sanchez Alonso5, M. Mata6, N. Olmedilla Gonzalez7, I. Mahillo Fernandez8

1Neurology, Fundacion Jimenez Diaz, Torrelodones Madrid, Spain, 2Neurology, Hospital Ramon y Cajal, Madrid, Spain, 3Neurology, Fundacion Jimenez Diaz, Madrid, Spain, 4Neurology, Fundacion Hospital Alcorcon, Madrid, Spain, 5Neurology, Hospital Puerta de Hierro, Madrid, Spain, 6Neurology, Hospital Infanta Sofia, Madrid, Spain, 7Neurology, Hospital Gomez Ulla, Madrid, Spain, 8Epidemiology, Fundacion Jimenez Diaz, Madrid, Spain

Objectives: Impulse control disorders (ICD) encompass a wide spectrum of abnormal behavior frequently found in Parkinson’s disease (PD) treated with dopamine agonists (DA). The main aim of this study was to analyze differ-ences in ICD prevalence with individual DAMethods: We carried out a multicenter, transversal study to evaluate the pres-ence of ICD in PD patients chronically treated (at least >6 months) with a single non-ergoline DA (pramipexole, ropinirole and rotigotine). Clinical evalu-ation of ICD was performed with the questionnaire for impulsive-compulsive disorders in Parkinson’s disease (QUIP)Results: 39% of patients (91/233) fulfilled clinical criteria for ICD. The group of patients with ICD symptoms (ICD+) differed from those without ICD symptoms (ICD-) in younger age and type of DA intake: oral DA treatment (pramipexole and ropinirole) is associated with higher risk of IDC compared with transder-mal DA (rotigotine): 84/197(42%) patients treated with oral DA developed ICD versus 6/37 (16%) patients treated with transdermal DA (Fisher < 0.01). Multivariant analysis confirmed that oral DA remained significantly associ-ated with ICD (p 0.0052) with an odds ratio of 3.59 (95% confidence interval 1.46–8.81).Conclusions: ICD was significantly more associated with the non-ergoline oral DA use than with transdermal DA. Since pramipexole, ropinirole and ro-tigotine are non-ergoline DA with very similar pharmacodynamic profile prob-ably other factors may explain the different risk of IDC including the route of administration (transdermal versus oral route).Reference1. Weintraub D, Koester J, Potenza MN, et al. Impulse control disorders in

Parkinson disease: a cross-sectional study of 3090 patients. Arch Neurol. 2010; 67:589–95.



47

Section 2 Imaging

167

CORONAL PLANE SPINAL MALALIGNMENT AND PARKINSON’S DISEASE: PREVALENCE AND ASSOCIATIONS WITH DISEASE SEVERITYJ. Baik1,*, Y. Ha2

1Neurology, Sanggye Paik Hospital Inje University, Seoul, Korea, 2Neurosurgery, Severance Hospital Yonsei University, Seoul, Korea

Objectives: Patients with Parkinson’s disease (PD) often present with pos-tural and structural spinal deformities. To investigate coronal plane deformities in patients with PD and evaluate the correlation between clinical features and coronal parameters.Methods: This study was a prospective assessment of consecutive patients with PD presenting to an academic neurology clinic over 12-months. Clinical and demographic parameters were collected, including Hoehn and Yahr (H&Y) stage and Unified Parkinson’s Disease Rating Scale (UPDRS) score. Full-length standing antero-posterior and lateral spine radiographs were used to assess global coronal alignment, Cobb angle, and C7 sagittal vertical axis (C7SVA). The threshold for scoliosis was 10°, and curve type was classified using Schwab’s classification.Results: 89 patients with PD were included (mean age = 68.1 years). Scoliosis was identified in 27 (30%) patients and was more common in women (p = 0.04). Back pain was more common in patients with scoliosis than in those without scoliosis (p = 0.036). Schwab Type IV (thoracolumbar major) was the most common type of scoliosis in PD. With adjustment for age and gender, multiple linear regression analysis revealed that PD severity (UPDRS, p = 0.037) and magnitude of coronal malalignment (p = 0.003) were associated with scoliosis Cobb angle (p = 0.037). Direction of scoliosis and side of coronal malalignment were not correlated with laterality of predominant PD symptoms (p > 0.05).Conclusions: Greater severity of PD was significantly associated with great-er magnitude of scoliosis, even after adjusting for patient age and gender. However, direction of scoliosis and side of coronal malalignment were not sig-nificantly associated with dominant laterality of PD symptoms.No conflict of interest

168

ADULT-ONSET LEUKOENCEPHALOPATHY WITH AXONAL SPHEROIDS AND PIGMENTED GLIA ACCOMPANIED BY BRAIN CALCIFICATIONS. Fujioka1,*, D. Broderick2, C. Sundal1, M. Baker3, R. Rademakers3, Z. Wszolek1

1Neurology, Mayo Clinic, Jacksonville, FL, USA, 2Radiology, Mayo Clinic, Jacksonville, FL, USA, 3Neuroscience, Mayo Clinic, Jacksonville, FL, USA

Objectives: Adult-onset leukoencephalopathy with axonal spheroids and pig-mented glia (ALSP) is a rare inherited neurodegenerative disorder caused by CSF1R mutations. Brain magnetic resonance imaging (MRI) is a useful diagnos-tic tool; brain computed tomography (CT) has provided less useful information[1]. The objective of this study is to review the brain CT studies in ALSP cases.Methods: We reviewed the available clinical charts and images from our col-lection of ALSP cases with brain CT.Results: We identified a familial case with brain calcification demonstrated by CT. The patient developed her symptoms at age 47 years that included

behavioral changes, pyramidal signs, and seizures. Brain CT revealed mild diffuse cortical atrophy and sparse punctuate hyperdense areas in subcortical white matter of the frontal and parietal lobes indicative of calcifications. She died at age 58 years. She was a carrier of G589E mutation.Conclusions: The distribution of brain calcification in our case was differ-ent from that present in disorders usually associated with brain calcifications. Brain calcifications may be a useful biomarker for clinical diagnosis. To confirm our result further radiological studies of ALSP cases are warranted.ZKW and RR are supported by the NIH/NINDS P50NS072187. CS is supported by Anna Lisa och Bror Björnsson foundation for neurological research 2013/2014.Reference1. Sundal C, Van Gerpen JA, Nicholson AM, Wider C, Shuster EA, Aasly J,

et al. MRI characteristics and scoring in HDLS due to CSF1R gene muta-tions. Neurology. 2012;79:566–74.

No conflict of interest

169

RELATIONSHIP BETWEEN ECHOGENICITY IN SUBSTANTIA NIGRA BY TRANSCRANIAL SONOGRAPHY AND CLINICAL FEATURES IN PARKINSON’S DISEASE PATIENTSC. Cao1, S. Yu1, L. Zuo1, C. Li2, Y. Hu1, F. Wang1, Z. Chen1, Y. Du1, W. Zhang1,*1Neurology, Beijing Tiantan Hospital Capital Medical University, Beijing, China, 2Ultrasound, Beijing Tiantan Hospital Capital Medical University, Beijing, China

Objectives: To detect the echogenicity in substantia nigra (SN) and investi-gate its relationship with clinical features in Parkinson’s disease ( PD ) patients.Methods: 122 PD patients and 45 controls were detected SN echogenicity by transcranial sonography. PD patients with echogenicity of grade I-II and grade III-IV were included in PDSN− and PDSN+ groups. The relationships between SN echogenicity and clinical features were analyzed.Results: (1) The incidence of SN hyperechogenicity in PD group was sig-nificantly higher than that in control group (P < 0.05); (2) DSN + incidence in male was dramatically higher than that in female, and the age and onset age of PDSN+ group were notably older than that of PDSN− group (P < 0.05); (3)H-Y staging, tremor score of UPDRS III in PDSN+ group were markedly higher than that in PDSN− group (P < 0.05); (4) Compared to PDSN− group, the incidence of PD with mild cognitive impairment was remarkably increased and MoCA score was significantly reduced in PDSN+ group (P < 0.05); (5) SCOPA-AUT score in PDSN+ group was prominently enhanced compared with PDSN− group (P < 0.05).Conclusions: PD patients have high incidence of SN hyperechogenic-ity. Factors relating higher incidence of SN hyperechogenicity in PD patients include male, older age and onset age; PDSN+ patients show significantly high-er H-Y stage, severer tremor and impaired cognitive and autonomic functions.No conflict of interest

170

RELATIONSHIP BETWEEN ECHOGENICITY IN SUBSTANTIA NIGRA BY TRANSCRANIAL SONOGRAPHY AND NEUROINFLAMMATION IN PARKINSON’S DISEASE PATIENTSC.J. Cao1, L.J. Zuo1, S.Y. Yu1, C. Li2, Z.J. Chen1, Y. Hu1, F. Wang1, T.H. Lian1, W. Zhang1,*1Neurology, Beijing Tiantan Hospital, Beijing, China, 2Ultrasound Department, Beijing Tiantan Hospital, Beijing, China

169 Table. The levels of neuro inflammatory factors in serum and CSF in PDSN+ group, PDSN− group and control group.

Serum Control group PDSN− group PDSN+ group P1 P2 P3

NO (mmol/l) 80.342 ± 48.328 68.963 ± 42.951 87.248 ± 46.640 0.468 0.349 0.127

H202 (mmol/l) 17.230 ± 8.480 25.371 ± 8.353 22.631 ± 8.468 0.002** 0.000** 0.206

PGE2 (pg/ml) 15.769 ± 14.371 8.408 ± 5.055 9.156 ± 6.156 0.049* 0.132 0.957

TNF-α (pg/ml) 63.009 ± 21.677 63.183 ± 22170 60.059 ± 21.877 0.508 0.976 0.576

IL-1β (pg/ml) 39.965 ± 24.631 35.349 ± 20.252 26.935 ± 15.672 0.008** 0.642 0.067

CSF Control group PDSN− group PDSN+ group P1 P2 P3

NO (mmol/l) 78.125 ± 41.633 126.875 ± 32.195 132.205 ± 32174 0.000** 0.001** 0.719

H1O2 (mmol/l) 7.817 ± 6.880 7.664 ± 4.609 9.437 ± 7.057 0.421 0.950 0.499

PGE2 (pg/ml) 30.223 ± 12.598 13.716 ± 9.326 12.358 ± 9.188 0.000** 0.000** 0.757

TNF-α (pg/ml) 49.676 ± 23.698 68.449 ± 22.820 54.715 ± 15.328 0.435 0.020* 0.107

IL-1β (pg/ml) 34.420 ± 12.458 78.812 ± 29.548 69.442 ± 12.542 0.000** 0.000** 0.893

P1: PDSN+ group vs. control group; P2: PDSN− group vs. control group; P3: PDSN+ group vs. PDSN− group; *: P < 0.05, **: P < 0.01.

3.Day 1 Monday, Section 2 Imaging.indd 473.Day 1 Monday, Section 2 Imaging.indd 47 10/28/13 5:42 PM10/28/13 5:42 PM


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171 Table. Levels of iron and its metabolism-related protein in serum and CSF of PD patients.

Serum Control group PDSN− group PDSN+ group P1 P2 P3

Fer(ng/ml) 32.125 ± 13.875 47.518 ± 21.456 44.514 ± 16.497 0.000** 0.001** 0.480

Tf(nmol/l) 0.054 ± 0.019 0.083 ± 0.014 0.080 ± 0.015 0.000** 0.000** 0.482

TfR(ng/ml) 192.973 ± 80.552 283.135 ± 114.959 298.754 ± 94.763 0.000** 0.004** 0.683

Ltf(μg/ml) 279.350 ± 146.724 166.142 ± 53.746 190.760 ± 111.734 0.000** 0.000** 0.764

CSF Control group PDSN− group PDSN+ group P1 P2 P3

Iron(nmol) 0.682 ± 0.230 0.625 ± 0.230 1.046 ± 0.230 0.011* 0.524 0.014*H-Fer(ng/ml) 2.335*0.0230 1.916*0.230 1.640*0.230 0.026 0.263 0.490

Tf(nmol/l) 0.06910.230 0.07710.230 0.06610.230 0.398 0.144 0.047*TfR(ng/ml) 184.921.230up3 267.383.230up3 248.808.230up3 0.013* 0.009** 0.569

Ltf(μg/ml) 168.953.230up3 91.0363.230up 130.210.230up3 0.087 0.001** 0.045*CP(ng/ml) 0.355**.230 0.428**.230 0.453**.230 0.021* 0.152 0.645

P1: PDSN+ group vs. control group; P2: PDSN− group vs. control group; P3 PDSN+ group vs. PDSN− group;*: P < 0.05, **: P < 0.01.

Objectives: To detect echogenicity in substantia nigra (SN) by transcranial sonography (TCS) and investigate its relationship with neuroinflammation in Parkinson’s disease (PD) patients.Methods: (1) 122 PD patients and 45 controls were detected SN echogenic-ity by TCS. PD patients with echogenicity of grade I-II and grade III-IV were included in PDSN− and PDSN+ groups, respectively; (2) Blood and cerebral spinal fluid (CSF) were collected and detect the levels of hydrogen peroxide (H2O2), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and prostaglandin E2 (PGE2).Results: (1) The levels of PGE2 and IL-1β in serum of PDSN+ group were sig-nificantly lower than control group;(2) The Levels of H2O2 in serum in PDSN+ and PDSN− groups were dramatically higher than control group; (3) The lev-els of NO and TNF-α in serum in PDSN+, PDSN− and control groups were not different;(4)In PDSN+ and PDSN− groups, the levels of NO and IL-1β in CSF were remarkably higher and PGE2 was markedly lower than control group; (5) TNF-α level in PDSN− group was notably higher than control group; (6) The levels of H2O2 in CSF in PDSN+, PDSN− and control groups showed no differences.Conclusions: SN hyperechogenicity is related to the declined levels of IL-1β and PGE2 in serum, demonstrating that neuroinflammation might be a poten-tial mechanism of SN hyperechogenicity.No conflict of interest

171

RELATIONSHIP BETWEEN IRON METABOLISM AND ECHOGENICITY OF SUBSTANTIA NIGRA BY TRANSCRANIAL SONOGRAPHY IN PARKINSON’S DISEASE PATIENTSC. Cao1, L. Zuo1, S. Yu1, C. Li2, Y. Hu1, F. Wang1, Z. Chen1, Y. Du1, W. Zhang1,*1Neurology, Beijing Tiantan Hospital Capital Medical University, Beijing, China, 2Ultrasound, Beijing Tiantan Hospital Capital Medical University, Beijing, China

Objectives: To investigate the relationship between iron metabolism and echogenicity of substantia nigra (SN) in patients with Parkinson’s disease (PD).Methods: 122 PD patients and 45 healthy controls were detected the SN echo-genicity by transcranial sonography. PD patients with echogenicity of grade I-II and grade III-IV were included in PDSN− and PDSN+ groups. Blood and cer-ebral spinal fluid (CSF) were collected and the levels of iron and its metabolism-relating proteins including ferritin (Fer), ferritin heavy chain (H-Fer), transferrin (Tf), transferrin receptor (TfR), lactoferrin (Ltf) and ceruloplasmin (Cp) were detected.Results: (1) The incidence of SN hyperechogenicity in PD group was signifi-cantly higher than control group; (2) Abnormal iron metabolism was found in PDSN− and PDSN+ group by the increased levels of Fer, Tf and TfR and the decreased Ltf level in serum and elevated TfR level in CSF; (3) In CSF, iron level in PDSN+ group was significantly higher than both control and PDSN− group; Ltf level was increased while Tf level was decreased in PDSN+ group compared with PDSN− group; Ltf level was decreased in PDSN− group com-pared with control group; Cp level was elevated while H-Fer level declined in PDSN+ group compared with control group.Conclusions: The abnormal iron metabolism in CSF might be related to SN hyperechogenicity in PD.No conflict of interest

172

IRON DEPOSITION IN PARKINSON’S DISEASE EVALUATED USING SUSCEPTIBILITY WEIGHTED IMAGING.H. Tachibana1,*, H. Nishimura2, T. Tokunaga2, H. Daikokuya3

1Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan, 2Department of Neurology, Nishinomiya Kyoritsu Neurosurgical Hospital, Nishinomiya, Japan, 3Department of Radiology, Nishinomiya Kyoritsu Neurosurgical Hospital, Nishinomiya, Japan

Objectives: To investigate iron deposition on patients with Parkinson’s dis-ease (PD) using susceptibility weighted imaging (SWI) in MRI and the relation-ship between the signal intensity of SWI and clinical variables.Methods: Forty patients with PD (mean age, 72.5 years) and 11 normal sub-jects (mean age, 69.4 years) underwent brain scans using SWI with 3T MRI. The mean duration of illness and mean Yahr stage in the PD patients were 6.5 years and 2.9, respectively. The SWIs images were obtained parallel to the orbitomeatal line. The bilateral substantia nigra (SN), red nucleus (RN), puta-men, lateral ventricle and straight sinus were identified. The signal intensity of all ROIs was quantitatively analyzed. In addition, the clinical correlates of the SWI values in the patients with PD were also investigated.Results: Significant differences were found in the signal intensity of the SN (P = 0.01) between the patients with PD and the normal subjects. There were no significant differences in the SWI values of the RN, putamen, lateral ventri-cle or straight sinus between the two groups. The SWI values in the SN were not associated with any of the variables, including age, Yahr stage, duration of illness, L-dopa equivalent dose and parts II & III of the UPDRS.Conclusions: Increased iron deposition in the SN may serve as a surrogate of PD; however, the SWI values in the SN may not function as in vivo biomark-ers for objectively evaluating the status of PD.No conflict of interest

173

BRAIN IRON DEPOSITION IN PARKINSON’S DISEASE BY HIGH RESOLUTION SUSCEPTIBILITY MR PHASE IMAGINGD.T.H. Li1,*, N. Yao2, S. Chua2, S.L. Ho3, P.L. Khong1, H.K.F. Mak1

1Department of Diagnostic Radiology, The University of Hong Kong, Hong Kong, Hong Kong China, 2Department of Psychiatry, The University of Hong Kong, Hong Kong, Hong Kong China, 3Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong China

Objectives: To evaluate the iron content of different brain regions of Parkinson’s Disease’s (PD) patients with susceptibility MR phase imaging.Methods: 20 PD patients (mean age = 63.5 ± 8.8 years) and 20 healthy control (mean age = 62.1 ± 5.6 years) were recruited. MR phase images were acquired with 3D-FFE gradient-echo sequence: TR/TE = 28/23ms, flip angle = 15°, NEX = 1, FOV = 230 × 201 × 180 mm3, resolution = 1 × 1 × 1 mm3; then were processed with both high-pass filtering only and phase unwrap with high-pass filter. ROI analysis was performed on the processed images and 6 brain regions were identified (Figure 1). Mean phase shift of each region was measured and compared between the 2 groups.Results: The mean phase shifts measured were shown in Figure 2. Results of the 2 processing techniques agreed well with each other. In comparing the phase shifts between brain regions, it was observed that SN and RN had



49

more negative values, indicating higher iron concentration in the midbrain. PD patients showed significantly lower phase values in SN (P < 0.01) and RN (P < 0.05) than control group. No significant differences were observed in other regions.Conclusions: This study revealed possible increment of paramagnetic iron in midbrain of PD patient. The increase of iron concentration induced oxidative

stress in the midbrain, which triggered neuronal loss in SN and leads to the onset of PD in the aging population.References1. A. Walsh et al. Neuroimage. 20112. Y. Wang et al. AJNR. 2012No conflict of interest

Phase Unwrap with High Pass Filter High Pass Filter Only

Bilateral ROI:

1. Substantia Nigra (SN)

2. Red Nucleus (RN)

3. Caudate Nucleus (CN)

4. Putamen (PUT)

5. Globus Pallidus (GP)

6. Thalamus (Th)

T1 MPRAGE

Figure 1. Processed phase images with the locations of the ROIs

0SN RN

High Pass Filter Only

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Figure 2. Comparison of mean phase shift at different brain region between PD and healthy groups



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174

PROGRESSIVE CHANGES IN NIGRAL IRON ASSOCIATED WITH THE EVOLUTION OF PARKINSON’S DISEASEM. Wieler1,*, M. Gee2, W. Martin1

1Movement Disorders Program, University of Alberta, Edmonton, Canada, 2Biomedical Engineering, University of Alberta, Edmonton, Canada

Objectives: Parkinson’s disease (PD) is a progressive disorder associated with evolving nigral pathology. Previous neuroimaging and pathological stud-ies have suggested the presence of increased nigral iron but longitudinal studies of iron content have not been reported. Our objective was to determine the changes in midbrain iron content associated with declining motor function in patients with progressing PDMethods: 19 PD patients (mean age 59.8 ± 7.3 years) and 13 controls (mean age 56.0 ± 6.9 years) were studied at 18 month intervals over a period of 3 years. Assessments of motor function were based on UPDRS motor scores obtained in the off medication state. Regional midbrain iron content was estimated from T2*-weighted magnetic resonance imaging (MRI) as described previously.1Results: Groups did not differ significantly with respect to age. UPDRS motor scores increased from 14.3 ± 5.1 at baseline to 26.1 ± 9.0 at 36 months. Increases in motor score correlated positively with increases in the lateral substantia nigra pars compacta (SNc; p < 0.01, corrected for multiple com-parisons). There was no significant correlation with MRI changes in the medial SNc, the substantia nigra pars reticulata, or the red nucleus.Conclusions: These results support the notion that increased nigral iron con-tent in PD is associated with the progression of motor dysfunction and may serve as a marker for disease severity.Reference1. Neurology 2008;70:1411–7No conflict of interest

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COMPARISON OF MAGNETIC RESONANCE IMAGING TECHNIQUES FOR RELIABLE DELINEATION OF BASAL GANGLIAS. Lorio1,*, A. Lutti1, F. Kherif1, A. Ruef1, F. Vingerhoets2, G. Helms3, N. Weiskopf4, B. Draganski11LREN – DNC, Centre Hospitalier Universitaire Vaudois (CHUV-UNIL), Lausanne, Switzerland, 2DNC, Centre Hospitalier Universitaire Vaudois (CHUV-UNIL), Lausanne, Switzerland, 3MR-Research in Neurology and Psychiatry, University Medical Centre Göttingen, Göttingen, Germany, 4Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, London, United Kingdom

Objectives: Movement disorders are associated with abnormal structure and function of the basal ganglia where most of the evidence comes from magnetic resonance imaging studies. The reliable delineation of basal ganglia using automated computational anatomy methods based on T1-weighted protocols remains challenging, which results in controversies in the literature. Recent study demonstrated marked improvement in automated detection of basal ganglia structures when using magnetization transfer (MT) saturation rather than T1-weighted images (1). Main goal of our study is to answer the question about the causes for this disparity and look for potential interactions with the effects of ageing on brain tissue properties.Methods: To this end we acquire longitudinal relaxation rate – T1, effective transverse relaxation rate – R2* and MT bias free maps from healthy subjects (n = 96, aged 20–78 years) according to a well-established multiparameter mapping protocol.Results: In the framework of voxel-based morphometry and quantification we demonstrate higher grey matter volume estimates in basal ganglia, cerebellar dentate and prefrontal cortex when tissue classification is based on MT maps com-pared with T1 maps. The grey matter differences are explained by the presence of iron, assessed with the transverse relaxation R2* and further modulated by the interaction between iron content and age, both in cortical and subcortical areas.Conclusions: We interpret our findings as direct evidence for the impact of age related brain tissue property changes on automated tissue classification of brain structures. Computational anatomy studies on aging and neurodegen-eration should acknowledge these effects, particularly when inferring basal ganglia volume changes.Reference1. Helms et al., 2009No conflict of interest

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PHARMACOLOGICAL AND IMAGING EVALUATION OF PARKINSON’S DISEASE PATIENTS WITH EXCESSIVE DAYTIME SLEEPINESSM. Chondrogiorgi1,*, L.C. Tzarouchi2, A. Zikou2, P. Kosta2, L. Astrakas3, M.I. Argyropoulou2, S. Konitsiotis1

1Department of Neurology, Medical School University of Ioannina, Ioannina, Greece, 2Department of Radiology, Medical School University of Ioannina, Ioannina, Greece, 3Department of Medical Physics, Medical School University of Ioannina, Ioannina, Greece

Objectives: To evaluate the contribution of dopaminergic treatment to exces-sive daytime sleepiness (EDS) in Parkinson’s disease (PD) and to detect pos-sible structural changes related to this disorder.Methods: Pharmacological and MRI data were acquired from 17 non-dement-ed PD-patients with EDS and 17 PD non-EDS subjects. The level of daytime somnolence was rated with the Epworth Sleepiness Scale (ESS). Differences in grey matter (GM) volume between groups were evaluated with voxel-based morphometry (VBM). Diffusion tensor imaging (DTI) was also performed for identification of abnormalities in fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD).Results: The total dopaminergic load (levodopa equivalent dose), but not the doses of levodopa and dopamine agonists separately, was significantly higher in the PD-EDS group (p < 0.05). ESS score was significantly positively corre-lated with the dose of with the total dopaminergic load (p = 0.02). VBM showed increased GM volume bilaterally in hippocampus, parahippocampal and fusi-form gyri (p < 0.05). Increased axial diffusivity values were also shown in PD-EDS group, in the left corticospinal tract and anterior thalamic radiation and in the temporal part of superior longitudinal fasciculus bilaterally (p < 0.05).Conclusions: The dopaminergic load in total, rather than the dose of levodo-pa or dopamine agonists separately increases the risk for EDS. Drug-induced plastic changes supplementary to the already established proliferative effect of sleep on neurogenesis could result in increases in regional GM volume and axonal packing density in certain neuronal tracts.No conflict of interest

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FREEZING OF GAIT IN NON-DEMENTED PARKINSON DISEASE (PD) PATIENTS IS ASSOCIATED WITH POSTERIOR PARIETAL LOBE VOLUME REDUCTIONA. Rubino1,*, F. Assogna2, M.E. Di Battista1, R. Scatozza1, M. Valente1, F. Fattapposta1, G. Meco1

1Neurologia e Psichiatria, Policlinico Umberto I, Roma, Italy, 2Neurologia, IRCCS Fondazione Santa Lucia, Roma, Italy

Objectives: Freezing of gait (FOG) is part of the intricate clinical picture in PD. Several patterns of cortico-subcortical networks are likely to be involved in the development of FOG. The aim of the present study was to explore the differences in cortical gray matter (GM) volume in patients with PD with and without FOG by using voxel-based morphometry (VBM), ruling out the poten-tial confounding contribute of discognitive pattern.Methods: We investigated 26 PD patients (7 women and 19 men). Thirteen patients classified as exhibiting FOG (FOG+) were matched for age, disease severity, disease duration and educational attainment with 13 nonfreezers (FOG-) patients. Detailed neuropsychopathological evaluations did not show any cognitive dysfunction in the included patients. All 26 participants under-went a GM cortical volumetry study using VBM derived from T1 weighted 3T MRI.Results: As expected from the matching procedure the patient groups did not significantly differ for age, disease severity and duration, as well as cognitive assessment. PD-FOG+ patients showed a pattern of GM relative atrophy in left posterior parietal gyrus (using the statistical threshold p < 0.001- uncorrected) compared with PD-FOG-.Conclusions: The findings of this study suggest that a specific pattern of cortical volume reduction involving posterior parietal cortices contributes to the occurrence of FOG in PD. Taking into account that parietal lobe is integrated in sensorial evaluation, these data would support the hypothesis of a “perceptual malfunction” in FOG pathogenesis.No conflict of interest

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THE MEDIAL TEMPORAL ATROPHY INDEX (MTAI) CORRELATES WITH MEMORY IN PARKINSON’S DISEASE WITHOUT DEMENTIAM. Menendez-Gonzalez1,*, M. Martínez-Rivera2, T. Álvarez-Avellón3, A. López-Muñiz4, J. Vega4

1Neurology, Hospital Álvarez-Buylla, Mieres, Spain, 2Geriatrics, Hospital Álvarez-Buylla, Mieres, Spain, 3Psychology, Universidad de Oviedo, Mieres, Spain, 4Morphology and Celular Biology, Universidad de Oviedo, Mieres, Spain

Objectives: Subtle changes in multiple cognitive domains in PD without dementia correlate with regional volumes in specific systems implicated in the development of cognitive impairment measured on MRI. The MTAi is a simple method for assessing the rate of MTA in relation to the global atrophy. In this study we aimed to correlate the functioning of different cognitive domains with the MTAi.Methods: We took a group of 10 patients with PD without dementia and a group of 10 matched controls. We assessed the executive functioning (Stroop Test; Letter Fluency), verbal memory (California Verbal Learning Test), visual memory (Benton Visual Retention Test), visuospatial cognition (Judgement of Line Orientation), and visuoconstruction (Pentagon Copy).



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We also performed an MRI to every subject and computed the MTAi on both hemispheres.Results: The composed (bilateral) MTAi correlated significantly with scores on the verbal and visual memory tests, while the MTAi did not correlate with the executive, visuospatial and visuoconstruction tests. The strongest correla-tions were found for the left-MTAi with scores on the CVLT and for the right-MTAi with scores with scores on the BVRT.Conclusions: The MTAi is a specific parameter for correlating memory with atrophy in patients with PD without dementia. The findings suggest that the MTAi is a valuable method for differentiating the specific systems implicated in the development of cognitive impairment in PD.Reference1. Menéndez-González M, López-Muñiz A, Vega J, Drucker-Colín R, Arias-

Carrión O. MTA index: a simple new method for assessing atrophy of the medial temporal lobe using clinically available neuroimaging. Frontiers in Aging Neuroscience 2013, in press.


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WHITE MATTER FRACTIONAL ANISOTROPY CHANGES IN PARKINSON DISEASE – A VOXELWISE ANALYSISM. Onu1, A. Enea2,*, G. Niculescu2

1Medical Imaging, Clinical Hospital “Prof. Dr. Th. Burghele”, Bucharest, Romania, 2Biotechnology and Medical Engineering, Politehnica University, Bucharest, Romania

Objectives: Previous studies have utilized brain imaging to probe altera-tions in the structural and functional organization of patients with PD. We used voxelwise statistical analysis in order to localize white-matter changes related to disease. The aim of the present study was to investigate the grad-ual white matter structures changes comparing fractional anisotropy (FA) maps from normal volunteers to early and, respectively, late stage of PD patients maps.Methods: Nine Controls, 7 early stage and 5 advanced PD patients were investigated with a 1.5 T MRI system and DTI acquisition. Diffusion data were analysed with FSL-TBSS tool.Results: Comparing Controls to early stage Patients, the largest and more significant FA reduction clusters (uncorrected p < 0.05) were located in forceps major tracts (left), forceps minor (genu of corpus calossum) and inferior fron-to-occipital fascicle, bilateral (red colour in Figure1). Comparing Controls to advanced patients, the largest and more significant FA reductions clusters (uncorrected p < 0.05) were located in splenium and body of corpus callos-sum, inferior fronto-occipital fascicle, bilateral (blue colour in Figure1; blue areas are transparent to show the partial overlap to red areas).

A R LRA R LR

Conclusions: Inferior fronto-occipital fascicle, bilateral, are areas with re-duced FA both in early and advanced Patients when compared to Controls. More interesting finding is the FA reduced area in genu of corpus callossum obtained for early diseased stages (no body or splenium) while in later stages the body and splenium of corpus callossum appear to be supplementary im-pacted by the disease progression.Reference1. Melzer TR, et al. White matter microstructure deteriorates across cognitive

stages in Parkinson disease. Neurology. 2013;80(20):1841–1849.No conflict of interest

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WHITE MATTER DISEASE AND HIPPOCAMPAL VOLUME IN THE PREDICTION OF MILD COGNITIVE IMPAIRMENT AND DEMENTIA IN PARKINSON’S DISEASEN. Kandiah1,*, N. Kaavya1, H. Zainal1, R. Chandler1, A. Ng1, A. Zhang1, W.L. Au1, L.C.S. Tan1

1Neurology, National Neuroscience Institute, Singapore, Singapore

Objectives: To study the role of cerebral white matter disease and hip-pocampal volume as risk factors for MCI and dementia in a cohort of mild PD subjects

Methods: Prospective longitudinal study of subjects with mild PD from 2010 to 2013. MRI volumetric quantification of white matter hyperinten-sity (WMH) and hippocampal volume (HV) was performed using SPM al-gorithms. Clinical and cognitive evaluations were performed at baseline and 6 month intervals. MCI and PD dementia was diagnosed based on the Movement Disorder Society Task Force Criteria. Linear regression model was used to study the influence of WMH and HV in predicting MCI and dementia.Results: 91 subjects with a mean age of 64.9 years, mean education of 10.5 years and mean H&Y score of 1.89 were studied. During the study pe-riod, 16 subjects developed MCI and 8 subjects with MCI developed dementia. After adjusting for confounders (age and MRI variables), HV was a significant factor in the development of MCI (HR 7.05, CI 1.5–34.1; p = 0.015) and de-mentia (HR 7.03, CI 2.39–25.2; p = 0.001). PV-WMH was a significant vari-able for the development of MCI and dementia on univariate analyses, but after correcting for HV, PV-WMH only demonstrated a trend towards signifi-cance for MCI (HR 1.25, CI 0.79–1.97; p = 0.095) and dementia (HR1.02, CI 0.81–1.27; p = 0.07).Conclusions: HV is the main factor predicting the development of MCI and dementia in PD. WMH is an additional factor influencing the development of MCI and dementia. Strategies to reduce the burden of WMH may be useful in reducing MCI and dementia in PD.No conflict of interest

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REGIONAL VOLUMETRIC CHANGE IN PARKINSON’S DISEASE WITH COGNITIVE DECLINER. Camicioli1,*, M. Gee2, J. Dukart3, B. Draganski4, W.R.W. Martin1

1Medicine, University of Alberta, Edmonton, Canada, 2Biomedical Engineering, University of Alberta, Edmonton, Canada, 3Neurosciences, Centre Hospilatier Universitaire Vaudois, Lausanne, Switzerland, 4Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

Objectives: Our objective was to determine longitudinal regional atrophy patterns in PD patients with progressive, significant cognitive decline and dementia (PDD).Methods: Thirty-three initially non-demented patients with prevalent PD were followed for 36 months. Ten showed significant cognitive decline, while 23 re-mained cognitively intact. T1-weighted scans were analyzed using optimized longitudinal Voxel-Based Morphometry in SPM8 to examine gray matter (GM) tissue densities.Results: Groups did not differ significantly with respect to age (overall mean (sd) 70.1 (3.25) years) or gender. More males developed cognitive decline (7 males, 3 females) compared to those remaining intact (12 males, 11 females). Clusters of lower GM tissue densities were found in PDD com-pared to PD in the cingulate gyri, insulae and left hippocampus. The cogni-tive status by scan interaction showed differential changes between groups in the right insula and bilateral hippocampi. Results were minimally affected by adjusting for age and gender.Conclusions: Region specific atrophy that is consistent with the pattern of cortical Lewy body changes seen in autopsy studies can be detected with MRI in PDD. MRI may be useful for tracking cognitive decline in PD.No conflict of interest

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COGNITIVE DEFICITS IN MILD PARKINSON’S DISEASE ARE ASSOCIATED WITH DISTINCT AREAS OF GRAY MATTER ATROPHYN. Kandiah1,*, E. Mak1, H. Zhou2, W.L. Au1, Y.Y. Sitoh3, L.C.S. Tan3

1Neurology, National Neuroscience Institute, Singapore, Singapore, 2Neurobehavioural Programme, Duke-NUS, Singapore, Singapore, 3Neuroradiology, National Neuroscience Institute, Singapore, Singapore

Objectives: To compare the gray matter atrophy patterns in PD patients with mild cognitive impairment (PD-MCI) with PD patients having no cognitive im-pairment (PD-NCI) using voxel-based morphometric analyses, and to exam-ine the relationship between atrophic regions and specific cognitive domains.Methods: 90 non-demented PD patients (64.95 ± 7.54 years old, Hoehn and Yahr = 1.88 ± 0.39) were classified using formal diagnostic criteria as PD-MCI (n = 23) or PD-NCI (n = 67). Gray matter volume differences were examined using voxel-based morphometry on structural MRI, and multivariate linear regressions were employed to assess the relationships between cognitive performance in specific domains and atrophic regions.Results: Patients with PD-MCI had lower global cognition scores compared with PD-NCI (MMSE: 26.9 vs.28.4, p = 0.011; MOCA: 24.5 vs.27.0, p < 0.001). PD-MCI group demonstrated significantly poorer performance on executive function, attention, memory, and language abilities. Patients with PD-MCI had reductions in gray matter volumes in the left insular, left superior frontal and left middle temporal areas compared to PD-NCI. Multiple regressions con-trolling for age, education and cardiovascular risk factors revealed significant



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positive correlations between left insular atrophy and executive-attention dysfunction.Conclusions: Domain specific cognitive impairment in mild PD is associ-ated with distinct areas of gray matter atrophy. These regions of atrophy are demonstrable early in the disease course and may serve as a biomarker for dementia in Parkinson’s disease.No conflict of interest

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GREY MATTER CHANGES IN COGNITIVELY IMPAIRED PARKINSON’S DISEASE PATIENTSI. Rektorova1,*, R. Biundo2, R. Marecek1, L. Weis2, D. Aarsland3, A. Antonini211st Department of Neurology, School of Medicine, Masaryk University St. Anne’s Hospital, Brain and Mind Research Program CEITEC MU, Brno, Czech Republic, 2Center for Parkinson’s Disease and Movement Disorder, Fondazione Ospedale San Camillo” – I.R.C.C.S., Venice-Lido, Italy, 3Department of Neurology and Clinical Neuroscience, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden

Objectives: Cortical changes associated with cognitive decline in Parkinson’s disease (PD) are not fully explored and require investigations with established diagnostic classification criteria. We used MRI source-based morphometry to evaluate specific differences in grey matter volume patterns across 4 groups of subjects: healthy controls (HC), PD with normal cognition (PD-NC), PD with mild cognitive impairment (MCI-PD) and PD with dementia (PDD).Methods: We examined 151 consecutive subjects: 25 HC, 75 PD-NC, 29 MCI-PD, and 22 PDD at an Italian and Czech movement disorder centre. Operational diagnostic criteria were applied to classify MCI-PD and PDD. All structural MRI images were processed together in the Czech centre. The spa-tial independent component analysis was used to assess group differences of local grey matter volume.Results: We identified two independent patterns of grey matter volume devia-tions: a) Reductions in the hippocampus and temporal lobes; b) Decreases in fronto-parietal regions and increases in the midbrain/cerebellum. Both pat-terns differentiated PDD from all other groups and correlated with visuospatial deficits and letter verbal fluency, respectively. Only the second pattern addi-tionally differentiated PD-NC from HC.Conclusions: Grey matter changes in PDD involve areas associated with Alzheimer-like pathology while fronto-parietal abnormalities are possibly an early marker of PD cognitive decline. These findings are consistent with a non-linear cognitive progression in PD.No conflict of interest

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GRAY MATTER MORPHOLOGICAL CHANGES IN PARKINSON DISEASE – A VBM ANALYSISA. Enea1,*, G. Niculescu1, A. Roceanu2, M. Onu3

1Faculty of Medical Engineering, University Politehnica of Bucharest, Bucharest, Romania, 2Neurology Department, University Hospital Bucharest, Bucharest, Romania, 3Medical Imaging Department, “Prof. Dr. Th. Burghele” Clinical Hospital, Bucharest, Romania

Objectives: The aim of the present study was to investigate the gray matter structures changes in PD patients using an unbiased technique – voxel-based morphometry (VBM) technique. We were also interested in the presence of any compensatory effect or self-reorganization of the gray matter, in the context of PD.

Methods: Ten PD patients and six controls were investigated with a 1.5 T MRI system, T1-3D (MPRAGE) sequence. Structural data was analysed with FSL-VBM.Results: Atrophy was found in several areas; the three most important clus-ters were located in: middle frontal gyrus, superior parietal gyrus, premotor cortex (uncorrected p < 0.001).With a lower degree of statistical significance (uncorrected p < 0.05), we found several areas with enlarged gray matter in patients compared to controls in-cluding subcallosal cortex, lingual gyrus, frontal operculum cortex, insular cor-tex and posterior right thalamus.Conclusions: Our results confirm previous studies results which found mixed impacts of the Parkinson disease on gray matter volume. Besides the cortical thinning, an interesting finding is the gray matter enlargement in several ar-eas like posterior thalamus. The increases in gray matter density might reveal compensatory effects or self-reorganization (enhanced sensorimotor interac-tion which is known to be present in PD).Reference1. Lin C-H, et al. VBM reveals brain volume differences between Parkinson’s

disease and essential tremor patients. Front Hum Neurosci. 2013;7:247;

2. Snijders AH, et al. Gait-related cerebral alterations in patients with Parkinson’s disease with freezing of gait. Brain J Neurol. 2011;134(Pt 1):59–72.


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SUBCORTICAL STRUCTURAL ABNORMALITIES IN ESSENTIAL TREMOR: MR VOLUMETRY AND VERTEX BASED ANALYSIS.S. Jitender1,*, K.S. Bhalsing2, R. Yadav2, P.K. Pal2, A.K. Gupta1, B.S. Bagepally3

1Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bangalore, India, 2Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India, 3Neurosciences, National Institute of Occupational Health, Ahmedabad, India

Objectives: To evaluate structural abnormalities of basal ganglia, thalamus and hippocampus in essential tremor [ET] using the techniques of volumetry and shape analysis.Methods: Twenty-two patients with ET (Mean age: 45. 4 ± 10.5 years, M:F 16:6) and 22 age, gender, education and handedness matched healthy controls (Mean age: 44.5 ± 11.17 years, M:F 15:7) were recruited for the study. ET was diagnosed using the National- Institute-of-Health collaborative Genetic Criteria. The severity of tremor was assessed using Fahn-Tolosa-Marin (FTM) tremor rating scale. All subjects underwent MRI using stand-ard protocol that included T1-3D TFE (Turbo Field Echo) images with 1 mm thickness. The volumes of deep subcortical GM structures were extracted and vertex-wise shape analysis was performed using FSL-FIRST software. Statistical comparison of the volumes of deep gray matter structures was carried out using ANCOVA after adjusting for age, sex and TBV. For shape analysis a priori decided significance level of p (FDR corrected) < 0.05 was considered statistically significant.Results: Tremor duration was 9.84 ± 6.63 years and total FTM score was 37.34 ± 17.67. ET patients showed significantly decreased volumes of left caudate, putamen and bilateral hippocampus as compared to the healthy con-trols. The shape analysis (FDR corrected, p < 0.05) revealed regional areas of significant shape difference in the left caudate nucleus, putamen, thalamus and bilateral hippocampus of ET patients.Conclusions: Significant volume loss was noted in the caudate nucleus, putamen and hippocampus. Hippocampal abnormalities support the possible link between other neurodegenerative diseases and ET.No conflict of interest

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THE CHOLINERGIC SYSTEM AND VISUAL HALLUCINATIONS IN PARKINSON’S DISEASE: A STRUCTURAL AND FUNCTIONAL MRI STUDYD. Hepp1,*, K.T.E. Olde Dubbelink2, F. Barkhof3, H.W. Berendse2, W.D.J. van de Berg4, M.M. Schoonheim5, E.M.J. Foncke2

1Anatomy and Neurosciences/Neurology, VU University Medical Center, Amsterdam, Netherlands, 2Neurology, VU University Medical Center, Amsterdam, Netherlands, 3Radiology, VU University Medical Center, Amsterdam, Netherlands, 4Anatomy and Neurosciences, VU University Medical Center, Amsterdam, Netherlands, 5Anatomy and Neurosciences/Radiology, VU University Medical Center, Amsterdam, Netherlands

Objectives: Visual hallucinations (VH) are common in Parkinson’s disease (PD) and lead to increased disability and nursing home placement. The neu-roanatomical basis of VH in PD is still unknown, although degeneration of cholinergic output structures is suggested to play an important role. The aim of this study is to evaluate structural and functional changes in the thalamus (the main projection site of cholinergic brainstem nuclei), the nucleus basalis of Meynert (NBM) and its main cortical projection areas in PD patients with and without VH.Methods: Clinical characteristics and MRI data of 16 PD patients with VH (PD + VH) and 39 PD patients without VH (PD-VH) were compared. Thalamus volume was examined using FIRST. Additional structural and functional image analysis is currently ongoing. Thalamus shape will be examined using FIRST and volumetric changes in the nucleus basalis of Meynert (NBM) will be evalu-ated using region-of-interest-based volumetric analysis. Brain activity and functional connectivity in these areas will be compared using resting-state functional MRI.Results: Age, gender distribution, disease duration and severity were compa-rable in PD + VH and PD-VH patients. PD + VH patients scored significantly worse on cognition and depression scales, compared to the PD-VH group. Preliminary volumetric analysis showed a trend for lower normalized left thala-mus volume in PD + VH (p < 0.10).Conclusions: Preliminary results of the present study suggest a possible dif-ference in left thalamus volume in PD + VH, compared to PD-VH. Further analysis of structural and functional properties of thalamus, NBM and its corti-cal projection sites might give more insight into the neuronal substrate of VH in PD patients.No conflict of interest



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CEREBELLAR VOLUMETRY IN ESSENTIAL TREMOR WITH OR WITHOUT THE PRESENCE OF CEREBELLAR SIGNSH. Shin1,*, J.W. Cho2, D.K. Lee3, J.M. Lee3

1Neurology, Eulji General Hospital Eulji University School of Medicine, Seoul, Korea, 2Neurology, Samsung Medical Center Sungkyunkwan University, Seoul, Korea, 3Biomedical Engineering, Hanyang University, Seoul, Korea

Objectives: The aim of this study is the comparison of whole and segmented cerebellar volumes in essential tremor (ET) patients groups with or without cer-ebellar dysfunctional signs, and normal controls using MRI volumetric analysis.Methods: We enrolled 39 patients with ET and age-and sex-matched 36 nor-mal healthy controls. All patients were assessed by clinical tremor rating scale of Fahn. To evaluate cerebellar signs, we scored the items of the ICARS, 20 patients had a cerebellar dysfunction. All processing and analyses steps of MRI-volumetry were done using functionality available within the CIVET pipe-line software. We compared statistically whole and segmented volume of the cerebellum between patients and control.Results: Whole volume of cerebellum was not different between ET group and control. The midline structures including vermian area showed smaller volume in ET patients than control according to segmentation of cere bellar volume. However, there was no difference in cerebellar whole and segmented volume between ET patients with and without cerebellar signs.Conclusions: Midline structures of cerebellum tended to be smaller in patients with ET than in normal controls. However, we could not find a differ-ence of cerebellar volume in ET according to the presence of clinical signs of cerebellar dysfunction.No conflict of interest

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DISRUPTION IN PEDUNCULOPONTINE NUCLEUS PATHWAY IN PARKINSON’S DISEASE PATIENTS WITH FREEZING OF GAITJ. Youn1,*, J.M. Kim2, H. Kwon2, J.S. Kim3, H.W. Yang1, J.W. Cho1

1Neurology, Samsung Medical Center, Seoul, Korea, 2Biomedical Engineering, Hanyang University, Seoul, Korea, 3Neurology, Soonchunhyang University College of Medicine, Seoul, Korea

Objectives: Freezing of gait (FOG) is a common and disabling symptom in Parkinson’s disease (PD). However, despite extensive research, the anatomic structures related with FOG have yet to be identified. To determine the ana-tomic pathophysiology of FOG, we analyzed diffusion tensor imaging (DTI) data between PD patients with and without FOG.Methods: We performed DTI on 19 PD patients with FOG (FOG (+) group) and 23 PD patients without FOG (FOG (−) group). There were no differenc-es in age, sex, disease duration, parkinsonism, mini-mental status exam score and white matter changes between groups. Mean diffusivity (MD) values and fraction anisotropy (FA) values of FOG (+) group were com-pared with those of the FOG (−) group using voxel-based analysis (VBA) and region of interest (ROI) analysis in pedunculopontine nucleus (PPN).Results: In VBA, MD values in FOG (+) group were reduced in cerebel-lum, thalamus, globus pallidus, putamen and caudate were increased compared with those in FOG (−) group. In ROI analysis, FOG (+) group showed lower FA value and higher MD value than FOG (−) group. Furthermore, sum FOG questionnaire score was moderately correlated with FA value of right PPN.Conclusions: We demonstrated neural damage of PPN and related struc-tures in PD patients with FOG. Based on our results, neuronal disruption in PPN pathway is the closely related with pathophysiology of FOG.Reference1. Youn J, Cho JW, Lee WY, Kim GM, Kim ST, Kim HT. Diffusion tensor imag-

ing of freezing of gait in patients with white matter changes. Mov Disord 2012;27:760–764.


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FUNCTIONAL CONNECTIVITY SHIFTS FROM POSTERIOR TO ANTERIOR PORTIONS OF THE CORTICO-STRIATAL CIRCUIT IN LATE PRE-SYMPTOMATIC AND EARLY SYMPTOMATIC PARKINSON’S DISEASER.C. Helmich1,*, A. Thaler2, B. Van Nuenen3, T. Gurevich2, A. Mirrelman4, T. Hendler4, N. Giladi2, I. Toni1, B.R. Bloem1

1Donders Institute for Brain Cognition and Behaviour and Department of Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, 2Movement Disorders Unit Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel, 3Department of Neurology, Catharina Hospital, Eindhoven, Netherlands, 4Functional Brain Center Wohl Institute for Advanced Imaging, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel

Objectives: Human studies of cerebral compensation in presymptomatic Parkinson’s disease (PD) are lacking, because it is difficult to predict who will

develop PD in the future. Here we address this issue by investigating compen-satory changes in the cortico-striatal circuit in a human model of pre-sympto-matic PD.Methods: Using resting state fMRI, we compared 39 healthy carriers of the autosomal dominantly inherited LRRK2 mutation – associated with an age-dependent risk of developing PD – to 31 matched non-mutation carriers and to 33 patients with early PD. We tested the hypothesis that cortico-striatal connectivity shifts from severely affected striatal subregions to less-affected striatal subregions, as previously shown in symptomatic PD (1).Results: In both groups, we observed the known topography of the cortico-striatal loops passing through the dorso-posterior, dorso-anterior, ventro- posterior and ventro-anterior putamen, and the caudate and nucleus accumbens. The right inferior parietal cortex of LRRK2 carriers had reduced connectivity with the dorso-posterior putamen, but increased connectivity with the ventro-anterior putamen. Furthermore, in LRRK2 carriers, connectivity be-tween ventro-anterior putamen and inferior parietal cortex increased with age. Conversely, in PD patients, connectivity between anterior putamen and right parietal inferior cortex decreased with striatal dopamine levels in the anterior putamen, as measured using DAT-SPECT.Conclusions: We conclude that mildly affected striatal regions compensate for severely affected striatal regions in a model of presymptomatic PD. This cortico-striatal reorganization depends on the stage of the disease, being maximum at the end of the pre-symptomatic phase and at the beginning of the symptomatic phase.Reference1. Helmich RC et al., Cereb Cortex 2010.No conflict of interest

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MOTOR SYMPTOMS LATERALITY-DEPENDENT RELATIONS BETWEEN RESTING FUNCTIONAL CONNECTIVITY AND UNIFIED PARINSON’S DISEASE RATING SCALE IN PARKINSON’S DISEASEK. Yoo1,*, S. Chung2, Y. Lee1, O. Choung1, M. Kim2, S. You2, Y. Jeong1

1Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon City, Korea, 2Neurology, Asan Medical Center University of Ulsan College of Medicine, Ulsan, Korea

Objectives: The goal of this study is to reveal a relation between resting state functional connectivity and Unified Parkinson’s Disease Rating Scale (UPDRS) in Parkinson’s disease (PD) according to the laterality of motor symptoms and signs.Methods: Eighty one PD patients and age-matched 79 healthy controls were recruited in this study. We acquired resting state fMRI and T1 MRI from every subject. First, we defined 18 ROIs; caudate, putamen, globus pallidus (GP), motor part of thalamus, premotor area, primary motor area, primary sensory area, substantia nigra (SN) and subthalamic nucleus (STN) in each hemisphere. Pearson’s correlation for pair-wise functional connectivity among these ROIs was calculated using rsfMRI data. Then, we performed correla-tion analysis with these connectivity matrices, and UPDRS total scores and 5 subparts of UPDRS scores, respectively.Results: With Bonferroni correction for multiple comparison (p < 0.05 corrected), we only could find correlation between Schwab and England activities of daily living scale, and connectivity between SN and STN in the left hemisphere, SN and motor thalamus in the left hemisphere, SN and GP in the right hemisphere, and caudate and motor thalamus in the right hemisphere. Under p < 0.001 (un-corrected), we could additionally found the laterality-dependent correlation in the left-more-affected PD group and right-more-affected PD group, separately.Conclusions: Resting functional connectivity would represent clinical infor-mation of patients with PD and this representativeness depends on the lateral-ity of motor symptoms and signs.No conflict of interest

191

A FOLLOW-UP 123I-MIBG SCINTIGRAPHY IS BENEFICIAL IN DIFFER-ENTIATING PARKINSON’S DISEASE FROM OTHER NEURO DEGENE-RATIVE DISORDERSK. Tsujikawa1,*, S. Yokoi2, K. Yasui1, Y. Hasegawa1

1Neurology, Nagoya Daini Red Cross Hospital, Nagoya, Japan, 2Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan

Objectives: 123I-MIBG scintigraphy (MIBG) assesses cardiac sympathetic nerve and shows low uptake in nearly all patients with Parkinson’s disease (PD). The purpose of this study is to evaluate the effects of repeated MIBG on the differentiation of PD from other neurodegenerative disorders.Methods: Eighty-nine patients with PD, 14 with multiple system atrophy (MSA), 11 with progressive supranuclear palsy (PSA), and two with corti-cobasal degeneration (CBD) underwent MIBG twice or more. The heart to mediastinum (H/M) ratio and washout ratio (WR) were calculated. A receiver operating characteristic (ROC) analysis was performed to differentiating PD



54

from other neurodegenerative disorders. The Kaplan-Meier method was used for time-to-event analysis.Results: A follow-up MIBG in patients with PD was carried out after a mean interval of 2.5 years, and revealed 6.5% decrease of early H/M ratio, 9.8% decrease of delayed H/M ratio, and 3.9% increase of WR, compared to the baseline. There was no significant chronological change in uptakes of MSA, PSP and CBD. Using delayed H/M ratio at the baseline and at the follow-up, ROC analysis provided AUC of 0.84 (sensitivity 77.5%, specificity 80.8%) and 0.90 (sensitivity 84.3%, specificity 88.5%), respectively. In 21 (23.6%) patients with PD whose delayed H/M was ≥ 2.0 at the baseline, the 2-year and 3-year rate to reach delayed H/M < 2.0 at the follow-up were 29.4% and 69.0%, respectively.Conclusions: Re-examination of MIBG should be taken in approximately three years to reinforce the diagnosis of PD.No conflict of interest

192

MRI, MÖSSBAUER SPECTROSCOPY AND ELISA COMPARATIVE STUDIES FOR BETTER UNDERSTANDING OF PARKINSON’S DISEASEA. Friedman1,*, J. Galazka-Friedman2, R. Kulinski3, D. Koziorowski11Neurology, Medical University in Warsaw, Warsaw, Poland, 2Faculty of Physics, Warsaw University of Technology, Warsaw, Poland, 3Neuroimaging Section, Brodno Hospital in Warsaw, Warsaw, Poland

Objectives: Neurodegeneration in Parkinson’s disease (PD) affects substan-tia nigra (SN), globus pallidus (GP) and hippocampus (Hip). We compared the results of MRI quantitative relaxometry, Mössbauer spectroscopy (MS) and enzyme-linked immunosorbent assay (ELISA) obtained from PD patients and control in vivo (MRI) and from post mortem tissue (MS and ELISA).Methods: 1.5 T MRI was used to get T1 and T2 relaxation times from SN, GP and Hip of PD and control subjects. MS and ELISA were performed on sam-ples obtained from PD and control brains. MS was used for the determination of the concentration of iron and ELISA for the assessment of the structure of ferritin.Results: In control brains longer T1 1094 (88) vs. ~700 ms and T2 66.3 (1.8) vs. ~54 ms in Hip than in GP and SN was found with lower concentration of iron in Hip 45 vs. ~180 ng/mg wet tissue compared to SN and GP.The comparison of PD vs. control demonstrated in SN a difference in the structure of ferritin H: 26.4 (3.) vs. 19.3 (1.5) L: 2.7 (0.5) vs. 5.0 (0.5) ng wet tissue/μg protein, and H/L ratio 11.1 (1.4) vs. 4.3 (0.3).No difference was found for GP. For Hip there is a shortening of T1: 863 (28) vs. 1094 (88) ms with an increase of H 7.3 (1.0) vs. 5.8 (0.5) ng wet tissue/μg protein.Conclusions: Relaxometry cannot differentiate SN in PD and control. Shorter T1 in Hip PD cannot be only iron related.No conflict of interest

193

SPECT/CT IMAGING OF PARKINSON’S DISEASE IN PRECLINICAL MODELST. Huhtala1, V. Jankovic2, U. Herzberg2, R. Pussinen1, T. Ahtoniemi1,*, P. Sweeney1, A. Nurmi11Discovery Research Services, Charles River, Kuopio, Finland, 2Cellular Therapeutics, Celgene, Warren, NJ, USA

Objectives: Parkinson’s Disease (PD) is a neurodegenerative disorder which includes, among other pathologies, death of dopaminergic cells in the sub-stantia nigra. Cocaine analogues such as β-CIT can be used to image do-pamine transporters (DAT) by SPECT. With small animal imaging scanners, the striatum can be visualized and ligand binding quantified in rodents. In this study, DAT density in two preclinical rat models of PD was studied using SPECT/CT.

Methods: Unilaterally induced PD was generated using intrastriatal 6-hy-droxydopamine (6-OHDA) injection or AAV-α-synuclein gene transfer to sub-stantia nigra. DAT imaging was performed 4 and 8 weeks after 6-OHDA lesion, and 3 and 8 weeks after AAV-α-synuclein gene transfer. For the quantification of DAT ligand binding, 123I- β-CIT was used.Results: SPECT/CT imaging of the 6-OHDA induced PD model in rat 4 and 8 weeks after lesion showed that DAT density decreased by 20% on the ip-silateral side at both time points. For the unilateral AAV-α-syn gene transfer model, overall DAT density of striatum imaged 3 weeks after transfection was decreased. When ipsi- and contralateral sides were compared in this model, DAT concentration on the ipsilateral side had decreased ca. 20%.Conclusions: Modern imaging modalities offer a translational method to study functional changes of PD in rodents. Fully quantitative results can be obtained in vivo, quickly and cost-efficiently over several time points, enabling longitudinal follow-up of disease progression within individual animals, and of-fering a valuable tool for preclinical research and efficacy studies.No conflict of interest

194

STANDARDIZED 123I-FP-CIT SPECT AND VOXEL-BASED MORPHOMETRY MAKE THE INVISIBLE VISIBLEA. Skanjeti1,*, G. Castellano2, M. Zotta2, B. Elia3, T. Angusti1, S. Grimaldi2, M. Balma2, E. Trevisiol1, S. Romana1, M. Iudicello4, M. Zibetti5, P. Ferrero6, P. Filippi7, R.E. Pellerito3, G. Bisi2, V. Podio1

1University of Turin, Nuclear Medicine Unit San Luigi Gonzaga Hospital, Torino, Italy, 2University of Turin, Nuclear Medicine Unit San Giovanni Battista Hospital, Torino, Italy, 3Umberto I Hospital, Nuclear Medicine Unit, Torino, Italy, 4University of Turin, Neurology 1 San Luigi Gonzaga Hospital, Torino, Italy, 5University of Turin, Neurology 4 San Giovanni Battista Hospital, Torino, Italy, 6University of Turin, Neurology 2 San Giovanni Battista Hospital, Torino, Italy, 7Maria Vittoria Hospital, Neurology, Torino, Italy

Objectives: In nuclear medicine field comparability of semi-quantitative results is still to be assured. Our aims were: 1) to perform standardized elaboration and evaluation of 123I-FP-CIT SPECT in three centres with different equipments; 2) to identify areas with low 123I-FP-CIT binding potential in parkinsonian patientsMethods: Two-hundred-twenty patients with suspected neurodegenerative parkinsonian syndrome (NPS) underwent 123I-FP-CIT in three centres (Philips/Axis; GE/Varicam; Siemens/E.cam). After at least 2 years, diagnosis was established by experienced neurologists, independently from SPECT report. Exams were reconstructed by filtered back-projection with same filter and same attenuation correction. SPM full factorial analysis was undertaken using unique template for all centres; patient age and acquisition centre were used as covariates (Proportional scaling, p-valueFWE < 0.01).Results: NPS-free patients, showed higher 123I-FP-CIT binding than NPS patients (p < 0.0001) in striatum. Furthermore, only in multicentre analysis, an area in the midbrain/diencephalon with significantly lower 123I-FP-CIT binding in NPS patients (p < 0.004) was detected (Figure 1). The latter area, probably hypothalamic one (Figure 2), rich in serotonin transporter[1] has been previ-ously identified as involved in PD pathophysiology[2].

A

P

RL

contrast(s)

4

SPM(T }212

SP

H.L

PL-

Z -F

.097

05. -

13.

5379

1

1 2 3 4Design matrix

5 6 7 8

Statistics: P–values adjusted for search volume

set-level

P FUE-corr FIR-corr

0.000 0.000 0.000

0.000 0.000

0.000

0.004

1.EEE

124

2

P uncorrP uncorrPFFI FFI FFI

qFUE-corr FIR-corr

0.0000.0000.000

0.0000.000

0.000

0.000

0.0000.0000.000

0.000

-322416

-2

-6-622

-8

-2-49

-100.000

P q

[nf[nf

[nf

5.62

13.7511.59

14.25

5.04

T (2g)Ekc

cluster-level peak-level

20

40

60

80

100

120

140

160

180

200

220



55

Conclusions: A large database and standardized procedures make visible un-seen areas in unicentric studies, enhancing the understanding of parkinsonian syndromes pathophysiology, in particular in extrastriatal areas. Voxel-based studies in standardized nuclear medicine could open new scenarios of diagnosis and treatment.References1. Koopman, JNM 12.2. Politis, Neurobiol Dis 10.No conflict of interest

195

DATSCANTM (ILOFLUPANE I 123 INJECTION), A RADIOPHAR MAC-EUTICAL INDICATED FOR VISUALIZATION OF THE STRIATAL DOPAMINE TRANSPORTER USING SPECT: SAFETY PROFILE REVIEWI.D. Grachev1,*, P. Sherwin2, D. Lane3, E. Moreno4, N. Bajaj5, R.A. Hauser6, J. Seibyl7, D.G. Grosset8, K. Marek9

1Medical Affairs, GE Healthcare, Princeton, NJ, USA, 2Clinical Development, GE Healthcare, Princeton, NJ, USA, 3Pharmacovigilance, GE Healthcare, Princeton, NJ, USA, 4Medical Affairs, GE Healthcare, Madrid, Spain, 5Neurology, Nottingham Univ, Nottingham, United Kingdom, 6Neurology, USF Byrd Parkinson’s Disease and Movement Disorders Center, Tampa, FL, USA, 7Nuclear Medicine, The Institute for Neurodegenerative Disorders, New Haven, CT, USA, 8Neurology, The Institute of Neurological Sciences, Glasgow, United Kingdom, 9Neurology, The Institute for Neurodegenerative Disorders, New Haven, CT, USA

Objectives: To assess DaTSCANTM ([123I]Ioflupane Injection) safety data from clinical trials (Phases I-IV) in clinical development and post-marketing experience.Methods: In GE-sponsored clinical trials, DaTSCANTM was administered to 1236 subjects (1171 patients and 65 healthy volunteers). Clinical trials col-lected adverse events (AEs), laboratory parameters, vital signs and electro-cardiograms (ECG). Administered activity of [123I]ioflupane ranged from 3 to 5 mCi (111 to 185 MBq), comparable to administered activities for other com-mercially available 123I-labeled products. The calculated whole body effective dose was 4 to 6 mSv, comparable to 1 year of natural background radiation (3 to 4 mSv).Results: Review of trial data on non-serious AEs, vital signs, laboratory parameters, and ECG identified no safety issues. There were mild and infre-quently reported AEs and no SAEs or deaths that were considered related to DaTSCANTM administration. The most common AE ascribed to DaTSCANTM by the investigator was headache (1%), followed by nausea, and vertigo, dry mouth, hunger, dizziness, and formication (<1% each). Most of these AEs were mild. The safety profile established in clinical trials is supported by lim-ited AE reports (including hypersensitivity reported as rash and pruritis shortly after dosing) from post-marketing exposure in over 300,000 patients who have been imaged.Conclusions: Comprehensive review of the safety data from clinical trials and 13 years of post-marketing use shows that AEs associated with DaTSCANTM are mild and infrequently reported, and DaTSCANTM is a safe product to use. DaTSCANTM is also considered to be low risk from a radiation dosimetry perspective.Conflict of interest

196

SENSITIVITY, SPECIFICITY, POSITIVE AND NEGATIVE PREDICTIVE VALUES, AND ACCURACY OF DATSCANTM FOR PREDICTION OF CLINICAL DIAGNOSIS OF EARLY PARKINSONIAN SYNDROMESN. Bajaj1, J. Seibyl2, K. Marek3, A. Kupsch4, M. Plotkin5, R.A. Hauser6, I.D. Grachev7*1Neurology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom, 2Nuclear Medicine, The Institute for Neurodegenerative Disorders, New Haven, CT, USA, 3Neurology, The Institute for Neurodegenerative Disorders, New Haven, CT, USA, 4Neurology, Otto-von-Guericke-University, Magdeburg, Germany, 5Nuclear Medicine, Leiter des Vivantes Instituts für Nuklearmedizin Mitte/Nord, Berlin, Germany, 6Neurology, USF Byrd Parkinson’s Disease and Movement Disorders Center, Tampa, FL, USA, 7Medical Affairs, GE Healthcare, Princeton, NJ, USA

Objectives: To assess the diagnostic efficacy data from clinical trial Kupsch et al. 2012 (data not previously published) conducted using DaTSCANTM ([123I]Ioflupane Injection).Methods: Study imaging group (n = 92) was used to assess the diag-nostic accuracy of DaTSCANTM in subjects with early, clinically uncertain Parkinsonian syndromes (PS) after 1 year follow-up. The reference standard was final clinical diagnosis 1 year after imaging (with DaTSCANTM results available), and it was compared to baseline clinical diagnosis (without

DaTSCANTM) and to baseline imaging diagnosis. Visual assessment of DaTSCANTM images was performed by local nuclear medicine physicians, which is consistent with current clinical practice. Acquisition of SPECT data with DaTSCANTM and their reconstruction were performed using a standard-ized imaging protocol.Results: The sensitivity of clinical diagnoses at baseline using clinical data was 92% when compared to final clinical diagnosis at 1 year, but the speci-ficity was only 52.4%. For the comparison of baseline DaTSCANTM images to the clinical diagnosis at 1 year, the sensitivity was 93.9%; specificity was 95.4% (p = 0.0005 as compared to baseline clinical diagnosis). The PPV, NPV and diagnostic accuracy for baseline clinical diagnosis or baseline im-aging diagnosis vs. final clinical diagnosis at 1 year (reference standard) were respectively: 69.7% vs. 95.8% (p < 0.0001), 84.6% vs. 93.2%, and 73.9% vs. 94.6%.Conclusions: High sensitivity and specificity, PPV, NPV and diagnostic accu-racy of DaTSCANTM in diagnosis of early clinically uncertain PS were demon-strated. Performance of DaTSCANTM compares favorably in this study to the performance of clinical diagnosis relative to final clinical diagnosis.Reference1. Kupsch A, et al. J Neurol Neurosurg Psychiatry 2012; 83:620–8.Conflict of interest

197

A CLINICAL FOLLOW UP STUDY ON THE DIAGNOSES BEHIND PATIENTS WITH PARKINSONIAN SYNDROME AND NORMAL DAT-SPECTM. Menendez-Gonzalez1,*, M. Martínez-Rivera2, N. Zeidan3, F. Tavares4, J.A. Vega5, A. López-Muñiz5

1Neurology, Hospital Álvarez-Buylla, Mieres, Spain, 2Geriatry, Hospital Álvarez-Buylla, Mieres, Spain, 3Nuclear Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain, 4Family Medicine, Hospital Álvarez-Buylla, Mieres, Spain, 5Morphology and Celular Biology, Universidad de Oviedo, Oviedo, Spain

Objectives: The [123I]ioflupane – a dopamine transporter radioligand – SPECT (DaT-SPECT) has proven to be useful in the diagnosis of Parkinson’s disease. Here, we investigate the diagnoses behind patients with parkinsonian syndrome and normal DaT-SPECT.Methods: 30 patients with parkinsonism and normal DaT-SPECT were fol-lowed up for 2 years. In 18 cases we were able to make a diagnosis. The residual 12 patients underwent a second DaT-SPECT, were then followed for additional 12 months and thereafter the diagnosis was reconsidered again.Results: The final diagnoses included cases of essential tremor, dystonic tremor, multisystem atrophy, vascular parkinsonism, progressive supra-nuclear palsy, corticobasal degeneration, fragile X–associated tremor ataxia syndrome, psychogenic parkinsonism, iatrogenic parkinsonism and Parkinson’s disease. However, for 6 patients the diagnosis remained uncertain.Conclusions: Repeating DaT-SPECTs over time may be useful in some cir-cumstances since it can reduce the remaining diagnostic uncertainty that is present even after a prolonged period of observation. However, after a second DaT-SPECT some patients still remain undiagnosed and other studies or even longer times of follow up are needed to move the diagnose of these patients from “SWEDDs” to true nosological entities.References1. Vlaar AM, de Nijs T, Kessels AG, Vreeling FW, Winogrodzka A, Mess WH,

et al. Diagnostic value of 123I-ioflupane and 123I-iodobenzamide SPECT scans in 248 patients with parkinsonian syndromes. European neurology. 2008;59(5):258–66

2. Tolosa E, Borght TV, Moreno E, Da TCUPSSG. Accuracy of DaTSCAN (123I-Ioflupane) SPECT in diagnosis of patients with clini-cally uncertain parkinsonism: 2-year follow-up of an open-label study. Movement disorders: official journal of the Movement Disorder Society. 2007;22(16):2346–51


198

FUNCTIONAL DEFICITS IN RESPONSE INHIBITION IN DE NOVO PARKINSON’S DISEASE PATIENTS CORRELATING WITH REDUCED CAUDAL [123I]FP-CIT BINDINGC. Vriend1,*, N.J.H.M. Gerrits2, P. Raijmakers3, H.W. Berendse4, Y.D. van der Werf2, O.A. van den Heuvel11Psychiatry, VU University Medical Center, Amsterdam, Netherlands, 2Anatomy & Neurosciences, VU University Medical Center, Amsterdam, Netherlands, 3Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands, 4Neurology, VU University Medical Center, Amsterdam, Netherlands

Objectives: Previous studies showed that Parkinson’s disease (PD) pa-tients display behavioral aberrancies in response inhibition, an often used



56

operationalization of impulsiveness. To date, no study has investigated re-sponse inhibition in PD patients prior to commencing dopamine replace-ment therapy (DRT) or the neural correlates of the stop-signal task in PD. Furthermore, the role of dopamine deficits in impulse control remains under debate. This study aims to provide answers to these issues.Methods: Twenty-one never-medicated (de novo) PD patients and 37 matched healthy controls (HC) performed a stop-signal task during fMRI. Task performance, trait impulsivity and PD-motor severity measures were acquired. Of these, 15 PD patients underwent [123I]FP-CIT dopamine transporter (DaT) SPECT imaging to obtain DaT availability measures in the caudate head, pos-terior putamen and nucleus accumbens, as an indicator of striatal dopamin-ergic denervation.Results: PD patients were independently slower on response initiation and inhibition. Task-related activity of the response inhibition network, including the inferior frontal gyrus (IFG), was reduced. This activity correlated negatively with PD-motor severity and motor impulsivity in PD patients but not HC. Lastly, only DaT availability in the caudate head correlated positively with task-related IFG activity.Conclusions: Never-medicated PD patients exhibit functional deficits in brain areas of the response inhibition network that is at least partly related to caudal dopaminergic denervation. This study provides insights into the neural under-pinning of impulse control deficits and the possible development of PD-related impulse control disorders.No conflict of interest

199

REDUCED DOPAMINE TRANSPORTER BINDING PREDATES IMPULSE CONTROL DISORDERS IN PARKINSON’S DISEASEC. Vriend1,*, A.H. Nordbeck1, J. Booij2, Y.D. van der Werf3, T. Pattij3, P. Voorn3, P. Raijmakers4, E. van de Giessen2, H.W. Berendse5, O.A. van den Heuvel11Psychiatry, VU University Medical Center, Amsterdam, Netherlands, 2Nuclear Medicine, Academic Medical Center, Amsterdam, Netherlands, 3Anatomy & Neurosciences, VU University Medical Center, Amsterdam, Netherlands, 4Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands, 5Neurology, VU University Medical Center, Amsterdam, Netherlands

Objectives: Examine whether reduced dopamine transporter (DaT) availabil-ity as measured by SPECT imaging precedes the development of impulse control disorder (ICD) symptoms in patients with Parkinson’s disease (PD) after receiving dopamine replacement therapy (DRT).Methods: We retrospectively procured follow-up data from 31 medication-naïve PD patients who underwent DaT SPECT imaging at baseline and were subsequently treated with DRT. We used questionnaires and a telephone in-terview to assess medication status and the development of ICD symptoms during the follow-up period (31.5 ± 12.0 months).Results: Eleven patients developed ICD symptoms during the follow-up period, eight of which were on dopamine agonists. PD patients with ICD symptoms at follow-up had higher baseline depressive scores and low-er baseline DaT availability in the right ventral striatum, anterior-dorsal striatum and posterior putamen compared with PD patients without ICD symptoms (Figure 1). There were no baseline between-group differences in age and disease stage or duration. Severity of ICD symptoms correlated negatively with baseline DaT availability in the right ventral and anterior-dorsal striatum.

Ventralstratium L

Age

-nor

mal

ized

[123 I]

FP-

CIT

bin

ding

(in%

)

Ventralstratium R

Anterior-dorsalstriatum L

Anterior-dorsalstriatum R

PosteriorPutamen L

ICDno ICD

PosteriorPutamen R

0

20

40

60

80

100

120

Baseline differences in daT availability between PD patients with and without ICD symptoms

Conclusions: The results of this preliminary study show that reduced striatal DaT availability predates the development of ICD symptoms after DRT and may constitute a neurobiological risk factor related to a lower premorbid DaT availability or a more pronounced dopamine denervation in PD patients sus-ceptible to ICD.No conflict of interest

200

DOPAMINERGIC TREATMENT INDUCES GREATER ALTERATIONS IN BRAIN ACTIVATION IN PD SUBJECTS WITH A HISTORY OF IMPULSE CONTROL DISORDERV. Sossi1,*, M. Gonzalez1, K. Dinelle2, J. Mckenzie3, N. Heffernan3, N. Vafai3, S. Floresco4, S. Cresswell5, M. McKeown5, A.J. Stoessl51PHAS, University of British Columbia, Vancouver, Canada, 2PPRC/PHAS, University of British Columbia, Vancouver, Canada, 3PPRC, University of British Columbia, Vancouver, Canada, 4Psycology, University of British Columbia, Vancouver, Canada, 5Neurology, University of British Columbia, Vancouver, Canada

Objectives: To investigate treatment-related alterations in executive func-tion in Parkinson’s disease (PD) subjects with a history of treatment-related impulse control disorder (PD-ICD).Methods: Six PD-ICD subjects and five age, disease and treatment-matched subjects without ICD history (PD) underwent two fMRI sessions while performing an impulsivity/risk-sensitive gambling task (1) on (ON) and off medication (OFF). Six controls were imaged without medication. All un-derwent a 11C-DTBZ (VMAT2 marker) PET scan to assess striatal dopamin-ergic integrity.Results: Most relevant fMRI results were obtained for the prefrontal cortex (PFC) and the right inferior frontal gyrus (rIFG). At card choice, the PD subjects had a significantly higher activation in the PFC com-pared to PD-ICD in the ON state (p = 0.024), with no significant differ-ence in the OFF state (p = 0.7). The difference was more pronounced when the card choice resulted in a loss (LOSS). Compared to controls, the activation was more significantly reduced for the PD-ICD ON (p = 0.008) compared to PD ON (p = 0.024), with no difference in the OFF state. In the rIFG (associated with regulation of response inhibition and emotion) the treatment-related activation reduction was more pronounced for the PD compared to the PD-ICD (p = 0.017), stronger for LOSS (p = 0.03) com-pared to WIN (0.06). No difference in 11C-DTBZ biding was observed between PD groups.Conclusions: Treatment-related ICD may be associated with an increased treatment-induced reduction in executive function, coupled with an alteration in the activation of the rIFG, especially pronounced in reaction to loss, inde-pendently of dopaminergic denervation levels.Reference1. Floden et al Neuropsychologia 46 (2008) 213–223No conflict of interest

201

ASSOCIATIONS BETWEEN WHITE MATTER TRACTOGRAPHY AND DOPAMINE TRANSPORTER AVAILABILITY ARE DISRUPTED IN PARKINSON’S DISEASED.J. Scott1, G. Klein1,*, J.L. Eberling2, J. Suhy1

1Science, Synarc Inc, Newark, USA, 2Research Programs, Michael J Fox Foundation, New York City, USA

Objectives: Dopaminergic deficits and white matter damage have been asso-ciated with Parkinson’s Disease (PD). We investigate the link between striatal dopamine transporter (DAT) availability, and tractography, assessed by diffu-sion tensor imaging (DTI).Methods: As part of the Parkinson’s Progression Markers Initiative (PPMI), 107 de-novo PD patients and 59 age-matched healthy controls underwent DaTSCAN SPECT imaging and 3T MRI scanning with DTI. DAT values were derived from striatal ROIs, while DTI studio was used to calculate fractional anisotropy (FA) and radial diffusivity (RD). SPM8 was used for image pre-processing, and to run t--tests across FA and RD maps. The MarsBaR tool-box was used to extract ROIs for post-hoc analysis. All voxelwise analyses were corrected for multiple comparisons using familywise error rate (FWE) corrected p < 0.05.Results: Disrupted white matter in PD patients manifested as reduced FA in striatonigral and striatopallidal fibers, and increased RD in nigrostriatal fibers. In controls, DAT availability was significantly positively correlated with FA, while this relationship was absent in PD patients; these correlations were



57

highly significantly different between groups. DR values in controls were sig-nificantly negatively correlated with DAT availability, a relationship absent in PD patients, and significantly different between groups. Across all subjects, FA and DR values were also significantly correlated with UPDRS clinical status.

all subs all subs all subs

corr1 corr2 r t two-tail p

FA ROI1 DAT 0.41 5.7 5.78E-08

FA ROI2 DAT 0.42 6 1.46E-08

FA ROI3 DAT 0.45 6.4 1.23E-09

FA ROI4 DAT 0.44 6.3 2.40E-09

DR ROI1 DAT -0.44 -6.3 2.46E-09

FA ROI1 UPDRS sum -0.17 -2.2 2.70E-02

FA ROI2 UPDRS sum -0.2 -2.6 0.010667

FA ROI3 UPDRS sum -0.22 -2.92 4.00E-03

FA ROI4 UPDRS sum -0.23 -2.98 3.20E-03

DR ROI1 UPDRS sum 0.27 3.68 3.13E-04

DAT UPDRS sum -0.66 -11.3 3.66E-22

Figure: FWE-corrected ROIs where FA is greater in controls than PD patients.

6

4

2

0

Conclusions: Healthy controls demonstrate tight associations between trac-tography and DAT availability, which are disrupted in PD.No conflict of interest

202

COMBINED DOPAMINE TRANSPORTER SPECT IMAGING AND OLFACTORY TESTING FOR DIFFERENTIAL DIAGNOSTICS OF PARKINSON’S DISEASE AND ATYPICAL PARKINSONISM – A PROSPECTIVE FOLLOW-UP STUDYP. Borghammer1,*, K. Knudsen1, K. Ostergaard2, E.H. Danielsen2, N. Pavese1, A. Arveschoug1, H. Bluhme1, M. Bode3, A. Morsing1

1Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Århus C, Denmark, 2Department of Neurology, Aarhus University Hospital, Århus C, Denmark, 3Department of Neurology, Odense University Hospital, Århus C, Denmark

Objectives: Dopamine transporter (DaT) imaging with single photon emis-sion computed tomography (SPECT) can detect loss of striatal dopaminergic innervation with very high sensitivity. However, it cannot distinguish idiopathic Parkinson’s disease (iPD) and Dementia with Lewy bodies (DLB) from atypi-cal disorders (aPD). However, most iPD/DLB patients are hyposmic, whereas most aPD patients have nearly intact olfactory sense. We conducted a pro-spective follow-up study to investigate the power of combined DaT imaging and olfactory tests to predict the final diagnosis of the patients.

Methods: A total of 162 patients received [123I]FP-CIT SPECT imaging and an olfactory test. Clinical follow-up was performed after 31 ± 12 months to obtain the final clinical diagnosis.Results: Stand-alone DaT imaging displayed sensitivity and specificity of 97% and 96% with respect to diagnosing a dopamine-depleting neurodegenerative disorder (Table 1). Combined DaT/olfactory test correctly classified 91% of iPD/DLB patients (PPV 91%) (Table 2). In the subgroup of severely hyposmic patients the PPV was nearly 100%. In contrast, the combined test only pre-dicted 38% of aPD patients. However, the aPD patients displayed significantly lower DaT caudate ratios. In this subgroup of patients, the combined test pre-dicted the aPD patients with 73% certainty.

Table 1. DaT scan as a stand-alone test.

Diagnosis

PD, DLB, PSP, MSA, CBD NDDN, AD

DaT + 104 2 106

− 3 53 56

107 55 162

SN 0.97 (95% CI: 0.92–0.99), SP 0.96 (0.87–0.99), PPV 0.98 (0.93–0.99), NPV 0.95 (0.85–0.99).

Table 2. Combined DaT scan/olfactory test for predicting iPD/DLB vs. aPD.

Diagnosis

iPD. DLB PSP, MSA, CBD

Olfaction Hyposmia (>2SD) 71 7 78

Normosmia 16 10 26

87 17 104

SN 0.82 (95% CI: 0.72–0.89), SP 0.59 (0.33–0.82), PPV 0.91 (0.82–0.96), NPV 0.38 (0.20–0.59).

Conclusions: Olfactory tests add predictive power to the stand-alone DaT SPECT scan. Most patients with abnormal DaT SPECT have iPD, so the high positive predictive value of combined DaT SPECT/olfaction tests for iPD could have substantial clinical importance.No conflict of interest

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MESOLIMBIC DOPAMINERGIC DYSFUNCTION IN PARKINSON’S DISEASE-DEPRESSION: EVIDENCE FROM A 123I- FP-CIT SPECT INVESTIGATION.R. Ceravolo1,*, D. Frosini1, E. Unti1, E. Fiasconaro2, G. Linsalata1, C. Del Gamba1, D. Volterrani2, U. Bonuccelli11Clinical and Experimental Medicine, Ospedale Santa Chiara, Pisa, Italy, 2Nuclear Medicine, Ospedale Santa Chiara, Pisa, Italy

Objectives: To assess with an exploratory approach the striatal and extras-triatal dopamine transporter (DAT) availability by using SPM on 123I-FP-CIT SPECT images in a population of PD patients and depression (PD-d), com-pared to PD patients without depression (PD-nd).Methods: We evaluated the FP-CIT SPECT images of 50 de novo PD pa-tients; among then 15 subjects had a diagnosis of major or minor depression according to DSM IV criteria (age 66.8 years ± 5.4; disease duration 1.0 ± 0.5; UPDRS III 15.7 ± 5.3; BDI 16.8 ± 3.8) the remaining 35 had no depression (age 68.3 years ± 7.1; disease duration 1.2 ± 1.0; UPDRS III 15.6 ± 7.0; BDI 2.5 ± 0.9). SPM2 was used for group comparison.Results: The two groups were comparable in all clinical and demographical parameters except for BDI score higher in PD-d group (p < 0.01).A cluster, with statistically significant (p < 0.001) lower binding of FP-CIT in PD-d with respect to PD-nd patients was found in right cingulate cortex, per-sistent after correction for age, disease severity and duration. When cingulate VOI radiotracer uptake was correlated with BDI scores in the whole group, an inverse correlation was observed (r −0.367, p < 0.01).Conclusions: Our data indicate no differences in striatal dopaminergic den-ervation in PD-d and PD-nd. As regards to extra-striatal areas a significant association between depression and cingulate dopaminergic denervation was observed, confirming the dopaminergic hypothesis of PD-depression.No conflict of interest



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CAN WE PREDICT EARLY DEVELOPMENT OF LEVODOPA-INDUCED DYSKINESIA USING FP-CIT PET?H. Lee1,*, S.J. Kang1, J.Y. Ahn2, J.Y. Kim3, Y.Y. Choi3, H.T. Kim1

1Neurology, Hanyang University Seoul Hospital, Seoul, Korea, 2Neurology, Seoul Medical Center, Seoul, Korea, 3Nuclear Medicine, Hanyang University Seoul Hospital, Seoul, Korea

Objectives: Physicians could not predict which patient has the risk of early developing LID. FP-CIT PET is good at diagnosis PD and reflect the stage of PD. In this study, we analyze whether the severity of the FP-CIT PET findings correlate with developing LID or not.Methods: We included 35 early PD patients and 16 controls. PD patients are divided into two groups, PD with early developed (within 48 months after disease onset) LID and PD without LID (within 60 months after disease onset). The FP-CIT PET was performed within 2 years after symptom onset. Group differences between PD with LID and without LID were tested by mean FP-CIT PET uptake of putamen and caudate.Results: There were no between-group differences in age at onset of PD symptoms, initial Hoehn & Yahr stage, UPDRS part III and disease duration at the time performing FP-CIT PET. Statistical analysis indicated a significant reduction of uptake in putamen and caudate of PD with LID group.Conclusions: We found that the severe binding defect of FP-CIT PET have positive predictable value in developing LID. In sub-analysis more severe defect of putamen and early bilateral caudate involvement correlated with early developing LID. So, physicians are careful with introducing levodopa treatment in patients with severely diminished uptake in initial FP-CIT PET findings.Reference1. C. Warren et al. 2013 Factors Predictive of the Development of Levodopa-

Induced Dyakinesia and Wearing-Off in Parkinson’s Disease.2. MA Cenci et al. 2007 Advances in understanding l-DOPA-induced

dyskinesia.No conflict of interest

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MRI AND 18 F-FDG PET FEATURES OF IDIOPATHIC PARKINSON DISEASE, MULTIPLE SYSTEM ATROPHY AND PROGRESSIVE SUPRANUCLEAR PALSYP. Zhao1, B. zhang2,*, S. Gao3

1Neurology, Second Hospital of Tianjin Medical University, Tianjin, China, 2Neurology, General Hospital of Tianjin Medical University, Tianjin, China, 3Nuclear Medicine, General Hospital of Tianjin Medical University, Tianjin, China

Objectives: The differential diagnosis between idiopathic Parkinson’s disease (IPD) and Parkinsonism-plus syndromes is often difficult in the early disease

stages. In this study, we aimed to characterize the differences in MRI abnormal-ity and glucose metabolism on 18F FDG PET for differential diagnosis among IPD, multiple system atrophy with Parkinsonism (MSA-P), and progressive su-pranuclear palsy (PSP).Methods: 30 IPD patients, 22 MSA-P patients and 17 PSP patients underwent MRI, and 18 IPD patients, 10 MSA-P patients and 13 PSP patients underwent 18 F-FDG PET. Imaging-based diagnosis was obtained by statistical paramet-ric mapping software.Results: MRI findings indicated that putaminal hyperintensive rim was signifi-cantly prominent in the MSA-P group. Midbrain atrophy with a ‚hummingbird sign’ in the MRI occurred in 64.7% of PSP patients, but not in the IPD and MSA-P patients. The 18 F-FDG PET images demonstrated that a reduction in glucose metabolism occurred in the bilateral parietal areas for IPD, in the bilateral putamen for MSA-P, and in the bilateral midbrain for PSP.Conclusions: This study identifies the characteristic features of IPD, MSA-P, and PSP, on MRI abnormality and 18 F-FDG PET images, which are important for differential diagnosis among these diseases. Thank you for creating an ac-count with PARKINSON.References1. Teune LK, Bartels AL, de Jong BM, Willemsen AT, Eshuis SA, de Vries

JJ, van Oostrom JC, Leenders KL. Typical cerebral metabolic patterns in neurodegenerative brain diseases. Mov Disord. 2010;25:2395–404.

2. Zhao P, Zhang B, Gao S. 18[F]-FDG PET study on the idiopathic Parkinson’s disease from several parkinsonian-plus syndromes. Parkinsonism Relat Disord. 2012;18 Suppl 1:S60–2.


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CLINICAL AND MRI,18F-FDG PET DIAGNOSTIC CHARACTERISTICS OF 27 PROGRESSIVE SUPRANUCLEAR PALSYX. Wang1,*1Neurology, Benzhou Medical College, Yantai, China

Objectives: To discuss the characteristics of clinical manifestation and imag-ining, also with diagnosing of PSP.Methods: Retrospective clinical analysis of 27 PSP patients.Results: The major clinical manifestation is that two eyes cannot look upward and downward, with walking inability and having psychiatric symptoms. PET and other auxiliary examinations are important to identify the diagnosis.Conclusions: The clinical characteristics of PSP are eye symptoms, move-ment disorders and psychiatric symptoms. Case history, clinical manifesta-tion, physical examination, MRI, and PET are important to make a definite diagnosis.References1. PSP:progressive supranuclear palsy.2. Clinical and MRI,18F-FDG PET diagnostic characteristics of 27 progres-

sive supranuclear palsy.No conflict of interest



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of these were present in 600 PD patients. However, exon sequencing of the candidate genes identified two other EOPD patients that were compound heterozygous carriers of missense and nonsense variants in the same gene. Furthermore, analysis of 14 WES data sets revealed clues for three other potential PD candidate genes.Conclusions: Functional characterization might provide insight into the puta-tive pathogenic nature of these mutations and the role of the candidate genes in disease processes.No conflict of interest

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GENDER DIFFERENCES OF CLINICAL AND ENVIRONMENTAL FACTORS IN PARKINSON’S DISEASE PATIENTSL.H. Hopes1,*, E.M. Mutez1, J.S. Salleron2, S.B. Bleuse1, N.W. Waucquier1, J.P.L. Legendre1, L.D. Defebvre1, A.D. Destée1, M.C.C.H. Chartier-Harlin3

1Neurology and Movement Disorders, CHRU Lille, Lille, France, 2Biostatistics Department, CHRU Lille, Lille, France, 3INSERM UMR837 Team 6, JPArc IRCL, Lille, France

Objectives: Parkinson’s disease (PD) is a multifactorial disease, with an in-teraction of environmental and genetic factors. PD occurs more often in men than female with a sex ratio from 1.5 to 2. Epidemiologic studies have shown a possible link between hormonal factors and PD risk and disease severity. The aim of our study is to evaluate if environmental or genetic factors are different between men and women, and if women hormonal factors have protective ef-fects on PD and its evolution.Methods: Data from controls (125 women and 72 men) and PD patients (474 women and 383 men) were collected in the Lille University Movement Disorders Department. This population includes sporadic PD patients and oth-ers with family history of PD or with genetic mutation.Results: No difference was found for the age of onset between women and men in this familial/genetic population. However, our results show a later age of onset and of diagnosis of the disease in sporadic PD women with a positive correlation with age of menopause, number of pregnancy and age of contra-ceptive use. Among the other clinical criteria, only dyskinesia delay is longer in female PD. Furthermore, the effect of protective (tobacco, coffee) and del-eterious (pesticides) environmental factors was more important in female PD than in male PD.Conclusions: Our study reveals clinical and environmental gender differenc-es in PD patients, suggesting that PD pathogenesis could be partially gender specific.No conflict of interest

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THE ERASMUS GENETIC PARKINSON STUDY (GPS) – CLINICAL FEATURES AND ANALYSIS OF KNOWN PD-CAUSING GENESJ.P.M.A. Rood1,*, J. Graafland2, M. Quadri2, J.A. Maat – Kievit2, V. Bonifati2, A.J.W. Boon1

1Neurology, Erasmus MC – University Medical Centre, Rotterdam, Netherlands, 2Clinical Genetics, Erasmus MC – University Medical Centre, Rotterdam, Netherlands

Objectives: The clinical, genealogical, and molecular characterisation of a Dutch cohort of patients with Parkinson’s disease (PD).Methods: Patients, affected relatives, unaffected relatives and healthy controls were included. Affected subjects were tested on cognitive and motor functions. Screening for copy number variants and rearrange-ments using multiplex ligation-dependent probe amplification and direct sequencing with Sanger methods for all exons of the known PD genes was performed.Results: 108 index patients were analyzed, of whom 57 had a positive family history and 47 had an age at onset (AaO) of <50 years. The average AaO was 51.1 with an MDS-UPDRS score of 37 and H&Y stage of 2.5. The analysis of the known PD-causing genes was performed. Parkin mutations were found in two index patients: one from a Turkish family, including three sisters with AaO’s of 36, 40 and 48 and a second sporadic PD with an AaO of 17. DJ-1 mutations were found in two index patients, one patient being sporadic with an AaO of 63, the second patient appeared to be familial with an AaO of 28 and a deceased affected first degree family member. The LRRK2 Gly2019Ser mutation was detected in a sporadic index patient of Moroccan origin with an AaO of 42.Conclusions: These initial findings underline the genetic heterogeneity of PD in The Netherlands. The presence of additional, still unknown genetic defects in this cohort is suggested because of the early age at onset and positive family history.Supported by the Internationaal Parkinson Fonds (The Netherlands).No conflict of interest

DAY 2, TUESDAY, DECEMBER 10, 2013

Section 1: Genetics

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A PROTOCOL FOR DISCLOSING GENETIC RESULTS FOR NEWLY IDENTIFIED GENES TO RESEARCH PARTICIPANTSA. Strongosky1,*, S. Traynor1, R. Rademakers2, O. Ross2, Z.K. Wszolek1

1Neurology, Mayo Clinic, Jacksonville, USA, 2Neuroscience, Mayo Clinic, Jacksonville, USA

Objectives: As genetic research advances in the era of new technologies, there will be an increased need to define a process for providing results to individual research subjects. The Movement Disorders Group at Mayo Clinic Florida has developed a protocol for delivering individual research results for newly identified genes.Methods: When a gene discovery is made, investigators present the findings to the IRB for approval to disclose results. Participants are informed that a genetic discovery has been made and are given the option to learn more. If patients opt to obtain more information, they are provided details about the findings and of-fered test results. Patients who wish to know their results must submit a written request. Test results are then confirmed with repeat testing on a second sample. Because testing for newly discovered genes is unavailable at CLIA-approved laboratories1, testing is repeated in the research laboratory where the discovery was made to provide confirmation of the result. Results are disclosed with the assistance of a trained professional who explains the implications of the results, as well as provide referrals for medical, psychological, and/or social support.Results: This protocol has been implemented with positive results following recent gene mutation discoveries associated with various neurodegenerative conditions.Conclusions: Establishment of standard procedures for disclosing research results related to newly identified gene mutations assists investigators to pro-vide important health information to research participants.Reference1. Fabitz, RR et al. Ethical and practical guidelines for reporting genetic re-

search results to study participants: updated guidelines from an NHLBI working group. Circ Cardiovasc Genet. 2010; 3(6): 574–580.


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NEXT-GENERATION SEQUENCING APPROACHES FOR THE IDENTI-FICATION OF NOVEL EARLY-ONSET PARKINSON DISEASE GENESA. Verstraeten1,*, D. Crosiers2, P. Cras3, B. Pickut3, S. Engelborghs4, P.P. De Deyn5, C. Van Broeckhoven1, J. Theuns1

1Neurodegenerative Brain Diseases Group Department of Molecular Genetics VIB Antwerp and Institute Born-Bunge, University of Antwerp, Antwerp, Belgium, 2Neurodegenerative Brain Diseases Group, Department of Molecular Genetics VIB Antwerp and Institute Born-Bunge University of Antwerp and Department of Neurology, Antwerp University Hospital, Antwerp, Belgium, 3Institute Born-Bunge University of Antwerp and Department of Neurology, Antwerp University Hospital, Antwerp, Belgium, 4Department of Neurology and Memory Clinic Hospital Network Antwerp Middelheim and Hoge Beuken and Institute Born-Bunge, University of Antwerp, Antwerp, Belgium, 5Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen Netherlands and Department of Neurology and Memory Clinic Hospital, Network Antwerp Middelheim and Hoge Beuken and Institute Born-Bunge University of Antwerp, University of Antwerp, Antwerp, Belgium

Objectives: Using next-generation sequencing technologies we aim at identi-fying novel genes for early-onset Parkinson disease (EOPD).Methods: We performed whole genome sequencing (WGS) in a Flanders-Belgian nuclear family comprising one EOPD patient (onset age 24 years) and unaffected parents, and whole exome sequencing in a series of 14 apparently sporadic EOPD patients (onset age: 37.9 ± 5.6 years). We filtered genetic variants based on sequence quality, location in exons or splice sites, different inheritance models and allele frequency in the 1000 genomes and Flanders-Belgian genomes. Variants were validated and genotyped in geographically matched control individuals (N = 1000) and in PD patients (N = 600) to identify additional carriers. In the 14 unrelated EOPD patients, we focused on genes mutated in multiple patients for further genetic follow-up. Eventually, we se-quenced the coding regions of candidate genes in 99 Flanders-Belgian EOPD patients to identify additional mutations.Results: In the nuclear EOPD family filtering resulted in 221 variants. Genotyping the control group reduced the number to 13 variants but none

4.Day 2 Tuesday, Section 1 Genetics.indd 594.Day 2 Tuesday, Section 1 Genetics.indd 59 10/28/13 5:42 PM10/28/13 5:42 PM


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GENETIC ANALYSIS OF MUTATIONS AND POLYMORPHISMS IN SOUTH INDIAN PARKINSON’S DISEASE PATIENTSP. Vishwanathan1, M. Jayaraman1,*, A.V. Srinivasan2, C.R.S. Srisailapathy1, A. Ramesh1

1Genetics, University of Madras, Chennai, India, 2Department of Neurology, The Tamil Nadu Dr. MGR Medical University, Chennai, India

Objectives: To determine the association of SNPs in genes DRD2, CYP1A1, CYP2D6*3, CYP2D6*4, NAT 2, SNCA, PARK2 and NR4A2. Analysis was carried out in the same patients who were investigated previously for SNCA, LRRK2 and PARK2 mutations.Methods: Genomic DNA (peripheral blood) was isolated from 140 patients (103M, 37F) and 201 controls (121M, 80 F). There were 16 early onset pa-tients (EOPD) and 26 patients with family history. Polymorphisms were stud-ied using PCR-RFLP method.Results:1. We earlier reported the absence of SNCA (A53T, A30P, E46K) and LRRK2

(G2019S) mutations in these patients.(1)68.8% of EOPD patients had PARK2 mutations among which a novel mutation (c.798_799insA) and four previously known genetic variants 1239G>C, 202>G, c.171 + 25T>C and 601G>A were reported.(2)

2. Analysis of genes DRD2, CYP2D6*4, CYP2D6*3 and NAT 2 showed no significant association with PD.

3. CYP1A1 (T6235C) locus was a significant factor in late onset sporadic PD patients

4. SNCA (C116G) polymorphism locus predisposes to the sporadic EOPD while NR4A2 (G12803T) SNP predisposes to sporadic PD patients and

5. While the PARK2 (G601A) had no significant association with PD, the in-tronic polymorphism in PARK2 c.171 + 25T>C was significantly associated in PD patients (40%) compared to the control group (11%).

Conclusions: This communication highlights the presence of various associat-ed SNPs in South Indian PD population. Analysis of SNPs may have significance for drug designing, testing and/or treatment including prognosis, in PD patients.References1. Parkinsonism and Related Disorders, 18 (2012) 801–8022. Neuroscience Letters, 523 (2012) 145– 147No conflict of interest

212

EXPLORING THE GENETIC LANDSCAPE OF PARKINSON’S DISEASE – AN EXOME STUDY IN SARDINIA, A MEDITERRANEAN GENETIC ISOLATEM. Quadri1,*, X. Yang2, G. Cossu3, S. Olgiati1, V. Saddi4, G. Breedveld1, L. Ouyang2, J. Hu2, N. Xu2, J. Graafland1, V. Ricchi3, D. Murgia3, L. Correia Guedes5, S. Tesei6, M.J. Marti7, P. Tarantino8, S. Asselta9, F. Valldeoriola7, M. Gagliardi8, G. Pezzoli6, M. Ezquerra7, A. Quattrone10, J.J. Ferreira5, G. Annesi8, S. Goldwurm6, E. Tolosa7, B.A. Oostra1, M. Melis3, J. Wang2, V. Bonifati11Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, Netherlands, 2BGI, BGI-Shenzhen, Shenzhen, China, 3Neurology Service and Stroke Unit, General Hospital S. Michele AOB “G. Brotzu”, Cagliari, Italy, 4Neurology Division, S. Francesco Hospital ASL No.3, Nuoro, Italy, 5Neurological Clinical Research Unit, Instituto de Medicina Molecular University of Lisbon, Lisbon, Portugal, 6Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy, 7Neurology Service, Hospital Clinic of Barcelona, Barcelona, Spain, 8Neurological Sciences, National Research Council, Cosenza, Italy, 9Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy, 10Neurology, University Magna Grecia, Catanzaro, Italy

Objectives: The etiologic landscape of Parkinson’s disease (PD) is complex. Rare, highly-penetrant mutations in different genes and common risk factors of small size-effects in several loci have been identified in patients with PD. We report the results of our genetic study on the etiology of PD in Sardinia.Methods: We performed exome sequencing in 100 unrelated Sardinian PD patients. We first removed non-functional variants and we selected the novel SNPs shared by at least five unrelated PD patients, and absent in dbSNP129 and 1000Genomes databases. This approach yielded a total of 3,881 SNPs, that were then genotyped in 500 independent Sardinian individuals (242 PD and 258 controls) using a custom platform. Association of each variant with dis-ease status was tested using Fisher’s exact test implemented in PLINK/SEQ.Results: Out of 155 variants with p-value <0.5 and odds-ratio >3, thirty were con-firmed by Sanger sequencing, and genotyped by TaqMan assays in 2,965 PD pa-tients and 2,678 matched controls from southern Europe. No variants surpassed the required level of significance according to Bonferroni correction (p value <1.28 × 10−5). The lowest p value was 1.16 × 10−3 for a variant with final OR 2.8.Conclusions: We identified a catalogue of interesting variants enriched in PD patients that might point to novel genetic determinants of PD with moderate/strong effect size. Our study suggests that, with regard to the inspected exome target region, the genetic bases of PD are highly heterogeneous.No conflict of interest

213

SCREENING FOR MUTATIONS IN PARKINSON’S PATIENTS IN SAUDI ARABIAS. Bohlega1,*, B. Tawil2, D. Khalil2, L. Al-Jomaa2, H.A. AbouAl-Shar2, A. Magrashi2, T. Alkhairallah1, N. Al Tassan2

1Neurosciences, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia, 2Genetics, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia

Objectives: Parkinson’s disease (PD) describe a heterogeneous condition with a variety of contributing factors some of are genetic. Genetic studies in familial cases have identified a number of genes involved in the etiology of PD. In addition, several risk loci were also identified. Mutations in PARKIN, SNCA, DJ-1, PINK1, LARRK2. Genes have been reported in patients with different mode of inherence of PD. The aim of this study is to screen Saudi patients for mutations in these genes.Methods: Fifty-five PD patients (11 with autosomal dominant inheritance, 11 with autosomal recessive inheritance and the remaining are sporadic cases) were screened by direct sequencing for mutations in the reported genes ac-cording to the mood of inheritance. A total of 47 SNV’s were identified.Results: Two pathogenic mutations were identified, a missense mutation V380L in PARKIN gene and a splice variant in exon 7 of DJ-1 gene.Conclusions: The lack of mutations in the reported genes in these patients indicate that these genes might be inactivated using another mechanism (i.e regulatory mutations, deep intronic mutations) or that other genes are impli-cated in these patients. Our data confirms the genetic heterogeneity and com-plexity of the disorder.No conflict of interest

214

AGING-RELATED MILD GENOMIC INSTABILITY PERTURBS THE DOPAMINERGIC SYSTEM AND ELICITS SALIENT FEATURES OF PARKINSON’S DISEASE PATHOLOGYS. Sepe1,*, C. Milanese1, S. Gabriels1, K. Derks1, C. Payan Gomez1, J.H. Hoeijmakers1, G. Battaglia2, F. Blandini3, P.G. Mastroberardino1

1Department of Genetics, Erasmus MC University Medical Center, Rotterdam, Netherlands, 2Department of Neuropharmacology, Neurological Institute “NeuroMed”, Pozzilli, Italy, 3Department of Neurodegenerative Diseases, National Institute of Neurology IRCCS “C. Mondino”, Pavia, Italy

Objectives: Our objective was to determine the consequences of genomic instability on the etiopathogenesis of Parkinson’s Disease (PD). Accumulation of macromolecular damage, and of DNA damage in particular, underlies bio-logical deterioration in aging, which remains the principal important risk fac-tor for PD. We hypothesize that, in PD, imperfect DNA repair potentiates the detrimental interactions between predisposing genotypes and environmental factors, to favor pathology.Methods: We determined DNA repair capacity in idiopathic and genetic PD patients’ fibroblasts by the unscheduled DNA synthesis method. We performed neuropathological analysis in a mouse model with mild genomic instability – the Ercc1delta/+ mice, which suffer from mild defects in the DNA repair machinery – to extent of overlap between this model and PD. Evaluation included neurochem-istry, striatal tyrosine hydroxylase innervation, glial activation, and α-synuclein phosphorylation. Mitochondrial bioenergetics was determined monitoring oxy-gen consumption. We compared brain transcriptomic profiles – which were determined by Next Generation RNA sequencing – of Ercc1delta/+ mouse model and patients diagnosed with incidental Lewy body disease (iLBD) or with PD.Results: PD patient exhibit declined DNA repair capacity. Ercc1delta/+ mice present pathological signs typical of PD, including decreased striatal DA in-nervation, mitochondrial dysfunction, α-synuclein phosphorylation, and activation of glia cells. Canonical pathway analysis indicates that the mild genomic instability induces deregulation in pathways highly relevant for PD; comparison with human PD or iLBD demonstrates a significant overlap between these human conditions and the mouse model.Conclusions: Inadequate DNA quality control may act synergistically with other genetic and environmental factors to elicit PD.No conflict of interest

215

EFFECT OF AGE AND STRESS ON TRANSCRIPTIONAL ACTIVATION OF LINE-1 ELEMENTSS. Mukherjee1,*, K.C. Upadhyaya1, D. Sharma1

1School of Life Sciences, Jawaharlal Nehru University, New Delhi, India

Objectives: Basic objectives were to analyze the transcriptional activation of L1Rn elements in response to (1) age, (2) heavy metals such as cadmium, mercury, aluminum, lead and nickel.



61

Methods: Real time PCR analysis using RNA isolated from various brain re-gions and various tissues from old and young wistar rats was carried out to determine the change in L1 transcripts.Results: There was no significant change in the expression of L1Rn in various brain regions of 2 month old and 18 month old rats except cerebral cortex.The heavy metals nickel, cadmium, lead, mercury and aluminum upregulates the expression of L1 in tissue specific and age dependent manner.Conclusions: The results of this investigation conclusively prove that LINE1 retroelements are transcriptionally activated in response to stress.No conflict of interest

216

EPIGENETIC CHANGES OF α-SYNUCLEIN DURING LIFETIMEL. de Boni1,*, L. Riedel1, I. Schmitt2, O. Kaut1, S. Akbarian3, U. Wüllner1

1Neurology, University Hospital of Bonn, Bonn, Germany, 2Neurology, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany, 3Psychiatry, Brudnick Neuropsychiatric Research Institute, Worcester, MA, USA

Objectives: DNA-methylation patterns undergo profound changes during ag-ing. Thus, age-related epigenetic alterations could be the missing link between genetic and environmental causes of presumed sporadic neurodegenerative diseases, i.e. Parkinson’s disease (PD). α-synuclein (SNCA) is a key player in synucleinopathies and we hypothesized that SNCA methylation could be alterated in ageing contributing to PD susceptibility. Therefore, we determined (i) whether alterations of DNA-methylation of SNCA occur during aging (ii) and whether these alterations differ between males and females or (iii) neurons versus whole brain tissue.Methods: Applying bisulfite sequencing, the SNCA -methylation levels were analyzed in brain samples from fetus, children, adults and seniors (n = 26), as well as FACS-sorted single neurons and non-neuronal brain cells (n = 6).Results: A weak correlation between age and mean methylation status was found. Some CpGs were more heavily methylated in senior compared to fetal samples. Female samples displayed reduced mean methylation levels over all analyzed CpGs at all ages compared to males. Additionally, neurons displayed slightly higher methylation levels than non-neuronal cells.Conclusions: Our results demonstrate that aging itself might be associated with increased DNA-methylation of SNCA. Furthermore, our results somewhat surprisingly suggest, that the methylation levels from females are reduced compared to males, although males are more commonly affected by PD. Non-neuronal cells revealed lower methylation levels than neuronal cells. Again these results were surprising, as SNCA is supposed to be expressed in neu-rons only. Consequently, we had hypothesized to find increased methylation levels, i.e. gene-silencing in non – neuronal cell (glial cells).No conflict of interest

217

COMPUTATIONAL ANALYSIS OF α-SYNUCLEIN ALA53THR MUTANT REVEALS A INCREASED PROTEIN STABILITYM. Simonetto1,*, F. Zonta2

1Depatment of Specialty Medicine, ULSS 15 “ALTA PADOVANA”, Cittadella (Padova), Italy, 2Department of Physics and Astronomy “G. Galilei”, University of Padua, Padova, Italy

Objectives: α-synuclein (AS) is a key protein in Parkinson’s disease (PD). It is found with other proteins in the “Lewy bodies”. AS is considered a potentially toxic agent for neurons.We have investigated with computational approach (using PASTA software and Molecular Dynamic simulation) AS mutants.Methods: We performed a statistical study of known natural variant and other experimental mutation of SNCA gene coding for AS linked with familial PD using PASTA software. Then we selected AS Ala53Thr mutant and performed Molecular Dynamic (MD) simulations.Results: PASTA predictions revealed that Ala53Thr mutant increases the ten-dency of AS to aggregate in two regions: “48–55” and “70–77”. MD analysis showed that AS wild-type tends to unfold apart NAC domain; instead Ala53Thr mutant has a folded region around Thr 53.Conclusions: PASTA results with MD simulations showed that mutant AS has an increased stability, which may suggest the mechanism of aggregation.References1. H Snyder, B Wolozin: Pathological Proteins in Parkinson’s Disease.

Journal of Molecular Neuroscience; 425–442 (24) 2004.2. A Recchia, P Debetto, A Negro, D Guidolin, SD Skaper, P Giusti:

α-Synuclein and Parkinson’s disease. The FASEB Journal 617–626 (18) 2004.

3. HA Lashuel, CR Overk, A Oueslati, E Masliah: The many faces of α-synuclein: from structure and toxicity to therapeutic target. Nature; 38–48 (14) 2013


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SNCA RS356220 POLYMORPHISMS DECREASES THE RISK FOR PARKINSON DISEASE IN CHINESE POPULATIONH. Shang1,*, X. Guo1, Y. Chen1, W. Song1, K. Chen1, J. Yang1, B. Zhao1, R. Ou1, B. Cao1, R. Huang1, X. Chen1

1Neurology, West China Hospital of Sichuan University, Chengdu, China

Objectives: Recently, rs356220 single-nucleotide polymorphism (SNP) of SNCA gene was reported to be associated with the risk of Parkinson dis-ease (PD) in Japanese (Miyake, et al., 2012). Ethnic specific effect is a very important factor for analyzing the GWAS association. The strength of association between rs356220 SNP of SNCA and PD has not to be proved in China.Methods: Five hundred and eighty-seven PD patients from Department of Neurology of West China hospital, Sichuan University were included. All medi-cal data for each patient were recorded in our database. Five hundred and thirty-seven health controls (HC) were from the same region were recruited as control group. The SNP was identified by polymerase chain reaction-restric-tion fragment length polymorphism (PCR-RFLP).Results: There were significant differences in genotype frequencies and MAF for rs356220 SNP between PD patients and HC (p = 0.0003 and p = 0.0001, respectively). We also found significant difference in the genotype frequen-cies and MAF for rs356220 between early-onset PD group and matched HC (p = 0.0439, 0.0216, respectively), and between late-onset PD group and matched HC (p = 0.0002 and p = 0.0004, respectively). The ORs of MAF for rs356220 in PD was 0.7212 (95% CI: 0.6100–0.8526).Conclusions: Our results provide strong support for the SNCA rs356220 de-creases the risk for sporadic PD in a Han Chinese population.Reference1. Miyake, Y., Tanaka, K., Fukushima, W., Kiyohara, C., Sasaki, S., Tsuboi, Y.,

Yamada, T., Oeda, T., Shimada, H., Kawamura, N., Sakae, N., Fukuyama, H., Hirota, Y., Nagai, M. 2012. SNCA polymorphisms, smoking, and spo-radic Parkinson’s disease in Japanese. Parkinsonism Relat Disord 18(5), 557–61. doi:10.1016/j.parkreldis.2012.02.016.


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ASSOCIATION OF POLYMORPHISM IN RS2736990 OF THE α-SYNUCLEIN (SNCA) GENE WITH PARKINSON’S DISEASE IN A CHINESE POPULATIONF. Pan1,*, X. Ding2, H. Ding2, H. Dong2, M.I.N. Ye3, W. Liu4, G. Cui5, J. Chen6

1Department of Neurology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China, 2Department of Neurology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China, 3Department of Neurology, The BenQ Neurological Institute, Nanjing, China, 4Department of Neurology, Nanjing Brain Hospital of Nanjing Medical University, Nanjing, China, 5Department of Neurology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou, China, 6Department of Neurology, the Second People’s Hospital of Lianyungang, Lianyungang, China

Objectives: Previous genetic studies of Parkinson’s disease (PD) provided conclusive evidence of association of genes with PD. Recently, several stud-ies in different populations have found a strong association between idiopathic PD and the single-nucleotide polymorphism (SNP) rs2736990, which is lo-cated within an intron of the SNCA gene. In this study, we aimed to verify these findings and to explore the characteristic of the association in a subset of Chinese Han PD patients.Methods: Five hundred and fifteen unrelated patients with sporadic PD and 450 healthy ethnically matched control subjects were recruited consecu-tively for the study. Patients and healthy controls were genotyped for SNCA rs2736990 variant by Polymerase chain reaction- ligase detection reaction (PCR -LDR).Results: Our data showed a significant association between the rs2736990 polymorphism and PD, the frequency of the allele C in PD patients was sig-nificantly higher than that in controls (p = 0.017,OR = 1.26,95%CI:1.04–1.51). The distribution of C>T genotypes was different between patients and controls (P = 0.027).Furthermore, allete C of SNP rs2736990 in early-onset PD was significantly more frequent than that in healthy controls (p = 0.007,OR = 1.60,95%CI:1.13–2.26).Conclusions: Our study demonstrated that SNCA rs2736990 C>T polymor-phism was associated with susceptibility to PD in Chinese Han population. Further studies are needed to replicate the association we found.References1. Mata IF, Yearout D, Alvarez V, Coto E, de Mena L, Ribacoba R, et al.

Replication of MAPT and SNCA, but not PARK16–18, as susceptibility genes for Parkinson’s disease. Mov Disord 2011;26:819–3.

2. Cookson MR.The biochemistry of Parkinson’s disease. Annu Rev Biochem 2005; 74:29–52.




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P53 AND THE TRANSCRIPTION FACTOR XBP-1 AT THE CENTER OF A MOLECULAR DIALOGUE BETWEEN PARKIN AND DJ-1F. Checler1,*, E. Duplan1, C. Alves da Costa1

1IPMC, UMR7275 CNRS-UNSA, Valbonne, France

Objectives: Parkinson’s disease (PD) is either due to autosomal dominant or recessive modes of inheritance. Recessive cases are linked to mutations in the genes of parkin, Pink-1 and DJ-1. Parkin interacts physically with DJ-1 monomers in oxidative stress conditions but did not promote its proteasomal degradation as could be suspected from its well characterized function as an E3 ubiquitin ligase. Therefore, we examined whether parkin could control DJ-1 via its function as transcription factor1.Methods: Methods include: Western blot analysis of proteins in neuronal cells and parkin knockout animals; promoter transactivation luciferase measure-ments; ChIP analysis.Results: We established that parkin controls DJ-1 by a mechanism in-dependent of its ubiquitin-ligase activity. This regulation is abolished by PD-related pathogenic mutations2. Parkin increases DJ-1 promoter trans-activation, mRNA levels and protein expression via repression of p53 at first. Subsequently, this activates another transcription factor, namely ER-stress induced X-box-binding protein-1S (XBP-1S). We show that XBP-1S physically interacts with DJ-1 promoter, thereby raising DJ-1 mRNA and protein levels.Conclusions: We have unraveled a functional interplay between parkin and DJ-1 that could control ER-stress response in physiopathological conditions.References1. da Costa et al. Nature Cell Biology, 2009, 11, 1370–1375.2. Duplan et al. Journal of Cell Science, 2013, 126, 2124–2133.No conflict of interest

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MITOCHONDRIA QUALITY CONTROL IN PD: THE INTERACTION BETWEEN PARKIN AND PGC-1A?L. Zheng1,*, P. Aebischer1, B. Schneider1

1Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

Objectives: Mitochondrial function is central in the pathology of Parkinson’s disease (PD), and is transcriptionally regulated by PGC-1α. The Parkin pro-tein, which is directly associated to recessive forms of PD, was recently found to promote mitophagy. Our goal was to explore the functional interaction be-tween Parkin and PGC-1α in neuronal systems, and determine how this inter-action may affect mitochondrial function.Methods: In vitro, we overexpressed PGC-1α and Parkin in mouse cortical neurons using infection with adeno-associated virus (AAV).In vivo, we overexpressed PGC-1α and Parkin in the adult rat substantia nigra using AAV vectors.Results: In vitro, Parkin increases the mitochondrial reserve capacity of pri-mary cortical neurons overexpressing PGC-1α, as compared to the PGC-1α alone condition, without impacting the mitochondria quantity.PGC-1α overexpression was previously found to specifically impact on nigral dopaminergic function. We show that PGC-1α overexpression reveals differ-ences in nigral neuron degeneration between Parkin WT and mutants. And Parkin WT but not its disease-associated mutants is able to correct ampheta-mine-induced rotametry under PGC-1α overexpression.Conclusions: Overall, these results reflect the concerted role of Parkin and PGC-1α on mitochondrial turnover, which is critical to the function of nigral dopaminergic neurons.References1. Zheng et al. Sci Transl Med (2010)2. Van et al. Hum Mol Gen (2011)3. Ciron et al. Hum Mol Gen (2012)No conflict of interest

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DJ-1 SWITCHES CELL SURVIVAL/DEATH IN RESPONSE TO OXIDATIVE STRESSS.M.M. Iguchi-Ariga1,*, H. Ariga2

1Laboratory of Environmental Molecular Bioscience, Faculty of Agriculture Hokkaido University, Sapporo, Japan, 2Laboratory of Molecular Biology, Faculty of Pharmaceutical Sciences Hokkaido University, Sapporo, Japan

Objectives: The product of DJ-1 = PARK7 interacts with various proteins to play different roles in a variety of functions, which are suggested to depend on the oxidative levels of DJ-1 at cysteine 106 (C106). The precise effects of DJ-1 oxidation on interaction with partner proteins were to be analyzed.Methods: We focused on the interaction between DJ-1 and p53, a tumor sup-pressor protein that activates transcriptional programs under various types of cellular stress including oxidative stress. Various mutants of DJ-1 and p53

were introduced into culture cells and the binding and transcriptional activities were examined.Results: DJ-1 moderately oxidized binds to p53 and interfered in weak in-teraction between wild-type p53 and relevant non-consensus recognition se-quence in the DUSP1 promoter, or between a mutated p53 and the consensus in the p21 promoter. DJ-1 thus regulates the expression of p53 target genes to inhibit apoptosis, depending on the oxidation of DJ-1 and the p53 DNA-binding affinity.Conclusions: Hyperoxidation of DJ-1 due to accumulation of oxidative stress-es involved in aging yields dysfunction of the protein and may thus result in unfavorable apoptosis leading the onset of various diseases including PD.

Figure. DJ-1 selects an appropriate responding system to oxidative stresses according to the level of stresses reflected by its oxidized states

reduced form oxidized/ activated formsHyperoxidized/inactive form

Oxidative StressStress-free

SH SH SOH

DJ-1 DJ-1 DJ-1 DJ-1 DJ-1 DJ-1 DJ-1 DJ-1

SOH SO2H SO2H SO3H SO3H

Cell survival/proliferation Cell survival/proliferation

Cell death/ Apoptosisfor the whole body

Give upROS scavange

Alert anti-oxidative stress systemstowards cell survivalin association with

various partner proteins

Absorb/scavangeROS by

self-oxidizationat Cys residues

References1. Mol. Cell. Biol. 33(2), 340–359 (2013)2. Oxid. Med. Cell. Longev. Article ID 683920 (2013)No conflict of interest

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LOSS OF PARK9 LEADS TO DEFECTIVE AUTOPHAGY WITH FAILURE TO UPREGULATE ATG8/LC3M. Madeo1, A. Yarrow1, T.N. Jepperson1, D. Langager1, S. Padilla-Lopez1, M.C. Kruer1,*1Pediatrics & Neurosciences, Sanford Children’s Health Research Center, Sioux Falls, USA

Objectives: Mutations in PARK9 cause an early-onset, aggressive form of Parkinsonism. PARK9 encodes a transmembrane protein of unknown func-tion, putatively localized to the lysosome/vacuole and acidic vesicles. Previous studies have shown that PARK9 is induced by toxic levels of Mn++ exposure. We sought to understand the mechanisms contributing to PARK9-associated neurodegeneration.Methods: We studied loss of function paradigms in both yeast deletion mu-tants and PARK9 patient-derived fibroblasts.Results: Our findings indicate that PARK9 expression is markedly upregulat-ed by diverse cell stressors, including heat shock, oxidative stress, starvation, and Mn++ exposure. We find that loss of PARK9 function leads to a marked im-pairment of autophagy activation in response to specific autophagy inducers. However, under conditions of caloric restriction, autophagy proceeds normally, suggesting that the autophagic machinery is preserved. PARK9-associated autophagic insufficiency is characterized by a failure to upregulate Atg8/LC3 appropriately despite intact autophagy induction and flux. Treatment with ra-pamycin partially rescues the Atg8/LC3 depletion phenotype and restores au-tophagy to near-control levels.Conclusions: These results suggest that PARK9 serves as a stress-response protein and normally activates autophagy at least in part by upregulating Atg8/LC3 levels.No conflict of interest

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SRY, A GENE ONLY IN MALES, AND SEX-BIAS IN PARKINSON’S DISEASEJ. Lee1, D. Czech1, J. Correia1, A. Russ1, V. Harley1,*1Brain and Gender, Prince Henry’s Institute of Medical Research, Clayton, Australia

Objectives: Introduction: In Parkinson’s disease (PD) and 6-hydroxydopa-mine toxin-induced animal models, males show increased severity. Attributed to sex hormones historically, we propose that SRY also contributes, based on its substantia nigra pars compacta (SNc) expression, transcriptional control of both dopamine biosynthesis, and motor function in males.



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Objective: To determine the function of SRY in rats and dopamine cell lines treated with 6-OHDA.Methods: In vitro M17 cells treated with 6-OHDA/p-quinone/hydrogen per-oxide and/or p38-MAPK agonist/antagonist; mRNA and protein expression measured by qRT-PCR and Western blot, cell viability by WST-1 assay; ROS production by H2DCFDA assay. In vivo: Daily injection of SRY antisense (or sense control) oligonucleotides into rat SNc of 6-OHDA lesioned male rats. Motor function assessed by limb-use asymmetry and rotarod tests.Results: In M17 cells, low 6-OHDA doses increased SRY levels, via the p-quinone stress pathway/GADD45g/MAPK signalling – a protective response since SRY knockdown increased cell death. At high 6-OHDA (causing >50% cell death), SRY levels fell below basal (no drug) levels, abolishing its protec-tive effect. In vivo, SRY knockdown impaired motor function in cylinder and rotarod tests (−21% and −24%), and further exacerbated motor impairment in 6-OHDA treated male rats (−19%) in the cylinder test, compared to the control group.Conclusions: The protective role of SRY in dopamine neurons is dysregu-lated under cell stress conditions. This may contribute to the susceptibility of males to nigral injury during PD progression.No conflict of interest

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MUTATION IN THE SYNJ1 GENE ASSOCIATED WITH AUTOSOMAL RECESSIVE, EARLY-ONSET PARKINSONISMS. Olgiati1,*, M. Fang2, M. Picillo3, M. Quadri1, G.J. Breedveld1, J. Graafland1, B. Wu2, F. Xu2, R. Erro3, M. Amboni4, S. Pappata5, M. Quarantelli5, H.F. Chien6, E.R. Barbosa6, B.A. Oostra1, P. Barone7, J. Wang2, V. Bonifati11Clinical Genetics, Erasmus MC, Rotterdam, Netherlands, 2BGI-Shenzhen, BGI, Shenzhen, China, 3Neurological Sciences, University of Naples “Federico II”, Naples, Italy, 4IDC Hermitage – Capodimonte, IDC Hermitage – Capodimonte, Naples, Italy, 5Biostructure and Bioimaging Institute, National Research Council, Naples, Italy, 6Neurology, University of Sao Paulo, Sao Paulo, Brazil, 7Medicine and Surgery – CEMAND, University of Salerno, Salerno, Italy

Objectives: Autosomal recessive, early-onset Parkinsonism is clinically and genetically heterogeneous. We report the identification of a SYNJ1 homozy-gous mutation (p.Arg258Gln) segregating with disease in an Italian consan-guineous family with Parkinsonism, dystonia, and cognitive deterioration. Response to levodopa was poor, and limited by side effects. Neuroimaging revealed brain atrophy, nigrostriatal dopaminergic defects, and cerebral hypometabolism.Methods: We identified the mutation by homozygosity mapping and exome sequencing. To investigate the causality between the SYNJ1 mutation and the disease, we perform Sanger sequencing of the family members, 180 ethnically-matched controls, and 118 unrelated patients with early-onset Parkinsonism.Results: SYNJ1 encodes synaptojanin 1, a phosphoinositide phosphatase protein with essential roles in the post-endocytic recycling of synaptic vesi-cles. The mutation is absent in variation databases and in ethnically-matched controls, is damaging according to all prediction programs, and replaces an amino acid that is extremely conserved in the synaptojanin 1 homologues and in SAC1-like domains of other proteins. Sequencing the SYNJ1 ORF in unrelated patients revealed another heterozygous mutation (p.Ser1422Arg), predicted as damaging, in a patient who also carries a heterozygous PINK1 truncating mutation.Conclusions: The SYNJ1 gene is a compelling candidate for Parkinsonism; mutations in the functionally linked protein auxilin cause a similar early-on-set phenotype, and other findings implicate endosomal disturbances in the pathogenesis. Our data delineate a novel form of human Mendelian Parkinsonism, and provide further evidence for abnormal synaptic vesicle recycling as a central theme in the pathogenesis.No conflict of interest

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ANALYSIS OF THE ASSOCIATION OF MINISATELLITE UPS29 OF ACAP3 GENE WITH PARKINSON’S DISEASEN. Borovkova1,*, I. Suchkova1, E. Borisova2, E. Belotcerkovskaya1, I. Milyukhina3, A. Rogozina1, A. Yakimovskii4, L. Sasina1, E. Patkin1

1Molecular Genetics, Institute of Experimental Medicine Russian Academy of Medical Sciences, St. Petersburg, Russia, 2Clinic of Neurology, Institute of Experimental Medicine Russian Academy of Medical Sciences, St. Petersburg, Russia, 3Physiology (Pavlov’s), Institute of Experimental Medicine Russian Academy of Medical Sciences, St. Petersburg, Russia, 4Physiology, St. Petersburg Pavlov State Medical University, St. Petersburg, Russia

Objectives: Among the pathologies of the nervous system, Parkinson’s dis-ease is one of the most frequently arising neurodegenerative diseases and

has a multifactorial nature with a clear genetic predisposition [Pankratz, and Foroud, 2004].The aim of this work was to identify new genetic markers as-sociated with different forms of Parkinson’s disease. The frequency of different allele variants of the minisatellite UPS29, localized in the intron of centaurin β5 gene (ACAP3; CENTB5), was evaluated for patients with this pathology. Parkinson’s disease patients (171 individuals) were divided into three groups depending on the age of disease onset. The control sample consisted of 178 volunteers.Methods: Genomic DNA was extracted from the leucocytes of periphery blood using the standard phenol-chloroform method. Allelic variants UPS29 were detected with PCR.Results: An increase in the frequency of UPS29 short alleles was observed for Parkinson’s disease patients. This value depended on patient sex and the time of disease onset. Statistically significant differences with the control were found only for females with early (30–50 years of age) and late (over 60 years of age) onset of Parkinson’s disease.Conclusions: It is suggested that UPS29 might be used as a new genetic marker for early (presymptomatic) diagnosis of predisposition to some forms of Parkinson’s disease.Reference1. Pankratz N., and Foroud?. (2004) Genetics of Parkinson Disease. J. Am.

Soc. Exp. NeuroTher., 1: 235–242.

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ASSOCIATION OF RS62063857 VARIANT OF THE SAITOHIN GENE WITH PARKINSON’S DISEASEE. Sonmez1,*, A. Sazci1, M.D. Ozel1, E. Ergul1, H.A. Idrisoglu2

1Medical Biology and Genetics, Kocaeli University Faculty of Medicine, Kocaeli, Turkey, 2Neurology, Istanbul University Faculty of Medicine, Istanbul, Turkey

Objectives: Saitohin gene located in the intron 9 of the human tau gene en-coding a protein of 128 amino acid is supposed to be involved in the patho-genesis of neurodegenerative diseases. The effect of the rs62063857 of the saitohin gene on Parkinson’s disease has not been revealed in different populations.Methods: Herein, we examined the association of the rs62063857 poly-morphism with Parkinson’s disease in 562 PD patients and 423 controls by genotyping the rs 62063857variant of saitohin gene with a polymerase chain reaction and restriction fragment length polymorphism method.Results: We identified a significant association between rs62063857 variant of saitohin gene and risk of PD in overall patients and controls (χ2 = 12.413, P = 0.002) as well as in genders (χ2 = 7.818, P = 0.020 in male; χ2 = 5.001, P = 0.082). The individuals with AA (QQ) genotype in overall patients showed significantly increased risk for PD (χ2 = 12.218, P = 0.000) and the G (R) allele revealed significantly increased protection against PD (χ2 = 12.218, P = 0.000). The individuals with AA (QQ) genotype in male PD patients had significantly increased risk for PD (χ2 = 7.817, P = 0.005). The individuals with AA (QQ) genotype in female PD patients showed also significantly increased risk for PD (χ2 = 4.361, P = 0.037). In male and female PD patients there were A (Q) allele association as well with PD.Conclusions: Our findings show that the rs62063857 polymorphism of the saitohin gene is statistically significantly associated with PD. Hence, the AA genotype and A allele are genetic risk factors for PD in the Turkish population studied herein.Reference1. Kwok JB, et al.Ann Neurol. 2004;55(3):329–34.No conflict of interest

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PREMOTOR ABNORMALITIES IN ASYMPTOMATIC CARRIERS OF THE VPS35 P.ASP620ASN MUTATIONF. Esposito1,*, F. Siclari1, J.O. Prior2, J. Ghika3, P.R. Burkhard4, C. Vilarino-Guell5, M.J. Farrer5, Z.K. Wszolek6, F.J. Vingerhoets1, C. Wider1

1Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, 2Service of Nuclear Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, 3Service of Neurology, Sion Hospital, Sion, Switzerland, 4Department of Neurology, Geneva University Hospitals, Lausanne, Switzerland, 5Department of Medical Genetics, University of British Columbia, Vancouver, Canada, 6Department of Neurology, Mayo Clinic, Jacksonville, USA

Objectives: To evaluate the presence of premotor abnormalities and assess their association with the VPS35 p.Asp620Asn mutation in unaffected mem-bers of the Swiss Parkinson’s Disease (PD) family which contributed to the identification of VPS35.Methods: Prior to the identification of VPS35, unaffected family members underwent neurological examination (including UPDRS); olfactory testing



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(UPSIT); questionnaires for sleep disturbances (PDSS, ESS, RBDSQ); and 18F-DOPA positron emission tomography imaging (FDOPA-PET) with Patlak determination of Kiocc. The VPS35 p.Asp620Asn mutation was screened with allele-specific PCR.Results: Eleven unaffected, at-risk family members were enrolled in the study. Five individuals carried the wild-type allele (WT) and 6 individuals har-bored the pathogenic mutation (Mut). Neurological examination was normal in all 11 individuals. Lower smell test scores were observed in Mut individ-uals compared to the WT group (36.5 vs. 29.4, p < 0.05). A trend towards higher scores for the three sleep scales was observed in Mut individuals, however without reaching statistical significance. Mut subjects had reduced striatal 18F-DOPA uptake (Kiocc = 0.01075 ± 0.00144) compared to WT subjects (Kiocc = 0.01229 ± 0.00155) (p < 0.05), with posterior predominance.Conclusions: The results show that smell alterations occur prior to motor man-ifestations in healthy carriers of the VPS35 p.Asp620Asn mutation. There was a trend towards sleep abnormalities among mutation carriers. Our study also shows that subclinical dopaminergic deficits can be demonstrated in asympto-matic individuals harboring the VPS35 p.Asp620Asn mutation, suggesting that FDOPA-PET may be a useful predictor of mutation status in at-risk individuals. Premotor abnormalities in VPS35 mutation carriers should be assessed in at-risk family members to estimate the risk of developing clinical PD.No conflict of interest

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SEVERE NIGROSTRIATAL DEGENERATION WITHOUT CLINICAL PARKINSONISM IN PATIENTS WITH POLG MUTATIONSC. Tzoulis1,*, G.T. Tran1, T. Schwarzlmüller2, K. Specht3, K. Haugarvoll1, N. Balafkan1, P.K. Lilleng4, H. Miletic5, M. Biermann2, L.A. Bindoff1

1Department of Neurology Centre for Mitochondrial Medicine & Neurogenetics, Haukeland University Hospital and University of Bergen, Bergen, Norway, 2Centre for Nuclear Medicine/PET Department of Radiology, Haukeland University Hospital and University of Bergen, Bergen, Norway, 3Department of Biological and Medical Psychology Department of Medical Engineering, Haukeland University Hospital and University of Bergen, Bergen, Norway, 4Department of Pathology The Gade Institute, Haukeland University Hospital and University of Bergen, Bergen, Norway, 5Department of Pathology Department of Biomedicine, Haukeland University Hospital and University of Bergen, Bergen, Norway

Objectives: Mitochondrial dysfunction is involved in the degeneration of the substantia nigra and Parkinson disease. Herein, we study the effects of pol-ymerase gamma (POLG) mutations – one of the most common causes of mitochondrial dysfunction and disease – on the structure and function of the substantia nigra.Methods: We studied the substantia nigra in eleven patients with POLG muta-tions. Mitochondrial and structural pathology were characterized in six patients and in vivo nigrostriatal integrity and cerebral metabolism were investigated in five us-ing dopamine transporter (DAT) imaging and positron emission tomography (PET).Results: POLG mutations cause severe mitochondrial DNA depletion and ac-cumulation of deletions in dopaminergic nigral neurons. This leads to a selective and progressive respiratory complex I deficiency, which causes neuronal loss.Histology and imaging show that the degree of nigral degeneration and ni-grostriatal denervation in our patients are even more pronounced than in idiopathic Parkinson disease. Despite this, our patients do not have parkin-sonistic features. The additional presence of thalamic and cerebellar dysfunc-tion in our patients suggests that these may play a role in counteracting the effects of basal ganglia dysfunction and preventing the development of clinical Parkinsonism.Conclusions: Our findings show that nigral neurons are highly vulnerable to mitochondrial dysfunction and in particular mitochondrial DNA damage.Moreover, we show that severe nigrostriatal depletion can occur without the clinical correlate of Parkinsonism. These results raise fundamental ques-tions about our current understanding of the pathophysiological model of Parkinsonism and suggests that other and yet unknown mechanisms contrib-ute to the generation of the parkinsonistic syndrome.No conflict of interest

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ASSOCIATION STUDY OF MITOCHONDRIAL DNA POLYMERASE G GENE POLYMORPHISMS WITH PARKINSON IN SOUTH INDIAN POPULATIONSB. Vellingiri1,*, S. Suresh kumar1, M. Arun1, K. Sankar1, K. Sasikala1, S.N. Dharwatkar2

1Zoology, Bharathiar University, Coimbatore, India, 2Zoology, KLE Medical University, Bangalore, India

Objectives: Mitochondrial DNA polymerase gamma (POLG1) mutations were associated with Parkinsonism. POLG1 gene contains a number of common non synonymous single nucleotide polymorphisms (SNPs) and intronic regu-latory SNPs which may have functional consequences.

The study was conducted in 19 sporadic PD patients and 19 healthy con-trols in SNPs of POLG1 gene. The genetic polymorphisms in POLG1 gene to evaluate it as potential candidate gene for PD was analyzed.Methods: We performed extensive screening of POLG1 gene by direct se-quencing to detect polymorphisms, and statistical analysis to examine the ge-netic effects on PD in selected subjects.Results: We provided evidence for strong association of four intronic SNPs of the POLG1 gene (2070-12T>A: 2070-64G>A in intron 11, P = 0.00011, OR = 1.727; 3105-11T>C and 3105-36A>G in intron 19, P = 0.00031, OR = 1.648) with PD. However, we did not identify any significant association between ten exonic SNPs of POLG1 and PD. Linkage disequilibrium analysis indicated that 2070-12T>A and 2070-64G>A could be parsed into one block as Haplotype 1 as well as 3105-11T>C and 3105-36A>G in Haplotype 2. In addition, case and control study on association of POLG1 CAG repeat (poly-Q) alleles with PD showed a significant association (P = 0.03, OR = 2.16) of the non-10/11Q variants with PD.Conclusions: Awareness that mitochondrial POLG1 mutations can underlie Parkinsonism is important for clinicians working in diagnosis of movement dis-orders, as well as for studies of the genetics of Parkinson’s disease.Reference1. Wong et al. 2008No conflict of interest

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MUTATION ANALYSIS OF COQ2 GENE IN ITALIAN PATIENTS WITH MSAG. Franco1,*, D. Ronchi1, L. Borellini1, I. Trezzi1, E. Di Biase1, V. Melzi1, M. Rizzuti1, S. Bonato1, S. Corti1, N. Bresolin1, G.P. Comi1, A. Di Fonzo1

1Department of Pathophysiology and Transplantation Neuroscience Section University of Milan, IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

Objectives: Multiple system atrophy (MSA) is a neurodegenerative disorder of unknown aetiology, clinically characterised by autonomic failure in combi-nation with poorly levodopa responsive Parkinsonism, cerebellar dysfunction and pyramidal signs. Recently mutations in the COQ2 gene have been identi-fied as causative in familial autosomal recessive MSA. We aim to screen the COQ2 gene in Italian MSA patients.Methods: We performed a sequencing analysis of the COQ2 gene in 14 pa-tients with a diagnosis of probable MSA-P (2 familiar and 12 apparently spo-radic) and 6 sporadic patients with MSA-C.Results: A homozygous Ala43Gly variant in the COQ2 gene (according to the NM_015697.7 accession number) was identified in a sporadic Italian patient with MSA-C and was absent in matched controls. In addition one patient was found harbouring a single heterozygous Asn180Ser which was absent in the control panel. The variant is located within the very conserved putative sub-strate-binding site (UbiA). Functional studies to demonstrate the pathogenicity of these variants are ongoing.Conclusions: Mutations in the COQ2 gene may represent a rare cause of MSA in Italian population. Further genetic and functional analysis to investi-gate the role of COQ2 in MSA are needed.Reference1. Mutations in COQ2 in familial and sporadic multiple-system atrophy.

Multiple-System Atrophy Research Collaboration. N Engl J Med. 2013 Jul 18;369(3):233–44. doi: 10.1056/NEJMoa1212115. Epub 2013 Jun 12. PMID: 23758206


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NO ASSOCIATION OF COQ2 VAL343ALA VARIANT IN CHINESE PATIENTS WITH SPORADIC MULTIPLE SYSTEM ATROPHYH. Shang1,*, B. Cao1, B. Zhao1, Y. Chen1, W. Song1, Q. Wei1, K. Chen1, X. Guo1, X. Chen1


Objectives: Multiple system atrophy (MSA) is a fatal neurodegenerative disorder without unknown aetiology, characterized by autonomic failure, poorly levodopa-responsive Parkinsonism, cerebellar ataxia, and pyramidal symptoms in variable combinations. Recently, the variant, Val343Ala, have been reported to increase the risk of MSA in familial and sporadic patients in Japanese population (2013). However, the association between the variant in COQ2 and MSA in Chinese population haven’t been reported.Methods: A total of 172 sporadic MSA patients from Department of Neurology, West China Hospital of Sichuan University were included. From the same region, 200 hundreds healthy individuals were recruited as a control group. Genotyping of the Val343Ala in the exon 8 of COQ2 was carried out by directly sequencing.Results: In the present study, mean onset age of all patients was 57.11 ± 10.05 years. The patients presented with MSA-C (56.40%) was more



65

than MSA-P (43.60%). Five patients with MSA-C were found to be carrying Val343Ala, but two with MSA-P. The mean onset age of patients carrying Val343Ala was 55.79 ± 7.44 years. We found no significant difference in the frequency of Val343Ala between MSA patients (7/172, 4.07%) and healthy controls (6/200, 3.00%). In addition, we found no mutation in the exon 8 of COQ2 in all MSA patients.Conclusions: Our results suggested that there was no association of COQ2 Val343Ala variant with sporadic MSA in ethnic Chinese. More association studies with larger numbers of participants will be needed to confirm our find-ing in the future.Reference1. 2013. Mutations in COQ2 in familial and sporadic multiple-system atrophy.

N Engl J Med 369(3), 233–44. doi:10.1056/NEJMoa1212115.No conflict of interest

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META-ANALYSIS OF C9ORF72 (G4C2)N REPEAT EXPANSIONS IN A GLOBAL COHORT SUPPORT A ROLE FOR INCREASED PD GENETIC RISKJ. Theuns1,*, A. Verstraeten1, K. Sleegers1, E. Wauters1, I. Gijselinck1, D. Crosiers2, B.A. Pickut3, S. Engelborghs4, P.P. De Deyn5, P. Cras3, M. Cruts1, C. Van Broeckhoven1, on behalf of the GEO-PD consortium1

1Neurodegenerative Brain Diseases Group Department of Molecular Genetics VIB Antwerp and Institute Born-Bunge, University of Antwerp, Antwerp, Belgium, 2Neurodegenerative Brain Diseases Group Department of Molecular Genetics VIB Antwerp and Institute Born-Bunge, University of Antwerp and Department of Neurology, Antwerp University Hospital, Edegem, Belgium, 3Institute Born-Bunge University of Antwerp and Department of Neurology, Antwerp University Hospital, Edegem, Belgium, 4Department of Neurology and Memory Clinic Hospital Network Antwerp Middelheim and Hoge Beuken and Institute Born-Bunge, University of Antwerp, Antwerp, Belgium, 5Department of Neurology and Alzheimer Research Center University of Groningen and University Medical Center Groningen Netherlands and Department of Neurology and Memory Clinic Hospital Network Antwerp Middelheim and Hoge Beuken and Institute Born-Bunge, University of Antwerp, Antwerp, Belgium

Objectives: Clinical heterogeneity has been established in carriers of a definite pathogenic (G4C2)n>60 repeat expansion in C9orf72 with 14–35% pre-senting with atypical Parkinsonism in early disease stages and an increased incidence of Parkinson disease (PD) in their relatives. The role of C9orf72 ex-pansions in the etiology of PD is less clear and we aimed to assess the global prevalence of C9orf72 repeat expansions.Methods: C9orf72 repeat expansions were assessed in a worldwide multi-center ‘Genetic Epidemiology of Parkinson disease (GEO-PD)’ cohort of 7,176 patients diagnosed with PD.Results: A definite pathogenic repeat expansion was detected in 4 PD pa-tients (4/7,176; 0.056%), all 4 with a positive familial history of neurode-generative dementia, ALS or atypical Parkinsonism. No definite pathogenic expansion carriers were detected in patients with a family history of PD or sporadic PD. Interestingly, meta-analysis of the participating GEO-PD cohorts revealed a significant increase in risk for carriers of intermediate G4C2 repeat alleles ≥10 units (10–40 units; p = 0.005).Conclusions: Our data for C9orf72 in PD, the largest meta-analysis per-formed to date, indicates that intermediate repeats (G4C2)10–40 likely play an important role in PD risk, whereas pathogenic repeat expansions (G4C2)n>60 are rare in PD patients. These findings may prove valuable in the molecular genetic reclassification of complex brain diseases which is of utmost impor-tance to improve differential diagnosis and to rationalize drug development.No conflict of interest

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THE POLYMORPHISM RS1572931 OF RAB7L1 REDUCES PARKINSON RISK IN HAN CHINESEH. Shang1,*, Y. Chen1, K. Chen1, W. Song1, X. Guo1, Q. Wei1, B. Zhao1, B. Cao1, R. Huang1


Objectives: Recently, rs1572931 single-nucleotide polymorphism (SNP) in putative promoter of RAB7L1 was reported to be associated with reduced risk for Parkinson disease (PD) in Ashkenazi Jewish population (Gan-Or, et al., 2012). The association between the rs1572931polymorphism and Parkinson disease has not been published in Chinese population.Methods: Five hundred and ninety-nine PD patients from Department of Neurology of West China hospital, Sichuan University were included. All medi-cal data for each patient were recorded in our database. Five hundred and twenty-two health controls (HC) were from the same region were recruited as control group. The SNP was identified by directly sequencing.

Results: There were significant differences in genotype frequencies and MAF for rs1572931 SNP between PD patients and HC (p = 0.0013 and p = 0.0048, respectively). We also found significant difference in the genotype frequen-cies and MAF for rs1572931 between early-onset PD group and matched HC (p = 0.0407 and p = 0.0162, respectively), and between late-onset PD group and matched HC (p = 0.0024 and p = 0.0212, respectively). The ORs of MAF for rs1572931 in PD was 0.7685 (95% CI: 0.6398–0.9231). Moreover, the fre-quency of PD patients with AA + AG genotypes was significantly lower than that in HC (p = 6.67E-05, OR = 0.6184, 95% CI: 0.4891–0.7820).Conclusions: Our results provide strong support for RAB7L1 rs1572931 de-creases the risk for sporadic PD in a Han Chinese population.Reference1. Gan-Or, Z., Bar-Shira, A., Dahary, D., Mirelman, A., Kedmi, M., Gurevich,

T., Giladi, N., Orr-Urtreger, A. 2012. Association of sequence alterations in the putative promoter of RAB7L1 with a reduced Parkinson disease risk. Arch Neurol 69(1), 105–10. doi:10.1001/archneurol.2011.924.


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CYTOGENETIC ANALYSIS AND OXIDATIVE DAMAGE ACTIVITY IN LYMPHOCYTES OF PARKINSON’S DISEASE (PD) PATIENTSM. Arun1,*, V. Balachandar1, S. MohanaDevi1, B. Balamuralikrishnan1, S. Suresh Kumar1, K. Sankar1, K. Sasikala1

1Zoology, Bharathiar University, Coimbatore, India

Objectives: Parkinson disease (PD) is a neurodegenerative disorder which causes dopaminergic neuronal loss in the nigro striatal pathway. The aim of our research is to explore the relation between chromosome instability and oxidative stress biomarkers in PD using a variety of strategies.Methods: We determined peripheral markers for oxidative damage in PD by testing for spontaneous and induced chromosomal damage, DNA strand breaks, in peripheral blood and cultured lymphocytes, and measured glu-tathione S-transferase activity in the plasma of patients and controls. The PD patient group comprised of 62 individuals and equal numbers of control groups were selected.Results: Compared to healthy controls, PD patients show higher frequencies of micronuclei (17.2 ± 4.8 vs. 9.0 ± 3.4, p < 0.001) and a significant increase in the levels of SSB. Significant differences were also obtained in the distribution of oxidised purine bases between the two groups. Glutathione S-transferase activity in plasma from PD patients and controls was also measured and the enzymatic activity in PD patients was lower than in healthy controls.Conclusions: Thus, we cannot speculate about the significance of our findings, although in brain, other authors have also reported no significant differences in GST activity between PD patients and controls. Further work needs to be carried out to increase the sample size in order to confirm our findings and to determine the contribution of each isoenzyme to the total GST activity in both PD and controls.Key words: Parkinson’s disease, comet assay, micronuclei, Glutathione S-TransferasesNo conflict of interest

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IDENTIFICATION OF CIRCULATING MICRORNAS FOR THE DIFFERENTIAL DIAGNOSIS OF PARKINSON’S DISEASE AND MULTIPLE SYSTEM ATROPHYA. Vallelunga1,*, M. Ragusa2, S. Di Mauro2, T. Iannitti3, M. Pilleri4, R. Biundo4, L. Weis4, C. DI Pietro2, M. Zappia5, M. Purrello2, A. Antonini41Molecular Neurobiology Laboratory, IRCCS Fondazione Ospedale San Camillo, Venice, Italy, 2Department GF Ingrassia Biology Genetic and Bioinformatic unit, University of Catania, Catania, Italy, 3School of Biomedical Sciences, University of Leeds, Leeds, United Kingdom, 4Department for Parkinson’s Disease, IRCCS Fondazione Ospedale San Camillo, Venice, Italy, 5Department GF Ingrassia Section of neurosciences, University of Catania, Catania, Italy

Objectives: Our starting hypothesis was differentiate Parkinson’s disease (PD) patients from healthy individuals based on the identification of a distinct set of circulating miRNAs (cmiRNAs), small noncoding RNAs also present in extracellular human body fluids such as serum (1). Moreover, we hypothesize that specific panels of cmiRNAs could distinguish PD from Multiple System Atrophy (MSA) patients.Methods: We studied 6 patients with PD, 9 with MSA (6 MSA-Parkinsonian subtype and 3 MSA-Cerebellar subtype) and 5 healthy subjects as control group. A total of 745 miRNAs was profiled from the serum of each patient by using the TaqMan Low Density Array technology. Result validation was ob-tained by single TaqMan assays by applying the Wilcoxon signed-rank test to statistically evaluate miRNA differential expression among different groups of patients. A p-value less than <0.05 was considered significant.



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Results: We identified a set of 5 differently expressed cmiRNAs in both PD and MSA compared to healthy controls. More specifically, mir-148b and mir-339-5p were down-regulated and mir-223*, mir-324-3p and mir-1274A up-regulated. Moreover, we found cmiRNAs that are specifically dysregulated in PD (down-regulation of miR-30c and up-regulation of miR-34b), as well in MSA (downregulation of miR-24 and upregulation of miR-1291). Finally, when comparing PD and MSA, we identified 3 up-regulated cmiRNAs in serum of PD patients (miR-24, miR-34b and miR-339-5p).Conclusions: Our results suggest that cmiRNAs signatures could be used to discriminate PD from MSA patients and healthy controls. Accordingly, cmiR-NAs may be potentially specific biomarkers for early identification of degen-erative parkinsonian disorders.Reference1. Meza-Sosa et al 2012; Journal of Neuroscience Research, 90:1–12.No conflict of interest

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IDENTIFICATION OF DIFFERENTIALLY EXPRESSED MICRORNAS IN PERIPHERAL BLOOD FROM PARKINSON’S PATIENTSC. Schwienbacher1,*, A. Serafin1, L. Foco1, H. Blankenburg1, S. Zanigni1, A. Zanon1, G. Giannini1, I. Pichler1, M.F. Facheris1, P.P. Pramstaller2, F.S. Domingues1, A.A. Hicks1

1Center for Biomedicine European Academy Bozen/Bolzano (Eurac) Bolzano Italy, Affiliated institute of the University of Lübeck Lübeck Germany, Bolzano, Italy, 2Center for Biomedicine European Academy Bozen/Bolzano (Eurac) Bolzano Italy Affiliated institute of the University of Lübeck Lübeck Germany, Department of Neurology General Central Hospital Bolzano Italy Department of Neurology University of Lübeck Lübeck Germany, BolzanoLübeck, Italy

Objectives: To identify and characterize blood miRNAs differentially expressed in Parkinson’s disease (PD) patients versus controls as potential diagnostic biomarkers for PD.Methods: MiRNA expression was evaluated by RT-qPCR and data analyzed using a two-tailed paired t-test. To detect reliable miRNA targets, publically available and in-house datasets were combined to generate an overall score for each gene using weighted-rank aggregation.Results: Our study revealed significantly increased expression of three blood microRNAs in PD patients versus controls. Moreover, we identified a reliable and stable pair of reference genes for performing qRT-PCR in PD blood samples. In order to place the miRNA expression data into a biological context, we per-formed an integrated in silico analysis of the putative target genes of these three miRNAs.Conclusions: MiRNAs are strong and specific gene regulators and there-fore promising candidates for diagnostic biomarkers. Unfortunately to date no proven biomarkers are available for the diagnosis of PD. Our study revealed three candidate miRNA biomarkers for PD. For two miRNAs we confirmed a documented altered expression in peripheral blood, while for the third we demonstrated for the first time increased blood levels in PD.No conflict of interest

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TRANSCRIPTOMIC PROFILING OF PARKINSON´S DISEASE PATIENTS SKINA. Planken1, L. Kadastik-Eerme2, L. Kurvits2, E. Reimann2, S. Koks2, P. Taba2,*1Research and development, North-Estonian Medical Centre, Tallinn, Estonia, 2Medicine, University of Tartu, Tartu, Estonia

Objectives: To perform whole genome transcriptomic profiling of Parkinson´s Disease (PD) patients skin using RNA sequencing, in order to character-ize molecular pathogenesis of PD in peripheral tissues and to identify novel biomarkers.Methods: RNA sequencing analysis was performed from 12 PD (6 female and 6 male) and 12 healthy age/sex matched control skin puncture biopsy samples, using Ovation RNA-Seq System (NuGen) and SOLiD 5500 System DNA fragment library (LifeTechnologies). qRT-PCR validation of RNAseq data was performed using TaqMan technology (Applied Biosystems). tRNA from 37 PD and 32 control samples was used for verification of RNA sequencing data.Results: 1159 genes were found to be differentially regulated between PD and control skin biopsy samples, with statistical significance below 0.05. Functional analysis of differentially regulated genes showed the mitochon-drial dysfunction pathway to be the most affected in PD skin. Other regulated networks included skin homeostasis, keratinocyte differentiation, eukaryotic Initiation factor 2 (EIF2) signalling pathway, pathogenesis of Multiple Sclerosis pathway, VDR/RXR activation, granulocyte adhesion and diapedesis path-ways. Serum amyloid A1 and A2 genes were among the top downregulated genes in PD samples.Conclusions: RNA sequencing analysis of PD patients skin biopsies result-ed in over thousand differentially regulated genes as compared to control.

Functional analysis of differentially regulated networks will provide insight for pathogenesis of disease as well as for potential novel biomarkers for PD.No conflict of interest

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LARGE-SCALE QUANTITATIVE PROTEOMIC ANALYSIS OF THE SUBSTANTIA NIGRA IN PARKINSON’S DISEASEV. Licker1,*, N. Turck1, E. Kövari2, K. Burkhardt3, M. Surini Demiri2, M. Côte1, J.A. Lobrinus3, J.C. Sanchez1, P. Burkhard4

1Human Protein Science, CMU, Geneva, Switzerland, 2Mental Health and Psychiatry, HUG, Geneva, Switzerland, 3Pathology, HUG, Geneva, Switzerland, 4Neurology, HUG, Geneva, Switzerland

Objectives: The substantia nigra (SN) of Parkinson’s disease (PD) patients exhibits a progressive loss of dopaminergic neurons in the presence of in-traneuronal proteinaceous aggregates termed Lewy bodies. The precise se-quence of biological events triggering the neurodegenerative process is still unknown. To explore the complex nature of PD pathogenesis, we conducted a large-scale proteomic investigation of nigral tissues from patients with PD compared to controls.Methods: Human SN tissue samples were obtained at autopsy (post-mor-tem delay <48 h) from PD patients (n = 6) and age-matched controls (n = 6). Protein expression profiles of the two groups were compared by an MS/MS based shotgun proteomic technique utilizing the six-plex chemical labelling TMT for quantification.Results: We catalogued 1795 protein groups representing the largest nigral proteome published so far. Of them, 204 proteins were modulated in PD versus control cases. These proteins were involved in several cur-rently novel or known pathogenic pathways such as mitochondrial dysfunc-tion, oxidative stress or cytoskeletal impairment. We further characterized a subset of 4 candidate proteins relevant for PD pathogenesis. Ferritin-L overexpression and Seipin underexpression in PD were confirmed by west-ern blot. Nebulette and Gamma Glutamyl Hydrolase, respectively over- and under-expressed in PD, were shown to localize inside neurons by immunohistochemistry.Conclusions: Overall, the complex proteome alterations emphasized in this study provide novel insights into the pathogenic pathways at work in the SN of PD patients. Our findings suggest a role for Nebulette in PD neurodegeneration through mechanisms that may involve neuronal cytoskeleton dynamics disruption.No conflict of interest

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PHARMACOGENOMICS OF PD: MAPK10, CAFFEINE AND A2A-RECEPTOR ANTAGONISTSH. Payami1,*, W. Wissemann1, E. Hill-Burns1, P. Ganguli1, W. Wolfgang2, C. Zabetian3, S. Factor4

1Genetics, Wadsworth, Albany, USA, 2Bacteriology, Wadsworth, Albany, USA, 3Neurology, Univ. Washington, Seattle, USA, 4Neurology, Emory Univ, Atlanta, USA

Objectives: Adenosine-A2A-receptor-antagonists are promising treatments for PD, but efficacy has been low. We propose that efficacy varies by geno-type. Caffeine, an A2A-receptor-antagonist, is inversely associated with risk of PD. Objective: identify genes with significant impact on drug-response.Methods: We conducted genome-wide interaction studies in humans and Drosophila. Human study included 1,450 cases and 930 controls, each with 7,255,236 genotypes and lifetime caffeine-consumption data. We tested each genotype in-turn for interaction with caffeine-consumption in altering risk of PD. Drosophila model was constructed by exposing flies to varying doses of paraquat, caffeine, both, or neither, testing paraquat-toxicity and rescue by caffeine. We repeated the experiment with the optimal doses and compared gene expression levels in the brains.Results: Human study PD risk-reduction by caffeine (OR = 0.68, P = 6E-5) was significantly dependent on MAPK10 genotype (interaction P = E-8): caf-feine had no effect for individuals with the common genotype (OR = 0.94, P = 0.58), but it reduced risk by 60% (OR = 0.40, P = 7E-7) and 80% (OR = 0.20, P = 0.01), for individuals with one or two copies of the protective allele. In Drosophila, paraquat (a risk factor for PD in humans which mimics PD in flies and shortens lifespan via mitochondrial-toxicity) caused 11-fold in-crease in expression of MAPK10_orthologue (P = 5E-5). Addition of caffeine (which extends lifespan of paraquat-treated flies) lowered paraquat-induced gene-expression by 50%.Conclusions: Hypothesis-free genome-wide-studies in Drosophila and humans suggest MAPK10 is involved in paraquat-induced toxicity and caf-feine-induced protection against PD. MAPK10 is a neuronal-specific kinase that acts in the signaling pathway connecting adenosine-A2A-receptor to neu-ronal apoptosis. Utility of MAPK10 as pharmacogenomic marker should be tested in clinical trials.No conflict of interest



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STUDY OF THE ASSOCIATION OF DOPAMINE METABOLISM RELATED GENE POLYMORPHISMS IN INDIAN PATIENTS WITH PARKINSON’S DISEASER. Borgohain1,*, K. Nadella2, V.K. Kutala3, R.M. Kandadai1, A. Jabeen1, M.A. Kannikannan1

1Neurology, Nizam’s Institute of Medical Sciences, Hyderabad, India, 2Biotechnology, Centre for Biotechnology Jawaharlal Nehru Technological Institute, Hyderabad, India, 3Clinical Pharmacology, Nizam’s Institute of Medical Sciences, Hyderabad, India

Objectives: To elucidate the association of polymorphisms in dopamine me-tabolizing genes in patients with idiopathic Parkinson’s disease (PD).Methods: 150 patients with PD and180 age matched controls were included in the study. All patients underwent detailed neurological examination and af-ter consent blood was drawn for genetic testing. Polymorphisms in catecho-o-methyl transferase (COMT) (Rs4680), mono amine oxidase B (MA0-B) (rs6347), dopamine transporter DAT1 (rs6347) and dopamine receptor DRD2 (TaqI A rs1800497, Taq1B rs1079597 Taq1D rs1800498) were studied using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique in all. Association of polymorphisms with PD patients was studied using multifactor dimensionality reduction analysis (MDR).Results: Only polymorphisms in COMT and MAO B showed significant as-sociation as demonstrated in table below.

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EXOME AND TARGETED SEQUENCING IDENTIFY A NEW GENE CAUSING ESSENTIAL TREMORH. Hor1,*, L. Bartesaghi2, S. Ortega-Cubero3, O. Lorenzo-Betancor3, F.J. Jiménez-Jiménez4, A. Gironell5, J. Clarimón6, J.A.G. Agúndez7, D. Kenzelmann Broz8, R. Chiquet-Ehrismann8, F. Coria9, E. García-Martin10, H. Alonso-Navarro4, M.J. Martí11, S. Ossowski1, J. Kulisevsky5, R. Chrast2, P. Pastor3, X. Estivill11Bioinformatics and Genomics Program, Center for Genomic Regulation {CRG), Barcelona, Spain, 2Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland, 3Division of Neurosciences, Center for Applied Medical Research (CIMA), Pamplona, Spain, 4Section of Neurology, Hospital Universitario del Sureste, Madrid, Spain, 5Neurology Department, Hospital de Sant Pau, Barcelona, Spain, 6Sant Pau Biomedical Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain, 7Department of Pharmacology, University of Extremadura, Cáceres, Spain, 8Faculty of Sciences and Department of Biomedicine, Friedrich Miescher Institute of Biomedical Research, Basel, Switzerland, 9Service of Neurology, Son Espases University Hospital, Palma de Mallorca, Spain, 10Department of Biochemistry and Molecular Biology, University of Extremadura, Cáceres, Spain, 11Neurology Service, Hospital Clinic, Barcelona, Spain

Objectives: Essential tremor (ET) is the most common movement disorder. To date, numerous genetic studies have failed to identify a common genetic cause for this condition. We aimed to identify new genes involved in the patho-genesis of ET by studying multiplex ET families.Methods: We performed exome sequencing in an ET family in which the causative genetic variant segregated in an autosomal dominant fashion. We then performed targeted resequencing in a sample of 392 unrelated ET cases to identify additional mutations in the coding region of the identified gene. Finally, we performed transfection experiments of two different mutant cDNAs in both HEK and oligodendrocyte precursor cells to evaluate the functional consequences of these mutations.Results: We first identified a missense mutation in TENM4 segregating in the ET family. In the targeted resequencing experiment we identified additional novel and damaging mutations in TENM4 in 18 of 392 (4.6%) unrelated ET cases. Following this analysis, we found two additional families in which two novel missense mutations were segregating with the disease phenotype. The transfection experiments of two different mutant TENM4 cDNAs showed a

mislocalization of the corresponding mutant proteins and a reduced ability to form mono- and dimers for one of the mutants.Conclusions: The genetic and functional data is corroborated by a knock-out mouse of Tenm4 displaying a clear and striking ET phenotype. The identifica-tion of TENM4, which is an important regulator of oligodendrocyte maturation, highlights the discovery of a major gene in the pathogenesis of ET.No conflict of interest

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EFFECT OF NEUROMUSCULAR DISORDER CAUSING K141N MUTATION ON STRUCTURE-FUNCTION RELATIONSHIP OF HSP22D. Singh1,*, S. Deswal1, T. Ramakrishna2, C.M. Rao2

1Biotechnology, Universal Institute of Technology, Hisar, India, 2Biophysics, Centre for Cellular and Molecular Biology, Hyderabad, India

Objectives: The missense mutation of lysine-141 to asparagine (K141N) in HSP22 leads to Charcot-Marie-Tooth (CMT) disease and distal hereditary motor neuropathy (dHMN). Our study aims to understand mechanism underlying such peripheral neuropathies by studying the effect of this mutation on structure-function relationship of HSP22.Methods: The structural changes in the mutant protein were studied using cir-cular dichroism and fluorescence spectroscopy, gel-filtration chromatography and glycerol density gradient centrifugation. Chaperone activity studies were performed using aggregation of citrate synthase.Results: Far-UV CD spectrum shows that the K141N mutation results in in-crease in negative ellipticity and a shift of the maximum towards lower wave-length compared to the wild-type protein indicating increase in unordered secondary structure. K141N-HSP22 near-UV CD spectrum shows decreased ellipticity compared to the wild-type suggesting further perturbation of its ter-tiary structure. Consistently, the intrinsic fluorescence spectrum of K141N-HSP22 exhibits higher fluorescence intensity indicating a structural change. A hydrophobic probe, bis-ANS, binding studies revealed an increase in the accessible hydrophobic surface of the mutant protein. Quaternary structur-al studies suggest slightly larger and less compact size for mutant HSP22. K141N-HSP22 exhibits decreased light scattering in chaperone assays high-lighting enhanced substrate binding capacity and/or its irreversible binding with substrates possibly leading to the toxic gain of function.Conclusions: The K141N mutation in HSP22 results in altered folding leading to enhance exposure of hydrophobic sites. Such properties may contribute to increased aggregation and defective reversible chaperone activity in neurons leading to neuropathology.No conflict of interest

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GNAL DELETION AS A POSSIBLE CAUSE OF DYSTONIA IN A PATIENT WITH THE 18P- SYNDROMEF. Esposito1,*, M.C. Addor2, A.M. Humm3, F.J. Vingerhoets1, C. Wider1

1Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, 2Department of Medical Genetics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, 3Unit of Neurology, Hôpital Cantonal de Fribourg, Fribourg, Switzerland

Objectives: To report the case of a 19-year-old female with the 18p- syn-drome who developed generalized dystonia and immunological abnormalities.Methods: Case report.Results: The patient presented with progressive dystonic movements of the head and upper limbs, rapidly extending to the lower limbs. She had short stature, round face and bilateral ptosis. No response to levodopa, biperiden and clonazepam was observed. Symptoms worsened rapidly, with the patient becoming disabled and displaying swallowing difficulties. Blood tests revealed abnormalities compatible with a “lupus-like immunological profile”. Topiramate led to a marked reduction of dystonic movements.

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Table

Polymorphisms studied MAF Cases Controls Crude OR (95%CI) P Adjusted OR (95%CI) P

COMTrs4680 37.3 29.5 1.42 (1.02–1.98) 0.03* 1.37 (0.99–1.88) 0.05*

MAOBrs1799836 32.3 40.3 0.71 (0.51–0.99) 0.04* 0.78 (0.60–1.00) 0.05*

DAT1 rs6347 22 16.8 1.39 (0.93–2.09) 0.114 1.34 (0.92–1.95) 0.13

DRD2 rs1800497 35 31.2 1.19 (0.85–1.66) 0.34 1.26 (0.89–1.78) 0.18

DRD2 rs1079597 32 29.6 1.11 (0.78–1.56) 0.60 1.15 (0.82–1.63) 0.41

DRD2 rs1800498 34 37 0.91 (0.65–1.27) 0.63 0.83 (0.59–1.18) 0.29



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Array-CGH showed a 14.7Mb deletion involving the entire short arm of chro-mosome 18, compatible with the 18p- syndrome. Dystonia and autoimmune abnormalities are rare manifestations of the 18p- syndrome.Conclusions: Patients with the 18p- syndrome should be assessed for dys-tonia and autoimmune disease and carefully followed over time. Topiramate may be considered a therapeutic option in patients non-responsive to classic first-line dystonia therapies.Our observation supports the existence of dystonia and autoimmunity loci on 18p, where the GNAL gene was recently identified as a novel dystonia gene. Several point mutations in GNAL have been reported in patients with dystonia. In contrast, in patients with the 18p- syndrome the deleted region includes the GNAL gene, which may contribute to dystonia by a mechanism of haploinsufficiency.No conflict of interest

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OVEREXPRESSION MUTANT THAP1 REGULATE THE EXPRESSION OF TOR1A IN NEURONAL CELLSF. Cheng1,*, T. Ott1, K. Grundmann-Hauser1

1Medical Genetics, Eberhard Karls Universität Tübingen, Tübingen, Germany

Objectives: Mutations in TOR1A and THAP1 have been associated with dystonia 1 and 6, respectively. Recent studies reported a physical interac-tion between THAP1 and TOR1A promoter and that wild type THAP1 is able to repress the expression of TOR1A, the regulated mechanism and results of THAP1 on TOR1A promoter and the pathogenic mechanism of dystonia 6 as-sociated THAP1 mutations causing primary dystonia are not clear.Methods: Wild-type and three mutant THAP1 (S21T, F81L, L180S) constructs were generated and transfected into neuroblastoma cell lines (SK-N-AS cells) to get stably transfected cell lines under the selection of G418. The expression level of TOR1A in these cell lines were quantified using Western blot and Real-time PCR methods. Chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR) was used to identify the interaction of wild-type or mutants THAP1 with the TOR1A promoter.Results: We found that the TOR1A expression level was decreased in mu-tant THAP1 overexpressing cell lines, compared to wild-type or empty vector transfected cell lines. This repressive function is parallel with the expression level of THAP1. ChIP- qPCR confirmed that the interaction of mutant THAP1 with TOR1A promoter was impaired in neuronal cells overexpressing the three mutant THAP constructs, which in turn leads to decreased expression levels of TOR1A protein.Conclusions: These results indicate that mutant THAP1 might exert it pathogenic effect by modulating the expression level of torsinA. Whether this is the underlying pathogenic mechanism leading to DYT6 dystonia hast o be further evaluated.No conflict of interest

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MUTATION ANALYSIS OF ATP7B GENE IN NORTHERN VIETNAMESE PATIENTS WITH WILSON DISEASEH. Nguyen1,*, P.A.H. Nguyen2, P.M. Nguyen3, D.N. Ngo3, T.L. Nguyen4

1Human Genetics, National Hospital of Pediatrics, Hanoi, Vietnam2Hepatology, National Hospital of Pediatrics, Hanoi, Vietnam3Human Genetics, National Hospital of Pediatrics, Hanoi, Vietnam4Human Genetics Hepatology, National Hospital of Pediatrics, Hanoi, Vietnam

Objectives: Wilson disease (WD) is an autosomal recessive disorder of cop-per metabolism, which is caused by mutation in copper- transporting P-type ATPase (ATP7B). The gene defect in WD is ATP7B located on long arm of chromosome 13(13q14.3). This study aimed to identify the characteristic of ATp7B gene mutation and to report a novel mutation which is prevalence in Vietnam.Methods: 12 unrelated Wilson patients were studied. Genomic DNA was extracted from peripheral blood samples. The most common mutation, p.Arg778Leu was firstly screened by PCR-RFLP then all 21 exons and exon-intron boundaries of the ATP7B gene were analyzed by direct sequencing.Results: We identified 8 different mutations, accounting for 95.8% mu-tant alleles, among them one was novel mutation (p.Thr850Ileu). Mutation p.Ser105* was the most prevalent (62.5%). Others mutation are listed as fol-lowing: p.Arg778Leu (12.5%), p.Pro992Leu (4.17%), p.Asp1270Ser (4.17%), p.Leu1371Pro (8.33%). 5 patients with hepatitis were homozygous for a single mutation, and 6 patients with neurological or neurological companied with he-patic disease were in a compound heterozygous, 1 patient with hepatic was a single heterozygous.Conclusions: Characteristic of ATP7B mutation in Vietnamese may be dif-ferent from other Asia countries. p.Ser105* is the most prevalent mutation in Vietnam, and should be screened firstly who have a higher risk with WD be-fore sequencing analysis entire gene. p.Arg778Leu is unspecific in Vietnam.

References1. Zhang Y, Wu Z. Y. 2011. Wilson’ disease in Asia. Neurology Asia.

1(2):103–9.1.2. Ferenci P. 2006. Regional distribution of mutations of the ATP7B gene

in patients with Wilson disease: impact on genetic testing. Hum Genet. 120(2):151–9.

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GENOME-WIDE ASSOCIATION ANALYSES IN HAN CHINESE IDENTIFY TWO NEW SUSCEPTIBILITY LOCI FOR AMYOTROPHIC LATERAL SCLEROSISM. Deng1,*, L. Wei2, X. Zuo3, K. Wang4, X. Ju.5

1Medical Research Center, Peking University Third Hospital, Beijing, China, 2Department of Neurology, No. 1 Hospital Anhui Medical University, Hefei, China, 3State Key Laboratory Incubation Base of Dermatology, Anhui Medical University, Hefei, China, 4Department of Neurology, Anhui Medical University, Hefei, China, 5Institute of Sports Medicine, Peking University Third Hospital, Beijing, China

Objectives: Amyotrophic lateral sclerosis (ALS) is a fatal and genetic dis-ease characterized by a progressive loss of motor neurons which leads to paralysis and muscle atrophy. The pathogenic mechanism of ALS is elusive. Previous GWASs have identified several genes for ALS, such as FLJ10986. ITPR2, DPP6 and UNC13A. However, the genetic basis of ALS remains poorly understood.Methods: To identify susceptibility genes for ALS, we carried out a two-stage GWAS of ALS involving 1,239 cases and 3,669 controls in Chinese population to identify additional susceptibility genes for ALS.Results: We conducted a GWAS in 533 patients with sporadic ALS and 1,892 controls of Chinese Han. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWA studies were analyzed in an inde-pendent cohort of 706 ALS patients and 1,777 controls of Chinese Han. We discovered 2 new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, Pcombined = 2.92 × 10−8, OR = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, Pcombined = 2.35 × 10−9, OR = 1.52).Conclusions: These 2 loci explain 12.48% of the overall variance of disease risk in the Chinese Han population. We found no association evidence for the previously reported loci in the Chinese Han population, suggesting the genetic heterogeneity of disease susceptibility for ALS between ethnic populations. Our study discovered new genetic susceptibility factors and suggested new biological mechanisms of ALS.Reference1. Deng M, Wei L, Zuo X, et al. Genome-wide association analyses in Han

Chinese identify two new susceptibility loci for amyotrophic lateral sclero-sis. Nat Genet.2013; 45(6):697–701(Apr 28 doi:10.1038/ng.2627)


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IDENTIFICATION OF ASSOCIATED MITOCHONDRIAL DNA VARIATIONS AND HAPLOGROUP DISTRIBUTION IN INDIAN FRIEDREICH’S ATAXIA (FRDA) PATIENTSI. Singh1,*, F. Mohammed2, M. Behari3, A.K. Srivastava3

1Neurology, All India Institute of Medical Science, Delhi, India, 2Functional Genomics Unit, Institute of Genomics and Integrative Biology, Delhi, India, 3Neurology, All India Institute of Medical Sciences, Delhi, India

Objectives: Friedreich’s ataxia (FRDA) is among the most common hereditary ataxia caused by deficit in FXN gene encoding frataxin, a protein expressed in mitochondrial. Mitochondrial DNA (mtDNA) is considered as a candidate mod-ifier factor for FRDA disease, since mitochondrial oxidative stress is thought to be involved in the pathogenesis of this disease.Methods: For study 30 FRDA patients genetically confirmed with southern blot and Triplet PCR protocols and 63 ethnically and age matched controls were recruited. Dloop, Complex 1 and ATP region of mitochondrial genome was sequenced by polymerase chain reaction followed by direct sequencing.Results: The obtained sequences were compared with revised Cambridge Reference Sequence (rCRS). Haplogroups were determined using HAPLOGREP program. 101 mitochondrial variations were observed in cod-ing region, while 84 were seen in non coding (D Loop) region. Variations at positions T16356C, C5178A and C4883T were found significantly associated with Indian FRDA patients (P < 0.05). Haplogroup analysis revealed significant association (P < 0.05) of Haplogroup M with patients, while Haplogroup N was found in higher frequency among controls.Conclusions: Significant association of three variations T16356C, C5178A and C4883T indicate mtDNA instability by affecting the OXPHOS activity of mitochondria in FRDA patients. These variations in combination with en-vironmental risk factors may affect disease progression. Study suggested haplogroup M as risk haplogroup, encompassing inherited mitochondrial DNA variations having impact on predisposition to FRDA patients of Indian ethnicity.



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Acknowledgements: This study was financially supported in part by the Indian Council of Medical research (project I548) and the Council for Scientific and Industrial Research, Government of India (Supra-institutional project SIP0006).No conflict of interest

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CYTOGENETIC BIOMARKERS AND OXIDATIVE STRESS AND MOLECULAR STUDY OF APO E GENE IN ALZHEIMER’S DISEASE IN SOUTH INDIAN POPULATIONS. Sureshkumar1,*, V. Balachanadar1, S. Mohanadevi1, B. Balamurali Krishnan1, M. Arun1, A. Karthick Kumar1, K. Sankar1, S. MustaqAhamed1, K. Sasikala1

1Zoology, Bharathiar University, Coimbatore, India

Objectives: Alzheimer’s disease (AD) is a fatal neurodegenerative disorder and is the leading cause of dementia in the elderly. To identify the genetic alterations of AD by using the conventional cytogenetic techniques Trypsin G- banding. To conduct the biochemical parameters to analyzed by measur-ing the Neurotransmitters in AD patients. Apo E gene polymorphism in AD patients by using the PCR – RFLP was analyzed.Methods: Totally 70 AD patients blood was collected. The subjects were categorized in to two groups (31 EOAD) and (39 LOAD) patients, in order to investigate the possible cytogenetic damage using PBLC, The MN assay was performed using the cytochalasin B technique, Biochemical analysis by HPLC with ECD and APO E gene polymorphism in AD patients by using the PCR – RFLP.Results: Comparative analysis of CSAs in EOAD patient and LOAD patient. The LOAD patient shows higher total CA level when compared EOAD pa-tient. MN frequency was also found to be higher in LOAD patients. A com-parison of the frequencies for APO E genotypes among the EOAD and LOAD subjects which demonstras a significant difference between the two groups. Captivatingly in the study observed mutations in the chromosomes 10q, 9p, 9q, and 14p 19q and 21 was observed.Conclusions: The lack of evidence for interaction when the Apo E genotypes were used as covariates, despite the strong association of Apo E with LOAD patients. Therefore, new treatments with the therapeutic target of improving mitochondrial function may prove to be promising.No conflict of interest

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POST AND PRENATAL DIAGNOSIS FOR BETA THALASSEMIA IN NORTHERN VIETNAMH. Ly1,*, D.N. Ngo1, B.T. Duong1, T.N. Ngo1, P.M. Nguyen1, M.H. Nguyen1

1Human Genetics, National Hospital of Pediatrics, Hanoi, Vietnam

Objectives: Beta thalassemia is one of the most common autosomal reces-sive disorders in the world, caused by mutations on Hbb gene. In Vietnam, the carrier rate for β-thalassemia varies between 1.5–25%. This study was carried out to find mutations on Hbb gen, initial study about rate of highest frequence mutations of beta thalassemia patients in Northern Vietnam, and then prenatal diagnosis for fetuses with high risk of major beta thalassemia.Methods: 500 blood samples of patients and 200 amniotic fluid cells in 16–18 weeks in families who were carriers or affected individual identified

by clinicals and haematology were screened with multiplex ARMS-PCR and diagnosed with ARMS-PCR.Results: Rate of nine common mutations was found, including two high-est common mutations: CD17(AAG-TAG): 41.6%, CD41/42(-TCTT): 34.7%. Other mutation was included HbE (GAG-AAG), IVS1-1(G>T), IVS1-5(G>C), −28 (A>G), CD71/72 (+A), IVS2-654 (C>T), CD95 (+A). 10 of 500 samples were not found mutation in nine common mutations, 55 fetuses were found to be beta thalassemia major, 145 fetuses were not found to be beta thalas-semia major.Conclusions: Beta thalassemia is a common genetic disease in Vietnam. Mutation CD17(AAG-TAG) (41.6%) and CD41/42(-TCTT) (34.7%) in Hbb gene are the highest in Northern Vietnam, accounting for 41.6%. We con-clude that prenatal diagnosis is a reliable and accurate screening method for beta thalassemia and is valuable in Vietnam because of high prevalence for thalassemia.Reference1. Huang H, Xu L, Lin N, et al.(2013).Molecular Spectrum of β-Thalassemia

in Fujian Province, Southeastern China. Hemoglobin. May 20No conflict of interest

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UNIQUE TRANSCRIPTOME PATTERNS OF GREY AND WHITE MATTER CORROBORATE STRUCTURAL AND FUNCTIONAL HETEROGENEITY IN THE HUMAN FRONTAL LOBEJ.D. Mills1,*, T. Kavanagh1, W.S. Kim2, B.J. Chen1, Y. Kawahara3, G.M. Halliday2, M. Janitz1

1School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia, 2School of Medical Sciences, University of New South Wales, Sydney, Australia, 3Agrogenomics Research Center, National Institute of Agrobiological Sciences, Tsukuba, Japan

Objectives: To comparatively analyse the transcriptome profiles of grey mat-ter (GM) and white matter (WM) from the superior frontal gyrus of the human brain.Methods: RNA-Seq was used for transcriptome profiling. Differentially ex-pressed genes (DEG) were identified using the Cufflinks package. Pathway analysis was completed using the Database for Annotation, Visualization and Integrated Discovery.Results: 1,652 genes were identified as differentially expressed between GM and WM. This included 1,218 genes that were up-regulated in GM and 434 that were up-regulated in WM. The transcriptome profiles of both tissues correlated well with known gene markers for neurons and oligodendrocytes. Many unique elements were identified including the up-regulation of the long intergenic non-coding RNAs (lincRNAs), LINC00162 and LINC00263 in WM, and the presence of numerous novel transcripts in both GM and WM. Pathway analysis of the DEG showed a prevalence of synaptic processes in GM and myelination regulation and axonogenesis in WM.Conclusions: This study identified a large number of differentially expressed genes between GM and WM that matched up well with previous studies and the known biology of the human cerebrum, underlining the accuracy and the advantages of using RNA-Seq for the analysis of complex transcriptomes. This set of results form a baseline expression database for healthy GM and WM and can be used as a resource to help detect abnormal gene expression between GM and WM tissues from sufferers of neurodegenerative diseases or psychiatric disorders.No conflict of interest



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Objectives: Subjective outcome measures in CNS clinical trials are prone to rating errors and increased variability. We conducted a preliminary analysis of Phase II and III data across multiple indications and sponsors, to assess the presence of ‘Identical visits’.Methods: We defined an ‘Identical visit’ as any visit sharing the same item score set as that immediately preceding it. We analyzed available data from multiple trials across several CNS indications for the presence of such ‘Identical visits’.Results: We analyzed 101 863 subject visits across three indications: Major depressive disorder (N = 54 011), Schizophrenia (N = 36 734) and Parkinson’s disease (N = 11 118). Of 101 863 visits, 85 087 subject visits were classifi-able as an ‘Identical visit’. We identified 5 434 Identical visits (6.4%) in the total dataset. Of these, 1 652 (16.8%) were observed in PD studies. When analyzed by visit, the largest proportion of identical visits in PD was observed in early termination (26%) and baseline visits (24.7%). All other subject visits showed a percentage of identical visits below 20%. The presence of identical visits does not appear randomly distributed. While the mean distribution of identical visits across sites is 14.3%, the median is only 4.2%. 34% of all sites show no Identical visits, whilst 5% of sites demonstrate more than 70%.Conclusions: We suggest that the presence of identical visits at a site be used in risk-based monitoring. Sites with a large proportion of identical visits should be carefully monitored to assess the reasons underlying the observed discrepancies.

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THE USE OF PATIENT REPORTED NON MOTOR SYMPTOMS QUESTIONNAIRE (NMSQUEST) SCORE BASED PARKINSON’S DISEASE BURDEN ASSESSMENT IN THE OUTPATIENT CLINICI. Cova1,*, L. Klingelhoefer1, A. Sauerbier1, A. Rizos1, S. Bassi1, L. Gallagher1, P. Martinez-Martin2, K.R. Chaudhuri11National Parkinson Foundation Centre of Excellence Department of Neurology, King’s College Hospital and Kings Health Partners London UK, London, United Kingdom, 2Research Unit of the Alzheimer Center Reina Sofia Foundation and CIBERNED, Carlos III Institute of Health, Madrid, Spain

Objectives: The NMSQuest is a widely used self reported tool and previously a simple grading system using the NMSQuest total score to address the NMS burden in PD has been published.1 Four levels of NMS load are recognized; scores 0–5 = very mild, 6–12 = mild, 13–20 = moderate and >20 = severe.Methods: 100 consecutive completed NMSQuest (mean age 67.18 years; range 29–92 years), 38 females, 15 non white, disease duration 6.44 years (0.5–49 years) data was analyzed and classified using the NMSQuest load assessment grading, and correlated with Hoehn and Yahr stages (HY), assessment based entirely on motor assessment.Results: In the whole sample, NMSQuest levels were 22% in level 1 (very mild), 41% in level 2 (mild), 24% in level 3 (moderate) and 13% in level 4 (severe). 4 patients had drug naive PD (DNPD) at HY 1 (n = 2) and HY 2 (n = 2) and only 1 had mild NMSQuest (level 1) while in the rest, 1 had NMSQuest level 4, and 2 level 2 (moderate). Furthermore, 14% in level 3 and 7% in level 4 NMSQuest were in HY stage 1 while 16% NMSQuest 3 and 6% NMSQuest 4 were in HY stage 2 showing discordance between NMSQuest scores and HY.Conclusions: This observational analysis outlines the importance of using the self reported NMSQuest in clinic: a substantial proportion of patients, in spite of being in early “motor” stage (judged by HY), had considerable NMS burden prompting specific treatment packages which would have been other-wise overlooked.Reference1. Chaudhuri KR, Martinez-Martin P et al. Neurology 2009; 72 (3) A322.No conflict of interest.

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EEG IN ASSESSMENT OF EFFICACY TREATMENT OF PARKINSON’S DISEASEU. Ashonov1,*, B. Gafurov2, G. Askhanov1

1Neurology, Neurological Clinic “Nevromed-Servis”, Namangan, Uzbekistan, 2Neurology, Tashkent Institute for Postgraduate Medical Education, Tashkent, Uzbekistan

Objectives: To assess the efficacy of treatment with coenzyme Q10 (CQ) and PK-MERZ (PKM) by the EEG in patients with early and mid stage Parkinson’s disease (PD).Methods: Sixty three PD patients (age = 65.2 ± 7.0) and 15 normal subjects were assessed using a neurological evaluation, modified Hoehn and Yahr (HY) scale for PD, an EEG analysis of absolute and relative band amplitude at rest. Two groups were compared: first one is 30 patients who take PKM, another one 33 patients who take CQ with PKM during 12 month and the control group. Were used dominant frequency, amplitude, index of waves, cor-relation analysis of EEG and electromagnetic tomography sLoreta.

Section 2: PD Therapy

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HISTORICAL OVERVIEW OF PATHOMECHANISM UNDERLYING PARKINSON’S DISEASE AND FUTURE PROSPECTS FOR THERAPYT. Nagatsu1,*, M. Sawada2

1Department of Pharmacology, Fujita Health University School of Medicine, Toyoake, Japan, 2Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan

Objectives: Parkinson’s disease [PD: mostly sporadic (sPD); a few familial (fPD)] is an aging-related neurodegeneration of catecholamine [CA; dopamine (DA) and noradrenaline (NA)] neurons. We herewith present historical over-view of pathomechanism and future prospects for therapy.Methods: Understanding of pathomechanism and therapy for PD have advanced in parallel with progress in basic science and new technologies: biochemistry; immunology; cellular/molecular biology; molecular imaging; and systems biology.Results: Basic studies of postmortem brains, animal models (monkeys, rodents, etc.), and cellular studies, especially on induced pluripotent stem (iPS) cells from PD patients, have contributed to the elucidation of patho-mechanism. Key basic findings are: CA-related enzymes [monoamine oxidase (MAO), tyrosine hydroxylase (TH), etc.]; CA receptors; plasma membrane DA-/NA- and vesicular monoamine-transporters; exogenous and endogenous neurotoxins [MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine); 3,4-dihy-droxyphenylacetaldehyde, etc.]; cytokines related to neuroinflammation; molecular imaging; causative genes of fPD (PARK 1–18; α-synuclein (SNCA; PARK1), parkin (PARK2), etc.); susceptibility genes identified by genome-wide association studies (i.e., SNCA, LRRK2).Conclusions: The present hypothesis of pathomechanism of PD is that mul-tiple genetic and environmental causes [oxidative stress; mitochondrial dys-function; misfolded protein (α-synuclein); endoplasmic reticulum (ER) stress; neurotoxins, and neuroinflammation with activated microglia] may be ultimately linked to a final programmed cell death, i.e., lysosome-linked autophagy and proteasome-linked apoptosis. DA therapy has been progressing from sympto-matic therapy such as neurotransmitter DA supplementation with L-DOPA and DA receptor agonists, to preventive/restorative therapy based on pre-morbid diagnosis, i.e., neuroprotective drugs, gene therapy, and cell therapy using embryonic stem (ES) cells or iPS cells.Reference1. Nagatsu T., Sawada M. Current Pharmaceutical Design, 11, 999–1016,

2005.No conflict of interest.

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BEHAVIORAL VS. CLINICAL: ETHICAL ISSUES IN RESEARCH INVOLVING SUBJECTS WITH PARKINSON’S DISEASEM. Kakoti1,*, D. Misra1, V. Narang1

1Centre for Linguistics, Jawaharlal Nehru University, Delhi, India

Objectives: The current paper aims to examine the ethical issues that arise in research involving patients with Parkinson’s Disease (PD). It is based on the hypothesis that ethical issues arising in behavioral studies are different from issues arising in clinical studies, and as an extension, it also suggests a reformed set of norms of consent for behavioral studies.Methods: For the current paper, a behavioral study with 80 participants also undergoing a clinical study was observed. The ethical issues arising simulta-neously could hence be observed.Results: The participants suffering from PD and hence having come to the hospital for treatment were eager to help in any study that their hospitals advised in the hope that it would help in their treatment. This puts a question mark on ‘voluntariness’.Conclusions: This poses the question ‘how much voluntary is their consent really?’ Answering this, the norms for Informed Consent and voluntariness need to be reformed in case of behavioral studies.Reference1. Jecker, Nancy S., Albert R Jonsen, Robert A. Pearlman. Bioethics: An

Introduction to the History, Methods, and Practice. 2nd Ed. Jones and Bartlett. India.


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IDENTICAL ITEM SCORES ACROSS VISITS IN CNS TRIALS WITH A FOCUS ON PARKINSON’S DISEASE. MAPPING THE TERRITORYJ. Swartz1,*, A. Kott2

1Neurology, Bracket Global, Goring-on-Thames, United Kingdom, 2Neurology, Bracket Global, Prague, Czech Republic

5.Day 2 Tuesday, Section 2 PD Therapy.indd 705.Day 2 Tuesday, Section 2 PD Therapy.indd 70 10/28/13 5:48 PM10/28/13 5:48 PM


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Results: The EEG showed significant differences between the control group and PD patients who receiving only PKM and PKM with CQ. Before the begin-ning treatment abnormalities on the EEG were essentially associated with the occurrence of slowing – down the frequency and in part of patients were regis-tered the flashes of sharp wave activity. Every quarter was registered EEG and compared with others. Were found positive changes of bioelectric activity and relationship between duration and frequency, amplitude of pathological activ-ity (p > 0,01). Were determined that frequency and amplitude of pathological activity more decreased in patient who take PKM with CQ than take only PKM.Conclusions: This study suggested EEG as a possible physiological tool in the assessment of efficacy of treatment in PD.Reference1. http://www.ncbi.nlm.nih.gov/pubmed/No conflict of interest.

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COSTS VARIATION RELATED TO ILLNESS SEVERITY AND MOTOR AND NON-MOTOR SYMPTOMS IN PATIENTS WITH PARKINSON’S DISEASEP. Martinez Martin1,*, C. Rodriguez Blazquez2, P. Ramirez Boix3, M.J. Forjaz4, B. Frades Payo1, E. Cubo5, J.P. Cuesta2, L. Lizan Tudela3, on behalf of the ELEP Group1Alzheimer Center Reina Sofia Foundation and CIBERNED Carlos III Institute of Health, Madrid, Spain, 2National Center for Epidemiology and CIBERNED Carlos III Institute of Health, Madrid, Spain, 3Outcomes’10, Castellon, Spain, 4National School of Public Health and REDISSEC Carlos III Institute of Health, Madrid, Spain, 5Neurology Department Complejo Asistencial Universitario de Burgos, Burgos, Spain

Objectives: To analyze the effect of disease severity, motor and non motor symptoms over costs in PD patients in the Spanish National Health System.Methods: Observational, longitudinal (4 years) study of PD patients from ELEP study. Clinical features (motor symptoms: SCOPA-Motor; non-motor symptoms: HADS; PPRS; SCOPA-Autonomic; SCOPA-Sleep; SCOPA-Psychosocial; SCOPA-Cognition; Visual Analog Scale (VAS) for pain; VAS for fatigue; disease severity: Hoehn and Yahr(HY) and CISI-PD, both 3 catego-ries; use of health resources and productivity loss were assessed. Direct and indirect costs (€2012) were estimated. Linear mixed models were applied to analyze the effect of disease severity (HY and CISI-PD as separated mod-els) and motor, non-motor symptoms on direct and indirect costs (dependent variables).Results: 174 patients were analyzed (men, 50%; age: 63 ± 11 years; PD history: 8 ± 6 years). Higher scores in SCOPA-Motor and SCOPA-Autonomic scales and lower scores in VAS for fatigue (HY; CISI-PD) resulted in sig-nificant (p < 0.05) increases of direct costs. Equivalent models showed that the intermediate stage of disease severity defined by HY (p = 0.008) was associated with higher indirect costs than the mild (HY = I–II) and the severe stages (HY = IV–V).Conclusions: Direct costs raise in patients with major motor dysfunction and dysautonomia, and indirect costs in intermediate stages of disease severity. Optimal control of motor and non-motor PD symptoms would aid at containing disease costs.No conflict of interest.

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DEVELOPMENT OF SCANNED AND DIGITIZED WEARING OFF DIARY FOR PARKINSON’S DISEASEM. Nagai1,*, N. Nishikawa1, H. Iwaki1, T. Tsujii1, M. Nomoto1

1Neurology and Clinical Pharmacology, Ehime University, Tohon, Japan

Objectives: To evaluate the usefulness of scanned and digitized wearing off diary for assessment of daily motor fluctuations in patients with Parkinson’s disease (PD).Methods: Fifty PD patients with motor fluctuations have been enrolled in this study. Either “on” or “off” state was written down in the wearing off diary every 30 min for 14 days. Levodopa administration time and mealtime were also written down in the diary. All pages in the diary were scanned in a scanner and digitized. A line graph which represented “Typical PD Day (representative pattern of fluctuated symptoms of each patient)” has been made by averag-ing procedure of the digitized data. A questionnaire survey was carried out to evaluate the usefulness of the new wearing off diary system.Results: Although about half of the patients was 70 years of age or older, approximate 90% of the patients could write down in the diary by themselves. The 14 days diary was sufficient to obtain “Typical PD Day” of each patient. The line graph contributed to the ease of recognizing a pattern of wearing off. A half of the patients answered that the diary was useful to know their state of wearing off. The line graph was useful for doctors to develop a plan of medication and assess drug efficacy by comparing two line graphs.Conclusions: The newly developed wearing off diary system is useful tool to assess a pattern of wearing off and drug efficacy.

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TREATMENT PROFILE OF 1000 PATIENTS WITH PARKINSON’S DISEASE AT THE TIME OF REFERRAL TO A TERTIARY CARE CENTRE IN INDIAS. Pratibha1,*, Anilkumar Sivan1, Ravi Yadav1, Pramod Kumar Pal11Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India

Objectives: To analyze the prescription pattern in a large cohort of patients with Parkinson’s disease (PD) before attending a tertiary care centre.Methods: A cohort of 1000 patients of PD, diagnosed by Calne’s criteria, attending Neurology Department of the National Institute of Mental Health and Neurosciences (NIMHANS) were included in the study. The types of medications and respective doses received by the patients, prior to the referral, were analyzed.Results: The mean age of patients was 55.7 ± 11.3 years; young onset PD (<40 years) comprised 16.4%. The diagnosis was made by general practition-ers in 33%, physicians in 16% and neurologists in 51%. Reason for attending NIMHANS was most often for confirmation of diagnosis (49%) or for better care (27%). Nineteen percent of the patients were not on any treatment. Among those on treatment, the mean disease duration was 3.69 ± 2.23 years. Majority (86.5%) were on levodopa-carbidopa (LD), 41.1% on trihexyphenidyl and approximately 20% on dopamine agonists (DA). Among these, 33.2% were on LD monotherapy, 63.8% were taking another drug with LD and 2.8% were either on DA or THP alone. The mean daily Levodopa Equivalent Dose (LEDD) was 497.65 ± 210.71 mg and 59% were receiving <500 LEDD (mg/day).Conclusions: In India, the treatment of Parkinson’s disease at primary care level may be inadequate with inappropriate choice of medications and dosages. Further awareness is warranted for appropriate treatment of these patients.No conflict of interest.

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IMPROVING CLINICAL OUTCOMES: DEVELOPING AND IDENTIFYING THE VALUE OF THE MOVEMENT DISORDER NURSE IN AUSTRALIA – A WORK IN PROGRESSV. McConvey1,*1Health and Clinical Information, Parkinson’s Victoria, Melbourne, Australia

Objectives: Explore the importance of community engagement in developing sustainable support for people living with movement disorders. Identify the value of access to a Movement Disorder Nurse for clinical staff, patients and families/carers. Identify methods of evaluating the health economic impact of a Movement Disorder Nurse. Discuss key messages general health care staff need to be aware of to provide effective and timely car for people with Movement Disorders.Methods: This presentation will explain the unique way Movement Disorder Nursing had developed to meet the needs of people living with movement disorders and the complex Australian healthcare system. Deficits in special-ist knowledge have directly contributed to suboptimal health care outcomes for people with movement disorders encountering Australian health institutions distressing Neurologists, patients and carers. Developing specialist Nurses who are able to liaise and provide the required clinical support has proven effec-tive in the United Kingdom and Europe. This paper will explain the Australian experience and identify how community engagement has been essential in the promotion and seed funding of the positions. This presentation will also explore the steps taken to evaluate the role, and to demonstrate the health economic value and its contributions to improvements in patient care and wellbeing.Results: Ongoing Project no results to dateConclusions: Ongoing Project no results to date.Reference1. Jarman B, Horwitz B, Cook A, Madhavi B, Lee A. (2002) Effects of commu-

nity based nurses specialising in Parkinson’s disease on health outcome and costs: randomised controlled trial. BMJ: Vol 324: 4 May.


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CATEGORIZING PARKINSON’S DISEASE SYMPTOMS, AN UNCON-VENTIONAL APPROACHL. Vucolova1,*1Automatic and Telemechanics, Saint-Petersburg Electrotechnical University, Ridgewood, USA

Objectives: To test an alternative perspective on the classification of PD symptoms to improve motor and neurological functions. PD motor symptoms can be classified according to their anatomical category in the body, where they manifest, and how those parts are mapped in the brain. The motor symp-toms such as abnormal posture, static and dynamic balance, slow motion, shuffling gait and asymmetrical arm swing, and excessive muscle contrac-tions involve the major parts of the body: torso, arms, legs, and head. The



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additional symptoms such as tremor, slurred speech, swallowing dysfunction, masked face, and micrographia involve minor parts of the body, (hands, fin-gers, face, eyes, jaw, and mouth). Both categories have their respective motor repertories. Actually, the motor repertories of minor parts have a greater total degree of brain innervation (80% vs. 20%). They also support language and cognition.Methods: The subject’s photographs and videotapes were tracked and evalu-ated for the amplitude and fluidity of motion in each type of activity. Instead of focusing only on the major repertories, the minor repertories are also inte-grated into the various movement therapy setsResults: Under this regimen, the array of PD symptoms of a patient of 12 years showed significant reduction after only a year of intense and guided therapy.

(patient in the corner)

Conclusions: These findings strongly support the new interpretation and classification of the PD symptoms and aid in the clinical care of patients.No conflict of interest.

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REVERSING PARKINSON’S DISEASE SYMPTOMS, AN UNCON-VENTIONAL APPROACHL. Vucolova1,*1Automatic and Telemechanics, Saint-Petersburg Electrotechnical University, Ridgewood, USA

Objectives: Parkinson disease manifests as a perpetuating downward spiral of abnormal and unstable postures, gait disturbances, slow movements and excessive muscle contractions. The objectives of this project were to:

• Demonstrate how restoration of posture can slow the deterioration of symptoms.

• Confirm the hypothesis that abnormal posture becomes a primary factor in perpetuating the symptoms of the disease.

Methods: With photos and videos the anatomical positions of body parts and joints, postural alignment to gravity, planes and axes of motion were measured and compared over time. Focus was on improving proprioception, kinesthetic awareness, body mechanics and bad habits. Techniques (e.g., restraints, resistance, asymmetrical training) were used to modify skeletal forces, and to change the angular alignment of the body parts to restore posture.

Results: After a year of an intense therapy, in group and private therapy sessions, a chronic PD patient of 12 years was able to improve posture, static and dynamic balance, arm swing and gait pattern, righting reflex, body mechanics in functional and work related daily activities and ease excessive muscle contractions.

Stoopposture

Tremor

Tremor

Short shuffling steps

Masklike facies

Ams flexed atelbows and

wrists

Rigidity

Hips andknees SlightlyFlexed



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Conclusions: The original findings show significant results in reducing PD symptoms by restoring posture, and may have major clinical implications in the care of patients.No conflict of interest.

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PREVENTION OF POLLUTED WATER-INDUCED PARKINSONISM (1)Xu1, Xu Han-You1,*1Department of Emergency Medicine Clinical Institute, Clinical Institute Workers Hospital of Nanyang Textile Corporation, Nanyang City, China

Objectives: On the Earth village, the dry, arid and green house effect have been continuing to be in critical situation. It is imperative to find the main rea-sons of dry, arid and green house effect.

Methods: The Beijing-Hangzhou Grand Canal and disappear of Kroraina and Lop Nor Lake had both occurred at the ancient time. Which has been providing rare, valuable and special example for exploring and research-ing on the reasons of dry, arid and green house effect. So that we may create strategies to prevent or cure the dry, arid and green house effect at modern time.Results: In this research project, the author has found that The Beijing-Hangzhou Grand Canal and disappear of Kroraina and Lop Nor Lake have been being in causal relationship. Based on this research, the author warned that the scientific value and scientificity of the present growing water diver-sion projects on the Earth around the world should be reproved. The author proposed the present growing water diversion projects should be replaced by other scientific project or methods, for example, the high quality pipelines of metal or plastics on the surface of the Earth. Which can not run counter to the nature. The emergency prevention of environment pollution are also needed immediately to prevent and cure the green house effect. So the dry, arid could be cured.Conclusions: The research is valuable to be referenced by China and the world for enhancing and promoting ecological balance and public health around the world.No conflict of interest.

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PREVENTION OF POLLUTED WATER-INDUCED PARKINSONISM (2)Xu1,*1Department of Emergency Medicine Clinical Institute, Clinical Institute Workers Hospital of Nanyang Textile Corporation, Nanyang City, China

Objectives: To find out the reason and cure for this critical bad situation of water.Methods: Summarizing the water shortage and water pollution, the completely reason for this critical bad situation has been researched. Propose the curing methods to mend the severe water shortage and water pollution.Results: The reason for this critical water bad situation is greenhouse effect. Since the greenhouse effect are caused by the environment pollution. The breakthrough proposals for revision of law of environmental protection, research project by Xu Han-You are very useful to cure the environment pol-lution and should be referenced to apply. The present water diversion projects around the world should be stopped at once. The other proposals are, the water diversion project should use pipelines of metal or plastics. Which should be planned and approved by the UN; The administration policies to cure the warming weather, greenhouse effect and the critical water bad situation must be created as soon as possible; The water in the Earth village should be used fairly and should be planned and approved by the UN; The modern technol-ogy to cure the warming weather, greenhouse effect and the critical water bad situation must be created as soon as possible; Weather the space exploration can be done should be judged by if the exploration can promote and enhance the warming weather, greenhouse effect.Conclusions: The proposals to cure the water shortage and water pollution around the world should be referenced by all nations and related organizations of the UN and other societies.No conflict of interest.

265

PERCEPTION OF GLASS – AN EYEWEAR COMPUTER ENABLING NOVEL DISEASE SELF-MANAGEMENT AND REHABILITATIOND. Roggen1,*, R. McNaney1, J. Vines1, P. Zhang1, M. Balaam1, P. Olivier1

1Culture Lab, Newcastle University, Newcastle upon Tyne, United Kingdom


266

PRESENCE OF SPOUSAL CAREGIVERS IN MOBILITY OF PERSONS WITH PARKINSON’S DISEASE: A GLOBAL POSITIONING SYSTEM (GPS) APPROACHC. Duval1,*, F. Rahimi2, L. Zhu3, C. Lavigne-Pelletier6, P. Boissy4, M. Jog5

1Kinanthropologie, Université du Québec à Montréal, Montreal, Canada, 2Clinical Neurological Sciences, Lawson Health Research Institute, London ON, Canada, 3Epidemiology and Biostatistics, University of Western Ontario, London ON, Canada, 4Chirurgie Orthopédique, Université de Sherbrooke, Sherbrooke, Canada, 5Lawson Health Research Institute, Clinical Neurological Sciences, London ON, Canada, 6Research Center, Montreal Geriatric Institute, Canada

Objectives: Parkinson’s disease not only affect the patients’ daily activities, but also the behavior of their spousal caregiver. We propose a new methodol-ogy to assess the interdependence of mobility of spousal dyads in the com-munity. Using GPS data, we measured the dichotomization level in mobility patterns of spousal dyads throughout the day.Methods: Participants included fifteen community dwelling patients (eleven males; Hoehn and Yahr stages I and II; 67.1 ± 7.6 years) and their spousal car-egivers (61.9 ± 9.1 years). Participants wore a GPS during 15 days. Traveled path and relative positioning to the home during day was tracked. Average distance to home, average length of path traveled, and percentage of time spent together were calculated.Results: Patients or spouses traveled an average length of 6.4 ± 14.4 km; had an average displacement of 13 ± 41 km from home, with an averaged 21% of the time being away from each other (separation >200 m).Conclusions: Our results suggest that the dynamics in spousal dyad mobil-ity can be reliably captured over the majority of the study period. We believe that dichotomization of mobility patterns could represent a strong marker of patients’ ability to maintain independence. Conversely, unification of mobility patterns could be a marker of increased stress on the spousal caregiver. The ongoing analysis will further separate types of travels (vehicle vs. on foot) and the relationship between the outcomes and factors influencing mobility such as symptomatology, disease duration, etc.No conflict of interest.

267

EFFECT AND POTENTIAL MECHANISM OF ELECTRO-ACUPUNCTURE ADD-ON TREATMENT IN PARKINSONIAN PATIENTSF. Wang1, L. Sun1, X. Zhang2, J. Jia3, Z. Liu1, X. Huang1, S. Yu1, L. Zuo1, C. Chao1, X. Wang3, W. Zhang1,*1Department of Neurology, Beijing Tiantan Hospital, Beijing, China, 2Department of Acupuncture, Beijing Tiantan Hospital, Beijing, China, 3Department of Physiology, Capital Medical University, Beijing, China

Objectives: To explore the effectiveness and potential mechanisms of electro-acupuncture (EA) treatment.Methods: 50 PD patients with stable dose of anti-parkinsonian drugs were recruited and randomly assigned to drug plus EA group (D + EA group) and drug alone group (D group). Subjects in D + EA group received stimulation in points of bilateral fengfu, fengchi, hegu and central dazhui followed by being given electrical pulses with voltage of 20 V and frequency of 100 Hz for 30 min. 10 times was a course and two courses were finished. Participants were evaluated by scales for motor and non-motor symptoms before and after EA treatment. Levels of neuroinflammatory factors and neurotransmitters in serum were detected.Results: EA treatment remarkably reduced scores of UPDRS III and its subitems of tremor, rigidity and bradykinesia, and conspicuously decreased UPDRS III score in patients with bradykinesia-rigidity and mixed types, and mild severity. Some non-motor symptoms were eased, which were reflected by increased scores of non-motor symptoms scales and elevated levels of NE and Ach. Effects of EA add-on treatment on motor symptoms and sleep disturbances were superior to drug treatment alone, thus, it markedly raised life quality of PD patients demonstrated by elevated scores of UPDRS? and PDQ-39. EA treatment decreased NO level in serum.Conclusions: EA treatment was effective on most of motor symptoms and part of non-motor symptoms for PD patients, which effectiveness is the earlier the better. Anti-neuroinflammation might be a mechanism for EA treatment.No conflict of interest.

268

ANMA MASSAGE (JAPANESE MASSAGE) THERAPY FOR OUTPATIENTS WITH PARKINSON’S DISEASE: EFFECTIVENESS FOR VARIOUS PHYSICAL SYMPTOMSN. Donoyama1,*, S. Suoh1, N. Ohkoshi21Acupuncture and Moxibustion, Tsukuba University of Technology, Tsukuba, Japan, 2Neurology, Tsukuba University of Technology, Tsukuba, Japan



74

Objectives: According to some surveys in Japan, Anma massage (Japanese massage) therapy is the complementary and alternative medicine most com-monly used by patients with Parkinson’s disease (PD), and 29.8% of neurolo-gists recommend it for improving muscle rigidity, movement disorders, and pain. The primary objective was to confirm the immediate physical effects of a single Anma massage session for outpatients with PD. The secondary objec-tive was to observe the effects of continuous Anma massage therapy.Methods: Twenty-one outpatients with PD (aged 46–82 years) received one 40-min session of Anma massage including exercise of the upper and lower extremities together with their standard conventional medication and a similar session that included no Anma massage intervention as a control. We also observed those patients who were able to complete eight weekly continuous Anma massage sessions.Results: After a single Anma massage session, severity of physical sub-jective symptoms (i.e., muscle stiffness, movement difficulties, pain, and fatigue) measured by a visual analogue scale were significantly lowered. The time required to complete the pegboard test was significantly shortened, gait speed was significantly shortened, military pace was significantly length-ened, and cadence was unchanged. For range of motion of the shoulder joint, flexion and abduction were significantly improved. We observed general improvements in the same outcomes with the continuous Anma massage sessions.Conclusions: Anma massage therapy appears to be effective for alleviating various physical symptoms of PD.No conflict of interest.

269

ANMA MASSAGE (JAPANESE MASSAGE) THERAPY FOR PATIENTS WITH PARKINSON’S DISEASE IN GERIATRIC HEALTH SERVICES FACILITIES: EFFECTIVENESS ON LIMITED RANGE OF MOTION OF THE SHOULDER JOINTS. Suoh1,*, N. Donoyama1, N. Ohkoshi21Acupuncture and Moxibustion, Tsukuba University of Technology, Tsukuba, Japan, 2Neurology, Tsukuba University of Technology, Tsukuba, Japan

Objectives: Range of motion (ROM) for shoulder joint flexion and abduction is associated with pain-free active movement. However, for most patients with Parkinson’s disease (PD) in geriatric health services facilities in Japan, they have reduced activities of daily living and spend long hours in a wheelchair or bed, causing contractures of the shoulder and upper and lower limbs, which reduce ROM of certain joints. To determine the efficacy of Anma massage therapy on the limited ROM of the shoulder joint in PD patients in geriatric health services facilities.Methods: (1) Immediate effects: 10 PD patients assigned to a massage group, all with Hoehn and Yahr stage V, received 30–40 min sessions of Anma massage, from the neck to lower limbs and the shoulder joint to upper limbs. In a control group, 6 PD patients did not receive the massage. We measured shoulder joint ROM before and after each session. (2) Continuous treatment effects: 6 PD patients in the massage group received the same intervention (8 treatments weekly for 2 months). We measured shoulder joint ROM 7 days after the treatment.Results: (1) Shoulder abduction on the more affected side showed significant immediate effects (p = 0.013). (2) Shoulder abduction on the more affected side (p = 0.004) and on the less affected side (p = 0.005) showed significant continuous treatment effects.Conclusions: The better results for continuous treatment suggest an accu-mulated treatment effect and the efficacy of successive Anma massage ther-apy for PD patients in geriatric health services facilities.No conflict of interest.

270

RHYTHMIC MUSIC IMPROVES CORTICOMOTOR EXCITABILITY AND FUNCTIONAL MOBILITY IN PATIENTS WITH PARKINSON’S DISEASEL. Tremblay1,*, G. Léonard2, J.G. Ménard3

1Health sciences, University of Quebec at Chicoutimi, Chicoutimi, Canada, 2Research Center on Aging, University of Sherbrooke, Sherbrooke, Canada, 3Community Group, Parkinson Society Quebec Saguenay-Lac-Saint-Jean, Saguenay, Canada

Objectives: The aim of the present study was to evaluate the effect of rhythmic music on the corticomotor excitability and functional mobility of PD patients, in order to determine if music could be used effectively to ease motor symptoms in PD.Methods: 46 participants (26 medicated patients with moderate PD and 20 healthy subjects; mean age 66 ± 6.8 years and 65 ± 7.1 years) partici-pated in two separate studies. In experiment #1 corticomotor excitability was determined by monitoring changes in the amplitude of motor evoked poten-tials (MEPs) elicited in the dominant leg quadriceps muscle by transcranial magnetic stimulation. MEPs were measured (1) at rest (control condition),

(2) at rest while listening to rhythmic music, (3) during an observation task and (4) during the same observation task supplemented with rhythmic music. In experiment #2, the functional motor status of PD patients and healthy subjects was evaluated using different clinical evaluations (Sit to Stand, Timed Up and Go, 2 Minute Walk Test) performed with and without rhythmic music.Results: Compared to the resting condition, the three experimental condi-tions (music alone, observation alone, and observation + music) increased corticospinal excitability in both PD patients and healthy subjects. The great-est facilitation was observed in the observation + music condition. Music also facilitated the completion of the different clinical tests for PD patients. No sig-nificant difference was observed between the music and no music condition for healthy subjects.Conclusions: The present results support the utilization of music as an effec-tive rehabilitation tool to facilitate movement in patients with PD.No conflict of interest.

271

RANDOM WHOLE BODY VIBRATION TRAINING OVER 5 WEEKS IN PARKINSON’S DISEASE LEADS TO SIMILAR QUANTITATIVE EFFECTS LIKE A PLACEBO TREATMENT: A CONTROLLED STUDYH. Gassner1,*, A. Janzen2, I. Mihaljevic2, A. Schwirtz3, P. Jansen1

1Institute of Sport Science, University of Regensburg, Regensburg, Germany, 2Department of Neurology, University of Regensburg, Regensburg, Germany, 3Department of Sport Biomechanics, Technical University of Munich, Munich, Germany

Objectives: In Parkinson’s Disease (PD) drugs show no or even a detrimental effect on postural instability1,2. Therefore other treatment methods are neces-sary. The aim of this study was to biomechanically assess a random whole body vibration (RWBV) training over 5 weeks in patients with PD compared to a placebo group (PG).Methods: Twenty one patients with PD were allocated to either an experi-mental group (EG) or a PG parallelized by age, gender and Hoehn and Yahr stage. Before and after the training period both groups performed multiple tasks (reaching forward task, climbing steps, gait analysis, timed up and go test (TUG), one leg stance) which were biomechanically assessed by motion capture. The RWBV training consists of 5 series of 60 s and was performed in double supported stance. The PG took the same standing position but vibra-tion was not switched on.Results: Both groups improved significantly in gait parameters, TUG and one leg stance from pre-test to post-test. In the TUG the EG performed significantly better than the PG [F(1,15) = 4.971; p < 0.05]. In the reaching forward task only the EG significantly improved reach distance [F(1,15) = 8.397; p < 0.05].Conclusions: RWBV training and the placebo treatment have shown similar effects in biomechanically measured everyday life tasks. More pronounced effects due to the vibration training could only be shown in those tasks which contain double supported stance phases.References1. Frank JS, Horak FB, Nutt J. Centrally Initiated Postural Adjustments in

Parkinsonian Patients On and Off Levodopa. J Neurophysiol 2000; 84: 2440–2448.

2. Jankovic J. Levodopa strengths and weaknesses. Neurology 2002; 58: 19–32.


272

CREATIVE THINKING AND CREATIVE BEHAVIOUR IN PARKINSON’S DISEASE AND HEALTHY CONTROLM. Canesi1,*, F. Moroni2, A. Ranghetti2, P. Gianni1, M. Rusconi21Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy, 2Department of Human and Social Science, University of Bergamo, Bergamo, Italy

Objectives: Creative behaviors may emerge in PD patients with dopaminergic therapy. They could be related to the compulsive and repetitive behaviors or might represent the emergence of innate qualities. We studied creative think-ing in PD patients with professional artistic job (i.e., painter, designer, archi-tect) (PD-A), patients who have experienced artistic abilities after the onset of PD (PD-C) and patients who have never developed creative drive (PD-NC).Methods: We included 36 PD patients (12 PD-A; 12 PD-C; PD-NC) and 24 matched healthy control (HC: 12 professional artists (HC-A) and 12 not artists (HC-NA). All the PD patients were submitted to neurological assessment. PD motor laterality was defined by means of UPDRS-III. The creative thinking has been investigated by means of Abbreviated Torrance Test for Adults (ATTA) that combines indices of verbal and visuo-spatial creativity. All subjects were submitted to neuropsychological evaluation behavioral (mMIDI) and mood’s assessment (GDS and HAM-A).Results: The ATTA sub-scores for elaboration and originality were sig-nificantly higher in PD-A, PD-C and HC-A when compared to PD-NC and



75

HC-NC. No significant differences were found in dopaminergic treatment (LEDDs), in moods (GDS, HAM-A), in behavioral compulsion and punding (mMIDI). Demographic and therapeutic data were similar in all PD groups, with the exception of PD-NC patients who were almost all not tremor-dom-inant PD.Conclusions: Creative thinking in PD, as assessed by the ATTA, appears to be unrelated to dopaminergic treatment. Along with this, creative drive seems to be associated with innate skills rather than impulse control disorder or punding.Reference1. Canesi M. et al 2012.No conflict of interest.

273

EFFECTS OF DIETARY THERAPY IN PATIENTS WITH PARKINSON’S DISEASEM. Melone1,*, T. Esposito2, G. Capaldo3, C. Dato3, D. Saracino3, G. Barbella3, S. Allocca4, M. Monda4, B. Varriale5

1Department of Clinical and Experimental Medicine and Surgery Division of Neurology, Second University, Naples, Italy, 2Department of Experimental Medicine Section “F. Bottazzi” Services Dietetics, Second University of Naples, Naples, Italy, 3Department of Clinical and Experimental Medicine and Surgery Division of Neurology, Second University of Naples, Naples, Italy, 4Department of Experimental Medicine Section “F. Bottazzi” Services Dietetics, Second University of Naples, Naples, Italy, 5Department of Experimental Medicine Section “F. Bottazzi” Laboratory of Biology and Molecular Genetics, Second University of Naples, Naples, Italy

Objectives: Finding a non-drug therapy to assist and improve the symptoms of PD patients.Methods: Fifty Patients with idiopathic PD (mean age 69 ± 9.8 years) were studied. Twenty-five patients received a low-calorie, dissociated, low-protein diet therapy, without foods containing tyrosine and phenylalanine, deprived of foods with high tyramine content, and using foods containing high levels of ellagic acid and using curcuma as spice (group A); a parallel group of twenty-five PD patients received a simple low-calorie diet (group B). Both groups were followed for 6 months with weekly checks. An analysis of nutritional parameters was carried out mainly by investigating height/body weight ratios, and the % of weekly changes in weight, index weighting, body circumferences and skinfold thickness. Moreover Bioimpedance Analysis (BIA) was used for estimating total body water, extracellular water, intracellular water, lean body mass, fat mass, weight ratio, slim/fat metabolically active mass, and basal metabolic rate (calories).Results: At baseline, there were no significant differences between the two groups concerning gender, age, disease duration, Hoehn and Yahr score, UPDRS, MMSE, levodopa dose, or levodopa equivalent daily dose. At 6 months, nutritional parameters and neurological status had significantly improved in group A (P = 0.0199) compared with group B.Conclusions: The diet therapy in the PD patients of group A was found to be a very promising non-drug therapy for PD as the evaluations performed reflect a real effectiveness of our therapeutic proposal, in addition to the dopaminergic therapy.No conflict of interest.

274

USE OF THE PHYSIOTHERAPY IN THE TREATMENT OF INITIAL STAGES OF PARKINSON’S DISEASEO. Tondiy1,*, O. Zavalna1, V. Florikyan1

1Neurology, Kharkiv Medical Academy of Postgraduate Education, Kharkiv, Ukraine

Objectives: The effect of the low-frequent variable magnetic field, the ultra-tone therapy and balneo therapy on the rigidity of the patients having initial stages of Parkinson’s disease was investigated.Methods: 56 patients aged from 60 to 75 (32 females and 24 males) having initial stages of Parkinson disease (PD) were observed. We chose the patients with prevalent muscle rigidity. The patients were divided into two groups. The first group (42 patients) received in addition their basic medication and physi-otherapy with ultratone therapy – variable sinusoidal high-tension (4–5 kV) high-frequent (22 kHz) low-intensive current (power 1–10 V), low-frequent var-iable magnetic field (frequency to 100 Hertz, magnetic induction 27 mTesla) and balneotherapy treatment of upper and lower extremities, with taking turn each other. The ultratone exposure was 12–15 min. The low-frequent variable magnetic field exposure was 10–12 min. The complete course was 10–12 procedures. The second group (control, 14 patients), received only the basic medication.

Results: The muscle rigidity and subjective sensation of constraint extremi-ties of the patients in the first group was reduced after 18–20 days of treat-ment (80,9% patients) compared to the control group, where muscle constraint reduced after 22–24 days of treatment (57,1% patients), p < 0,05.Conclusions: The addition of the complex (low-frequent variable magnetic field, balneotherapy and ultratone therapy) to the treatment of initial stages of PD resulted in earlier reducing of subjective sensation of constraint extremities.The proposed rehabilitation can improve the quality of life of the initial stages of PD patients.No conflict of interest.

275

CHANGE IN MOBILITY AFTER INPATIENT REHABILITATION AND THE IMPACT OF CONTEXTUAL FACTORS IN PATIENTS WITH PARKINSON’S DISEASEA. Menig1, M. Oechsner1,*1Parkinson’s Disease Center, Rehaklinik Zihlschlacht, Zihlschlacht, Switzerland

Objectives: The aim was to assess mobility changes after inpatient rehabilita-tion, with a special focus on the impact of personal factors and health-related quality of life (HRQOL) on these changes.Methods: 45 inpatients with PD participated. Evaluations were carried out using the Unified Parkinson’s Disease Rating Scale (UPDRS) II/III and the Lindop Parkinson’s Assessment Scale (LPAS) at the beginning (B), and the end (F1) of the inpatient rehabilitation and at follow-up 3 months (F2) after dis-charge. In addition, participants answered questions related to personal factors and HRQOL.Results: Between measurement points B and F2, significant changes were observed on the UPDRS II/III and the LPAS. The motor improve-ments and skills in activities of daily living (ADL) participants achieved through rehabilitation were consistent over a period of 3 months. Personal factors like age or education and HRQOL were found to have no influence on the changes in mobility, and neither did potential control parameters (“outpatient treatment”, Mini-Mental-State-Examination (MMSE) or dura-tion of disease).

Unified Parkinson’s Disease Rating Scale

measurement points

Part

II S

core

Baseline0

10

20

30 128

126

13291

105134

B - F2 p= 0.005F1 - F2 p= 0.597

40

Follow- up 1 Follow- up 2

Unified Parkinson’s Disease Rating Scale

measurement points

Part

III S

core

Baseline0

10

20

30

B - F2 p= 0.004F1 - F2 p= 0.69

40

50

60




76

Lindop Parkinson’s Assessment Scale (LPAS)

measurement points

Scor

e

Baseline

10

15

20

25

B - F2 p= 0.003F1 - F2 p= 0.792

30


*6*

6

22 44

528

6

Descriptive data

N (%) Mean SD Median Min Max

Gender

female 33.3

male 66.7

Age 66.1 9.53 68.0 44 81

Age

female 67.4 9.92 69.0 47 79

male 65.4 9.44 67.5 44 81

MMSE 27.0 28.0 28.0 21 30

Hoehn–Yahr 3.1 0.64 3.0 1 4

Duration rehabilitation/days

25.3 5.92 26.0 16 40

Years of disease 10.3 6.3 9.0 1 28

Conclusions: People with PD benefit from inpatient rehabilitation. Following rehabilitation, improvements in motor skills and ADL can be maintained for a period of at least 3 months. Personal factors have no significant influence on sustainability following rehabilitation, and there is no influence of HRQOL.No conflict of interest.

276

A TRANSLATIONAL PLATFORM FOR NEUROMOTOR DISEASE RESEARCH AND THERAPEUTIC VALIDATION: APPLICATION TO PARKINSON’S DISEASED.A. Borton1,*, I. Vollenweider1, Y. Lang2, E. Bezard2, G. Courtine1

1Center for Neuroprosthetics, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland, 2Institute des Maladies Neurodegeneratives, Universite Victor Segalen Bordeaux, Bordeaux, France

Objectives: We have developed a multimodal neuromotor analysis platform in non-human primates that integrates a range of state-of-the-art wireless technologies to achieve unprecedented resolution. Our aim was to establish a practical and mechanistic framework for basic neuroscientific research and translational therapeutic development.Methods: Two non-human primates were implanted with a 96-channel micro-electrode array in the leg area of primary motor cortex, a 6-channel elec-tromyography system into selected hind limb muscles, and a fully implanted spinal stimulation system combining a flexible epidural electrode array and a multi-channel pulse generator.Results: For the first time, we monitored population dynamics of the motor cortex, muscle activity, and whole-body kinematics while non-human primates behaved naturally without any constraints or burdensome cables. We lever-aged this connection-free multimodal platform to evaluate motor control strat-egies underlying natural locomotion on a treadmill, along a straight runway, and across complex horizontal ladders imposing precise paw placement. Using dimensionality reduction techniques, including Gaussian process factor analysis and principal component analysis, we extracted task-specific correla-tive structures between gait kinematic patterns, muscle synergies, and motor cortex neuronal modulations. Finally, we exploited the spinal stimulation sys-tem to elicit monosynaptic and polysynaptic responses in hindlimb muscles. These segmental reflexes can be used as a diagnosis tool to monitor spinal circuit function during dynamic states.Conclusions: This neuromotor analysis platform represents advancement in our ability to decipher healthy and diseased motor states through multimodal repre-sentations, and provides unparalleled opportunities to test the safety and efficacy of therapeutic interventions to improve locomotion after neuromotor disorders.No conflict of interest.

Freely moving NHP Study Wireless EMG recordings Wireless intracortical recordings

100-ch neural data

StanceAverage

neurons

SwingStance

toe ext.

ankleflex.

ankleext.

kneeflex.

joint motion tracking

Treadmill walking task

Ankleextensor

Ankleflexor

2-2

-4

4

-1.5

Late

nt d

imen

stio

n 1

(a.u

.)

Neural trajectories Locomotor-related neural data

LD 2 (a.u.) LD 3 (a.u.)

2

00

0Swing

1 cm

A B

D E

C

276



77

277

SPINAL EXCITABILITY MODULATION INDUCED BY TREADMILL WALKING IN PARKINSON’S DISEASE: A PRELIMINARY STUDYH. Fernández Lago1,*, O. Bello Rodríguez1, M. Fernández-Del-Olmo1

1Learning and Human Movement Control Group, Faculty of Sports Science and Physical Education, A Coruña, Spain

Objectives: To explore the modulation of the H reflex induced by walking on a treadmill in patients with Parkinson’s disease (PD).Methods: Twelve individuals with PD and 12 healthy controls participated in this study. Soleus H-reflex was evaluated at rest before (baseline) and after (Post) 20 min of walking on a treadmill. The Post measurements were obtained immediately (Post1), 5 min (Post2) and 10 min (Post3) after the walking tread-mill. Maximal H and M amplitudes (Hmax and Mmax) from soleus muscle were recorded. Ratio Hmax/Mmax was calculated as an index of spinal excitability.Results: Soleus Hmax/Mmax ratio decreased immediately after the treadmill walk-ing (Post1) in both groups (P < 0.05) in comparison with the baseline values. This reduction persisted in the PD group during Post2 and Post3 (P = 0.05 and P < 0.01, respectively). However, in the control group the Hmax/Mmax ratio remained decreased only for the Post2 (P < 0.01), returning to baseline values at Post3.Conclusions: Walking on a treadmill induces longer-lasting modulation on spinal excitability in PD patients that in control subjects. The functional signifi-cance of this finding could be related with the therapeutic effect of treadmill walking in PD patients.References1. Bello O, Sanchez JA, Fernandez-del-Olmo M. Treadmill walking in

Parkinson’s disease patients: Adaptation and generalization effect. Movement Disorders 2008; 23(9):1243–1249.

2. Fisher BE, Wu AD, Salem GJ, Song J, Lin C, Yip J, et al. The Effect of Exercise Training in Improving Motor Performance and Corticomotor Excitability in People With Early Parkinson’s Disease. Arch Phys Med Rehabil 2008 7; 89(7):1221–1229.


278

MECHANICAL FOOT STIMULATION IN THE TREATMENT OF PARKINSON’S DISEASEF. Stocchi1,*, M. Galli2, P. Grassini3, M. Casali3, F.G. Radicati3, M. Torti4, L. Vacca4, C. Fossati4, P. Sale3, M.F. De Pandis5

1Department of Neurology, IRCCS San Raffaele Pisana, Rome, Italy, 2Department Electronic Information and Bioengineering, Politecnico di Milano, Milano, Italy, 3Department of Neurology, IRCCS San Raffaele Pisana, Roma, Italy, 4Department of Neurology, IRCCS San Raffaele PIsana, Roma, Italy, 5Department of Neurology, IRCCS San Raffaele Cassino, Cassino, Italy

Objectives: The objective of this prove of concept randomized cross-over trial was to evaluate the efficacy of mechanical foot stimulation in the treatment of Parkinson’s disease (PD).Methods: The study was a prove of concept randomized controlled double-blind cross-over design. The foot stimulation was provided with a mechanical device (GONDOLA). Twenty PD patients have been recruited, 18 were rand-omized to receive active GONDOLA first and GONDOLA sham after or vice versa. Between treatments subjects underwent a washout period of 3 weeks. Each treatment period lasted 4 weeks and included 1 stimulation every 3 days. Patients were evaluated at baseline, after the first period and after the second period. Evaluations included computerized Gait Analysis and clinical evaluation.Results: Results are reported in tables.Clinical characteristics 18 PD patients:

Subjects n. Age (/) H&Y UPDRS

18 68 3.1 30.9

Gait analysis results. Here we report the data at baseline (Pre) and after active treatment (Post). We also report data from a normal control group (CG). No significative differences were induced by the SHAM stimulation.

Parameters Pre Post 6FMS CG 60 ys

Velocity [m/s] 0.61 (0.31)+ 0.78 (0.27)*+ 1.19 (0.07)

Stride length [m] 0.73 (0.31)+ 0.83 (0.25)*+ 1.24 (0.05)

Cadence [step /min] 100.08 (12.5)+ 110.22 (14.59)* 115.58 (6.47)

Double support [% cycle]

14.28(5.10)+ 10.81 (5.32)* 12 (0.9)

*Post vs pre = p < 0.05.+Pre/post vs CG = p < 0.05.%Stance fase, % swing fase, velocity swing, velocity stride = statistically significant.

Scale/val Pre Mean (sd) Post 6FMS Mean (sd)

UPDRS III 30.9 (8.15) 23.02 (8.5)*

H&Y 3.16 (0.77) 3.1 (0.63)*

Pdq-39 63.18 (29.64) 50.5 (26.75)*

NMS 12.87 (5.34) 8 (3.46)*

Funct amb. 3.37 (1.45) 4.3 (0.80)*

Ten m wlk test [m/s]

0.46 (0.08) 0.50 (0.08)*

TUG [s] 18.26 (8.82) 13.54 (6.09)*

Tinetti 9.86 (4.06) 13.93 (4.04)*

Conclusions: This prove of concept study on a small population showed that GONDOLA induced a statistically significant improvement in velocity of gait; in stride length, in the UPDRS III and in the quality of life of PD patients. The improvement could be due to the activation of proprioceptive pathways.No conflict of interest.

279

THE RELATIONSHIP BETWEEN AEROBIC CAPACITY, EXERCISE CAPACITY AND PHYSICAL ACTIVITY IN IDIOPATHIC PARKINSON’S DISEASER. White1,*, A. O’Callaghan2, V. van Hees3, W. Gray4, D. Jakovljevic3, M. Trenell3, R. Walker2

1Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom, 2Department of Medicine, Northumbria Healthcare NHS Foundation Trust, Newcastle upon Tyne, United Kingdom, 3MoveLab – Physical Activity and Exercise Research, Newcastle University, Newcastle upon Tyne, United Kingdom, 4Research and Development, Northumbria Healthcare NHS Foundation Trust, Newcastle upon Tyne, United Kingdom

Objectives: Cardiorespiratory fitness (a reflection of habitual physical activity in the general population [1]) can help guide Parkinson’s disease (PD) management. Our objective was to establish if exercise capacity, measured by the Six Minute Walk Test (6MWT), and/or objective accelerometry measurement of free living physical activity could replace the gold standard technique of Cardiopulmonary Exercise Tests (CPETs) to measure VO2 max (aerobic capacity).Methods: 28 participants with idiopathic PD, Hoehn and Yahr stages 1–3, were recruited and PD symptom dominant side, UPDRS tremor scores and handedness were recorded. CPETs were undertaken with maximal ramp protocol on an electromagnetically controlled recumbent bicycle ergometer. Participants wore GeneActiv accelerometers for 48 h while continuing normal activities. The distance covered on 6MWT was measured.Results: 6MWT and VO2 peak correlated significantly. There were non-signif-icant moderate correlations between VO2 max percent predicted and physical activity of non-dominant handedness side, left wrist data and PD dominant side. No significant correlation between physical activity and 6MWT.Conclusions: There is potential for use of 6MWT in place of CPETs in similar populations. Lack of correlation between physical activity and VO2 max may be explained by motor symptoms complicating accelerometer data analysis. Future work should involve more participants, longer accelerometer time and efforts to distinguish PD motor symptoms.Reference1. Lee, D.C., et al., Mortality trends in the general population: the importance

of cardiorespiratory fitness. J Psychopharmacol, 2010; 24(4 Suppl):27–35.No conflict of interest.

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PARKINSON’S DISEASE AND FORCED EXERCISE: A PRELIMINARY STUDYA. Qutubuddin1,*, T. Reis1, R. Alramadhani2, D. Cifu1, A. Towne3

1PM&R, Virginia Commonwealth University, Richmond, USA, 2Neurology, Richmond VAMC, Richmond, USA, 3Neurology, Virginia Commonwealth University, Richmond, USA

Objectives: Forced exercise has drawn attention for the treatment of Parkinson’s disease symptoms with anecdotal reports of success. This study sought to ascertain any significant effect of forced exercise using a motorized stationary bicycle when compared to controls on Parkinson’s disease symp-toms in a blinded, randomized, controlled setting.Methods: We assessed 23 patients (13 experimental and 10 controls) on a number of standard Parkinson’s measures at baseline, after participation in eight weeks of twice weekly forced exercise or eight weeks of conventional clinic care, and then after a 3 months period had elapsed. Dependent meas-ures were UPDRS-III, Berg Balance Scale, Finger tapping, and the PDQ-39.



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Results: Results did not demonstrate any main effect differences between the exercise and control groups on any measure at any point in time. A within subjects effect was demonstrated for the forced exercise group on overall UPDRS-III scores at the 3 months end point. No other within group effects were noted.Conclusions: This study failed to show significant treatment effects when compared to controls. Aside from a within subject improvement on UPDRS-III scores in the FE group no benefit was seen from forced exercise Larger controlled studies are warranted but our investigation highlights a number of clinical and logistical challenges that should be considered prior to undertak-ing such studies.Reference1. Alberts JL, Linder SM, Penko AL, Lowe, Mark J, Phillips M. It Is Not About

the Bike, It Is About the Pedaling: Forced Exercise and Parkinson’s dis-ease. Exer & Sport Sci Rev, Oct 2011 – Volume 39 – Issue 4 – pp 177–186.


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INTERVAL TRAINING-INDUCED ALLEVIATION OF RIGIDITY AND ELBOW FLEXOR MUSCLE HYPERTONIA IN PARKINSON’S DISEASE PATIENTS IS ACCOMPANIED BY AN INCREASE OF BASAL SERUM BDNF LEVELJ. Marusiak1,*, E. Zeligowska1, J. Mencel1, K. Kisiel-Sajewicz1, J. Majerczak2, J. Zoladz2, A. Jaskólski1, A. Jaskólska1

1Department of Kinesiology, University School of Physical Education Faculty of Physiotherapy, Wroclaw, Poland, 2Department of Physiology and Biochemistry, University School of Physical Education, Krakow, Poland

Objectives: The study was aimed to estimate an effect of cycloer-gometer Interval Training (IT) on: (i) parkinsonian rigidity, (ii) electrical and mechanical properties of relaxed elbow flexor muscle in affected upper extremity, and (iii) the level of serum Brain Derived Neural Factor (BDNFs).Methods: Eleven mildly-moderately affected Parkinson disease patients (PD) performed 8-weeks IT on a stationary cycloergometer (pedaling with lower extremities) and were examined (clinically and physiologically) before (PRE) and after (POST) the IT. We measured: (i) affected upper extremity’s parkinso-nian rigidity and (ii) affected upper extremity’s resting muscle tonus in biceps brachii muscle (BB) using EMG mean frequency (MF-EMG), myometric stiff-ness (S-MYO) and frequency (F-MYO), and (iii) basal serum Brain Derived Neural Factor (BDNFs) level before and after IT cycle.Results: In the POST-IT, compared to PRE-IT session: (i) parkinsonian rigid-ity significantly decreased by 24% (5.1 ± 2.7 vs. 3.9 ± 2.4 [score], P = 0.048, respectively); (ii) the MF-EMG BB tended to decrease by 11% (36 ± 8 vs. 32 ± 4 [Hz], P = 0.178, respectively); (iii) the S-MYO BB significantly decreased by 18% (247 ± 69 vs. 203 ± 31 [N/m], P = 0.030, respectively), (iv) the F-MYO BB significantly decreased by 13% (15 ± 2 vs. 13 ± 1 [Hz], P = 0.006, respectively) and (v) the level of BDNFs significantly increased by 34% (P = 0.035). Moreover, we found statistically significant positive correlation of IT-related an increase in BDNFs with IT-related improvement (decrease) in parkinsonian rigidity (P = 0.603, P = 0.025), S-MYO BB (r = 0.827, P = 0.001) and F-MYO BB (r = 0.782, P = 0.002).Conclusions: The training-induced alleviation of parkinsonian rigidity and the decrease of muscle tonus might be related to the training-induced increase of serum BDNF level.No conflict of interest.

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VISUAL CUEING DURING TREADMILL WALKING AS A NEW TOOL FOR GAIT TRAINING IN NEUROREHABILITATION: A FEASIBILITY STUDY IN HEALTHY INDIVIDUALSP. Terrier1,*1Service de Recherche, Clinique Romande de Réadaptation SUVACare, Sion, Switzerland

Objectives: It is widely recognized that synchronizing steps with rhyth-mic auditory cues can facilitate ambulation in PD patients. It has been also observed that adjusting step length to floor markers could be beneficial. While the effects of auditory cues have been already investigated, the benefits of visual cueing have not been thoroughly documented. The objective of the pre-sent pilot study is to address the feasibility of the use of visual cueing for gait rehabilitation.Methods: The C-Mill is a 3-m long instrumented treadmill with stepping tar-gets (or stepping stones) projected on the belt to facilitate practice of foot placement. In order to be considered as sufficiently efficient to mobilize alternative gait control modalities, and hence be valid for gait rehabilitation, we postulated that visual cueing should induce the same change in step-to-step fluctuations as the already documented changes that the auditory

cueing induces. Consequently, we compared the responsiveness of several variability indexes under uncued (normal) condition, under rhythmic auditory cueing (metronome) condition, and under visual cueing (stepping stones) condition.Results: Preliminary results indicate that both auditory and visual cueing simi-larly modified the stride-to-stride fluctuation pattern as compared to normal walking. (Figure source: Ooijen et al. BMC Geriatr. 2013).

Treadmill is instrumentedwith a force platform

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Conclusions: In healthy individuals, both auditory and visual cueing induced sim-ilar adaptation of the gait pattern in terms of lower variability and increased station-arity. Therefore, it is likely that combining visual cueing with treadmill walking could be used as an alternative training method for gait rehabilitation in PD patients.No conflict of interest.

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FOLLOW UP IN LONG-TERM GLOBAL MOTOR TRAINING WITH RYTHMICAL AUDITORY CUES IMPROVE AND MAINTAIN GAIT AND BALANCE CONTROL IN PARKINSON’S DISEASE (PD)T. Capato1,*, E.R. Barbosa2, M.E.P. Piemonte1

1Physiotherapy, University of Sao Paulo, Sao Paulo, Brazil, 2Neurology, University of Sao Paulo, Sao Paulo, Brazil

Objectives: This study extend previous research by evaluate the efficiency of a global motor training (MT) connected to rhythmical auditory cues (RAC) not associated to specific movements on balance and gait and verify the follow up in long-term.Methods: Assessments were carried out by a blinded examiner in 20 PD mean age of 67.91 years (DV = 6,51) at stages 2–3 of H&Y, before and after 10 training sessions, and after 1, 6 and 18 months the end of training. The sub-jects were assessment through TUG, BBS, Mini BESTest and Postural Stress Test (PST), also carried out an assessment of independence to the AVDs and motor performance through UPDRS. Patients were divided in 2 groups ran-domly. One of the groups (GI), carried out a MT associated RAC and training were self-perception, motor performance, attention, during 5 weeks with 45 m, divided in 5 m warm-up, 30 m main part, 10 m cool down. The GI continuing, the MT during 12 months. The other group (GII) carried out the same program and stopped the training in 6 months.Results: After training the both groups showed significant improvement in BBS, Mini BESTest and TUG. The follow up show the improvement was main-tained in 1, 6 months in both groups, after 12 months the there were decrease in motor aspects in GII and the GI maintained Balance BBS (p = 0,001), Mini BESTest (p = 0,000) and Gait TUG (p = 0,001).Conclusions: MT improves Gait and Balance in PD and the exercises must be continuing for maintained and prevent decline of the motor conditions.No conflict of interest.

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THE EFFECTS OF VISUAL AND AUDITORY CUES ON BRADYKINESIA IN PARKINSON’S DISEASE: EFFECT ON FINGER TAPPINGS. Kang1,*, H. Lee1, H. Kim1, J. Ahn2

1Neurology, Hanyang University Medical Center, Seoul, Korea, 2Neurology, Seoul Medical Center, Seoul, Korea



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Objectives: Bradykinesia and disturbances of rhythm formation that occur in PD are usually assessed through the finger tapping test. Bradykinesia espe-cially finger tapping test which is most widely using tools in PD, have not been studied about the effects of visual and auditory cues. The object of this study was to investigate the effects of visual and auditory cues on finger tapping using gyrosensor.Methods: 19 patients with PD were enrolled. All patients performed finger tapping tasks at “ON” and “OFF” medication state. Finger tapping task was performed with wearing motion sensors on index finger of measuring hand during 15 s. In addition, same patients performed finger tapping tasks with visual cue and then auditory cue. Quantitative variables representing speed, amplitude, and rhythm were extracted from kinematic data.Results: In “ON” and “OFF” medication state, visual cue improves in variation of amplitude, but speed and rhythm were not improved. Auditory cue improved in speed and rhythm, but not in amplitude. When the amplitude of visual cue or frequency of auditory cue were same as amplitude or frequency in uncued condition, there were maximized effects on bradykinesia.Conclusions: Visual cues influenced tapping amplitude than speed and rhythm. Auditory cues demonstrated a greater influence on speed and rhythm than amplitude. So, these results suggest that visual and auditory cues could activate a motor plan and effectively trigger movement in PD.Reference1. Espay AJ et al. Differential response of speed, amplitude, and rhythm to

dopaminergic medications in Parkinson’s disease. Mov disord. 2011 Dec; 26(14):2504–8.


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CUEING FOR DROOLING IN PARKINSON’S USING A NOVEL DIGITAL DEVICE: PRELIMINARY QUALITATIVE FEEDBACK FROM A SUBSET OF PARTICIPANTSR. McNaney1,*, R. Walker2, N. Miller2, P. Olivier1

1Computing Science, Newcastle University, Newcastle upon Tyne, United Kingdom 2Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United KingdomObjectives: The ongoing ‘Cueing for drooling in Parkinson’s’ study aims to trial the clinical effectiveness of a wrist-worn digital cueing device [1], which vibrates at regular intervals to remind the wearer to swallow their saliva more frequently, thus reducing the risk of drooling from occurring.Methods: Participants trialed this device for 4 weeks, for at least 2 separate hours per day and kept a diary of how frequent and severe they felt their drool-ing was both when wearing the device and when not wearing it. All participants had a MMSE of 24+ and had an identified problem with drooling.Results: We present preliminary, qualitative feedback on the perceived effec-tiveness of the device on a subset of 16 participants. 12/16 participants said that they felt their drooling had improved over the course of the trial and would try the intervention for a longer period. Interestingly, several of the participants also noted that their drooling had improved even when not wearing the device. The 4 who did not see an improvement had reported the impact of their drool-ing as mild pre-trial.Conclusions: The majority of participants felt that the cueing device helped their drooling. Further quantitative analysis is to be carried out on their diary entries and a range of assessment measures (e.g., ROMP-Saliva, UPDRS saliva and drooling item) which were carried out pre and post trial.Reference1. McNaney et al. Cueing for drooling in Parkinson’s disease. In proc. of

Conference on Human Factors in Computing Systems (CHI). 2011, Vancouver, Canada: ACM Press.


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APPLICATION OF LSVT BIG INTERVENTION TO ADDRESS GAIT, BALANCE, BED MOBILITY AND DEXTERITY IN PARKINSON’S DISEASE: A CASE SERIESJ. Janssens1,*, K. Malfroid2, T. Nyffeler3, S. Bohlhalter3, T. Vanbellingen3

1Neurorehabilitation, Klinik Bethesda Tschugg, Tschugg, Switzerland, 2Neurorehabilitation, Physiotherapie Robellaz, Köniz, Switzerland, 3Department of Internal Medicine, Neurology and Neurorehabilitation Center, Luzern, Switzerland

Objectives: Lee Silverman Voice Treatment Big (LSVT BIG) is characterized by intensive exercising of high-amplitude movements to overcome hypokine-sia in patients with Parkinson’s disease (PD)1. The aim of the present case series was to explore possible beneficial effects of LSVT BIG on gait, balance, bed mobility and dexterity.Methods: Three patients with mild to moderate PD, completed a 4-week LSVT BIG training and an intensive home training according to the LSVT BIG proto-col. The outcome measures for gait and balance included the Functional Gait Assessment (FGA), Functional Reach Test (FRT), Timed Up and Go (TUG), Freezing of Gait Questionnaire (FOGQ) and Unified Parkinson Disease Rating

Scale (UPDRS Part III – motor scale). Bed mobility was addressed by the Lindop Parkinson’s Disease Mobility Assessment (LPA). The Nine Hole Peg Test (9HPT) was used to measure dexterity.Results: The three patients improved on balance and gait, indicated by higher scores on FGA and FRT. Furthermore, the patients were quicker in tasks related to bed mobility (LPA). Two out of three patients demonstrated a better performance on the TUG, FOGQ and UPDRS Part III. Patient’s dexterous skills did not improve for their dominant right hand (9HPT).Conclusions: This case series suggest that LSVT BIG may be beneficial for gait, balance and bed mobility.

Reference1. Fox C, Ebersbach G, Ramig L, Sapir S. LSVT LOUD and LSVT BIG:

Behavioral Treatment Programs for Speech and Body Movement in Parkinson Disease. Parkinsons Dis. 2012:1–12.


287

THE INFLUENCE OF VESTIBULAR STIMULATION ON FREEZING IN PARKINSON’S DISEASEJ. Van Vaerenbergh1,*, R. Vranken2, F. Baro3

1CMAT BRAIN UNIT, Center for Multidisciplinary Approach and Technology, Dilbeek, Belgium, 2Faculty of Physical Education and Physiotherapy, Katholieke Universiteit Leuven, Leuven, Belgium, 3Department of Neuropsychiatry, Katholieke Universiteit Leuven, Leuven, Belgium

Objectives: Freezing is often resistant to drug therapy, therefore the effect of vestibular stimulation on freezing was investigated.Methods: Eight Parkinson patients with freezing participated in the study. The mean degree of disability was disease stage 3(+) on the Hoehn and Yahr Scale and a mean Unified Parkinson’s Disease Rating Scale (UPDRS) motor score of 46 (SD = 11). The test consisted of an aut-omized, sudden, ‘STAND UP AND GO’ instruction during the performance of a standardized foot lifting test. During the foot lifting the mean OPMSP Onset of Premotor Silence Period (OPMSP) in the EMG of the m. tibi-alis anterior was analyzed. Results before and after vestibular stimulation were comparedResults: The sudden instruction of ‘stand up and walk’ provoked freezing in all tested patients. The mean OPMSP in the EMG of the m. tibialis anterior during the ‘foot-lifting’ sessions preceding freezing was 124 ms. This value, together with a striking repetition of the EMG discharges in the m. tibialis ante-rior after the instruction of ‘stand up and walk’, was related to freezing onset, as a decrease of 42 ms in the OPMSP (t = 2.61; p = 0.01) after rotational stimulation abolished freezing and the related EMG disturbances. Vestibular stimulation also reduced freezing frequency during daily life with almost 50% (t = 5.58; p = 0.001).Conclusions: The rather long-lasting effect of the stimulation suggests a pos-sible modulation of neurochemical transmission.No conflict of interest.

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ADAPTABILITY OF REACTIVE POSTURAL RESPONSES AS A FUNCTION OF VOLUNTARY TASK CONSTRAINT: INFLUENCE OF PARKINSON’S DISEASEA.C. de Lima-Pardini1,*, S. Papegaaij2, R. Cohen3, L.A. Teixeira1, B. Smith4, F.B. Horak4

1Biodynamics of Human Movement, University of São Paulo, São Paulo, Brazil, 2Center for Human Movement Sciences, Faculty of Medical Sciences University of Groningen, Groningen, Netherlands, 3Psychology and Communication Studies, University of Idaho, Moscow, USA, 4Neurology, Oregon Health and Science University, Portland, USA

Objectives: This study aimed at assessing the effect of stabil-ity constraints imposed by a voluntary task on the adaptation of pos-tural responses to an external perturbation in elderly individuals with Parkinson’s disease (PD).Methods: Subjects with PD and age-matched controls were perturbed through a backward translation of the support surface while standing and performing two versions of a voluntary task: holding a tray with a cylinder placed with the flat side down (LC) or with the rolling round side down (HC). Participants performed alternating blocks of low and high constraint trials.Results: Parkinson’s disease participants accomplished the voluntary task as well as controls, showing slower tray velocity in the high, as com-pared with the low, constraint context. Latency of postural responses was longer in the high constraint context only for control subjects. Control sub-jects presented different patterns of hip-shoulder coordination as a func-tion of task constraint, whereas PD subjects had a relatively invariable pattern.



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Conclusions: These results suggest that Parkinson’s disease impairs the capacity to adapt postural responses to constraints imposed by a voluntary task.Reference1. de Lima-Pardini, A.C., Papegaaij, S., Cohen, R.G., Teixeira, L.A., Smith,

B.A. & Horak, F.B. (2012a). The interaction of postural and voluntary strat-egies for stability in Parkinson’s disease. Journal of Neurophysiology. 108, 1244–1252.


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IMPROVING OF BALANCE IN PATIENTS AFFECTED BY PARKINSON’S DISEASE BY DECREASING RIGIDITYA.P.C. Loureiro1,*, V. Bauer1

1Physical Therapy Department School of Health and Biosciences, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil

Objectives: The deficiency of trunk mobility can lead to a loss of balance and unexpected falls in individuals with Parkinson’s disease (PD). The aim of this study was to verify the improvement of postural balance by decreasing trunk rigidity with the approach of aquatic physical therapy in patients with PD.Methods: Participated in these studies 33 individuals diagnosed with PD. They were randomly divided into two groups. Control group (15 individuals) who did conventional physiotherapy, and the Intervention group (18 individuals), which in addition to participate in conventional physiotherapy, they attended aquatic therapy in a therapeutic pool with the Watsu Method. Patients received 18 indi-vidual treatments of 30 min each, twice a week. The following main outcomes measures were used for both groups in the beginning and end of the research:

Trunk Mobility Scale ((TMS), Berg’s Balance Scale (BBS), Time Up and Go Test (TUG) and a 6 Minute Walk Test (6MWT).Results: Only 28 participants were able to conclude the study. After statisti-cal analysis it was verified that the Intervention Group showed higher thera-peutic efficacy when compared to the Control Group, presenting statistically significant results in instruments: TMS (ANOVA; P = 0,02758), BBS (ANOVA; P = 0,00077) and 6 Minute Walk Test (ANOVA; P = 0,00893).Conclusions: The therapeutic program using Watsu Method had favored the work of muscle relaxation, gaining movement amplitude and overall mobility facilitated contributing to postural stability.No conflict of interest.

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TAU, PHOSPHO-TAU, β-AMYLOID42 AND α-SYNUCLEIN IN THE CEREBROSPINAL FLUID OF PATIENTS WITH PARKINSONISMA. Bougea1,*, G. Paraskevas1, V.C. Constantinides1, E. Kararizou1, E. Kapaki11Neurology, Eginition Hospital of Athens, Athens, Greece

Objectives: The study of CSF biomarkers in neurodegenerative diseases provides information on the underlying biochemical pathology and may also facilitate their differential diagnosis. The purpose of this study was to identify tau, phospho-tau, β-amyloid42 and α-synuclein levels in the CSF of patients presenting with parkinsonism of neurodegenerative etiology.Methods: The above mentioned biomarkers were measured by ELISA in 28 patients with Parkinson’s disease (PD), 14 patients with multiple system atro-phy (MSA), 30 patients with either progressive supranuclear palsy or cortico-basal degeneration (PSP/CBD) and a control group (CG) of 108 comparable healthy.Results: Tau protein levels were significantly increased in MSA and PSP/CBD patients compared to the control group and PD patients. Phospho-tau and Ab42 levels did not differ among the 4 groups, whereas α-synuclein levels were significantly decreased in PD and PSP/CBD patients compared to the control group and MSA patients.Conclusions: These results indicate that the combined measurement of CSF levels of tau protein and α-synuclein could facilitate the differential diagnosis between patients with PD, MSA or PSP/CBD.No conflict of interest.

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CORTICAL INFLUENCE ON SWALLOWING FUNCTION IN PATIENTS WITH PARKINSON’S DISEASEJ. Kim1,*, H. Shin2, J. Youn3, M. Suh3, J. Chin3, J. Cho3

1Neurology, Soonchunhyang University Hospital, Seoul, Korea, 2Neurology, Eulji General Hospital, Seoul, Korea, 3Neurology, Samsung Medical Center, Seoul, Korea

Objectives: Dysphagia is common and may be an important factor for prog-nosis in Parkinson’s disease (PD). Although cortical dysfunctions may contrib-ute to dysphagia in PD patients, the exact nature of an association between cortical and swallowing functions is unclear. We evaluated the associations of cortical functions assessed by detailed neuropsychological profiles and motor functions as contributing factors for swallowing components measured by video fluoroscopic swallowing (VFS) studies.Methods: We prospectively enrolled 56 non-demented PD patients. All participants received neuropsychological tests covering general mental status, visuospatial function, attention, language and related functions, learning and memory function and frontal executive function. The Unified Parkinson’s Disease Rating Scale and Hoehn and Yahr stage of all subjects were measured. VFS studies were performed, and the validated and reliable Modified Barium Swallow Impairment Profile scoring system was applied to quantify the nature of the physiologic swallowing impairment. We analyzed the correlations of neuropsychological and motor functions for swallowing components.Results: Most significant correlations were found between frontal, temporal domains and oral phase of swallowing function including hold position/tongue control, bolus preparation/mastication and bolus transport/lingual motion, and a minority component of pharyngeal phase had an association with frontal functions. Motor functions were concerned with the pharyngeal phase as well as the oral phase.Conclusions: Our findings suggest that cortical dysfunctions are associ-ated with mainly the oral phase of swallowing in early stage PD patients. Furthermore, the severity of motor symptoms concern overall swallowing func-tion may encompass the whole stage.Reference1. Gastrointestinal dysfunction in Parkinson’s disease. Parkinsonism Relat

Disord 2011, 17:10–15.No conflict of interest.



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JOINED-UP THINKING: EXPERIENCES AND OUTCOMES IN CONDU-CTING PARALLEL PARKINSON’S DISEASE AND SYNCOPE OUT-PATIENT CLINICS FOR OLDER ADULTSA. Thomson1,*, C. Miller1, L. Partington1, J. Staniland1

1Ageing and Complex Medicine, Salford Royal NHS Foundation Trust, Manchester, United Kingdom

Objectives: Orthostatic hypotension (OH) is a common problem in patients with idiopathic Parkinson’s disease (iPD). It may be worsened by levodopa treatment and exacerbated by multi-morbidity and polypharmacy. This is particularly challenging in frail older adults. This work aimed to assess how closer collaboration between syncope and movement disorder services for older adults might optimize management of OH. This included comprehensive specialist assessment, investigations, and interventions including prescription of midodrine and other vasoactive agents.Methods: Separate out-patient clinics for syncope and iPD were re-organized to run parallel in a shared clinic area. This aimed to promote real-time discus-sion and decision-making. Records for all patients with iPD attending clinic follow-up were retrospectively examined to identify those who had also been seen jointly with the syncope service.Results: 117 patients (ages 64–92 years, mean 81.3 years) with iPD were identified to be under follow-up between July 2008 and June 2013 in the Movement Disorders clinic. 42 (35.9%) died and 11 (9.4%) had their follow-up transferred elsewhere. 32/117 (27.3%) had symptomatic OH. 13/32 (40.2%) had particularly complex problems with OH, and were assessed jointly. 10/32 (31.2%) had conventional management plus add-on treatment with midodrine.Conclusions: This re-organization of services has been associated with smoother medical management and a better patient-experience. We recom-mend that other units look at this type of inter-disciplinary model and consider how it could be mapped to their own local service-provision.No conflict of interest.

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PSYCHOLOGICAL INTERVENTION FOR PARKINSON’S DISEASE: A LITERATURE REVIEWK.M. Holmes1,*1NE DeNDRoN, Northumberland Tyne and Wear NHS Foundation Trust, Newcastle Upon Tyne, United Kingdom

Objectives: Review literature related to Parkinson’s Disease (PD) and Psychological Intervention. Provide aims for future study.Methods: Online journal articles were searched.Results: A review of the literature yielded few articles on psychological inter-vention for mental health issues associated with PD. Of the articles sourced, all focused on using Cognitive Behavioral Therapy (CBT) for depression in PD (Dobkin et al., 2012; Cole and Vaughan, 2005; Feeney, et al., 2005). These articles concluded that CBT can be a valuable tool in managing depression in PD sufferers however, there currently does not exist enough research into psychological interventions for mental health issues associated with PD.Conclusions: According to the British Psychological Society (BPS) guide-lines for PD, psychological intervention is invaluable to improving quality of life (BPS, 2009). Current treatments for PD are mostly medical in nature and address the physical symptoms such as tremors (Feeney, et al., 2005) how-ever, issues such as: depression; anxiety; psychosis; sleep disorders; and neurobehavioral disorders are also commonly experienced with PD.Cole and Vaughan, (2005) describe people with PD depression as a vulnerable and emotionally neglected group, the literature suggests that psychological inter-ventions together with medical treatment is improving the quality of life for PD sufferers (Dobkin, et al., 2012). The literature represents a very small sample of the use of psychological interventions for PD sufferers and depression. It would appear that there is a need to continue to research mental health and the effects of psychological intervention for PD sufferers with the aim of improving quality of life.No conflict of interest.

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MEMORY IMPAIRMENT IN PARKINSON’S DISEASE: EFFICACY OF COGNITIVE TRAININGK.V. Kotenko1, I.G. Smolentseva2, N.A. Amososva2, O.V. Krivonos2, O.V. Karpova2, L.P. Chupina3, O.A. Maslyuk2

1Administration, Federal Medical Biophysical Center, Moscow, Russia, 2Federal neurological center of movement disorders and mental health, Federal Medical Biophysical Center, Moscow, Russia, 3Department of Neurology, Federal Medical Biophysical Center, Moscow, Russia

Objectives: Profile of cognitive impairment in PD is heterogeneous, with fre-quent memory impairments. One possible approach to non-pharmacological treatment memory can be training.Methods: The study included 37 patients with PD, with average age of 56,5 ± 7,7 years, disease duration 5,8 ± 3,4 years and stage by Hoehn and

Yahr 2,4 ± 0,5. The control group had 28 patients with PD with similar values. The patients in study and control group hadn’t dementia. We used a computer-ized memory training for 12 weeks, 2 times a week, one session was 60 min. After the primary course of training the patients continued training at home. Assessment of cognitive function was performed with the Scopa–Cog Scale, assessment of memory was performed with the computerized training program CogniPlus before, immediately after, 12 weeks after, 3 and 6 months after the training.Results: On the background of training the study group showed significant improvement by the Scopa-Cog scale by 16.6%, in the subtest for the verbal recall – by 14.2%, subtest on the delayed recall – by 10.2%. The computerized tests of visual memory showed significant decrease in runtime (p < 0,05) and increased number of correct answers (p < 0,01). In the control group there was a trend of decrease of memory. Assessment showed significant increase in the time of audiomotor reaction by 12.5 %, while increase the time of visuomotor reaction had loose correlation.Conclusions: After the training PD patients showed improvement of memory.References1. Scopa–Cog Scale (Visser M., 2004).2. Digital values of program CogniPlus.No conflict of interest.

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SAFETY AND EFFICACY OF COGNITIVE REHABILITATION IN PARKIN-SON’S DISEASER. Biundo1,*, L. Weis1, S. Facchini1, M. Campo1, G. Gentile1, L. Fiorenzato1, M. Pilleri1, A. Antonini11UOS Parkinson and Movement Disorders, IRCCS Fondazione Ospedale San Camillo, Venice, Italy

Objectives: The effect of cognitive training (CT) alone or in association with non-invasive brain stimulation (t-DCS or r-TMS) of left dorsolateral prefrontal cortex (DLPFC) in PD patients with cognitive impairment (PD-CI) is debated. The aims of our double blind study are: 1) to test whether t-DCS of left DLPFC enhances the effect of CT on cognitive performance in PD-CI 2) to investi-gate with MRI whether cognitive improvements are associated with discrete regional modifications of brain perfusion and cortical excitability.Methods: Twelve PD-CI subjects [mean age 64 (SD 20.4), education 9.3(SD4.1) and disease duration 9(SD 6.9)] randomly received 4-week trial of CT (4 times per week) paired with 20 min sham or real anodal t-DCS over left DLPFC. Patients received a structural volumetric as well as functional MRI at study entry and 48 h after study end along with an extensive clinical, cognitive-behavioral, and electrophysiological examination.Results: The whole PD-CI group significantly increased their performance at fronto-striatal based cognitive tests during computer-based treatment (p < 0.000). Within-subject analysis showed significant increase at MoCA score (from 20.5 mean score to 21.9, p < 0.5) and significant decrease at BDI score (from 15.1 mean score to 9, p < 0.5) after treatment. Between-subject analysis showed a clinically meaningful cognitive effect in one treatment group compared with the other one.Conclusions: Specific non-pharmacologic therapeutic strategies can amelio-rate cognitive and behavioral performance in PD.No conflict of interest.

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PSYCHOLOGICAL AND COMPUTER BASED COGNITIVE REHA-BILITATION OF PARKINSON DISEASE: NIRS STUDYS. Payzieva1,*, D. Maxmudova2

1Biomedical Engineering, Tashkent State Technical University, Tashkent, Uzbekistan, 2Applied Psychology, Tashkent State Pedagogical University, Tashkent, Uzbekistan

Objectives: NIRS research Psychological and Computer based Cognitive Rehabilitation of Parkinson Disease patients: how Cerebral Blood Oxygenation changes occur in the frontal lobe when brain stimulated by Computer Based Cognitive Rehabilitation (CBCR) tasks and psychotherapy.Methods: Psych correction and methods of a relaxation, meditation, visuali-zation were used for 1 h during 10 days with the recommendation of repeti-tion of a cycle in 3 months. CBCR were used for improving cognitive abilities such as memory, attention, speed of thinking, flexibility and problem solving. Using NIRS, changes of deoxy-Hb, oxyhemoglobin (oxy-Hb) and total hemoglobin (total Hb) were measured in the frontal lobes during various stimulus conditions: psychotherapy and CBCR. 15 patients with PD (rate severity < 2.5, without symptoms of Dementia) were studied.Results: Computer exercises stimulation increased oxy-Hb and total Hb with a decrease of deoxy-Hb in an intensity and time dependent manner. Experiments were carried out with different CBCR exercises during 20 min a day for 5 weeks. Brain Performance Index (BPI) served as indicator improving cognitive abilities. Psychotherapy led to reduction of block, feeling of depres-



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sion and feeling of loneliness and alarm for the future. Improvement of psycho-logical health marked out 85% patients.Conclusions: Results of experiment lead to future detailed NIRS investiga-tion influence each cognitive exercise to CBO changes and will be developed standardized protocol of experiments for cognitive rehabilitation.No conflict of interest.

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PROSPECTIVE MEMORY FUNCTIONING IN PATIENTS WITH PARKINSON’S DISEASE: EFFECT OF COGNITIVE REHABILITATIONA. Costa1, A. Peppe1, F. Serafini1, S. Zabberoni1,*, F. Barban1, C. Caltagirone2, G. Carlesimo2

1Behavioral and Clinical Neurology, IRCCS Fondazione Santa Lucia, Roma, Italy, 2Behavioral and Clinical Neurology, IRCCS Fondazione Santa Lucia Rome University “Tor Vergata”, Roma, Italy

Objectives: This study was aimed at investigating the effect of a cognitive training focused on shifting capacities on the ability of patients with Parkinson’s disease (PD) to perform prospective memory (PM) tasks.Methods: In a double-blind protocol, 17 PD patients were randomly assigned to two arms. In the first experimental arm (n = 9), a shifting training was administered; in the second placebo arm (n = 8), simple attention exercises plus a phoniatric therapy were administered. Both treatments consisted of 12 sessions to be executed in 4 weeks. Two PM computerized procedures and two measures of shifting (i.e., Trail Making Test and Alternate Fluency) were administered at T0 (before treatment) and T1 (immediately at the end of treat-ment). Mixed ANOVA was applied to data.Results: The critical interaction between Group (experimental vs. placebo) and Time of Assessment (T0 vs. T1) was significant for the performance accu-racy on the PM task (p < 0.05) and shifting tasks (p ≤ 0.05). Tukey HSD tests showed that, in all cases, passing from T0 to T1, performance significantly improved in the experimental group (in all cases p ≤ 0.02), while it remained unchanged in the placebo group (all p consistently > 0.10).Conclusions: The results of the study document that cognitive training may sig-nificantly improve PD patients’ performance on PM tasks. The same data sus-tain, in these patients, the dependency of PM functioning from shifting abilities.No conflict of interest.

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COGNITIVE BEHAVIORAL THERAPY, AN EVIDENCE-BASED TREATMENT FOR PARKINSON’S DISEASE PSYCHOSISH. Montero1,*1Psychology, Capella University, Brooklyn, USA

Objectives: Parkinson’s Disease Psychosis (PDP) is a Non-Movement Symptoms (NMS). PDP, a NMS is present in 40% of PD patients and is characterized by hallucinations, which are difficult to treat. For example, dopamine agonist interacts with typical and Atypical Antipsychotics (AA) (Weintraub and Stern, 2005). There is a high likelihood serious life threat-ening interaction between dopaminergic agonist and typical; antipsychotic (Clozapine) medication (Rabey et al., 1995). These interaction may cause psychotic symptoms.Methods: The proposed idea is to research Cognitive Behavioral Therapy (CBT) for PDP. The model is intended to be used for this research is Zubin and Spring (1977) stress vulnerability model that holds that individuals have unique biological, psychological and social perceptions. These perceptions include strengths and vulnerabilities for dealing with the stressor (psychosis).Results: CBT has been demonstrated to work with patients with primary psy-chosis for over 30 years.Conclusions: CBT has clear goals, it allows the treatment to be defined as a technique to be examined as a scientific treatment.References1. Rabey, J., Treves, T., Neufeld, M., Orlov, E., Korczyn, A (1995). Low-dose

clozapine in the treatment of levodopa-induced mental disturbances in Parkinson’s disease. Neurology Journal, 432–434.

2. Weintraub, D., & Stern, M. (2005). Psychiatric complications in Parkinson disease. American Geriatric Psychiatry, 844–51.

3. Zubin, J. a. (1977). Vulnerability: A New View on Schizophrenia. Journal of Abnormal Psychology, 86,103–126.


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COGNITION AND EDUCATION TO SPEECH TELEREHABILITATION IN PARKINSON’S DISEASEA. Dias1,*, J. Limongi1, E.R. Barbosa1

1Department of Neurology, Hospital das Clínicas School of Medicine of the University of Sao Paulo, São Paulo, Brazil

Objectives: To analyze the impact of cognitive performance and formal edu-cation in the acceptance of telerehabilitation.Methods: Fifty patients with diagnosis of Parkinson’s disease were evaluated for voice intensity (VoxMetria 4.7) before and after face-to-face conventional Lee Silverman Voice Treatment and were asked to answer a questionnaire to evaluate basic computer knowledge and eventual preference regarding either face-to-face or online therapy. Statistical analysis with Spearman correlation method was performed.Results: Age ranged between 45 and 87 years old, Hoehn-Yahr stage 2–4, MMSE between 19 and 30 and time of education between 4 and 17 years. Speech therapy resulted in an increase of 18 dBSPL in mean intensity of voice (pre-treatment 45dBSPL; post-treatment 63dBSPL) and all patients were favorably impressed with conventional therapy. When questioned, the major-ity (76%) was inclined to be treated with online therapy and 26% of this group were familiar with computers in contrast with 24% in the group not inclined towards online therapy. The opinions did not correlate with stage of the dis-ease, age or sex but correlated significantly with cognitive performance and years of education.Conclusions: This study suggests that speech therapy involving telereha-bilitation may be better accepted in patients with higher scores of cognitive performance and more years of formal education. On the other hand, tech-nological competence (to own a computer or to kwon the basics of computer using) was not a determinant factor.No conflict of interest.

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ACCESS TO REHABILITATIVE THERAPIES FOR COMMUNITY-DWELLING PEOPLE WITH PARKINSON’S IN THE BRITISH NATIONAL HEALTH SERVICEH. Gage1,*, L. Grainger1, S. Ting1, P. Williams2, C. Chorely1, G. Carey1, N. Borg1, K. Bryan3, B. Castleton4, P. Trend5, J. Kaye5, D. Wade6

1Economics, University of Surrey, Guildford, United Kingdom, 2Mathematics, University of Surrey, Guildford, United Kingdom, 3Health and Social Care, University of Surrey, Guildford, United Kingdom, 4Gerontology, Runnymeade Hospital, Surrey, United Kingdom, 5Neurology, Royal Surrey County Hospital, Guildford, United Kingdom, 6Neurology, Oxford Centre for Enablement, Oxford, United Kingdom

Objectives: To explore access to rehabilitative therapies by people with Parkinson’s in the context of best practice management guidelines in the British National Health Service that recommend a central role for specialist nurses and regular access to physiotherapy, occupational therapy and speech and language therapy from diagnosis (1).Methods: Patients recruited to the Specialist Parkinson’s Integrated Rehabilitation Team Trial (SPIRiTT), in Surrey, England, were asked at base-line to report recent contacts with Parkinson’s specialist nurses and access to rehabilitative therapies.Results: 269 people with Parkinson’s provided data; 105 (39%) female, 162 (60%) diagnosed ≥5 years earlier. There were 53 (19.7%) people with Parkinson’s who either did not have a Parkinson’s nurse, or had not seen a nurse within 2 years. Of 231 participants diagnosed more than 2 years earlier, 72 (31.2%) had seen a physiotherapist within 6 months, 97 (42.0%) had not seen a physiotherapist in over 2 years, or had never / did not know if they had seen one. The proportions that had seen an occupational and speech and language therapist in the last 6 months was much lower (11.7%, 9.1%), and the proportions without contact with these therapists in the previous 2 years were much higher (74.9%, 77.5%).Conclusions: Many people with Parkinson’s do not have access to reha-bilitative therapies in line with recommended guidelines, and this may reflect capacity constrains within community services. People with Parkinson’s showed benefit following rehabilitation in the SPIRiTT trial and reported knowl-edge gains.Reference1. NICE. Diagnosis and management of PD, Clinical Guideline 35, 2006.

ISRCTN: 44577970.Acknowledgments: This project was funded by the National Institute for Health Research Health Services and Delivery Research (NIHR HS&DR) programe (pro-ject number 08/1909/251). Visit the HS&DR website for more information. The views and opinions expressed therein are those of the authors and do not neces-sarily reflect those of the NIHR HSDR programe or the Department of Health.No conflict of interest.

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A NOVEL WIRELESS SENSORS-BASED TOOL FOR IMPROVING PD PATIENTS REHABILITATIOND. Alimonti1,*, M.C. Rizzetti2, M. Poloni1, D. Comotti3, M. Galizzi4, M. Caldara4

1Neurosciences – Neurology Unit, Papa Giovanni XXIII Hospital, Bergamo, Italy, 2PD Rehabilitation Unit, “San Isidoro” Hospital, Trescore Balneario



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Bergamo, Italy, 31) Department of Electrical Computer and Biomedical Engineering 2) Department of Engineering, 1) University of Pavia 2) University of Bergamo, Bergamo, Italy 4Department of Engineering, University of Bergamo, Bergamo, Italy

Objectives: To provide an accurate and simple body-motion tracking tool for enhancing the PD-patients evaluation and their rehabilitation.Methods: First trials involved four PD-subjects with moderate-severe disease, who wore the wireless sensors network composed by five nodes (wrists, legs and spine) while performing timed Up-and-Go test; data were evaluated with synchronous video recordings of the exercises. Patients were in their ON-state and scored for the UPDRS.Results: The acquired data were used to represent in real-time posture, arms oscillation angles and symmetry during gait, tremors/dyskinesia, quality of gait, and exercise’s duration. At the same time data were translated in a virtual human-model on a PC-video.

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Conclusions: Our wireless-device resulted wearable and reliable in recording different movement variables of PD, without a typical gait analysis laboratory. In particular, it may translate real-time a visual feed-back which might be used by physiotherapists and clinicians during rehabilitation; as well it might offer a fine measure of motor outcomes after a treatment (whether physical or phar-macological). As possible application, it might be wore at home by PD-patients offering them a visual feed-back for a better motor performance; the same data will be useful for the clinicians detecting motor fluctuations and drugs response.No conflict of interest.

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IAB – AN INTERDISCIPLINARY WORKING GROUP FOR PROMOTING MULTIMODAL THERAPY OF MOVEMENT DISORDERSF. Adib Saberi1,*, H. Pickenbrock2, D. Dressler2

1Neurology, IAB – Interdisciplinary Working Group for Movement Disorders, Hamburg, Germany, 2Neurology, Movement Disorders Section Hanover Medical School, Hanover, Germany

Objectives: Increasing complexity of therapeutic strategies for movement disorders (MD) requires interdisciplinary therapies involving various health professionals and physicians. Coordinating all professions involved is difficult. Interdisziplinärer Arbeitskreis Bewegungsstörungen (IAB) serves to promote and to improve interdisciplinary therapies of MD.Methods: IAB was started 7 years ago in Hamburg, Germany as an interdis-ciplinary special interest group with about 25 physiotherapists, occupational therapists, speech therapists, nurse specialists, physicians and invited guests regularly meeting each quarter.

Results: IAB expanded and now also includes a special interest group for Parkinson assistants, a webpage with data bases of the members and addi-tional informations relevant to IAB members and the public visitors, a meeting arm for organizing meetings accredited by continuous medical education authorities for professionals and patients and a publication arm for production of educational and communication materials including a ‘communication form’, a ‘communication calendar’ and a ‘patient diary’ developed by IAB. Recently, IAB acquired a video production enterprise producing educational MD vid-eos. In the meantime, two more IAB groups were founded in other regions of Germany.Conclusions: IAB’s stability over more than 7 years and its expansion into more regions and other tasks documents the demand for promotion of inter-disciplinary therapies for MD.Reference1. Adib Saberi F, Dressler D (2012). Interdisziplinaerer Arbeitskreis

Bewegungsstoerungen (IAB): an interdisciplinary working group for pro-moting multimodal therapy of movement disorders: J Neural Transm. doi: 10.1007/s00702-012-0932-6.


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THE EXPERIENCE OF STUDY CENTRE “ACHILLE E LINDA LORENZON” ON PARKINSON’S DISEASE: A PATIENT-CAREMATE MEETING METHODOLOGYM. Pomponi1,*, D. Ricciardi1, B. Morabito1, L. Ricciardi1, A. Di Vossoli2, R. Bernabei3, A.R. Bentivoglio1

1Department of Geriatrics Neuroscience and Orthopaedics, Università Cattolica del Sacro Cuore, Roma, Italy, 2Centro Studi “Achille e Linda Lorenzon” Treviso, Università Cattolica del Sacro Cuore, Roma, Italy, 3Department of Geriatrics Neuroscience and Orthopaedics and Centro Studi “Achille e Linda Lorenzon”, Università Cattolica del Sacro Cuore, Roma, Italy

Objectives: We offer a multidisciplinary group rehabilitation program for Parkinsonian patients and their care-givers, named ‘Lorenzon Methodology’.Methods: Patients and care-givers (hereafter: caremates), hosted by the Centro Studi ‘Lorenzon’, along with the Parkinson Association of Treviso, attend educational lectures about the aspects of this disease and partake a psychological support group and group rehabilitation activities, organized by a multidisciplinary team chaired by a neurologist, a psychiatrist, a physiotherapist and an occupational therapist at the Department of Geriatrics, Neuroscience and Orthopaedics at the Rome ‘Agostino Gemelli’ Hospital. Additional guest specialists are geriatricians, physiatrists and logopedists. This free course consists in 12 two-day monthly meetings (Friday and Saturday).Results: 100 people attended. 30 patient-caremates couples were assessed, at baseline and after six monthly meetings, by Hamilton Depression (HDRS) and Anxiety Rating Scales (HARS), Empathy Quotient (EQ) and Alexithymia Scale (AS). Patients were then assessed by Unified Parkinson’s Disease Rating Scale (UPDRS) and Parkinson’s Disease Quality of Life Scale [PDQL39]. Caremates were checked by Care-giver Burden Inventory (CBI).Conclusions: A multidisciplinary rehabilitation course, answering patients’ and caremates’ unmet needs, may improve motor and non-motor aspects of the disease comprehension, applying strategies for better mobility, aware-ness and mutual understanding, prevention of burn-out. This course ends in December 2013.Reference1. Wade DT, Gage H, Owen C, Trend P, Grossmith C, Kaye J. Multidisciplinary

rehabilitation for people with Parkinson’s disease: a randomized controlled study. J Neurol Neurosurg Psychiatry. 2003; 74(2):158.


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DEVELOPING A REGIONAL COMMUNITY-BASED EXERCISE NETWORK FOR PARKINSON’S DISEASEM.A. Hirsch1,*, S.S. Iyer2, M. Sanjak2

1Physical Medicine and Rehabilitation, Carolinas Rehabilitation, Charlotte, USA, 2Neurology, Carolinas Medical Center, Charlotte, USA

Objectives: To share experiences by researchers and clinicians involved in developing a patient-centered, trans-regional Parkinson network to promote a culture of active lifestyles and wellness.Methods: We are developing a regional Parkinson network consisting of 40 physical therapists, registered nurses, neurologists and fitness professionals providing care at 11 outpatient physical therapy clinics and 6 YMCA fitness facilities within Mecklenburg County, North Carolina (1370 km2, 1 million pop-ulation). The network is patient-centered, combines elements of the Dutch ParkinsonNet healthcare concept with a neuroplasticity-based PD paradigm, and aims for implementation in the U.S. healthcare market [1–3].



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Results: Key developmental elements include (1) recruitment of highly moti-vated healthcare professionals to participate in research and highly motivated to treat individuals with PD; (2) patient-as-partner in care centered; (3) creat-ing partnerships linking medical specialties to break down silo thinking; (4) promoting leadership and sharing of power with community partners.Conclusions: The process of developing regional patient-centered networks is well worth the effort to improve the quality of PD careReferences1. Farley BG, Fox CM, Ramig LO, McFarland DH. Intensive amplitude-spe-

cific therapeutic approaches for Parkinson’s disease: Toward a neuroplasti-city-principled rehabilitation model. Topics in Geriatric Rehabilitation. 2008; 24(2):99–114.

2. Keus SHJ, Oude Nijhuis LB, Nijkrake MJ, Bloem BR, Munneke M. Improving community healthcare for patients with Parkinson’s disease: The Dutch model. Journal of Parkinson’s disease. 2012, Article ID 543426, doi: 10.1155/2012/543426.

3. Hirsch MA, Simpson A. Why bother with shared decision-making in Parkinson’s disease? Parkinsonism and Related Disorders. DOI: 10.1016/j.parkreldis.2013.06.02.


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WIDESPREAD DEVELOPMENT OF INTERDISCIPLINARY PARKINSON’S REHABILITATION TEAMS IN ORDER TO TREAT UNDERSERVED POPULATIONSJ. Dean1,*1Rehabilitation, Life Care Centers of America, Boulder, USA

Objectives: This is a discussion about the development of interdisciplinary Pd rehab teams in unusual settings in order to provide access to underserved or outlying regions.Methods: The lecture will begin by identifying successful iterations of these concepts around the world including an overview of network models in the Netherlands (ParkNet) and Oregon (Team PD at OHSU). It will also discuss how to bring a high level of expertise to regions and populations that are unde-served, including the emergence of informal networks of programs in suba-cute, LTC and home health environments.Results: This lecture will outline steps involved in developing interdisciplinary PD treatment expertise in various clinical environments. Furthermore, it will provide concrete information about reliable sources of expertise and training.Conclusions: Interdisciplinary rehab treatment is widely considered the gold standard of care for Parkinson’s disease, resulting in both improved quality of life and reduced costs for the medical system (van der Marck et al., 2009; Post et al., 2011). It is incumbent upon health care providers around the world to bring these treatment concepts to the Parkinson’s populations throughout their respective countries. This lecture will help to demystify the process of building these programs and developing this expertise.References1. Post, B., van der Eijk, M, Munneke, M, Bloem, B, Multidisciplinary care for

Parkinson’s disease: not if, but how. Postgrad Med J 2011; 87:575e578.2. van der Marck M, Kalf J, Sturkenboom I, et al. Multidisciplinary care

for patients with Parkinson’s disease. Parkinsonism Relat Disord 2009; 15(Suppl 3):S219–23.

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CLINICAL PROFILE OF A COHORT OF ELDERLY PATIENTS WITH PARKINSON’S DISEASE (PD) AND RELATED DISORDERS ATTENDING A DAY HOSPITAL PROGRAMMEC. Padmakumar1,*, A. Withanage1, G. Padmakumar2, A. Lewis3, A. Johnson3

1Geriatric Medicine, Rankin Park Centre, Newcastle, Australia, 2Student, University of Western Sydney, Campbelltown, Australia, 3Geriatric Medicine, Rankin Park Centre, Newcastle, Australia

Objectives: Our day hospital programe for Parkinson’s disease and related disorders focuses on the provision of Multi-disciplinary care for patients in Newcastle, NSW, Australia. Identification of the clinical profile of this popula-tion could help in improving the quality of our service and may assist in design-ing similar services.Methods: We carried out a retrospective and observational analysis of the patients presenting to our service over the period January 2009–August 2013.Results: Study population – 166 patients (N = 166). Mean age 73.7 (52–92) years; all living in the community. They tend to have advanced disease (Hoehn and Yahr stage 3–4) with complications of PD including limited mobility, falls, disordered sleep, pain, speech/swallowing complaints, cognitive impairment and depression. They were mostly on Levodopa/Carbidopa. Only small num-bers were on dopamine agonist, entacapone and MAO-B inhibitors. Treatment complications were noted in 33%. Hypertension, Ischemic heart disease,

visual/hearing impairment and osteoporosis were common co-morbidities; poly-pharmacy noted in over 90%. None were employed or driving any longer. Majority required assistance with at least 1 ADL. Carer stress was identified in a significant proportion.Conclusions: Multi-disciplinary care is essential in the advanced stages of PD in older patients to manage the motor and non-motor aspects of the dis-ease. Concurrent management of PD and related complications, co-morbid-ities and psychosocial issues should be the focus in a programe designed to cater similar populationsNo conflict of interest.

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PREVENTION AND DISEASE MODIFICATION OF PARKINSON’S DISEASE BY TRACING THE PATHOPHYSIOLOGY OF APOPTOSIS IN SUBSTANTIA NIGRAF. Subhani1,*, A. Subhani21N/A, Independent Drug Discovery/Reprofiling Consultant, Lahore, Pakistan, 2Neurosurgery, Quaid E Azam International Hospital, Islamabad, Pakistan

Objectives: Parkinson’s disease (PD) is one of common movement disorders. When >80% of dopaminergic neurons of substantia nigra (SN) are dead then symptoms of PD appear and with this speed of apoptosis, it should >60 years to reach the stage of PD and ar age of 85, there should be firstly appearance of PD. But we know that 1% population over 50 years has PD. Why substantia nigra has potential for apoptosis for dopaminergic neurons?Methods: This is a review in which up-to date mechanism and causes of pathophysiological apoptosis in SN will be elaborated along with probable hypothesis for prevention and disease modification of PD.Results: PD is unique in its model that in the young age, every individual becomes the candidate for this lethal disease condition. About 13% of the cells of SN are lost per decade from age 25 years onward [1,2]. It is first region of human brain which starts degeneration without parallel neurogenesis. Two others are olfactory neurons and hippocampus but continuous neurogenesis is present here. This all seems to be the pathophysiological cascade of apop-tosis in the cells but still it mimics the initial stage of PD.Conclusions: It might be increased inducing factors which lead to increased degeneration of SN neurons and appearance of symptoms in PD patient, or it is interactive action of neuromelanin and α-synuclein which induces lethal consequences? Here proposed mechanism and solution would be offered.Reference1. VW Rodwell, DK Granner, RK Murray. Harper’s Biochemistry. 24th ed.

London, UK: Lang publisher; 1996.794–813.No conflict of interest.

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INITIAL MEDICATION IN PATIENTS OF NEWLY DIAGNOSED PARKIN-SON’S DISEASE IN TAIWAN – A STUDY FROM THE NATIONAL HEALTH INSURANCE RESEARCH DATABASEM. Chang1,*1Neurology, Taichung Veterans General Hospital, Taichung, Taiwan

Objectives: Many guidelines were proposed for the treatment of PD in recent decades. The aim of current study was to investigate the initial medication in newly diagnosed PD subjects in Taiwan during an eleven-year period.Methods: We retrospectively collected 7550 patients with newly diagnosed Parkinsonism (ICD-9-CM code 332.x) from the National Health Insurance Research Database (NHIRD) of Taiwan from 2000 to 2010. After excluding patients with risk of secondary or atypical Parkinsonism, never receiving medication and incomplete data, 1645 subjects were included. They were divided into four treating regimens (LD only, DA only, LD + DA and no-LD, no-DA).Results: LD only (49.9%) and no-LD, no-DA regimens (42.6%) remained the main initial selections of Taiwanese doctors. LD containing drugs were most often prescribed in elderly population (65.3%), while no-LD, no-DA medication were the chief initial drug of choice in younger patients (60.6%). DA only regi-men occupied only 3–4% of the initial PD prescription despite of ages. Most patients (51.4%) received their first medication from regional hospital and 48.1% of them were treated by neurologists. Most DA were given by neurolo-gists, while non-neurologists, especially in medical center, preferred to choose no-LD, no-DA initially.Conclusions: This is the first long-term study to explore initial pharmaco-therapy in Asian PD population which showed higher percentage of usage of no-LD, no-DA regimen and lower ratio of prescribing DA comparing to Western PD patients.No conflict of interest.



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CLUSTER OF INDIVIDUALS WITH SIMILAR PATTERNS OF MOTOR AND NON-MOTOR SYMPTOMS IN PARKINSON’S DISEASE: POTENTIAL THERAPEUTIC IMPLICATIONSP. Martinez Martin1,*, C. Rodriguez Blazquez2, S. Paz Ruiz3, M.J. Forjaz4, B. Frades Payo1, E. Cubo5, J.P. Cuesta2, L. Lizan Tudela3, on behalf of the ELEP Group1Alzheimer Center Reina Sofia Foundation and CIBERNED Carlos III Institute of He, Madrid, Spain, 2National Center for Epidemiology and CIBERNED Carlos III Institute of Health, Madrid, Spain, 3Outcomes’10, Castellon, Spain, 4National School of Public Health and REDISSEC Carlos III Institute of Health, Madrid, Spain, 5Neurology Department Complejo Asistencial Universitario de Burgos, Burgos, Spain

Objectives: To identify homogeneous groups of PD patients according to the development of motor (MS) and non-motor symptoms (NMS) throughout the time.Methods: Observational, longitudinal (4 years) study of PD patients from ELEP study. Assessment of MS (SCOPA-Motor); psychiatric NMS (HADS, PPRS, SCOPA-Sleep, SCOPA-Psychosocial); non-psychiatric NMS (SCOPA-Autonomic, SCOPA-Cognition, visual analog scale (VAS) for pain and fatigue) and disease severity (CISI-PD). Kml3D algorithm was applied to identify clusters of patients according to MS, psychiatric and non-psychiatric NMS and disease severity.Results: 174 patients were included (men 50%; age: 63 ± 11 years; PD his-tory: 8 ± 6 years at inclusion). Two profiles (A/B) were identified: MS and disease severity: A(66.1% of patients; CISI-PD 5.5–7.0; fatigue 20.0–29.6; mild motor dysfunction); B(33.9% of patients; CISI-PD 10.6–12.5; fatigue 35.7–41.5; moderate motor dysfunction). Psychiatric symptoms and sever-ity: A(56.3% of patients; CISI-PD 5.6–7.4; without anxiety and depression; mild sleep and psychiatric problems); B(43.7% of patients; CISI-PD 9.1–10.7; anxiety and depression; moderate sleep and psychiatric problems). Non-psychiatric NMS and severity: A(54.3% of patients; CISI-PD 5.2–6.8; fatigue 16.2–28.0; pain 10.7–19.6; mild dysautonomy and moderate cognition dys-function); B(45.7% of patients; CISI-PD 9.0–11.2; fatigue 35.9–45.7; pain 26.2–27.2; moderate dysautonomy and cognition dysfunction).Conclusions: Kml3D algorithm identified two profiles of patients character-ized by mild differences in disease severity, motor dysfunction and dysau-tonomy throughout the four studied years. Together with motor dysfunction, non-motor symptoms allow for characterizing PD patients. Their potential therapeutic implications needs to be addressed.No conflict of interest.

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PARKINSON’S DISEASE AND THE “SUNSHINE” VITAMINL.E. James1,*, A.A. Asuni21Biomedical Sciences Undergraduate Program, Institute for Life Sciences University of Southampton, Southampton, United Kingdom, 2Centre for Biological Sciences, Institute for Life Sciences University of Southampton, Southampton, United Kingdom

Objectives: Accrued evidence suggesting that hypovitaminosis D acts as a risk factor for developing Parkinson’s disease (PD) remains controversial. Herein we evaluated existing results, and outline several biological mecha-nisms by which the hypovitaminosis D-PD relationship may occur.Methods: We performed a meta-analysis, using data obtained from a search of PubMed from July 2002 to July 2012, for studies reporting serum vitamin D levels in PD and control patients. We found that in comparison to healthy individuals, those with PD had lower levels of serum vitamin D. Furthermore, we explore a number of potential associated biological mechanisms, including the actions of reactive nitrogen species (RNS), glutathione (GSH), and glial-derived neurotrophic factor (GDNF) in the brain. We also examine the roles of Nurr1 and VDR genes in PD.Results: Although a unifying hypothesis remains challenging, there is evi-dence to demonstrate that supplementation with the vitamin can have a posi-tive effect on PD pathobiology.Conclusions: We surmise that hypovitaminosis D does act as a risk factor in the development of PD. However, the need for new epidemiological stud-ies and further research around vitamin D metabolism is highlighted. Urgent efforts to correct vitamin D deficiency through supplementation are warranted as they may improve either motor and/or non-motor symptoms in PD.No conflict of interest.

311

CARRIER MEDIATED DELIVERY SYSTEM BEARING DOPAMINE FOR EFFECTIVE MANAGEMENT OF PARKINSONISMS. Bhargava1,*, V. Bhargava2

1Department of Pharmacy, Manav Bharti University, Kanpur, India, 2R&D, KRV Hospitals Pvt. Ltd., Kanpur, India

Objectives: Delivery of drug and sustaining it in effective concentration in brain is challenging due to blood brain barrier. In the present investigation, amino acid coupled liposomes bearing dopamine-HCl were prepared to deliver drug to the brain utilizing receptor-mediated transcytosis for effective management of parkinsonism.Methods: L-lysine stearylamine conjugate (LSC) was synthesized and LSC coupled liposomes bearing dopamine HCl was prepared by lipid cast film method. Formulations were analyzed for average vesicle size, drug entrap-ment, in-vitro drug release and in-vivo efficacy of the formulations was assessed by measuring the reduction in the degree of drug induced catatonia in albino ratsResults: Average particle size was found in the range of 1.92–0.80 mm. There was increase in the size for coupled liposomes due to the inclusion of LSC in liposomal bilayers. The percent encapsulation efficiency decreased from 46.82 ± 2.17% in uncoupled to 38.13 ± 1.18% in coupled liposomes. The in-vitro drug release after 24 h was 58.9 ± 2.94% with uncoupled while the coupled liposomes showed 43.7 ± 2.18% drug release. The lower value for coupled formulation could be due to the retardation of drug release caused due to the incorporation of LSC in the liposomal bilayers, which enhanced the structural integrity of the bilayer. In-vivo study reveals that the animals receiving uncoupled liposomes showed partial reduction and animals that received coupled liposomes showed almost complete reduc-tion in catatonia.Conclusions: Fluorescence study clearly indicates the uptake of 6-CF in blood vessels and accumulated in brain. This could be due to enhanced uptake of Lysine coupled liposomes through amino acid transporters present at BBB surfaceNo conflict of interest.

312

OPTIMIZING CNS-DELIVERY BY LACTYL STEARATE-COUPLED LIPOSOMESM. Bhargava1,*, S. Bhargava2

1IUD, ICFAI University Dehradun, Kanpur, India, 2Department of Pharmacy, Manav Bharti University, Kanpur, India

Objectives: To prepare lactyl stearate coupled liposomes bearing rifampicin for effective management of meningitis.Methods: Lactyl stearate was synthesized from stearic acid and lactic acid. Lactyl stearate coupled and uncoupled liposomes bearing rifampicin were prepared by cast film method using phosphatidylcholine, cholesterol. Formulations were analyzed for average vesicle size, drug entrapment effi-ciency, in-vitro drug release and the drug distribution in various organs and blood of albino rats was assessed after I.V. administration of formulations. The quantitative uptake of the formulations by the brain in albino rats was assessed by fluorescent microscopy.Results: The average particle size was found in the range of 2.33 to 1.0 mm for uncoupled and coupled liposomes. The percentage encapsulation effi-ciency of liposomes was found to be 41% and 34% in uncoupled and coupled liposomes. Brain uptake was increased about 2–3 times in case of uncou-pled liposomes as compared to plain drug. Accumulation was increased about 6–8 times with coupled liposomes in comparison to uncoupled liposomes and about 10–12 times higher compared to plain drug solution. Higher uptake of lactyl stearate coupled liposomes can be explained as, that mono carboxylic acid transporters present on brain endothelial cells and cross the BBB through carrier mediated transport mechanism. Fluorescence study clearly indicates that the preparation is crossing the basal carotid system and accessing to the nervous system. 6-CF was distributed in blood vessels and accumulated in cerebellum and cerebrum.Conclusions: Lactyl stearate coupled liposomes effectively delivers the drug to the brain and has great potential for brain targetingNo conflict of interest.

313

PHARMACEUTICAL QUALITY OF SEVEN GENERIC LEVODOPA/BENSERAZIDE PRODUCTS COMPARED WITH ORIGINAL MADOPAR® / PROLOPA®G. Vital-Durand1,*, I. Arnet2, U.E. Gasser3

1GMA, Hoffman-La Roche Ltd., Basel, Switzerland, 2Pharmaceutical Sciences, University of Basle, Basel, Switzerland, 3Development, Clin Research, Aesch, Switzerland

Objectives: To compare the pharmaceutical quality of seven generic levo-dopa/benserazide combination products marketed in Germany with the origi-nal product (Madopar®/Prolopa® 125, Roche).Methods: Madopar® / Prolopa® 125 tablets and capsules were used as refer-ence. The generics tested (all 100/25 mg formulations) included four tablet



86

(Betapharm, CT, MYLAN and ratiopharm) and three capsulated formulations (HEXAL, STADApharm and TEVA). Shape, color, appearance and hardness (tablets) or surface, color, imprint and content, mass, content, degradation products, disintegration and dissolution were tested.Results: For all seven generic products some parameter fell outside speci-fications. Content requirements were unmet by two tablet formulations for L-Dopa (specs: 100 mg ± 5%; test results: −5.6% and −7.6%) and for bens-erazide (specs: 28.5 mg ± 5%; −6.6% and +8.4%). Average mass (specs: 275 mg ± 3%) was not reached for two tablet formulations (+3.3%), and aver-age fill mass (specs: 150 mg ± 5%) was not reached for three capsule formula-tions (+48.2%, +99.1%, +99.3%).Conclusions: All seven analyzed generic L-Dopa/benserazide products exhib-ited deviations. These ranged from +8.4% (benserazide) to −7.6% (L-Dopa) in two tablet products, with potential clinical consequences. Furthermore, two of the degradation products were 26.5% above standard. These results should lead to caution when prescribing a generic of Madopar® / Prolopa®, and also invite further investigations, both pharmaceutical and clinical.References1. Tschabitscher D. Generika: Qualität, Wirksamkeit, Sicherheit und

Austauschbarkeit. Wien Klin Wochenschr 2008; 120: 63.2. Ferner RE et al. Controversy over generic substitution. Brit Med J 2010; 340:

c2548.3. Go C et al. A generic vs branded pharmacotherapy in Parkinson’s disease.

Parkinsonism Relat Disord 2011; 17: 308.

314

THE EFFECT OF DOPAMINERGIC MEDICATION ON DEPRESSIVE SYMPTOMS IN PATIENTS WITH PARKINSON’S DISEASEC. Degroot1, M.A. Bruneau1, A. Hanganu1, C. Bedetti2, B. Mejia-Constain1, A.L. Lafontaine3, O. Monchi1,*1Centre de Recherche de l’Institut Universitaire de Gériatrie de Montréal, Université de Montréal, Montreal, Canada, 2Centre d’Études Avancées en Médicine du Sommeils, Hôpital du Sacré Cœur de Montréal, Montreal, Canada, 3Movement Disorders Unit, McGill University Health Center, Montreal, Canada

Objectives: We aimed to assess the effect of L-DOPA and dopaminergic ago-nist (DA) medication on depressive symptoms in patients with Parkinson’s disease (PD) and determine whether some cognitive deficits could also be associated with these treatments.Methods: We analyzed 40 PD patients at the early stages of the disease and divided them in two groups: with significant depressive symptoms (N = 20) and without (N = 20). Using SPSS17, a correlation study was performed between the dopaminergic medication dosage, the Beck Depression Inventory scale II (BDI-II) and various neuropsychological tests: MoCA, Brixton, RAVLT, MEC, WMS-III, Hooper, Stroop Color and Word, Trail Making, Digit span, Tower of London and Boston naming tests. There was no difference between the groups with respect to disease severity.Results: Results revealed a significant positive correlation between L-DOPA and BDI (i.e. increased depressive symptoms) in all PD patients. No correlation was found between DA-agonists and BDI. Patients with sig-nificant depressive symptoms had a negative correlation between L-DOPA with the RAVLT recognition (memory recall) and Brixton (executive func-tion) tests.Conclusions: Our results indicate that dopaminergic medication does not alleviate depressive symptoms in PD and that L-DOPA might even increase them. This last possibility is supported by studies showing that L-DOPA can have deleterious effects on ventral striatum mediated cognitive function and that depression increases cognitive deficits in the elderly. Taken together these results advocate the use of therapeutical approaches targeting serotoninergic as well as dopaminergic pathways, in PD patients with depressive symptoms.No conflict of interest.

315

INTRAJEJUNAL LEVODOPA INFUSION IN ADVANCED PARKINSONISM: THE TEL-AVIV MEDICAL CENTER’S EXPERIENCES. Herzel1,*, Y.L. Yalon1, H.A. Hilel1, B.Y. Balash1, E.A. Ezra1, K.J. Knaani1, G.N. Giladi1, G.T. Gurevich1

1Movement Disorders Unit Department of Neurology, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel

Objectives: Intrajejunal levodopa infusion (IJL, Duodopa treatment) is now an established treatment for advanced Parkinson’s disease (PD). Here we sum-marize our 4-year experience with IJL.

Methods: Medical files of patients on IJL were reviewed. The clinical global impression of changes scale (CGICS) was assessed by patients, physi-cians and caregivers. Twelve patients (duration of IJL 14.0 ± 8.6 months) participated in a structured telephone interview on changes in their situation.Results: Twenty-six patients had undergone Duodopa titration with a nasojejunal tube. Percutaneous endoscopic jejunostomy feeding tubes were inserted into 22 of them (14 males; 19 with PD, 3 with probable mul-tiple system atrophy parkinsonian type [MSA-P]). The cohort’s age was 64.4 ± 10.8 years; disease duration 15.1 ± 6.3 years; H&Y OFF stage 4 ± 0.8. Nine of the 12 interviewed patients reported improvement in OFF states and in quality of life, 4 had improvement in dyskinesias and gen-eral mobility, 2 had worsening of dyskinesias and gait. Hallucinations and nightmares worsened in 3 patients. Nine patients will recommend IJL and 2 will not. Two patients stopped treatment after 1.5 months due to intractable dyskinesias. The daily levodopa equivalent increased (from 1163 ± 475.7 mg pre-IJL to 1744.6 ± 615.8 mg). There were no serious gastrointestinal or infectious complications or clinically significant polyneuropathy. Response to IJL in PD and MSA-P patients was similar, without worsening of orthos-tatic hypotension.Conclusions: Our experience was that IJL may allow increasing the dopa dose with improvement of OFF states and quality of life, without significant worsening of dyskinesias in advanced parkinsonian patients.No conflict of interest.

316

E-DUO STUDY: USE OF LEVODOPA-CARBIDOPA INTESTINAL GEL (LCIG) IN SPANISH PARKINSON’S DISEASE (PD) PATIENTSJ. Parra1,*, F. Grandas2, D. Santos3, F. Valldeoriola4

1Medical, AbbVie, Madrid, Spain, 2Neurology, Hospital Gregorio Marañon, Madrid, Spain, 3Neurology, Hospital Arquitecto Marcide, Ferrol, Spain, 4Neurology, Hospital Clinic, Barcelona, Spain

Objectives: Assess patient’s clinical characteristics, effectiveness and toler-ability of LCIG in advanced PD in Spain.Methods: PD patients treated with LCIG between January, 2006 and December, 2011 were included in this post-authorization, observational, ret-rospective, multi-centre study. Participant centers must have an experience of at least 5 LCIG patients. Data were collected from clinical examination and questionnaires performed in an actual scheduled visit and from the review of medical records.Results: Of 185 PD patients treated with LCIG evaluated in 18 centers, 177 were finally included for analysis (figure 1). Socio-demographic and clini-cal characteristics are shown in table 1. Mean LCIG treatment duration was 2.58 ± 1.65 years (range from 0.01 to 7.26). Patients who continue on LCIG (n = 123) experienced a reduction in the percentage of daily ‘off-time’ (16.1 vs 47.6 before LCIG; p < 0.0001) and an increase in the percentage of daily ‘on-time without disabling dyskinesia’ (55.5 vs 21.6 before LCIG; p < 0.0001), with no significant change in ‘on-time with disabling dyskinesia’. Improvements in different motor and non-motor symptoms are shown in figures 2 and 3. Complications related to system, gastrostomy and levodopa were 43.5%, 42.4% and 36.2%, respectively.

Total sample size185 patients

177 (95,6%)Patientsincluded

* At the moment of actual schedule visit

** More than one option could be selected

8 (4,3%)patientsNon valid due toprotocol violation

Reasons for discontinuation**

Neurologist decision N (%) 23 (47.59)17 (31.48)15 (27.78)14 (25.93)11 (20.37)9 (16.67)

3 (5.56)7 (17.96)

12 (22.22)

Total

(N=54)

N (%)N (%)N (%)N (%)N (%)N (%)N (%)N (%)

Drug related reasonsDeathsPatient decision

Disease progressionPEG related adverse eventsCaregiver/family decisionSystem related reasons

Other

54 (30,5%)Patients already

Discontinue LCIG*

123 (69,5%)Patients continue

on LCIG*

Figure 1. Patients’s distribution.



87

Table 1. Baseline characteristics.

N = 177Mean age years (SD) 70.6 (8.4)

Weight kg (SD) 57.8 (27.8)

Gender n (%) (male/female) 93 (52.54); 84 (47.46)

Years since PD diagnostic mean (SD) 14.28 (6.91)

Race n (%)

Caucasian 173 (97.74)

Black 1 (0.56)

Other (1 Arabian; 1 Aymara) 2 (1.13)

No data 1 (0.56)

Place of residence n (%)

Rural area (<5,000 inhab.) 25 (14.12)

Semi urban area (5,000–20,000 inhab.) 30 (16.95)

Urban area (>20,000 inhab.) 122 (68.93)

Educational level n (%)

No complete primary school 41 (23.16)

Primary school 90 (50.85)

Secondary/high school 27 (15.25)

University 19 (10.73)

Phenotype n (%)

Tremor dominant 41 (23.16)

Akinetic rigid dominant 74 (41.81)

Mixed 62 (35.03)

Hemibody onset n (%)

Left 78 (44.07)

Right 69 (38.98)

Symmetric 30 (16.95)

Number of previous treatment for PD median (min; max)

4,00 (1,00; 14,00)

Other concomitant treatments median (min; max)

5,00 (0,00,23,00)

100

90

80

69,170

60

50

40

30

20

10

0Tremor Dystonia*

* 2 Patients data missing** 1 Patients data missing

Freezing** Falls* Hypophonia Dysphagia

28,46Per

cent

age

of p

atie

nts

[%]

39,03

4,88

13,0110,57

54,47

75,61

51,22

34,15

13,01

48,78

Improvement

No change

Worse

39,84

11,38

22,7617,9

59,35

2,44

Figure 2. Effectiveness of LCIG in relation with different motor symp-toms (n = 123).

Improvement no change

Dizziness (n=77)Falls (n=38)

Falls asieep during daytime (n=76)Fatigue during daytime (n=106)

Insomnia (n=111)Restlessness in legs (n=87)

Lost interest on surroundings (n=113)Lost interest on activities (n=110)

Nervous (n=96)Sadness (n=106)

Flat mood (n=100)Apathy (n=112)

Hallucinations (n=58)Paranoia beliefs (n=58)

Double vision (n=35)

Concentration problems (n=96)Forget things (n=86)

Forget to do things (n=78)

Drooling (n=62)Swallowing problems (n=75)

Constipation (n=102)

Urinary incontinence (n=93)Urinary urgency (n=91)

Nocturia (n=99)

Altered interest in sex (n=100)Sexual difficulties (n=92)

Pain (n=81)Altered taste or smell (n=90)

Weight changes (n=113)excessive sweating (n=95)

Impulse behavior (n=66)

worse

6047 37 16

1426

53 25 2258 16 26

5251 31 18

1532

4847 29 24

2428

45 34 2151 26 23

56 29 1544 33 23

47 22 3231 33 36

23 57 20

33 27 4021 29 50

24 37 38

32 35 3231 37 32

23 57 21

20 43 3716 56 2719 57 24

09 67 24

08 77 1622 39 39

3339 44

41 2617

02 73 25

46 31 23

Figure 3. Effectiveness of LCIG in relation with different non-motor symptoms.

Conclusions: LCIG improved motor symptoms with a safety profile similar to previous reportsNo conflict of interest.

317

GLOBAL LONG-TERM REGISTRY ON EFFICACY AND SAFETY OF DUODOPA IN PATIENTS WITH ADVANCED PARKINSON’S DISEASE IN ROUTINE CARE (GLORIA): 12-MONTH INTERIM FINDINGSA. Antonini1,*, A. Yegin2, D. Preda2, W. Poewe3

1Parkinson and Movement Disorders, IRCCS San Camillo Hospital – 1st Neurology Clinic, Padua, Italy, 2Neurology, AbbVie, Abbott Park, USA, 3Neuroscience, Neurology, Innsbruck, Austria

Objectives: Levodopa-carbidopa intestinal gel, Duodopa®, is intended for con-tinuous infusion into the jejunum via percutaneous endoscopic gastrostomy (PEG) using a portable pump. Duodenal levodopa infusion may represent an effective strategy for managing long-term motor and non-motor complications in patients with advanced PD. We evaluate efficacy, safety and quality of life (QoL) in advanced PD during 24-month Duodopa treatment, utilizing Unified Parkinson’s Disease Rating Scale (UPDRS), Non-Motor Symptoms Scale (NMSS), disease-specific (PDQ-8) and generic (EQ-5D) QoL.Methods: 372 patients were enrolled in this registry (18 countries, 74 centers). This interim analysis assessed the first 12 months of treatment and included all patients enrolled 14 months before database lock (n = 170).Results: Mean UPDRS II and III “ON” scores (baseline: 16.5 ± 10.7 and 26.5 ± 12.3) were reduced at M12 by 3.1 ± 8.7 and 3.3 ± 11.0 (paired t-test: p = 0.0107 and 0.0128), respectively. Mean daily hours spent with dyskinesias or in “Off” state (UPDRS IV, item 32 and 39; baseline: 5.2 ± 4.5 and 7.1 ± 3.5 h) were reduced at M12 by 1.7 ± 5.0 and 4.7 ± 3.4 h (p = 0.0228 and p < 0.0001), respectively. Mean NMS score (baseline: 75.3 ± 42.2) was reduced at M12 by 22.2 ± 50.6 (p = 0.0014). Mean PDQ-8 score (baseline: 48.6 ± 19.0) and the EQ-5D visual analogue scale were improved at M12 by −8.6 ± 22.6 and + 0.17 ± 0.25 (p = 0.0100 and p = 0.0001), respectively. Duodopa was well tolerated and adverse drug reactions were consistent with known safety profile.Conclusions: This long-term observational study in a large cohort of advanced PD patients supports long-term safety and efficacy of Duodopa on motor symptoms, non-motor symptoms and QoL.Reference1. Antonini A, Tolosa E Expert Rev Neurother. 2009 Jun; 9(6):859–67.

318

LONG-TERM SAFETY AND MAINTENANCE OF EFFICACY FROM AN OPEN-LABEL EXTENSION OF THE DOUBLE-BLIND PIVOTAL STUDY OF LEVODOPA-CARBIDOPA INTESTINAL GEL (LCIG) IN ADVANCED PARKINSON’S DISEASE PATIENTSH. Fernandez1,*, R. Krüger2, J.T. Slevin3, C. Hall4, S. Eaton5, J. Dubow5, K. Chatamra5, J. Benesh5

1Center of Neurological Restoration, Cleveland Clinic, Cleveland, USA, 2Department of Neurodegenerative Diseases, University of Tübingen,



88

Tübingen, Germany, 3Department of Neurology, University of Kentucky Medical Center, Lexington, USA, 4Data and Statistical Sciences, AbbVie Inc., North Chicago, USA, 5Clinical Development, AbbVie Inc., North Chicago, USA

Objectives: LCIG is delivered continuously via an intrajejunal percutaneous gastrostomy tube. This study examined the long-term safety and mainte-nance of efficacy in patients who received open-label LCIG treatment after completing a 12-week double-blind, double-dummy trial in which they were randomized to either LCIG or LC-Oral.Methods: At the start of the 52-week, open-label extension, patients were reiterated to establish the optimum LCIG dose. For efficacy analyses, patients were grouped by whether they had received LCIG or LC-Oral in the previous double-blind trial (continuing-LCIG vs. LCIG-naïve patients); the change from baseline was evaluated.Results: LCIG-naïve patients (N = 29) showed improvement in ‘Off’ time (Figure 1) and ‘On’ time without troublesome dyskinesia (Figure 2) starting at week 4, while continuing-LCIG patients (N = 33) showed maintenance of effect or further improvement.PDQ-39 scores improved in LCIG-naïve patients as early as 12 weeks, while sustained improvement was noted among contin-uing-LCIG patients (Figure 3).

Most subjects (95.2%) reported ≥ 1 adverse event, yet only 3 subjects (4.8%) discontinued due to an adverse event (Table 1).

BL 4 12 24 36 52 EP

32 31 32 31 28 30 3227 25 23 23 21 21 27

Visit (week)

Tim

e (h

ours

)

IMP

RO

VE

ME

NT

n=n=

Continuing LCIGLCIG Naïve

Continuing LCIG LCIG Naïve

-1012345678

****

****

**

*

Figure 1. Average daily “Off” time by visit.

BL 4 12 24 36 52 EP

32 31 32 31 28 30 3227 25 23 23 21 21 27

Visit (week)

Tim

e (h

ours

)

IMP

RO

VE

ME

NT

n=n=

Continuing LCIGLCIG Naïve


789

10111213141516

* ** * *

**

* **

* *

Figure 2. Average daily “On” time without trou-blesome dyskinesia by visit.

BL 12 24 52

32 31Visit (week)

Mea

n S

core

IMP

RO

VE

ME

NT

31 3126

n=n=

Continuing LCIGLCIG NaïveMean (SD): PDQ-39= 39- item Parkinson’s Disease Questionairre, BL=BaselineBaseline presented is for subjects with at least 1 post-baseline observation.*P<0.05: P-value reflects change from baseline


25 25 22

05

101520253035404550

Figure 3. PDQ-39 summary index by visit.

Table 1. Adverse events.

Total subjects, N = 62 n (%)

Subjects with at least one AE 59 (95.2)

Subjects with at least one 5AE 14 (22.6)

Subjects with an AE leading to discontinuation 3 (4.8)

Deaths 0

Most common AEs reported:

Incision site erythema 18 (29.0)

Fall 13 (21.0)

Vitamin B6 decreased 13 (21.0)

Postoperative wound infection 11 (17.7)

Conclusions: Continuing-LCIG patients continued to derive benefit from LCIG without developing tolerance while the magnitude of benefit among LCIG-naïve patients was similar to that observed in the pivotal study1. AE pro-file was similar to that observed in other phase 3 studies2.References1. Olanow, MDS, 2012.2. Fernandez, 2013; Support: AbbVie.

319

PEG DEVICES REPLACMENT IN DUODOPA-TREATED PARKINSON DISEASE PATIENTS: A WIRE GUIDE FOR AN EASY MANAGEMENTR. Scatozza1,*, G. Della Vida2, A. Tesi3, M. Morucci4, M. Valente5, A. Rubino5, G. Meco5

1Neuologia, “Sapienza” University of Rome Policlinico Umberto I, Rome, Italy, 2Geriatria, Az. Ospedaliera S. Camillo Forlanini, Rome, Italy, 3Gastroenterologia, Az. Ospedaliera S. Camillo Forlanini, Rome, Italy, 4Radiologia Vascolare, Az. Ospedaliera S. Camillo Forlanini, Rome, Italy, 5Neurologia, “Sapienza” University of Rome Policlinico Umberto I, Rome, Italy

Objectives: Levodopa/carbidopa intestinal gel infusion (LCIG) is a recent therapeutic advance for patients with PD and severe motor fluctuations. The drug-containing gel is steadily pumped into the upper jejunum through a Jet-PEG, an extension tube inserted through a percutaneous endoscopic gastrostomy (PEG). A growing body of evidence suggests considerable poten-tial adverse effects under LCIG, related to surgical procedures and deteriora-tion or dislocation of enteral devices. We propose an easy procedure for the management of replacement of Jet-PEG in order to minimize adverse effects during the treatment course with LCIG.Methods: Four PD patients underwent this procedure for the developing of complication during treatment course with LCIG (2 device displacements, 1 duodenal bezoar, 1 leak of gastric fluids). The replacement procedure was achieved using a wire-guided that passed thought the existing gastrostomy. Subsequently, a balloon tip tube (GASTROTOMY TUBE FLOCARE) featuring an “adapted” nasodigiunal tube (FLOCARE BENGMARK) was inserted along the wire guide. Then wire-guide was removed. Wire-guide allowed to confirm the correct placement of the devices (Seldinger technique) using radioscopic examination. Replacement procedures described have been repeated periodi-cally every 4 months.Results: In all four patients enteral tubes were successfully replaced; no adverse effect was reported after an average observation period of 8 months.Conclusions: This simple method, avoiding the need of sedation and the discomfort due to endoscopic procedures, allows periodic mini-invasive PEG tube replacement. This approach could prevent devices deterioration (calcifi-cation, vulcanization) as well as reduce the risk of bacterial/fungal aggregates and bezoars.No conflict of interest.

320

ADVERSE DRUG REACTIONS WITH SELEGILINE AND RASAGILINE COMPARED TO LEVODOPA AND ROPINIROLE: A STUDY IN THE FRENCH PHARMACOVIGILANCE DATABASES. Perez Lloret1,*, M.V. Rey1, J.L. Montastruc1, O. Rascol11Pharmacology Department, Paul Sabatier University, Toulouse, France

Objectives: To compare spontaneous Adverse Drug Reaction (ADR) reports to the French PharmacoVigilance Database (FPVD) between selegiline and rasagiline with levodopa and ropinirole.Methods: All ADRs in which selegiline, rasagiline, levodopa or ropinirole were considered as ‘suspected’ drugs were retrieved.



89

System Organ Class Selegiline (n = 199) Rasagiline (n = 132) Levodopa (n = 1851) Ropinirole (n = 432) Overall p-value

Cardiac 8 (4%) 7 (5%) 81 (4%) 18 (4%) 0.6

Congenital 0 (0%) 0 (0%) 0 (0%) 0 (0%) -

Otological 5 (3%) 2 (2%) 23 (1%) 6 (1%) 0.7

Cutaneous 15 (8%) 15 (11%) 148 (8%) 24 (6%) 0.5

Reproductive system 1 (1%) 1 (1%) 10 (1%) 3 (1%) 0.7

Urinary 2 (1%) 8 (6%)*$a 56 (3%) 4 (1%) 0.02

Immune 0 (0%) 0 (0%) 0 (0%) 0 (0%) -

Neurologic 39 (20%)$ 32 (24%) 397 (21%) 141 (33%) <0.001

Endocrine 2 (1%) 0 (0%) 10 (1%) 1 (0%) 0.7

Gastrointestinal 21 (11%) 12 (9%) 195 (11%) 48 (11%) 0.5

Pregnancy 0 (0%) 0 (0%) 0 (0%) 0 (0%) –

Hematological 5 (3%)* 1 (%)* 129 (7%) 6 (1%) <0.001

Hepatobiliar 4 (2%) 3 (2%) 42 (2%) 6 (1%) 0.4

Musculoskeletal 4 (2%) 15 (11%)*$b 36 (2%) 14 (3%) <0.001

Ocular 2 (1%) 5 (4%) 22 (1%) 6 (1%) 0.4

Psychiatric 82 (41%)* 42 (32%) 509 (27%) 163 (38%) <0.001

Respiratory and Mediastinic 8 (4%) 3 (2%) 74 (4%) 3 (2%) 0.2

Vascular 23 (12%)$ 11 (8%) 176 (10%) 20 (5%) 0.04

Socio-environmental 0 (0%) 0 (0%) 4 (<1%) 1 (<1%) 0.2

Infections 0 (0%) 1 (<1%) 14 (1%) 1 (<1%) 0.7

Investigations 14 (7%) 8 (6%) 85 (5%) 18 (4%) 0.7

Intoxications and Lesions 1 (1%) 5 (4%) 72 (4%) 16 (4%) 0.4

Metabolic 10 (5%) 4 (3%) 67 (4%) 5 (1%) 0.2

Cancer 2 (1%) 7 (5%)*$c 17 (1%) 3 (1%) <0.001

Otological

Vergtigo 5 (3%) 1 (1%) 22 (1%) 4 (1%) 0.4

Neurological

Headache 2 (1%) 7 (5%)* 21 (1%) 10 (2%) 0.003

Somnolence 8 (4%)# 1 (1%)*# 116 (6%) 68 (16%) <0.001

Gastrointestinal

Nausea and vomits 6 (3%) 3 (2%) 71 (4%) 29 (7%) 0.07

Psychiatric

Depression 3 (2%) 0 (0%) 19 (1%) 4 (1%) 0.4

Confusion and disorientation

37 (19%)# 11 (8%)$ 237 (13%) 28 (6%) <0.001

Hallucination 24 (12%)# 6 (5%) 159 (9%) 28(6%) 0.05

Delirs 6 (3%) 2 (2%) 44 (2%) 12 (3%) 0.24

Agitation 11 (6%) 0 (0%) 63 (3%) 11 (3%) 0.09

Pharmacodependance 2 (<1%) 0 (0%) 14 (1%) 13 (3%) 0.2

Impulse control disorders 1 (1%)*# 5 (4%)# 78 (4%) 51 (12%) <0.001

Obsessive-compulsive

Disorders 0 (0%) 1 (1%)$ 10 (1%) 6 (1%) 0.2

Vascular

Orthostatic hypotension 17 (9%)# 1 (1%) 102 (6%) 10 (2%) 0.002

Edemas 1 (1%) 3 (2%) 20 (1%) 15 (3%) 0.07

Investigations

Low weight 5 (3%) 5 (4%) 15 (1%) 2 (<1%) 0.3

*p < 0.0017 vs levodopa, *p < 0.0017 vs ropinirole, $p < 0.0017 vs selegiline (overall chi-square test with holms step-down procedure followed by pairwise chi-square tests).aUrinary ADRs with rasagiline were pollakiuria and urinary urgency.bMusculoesqueletal ADRs with rasagiline included arthralgia, myalgia and cramps.cMalignant ADRs reported with rasagiline were melanoma in 5 cases, rectal adenocarcinoma in 1 case and pheochromocytoma in 1 case.*p < 0.0017 vs levodopa, *p < 0.0017 vs ropinirole, $p < 0.0017 vs selegiline (overall chi-square test with holms step down procedure followed by pairwise chi-square tests).

320 – Frequency of Adverse Drug Reactions per system organ class reported with selegiline, rasagiline, levodopa or ropinirole in the French Pharmacovigilance Database.



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Results: Selegiline was related to less frequent total or ‘serious’ ADR reports. Frequency of impulse control disorders or somnolence was lower with selegiline or rasagiline compared to ropinirole. Confusion, hallucinations or orthostatic hypotension were more frequent with selegiline compared to ropinirole. Headache, renal and musculoskeletal ADRs were more frequent with rasagiline compared to all other drugs. Detailed information is shown in the following tables:Conclusions: Selegiline and rasagiline showed good safety profiles. Orthostatic hypotension and psychosis were more frequent with selegiline, whereas headaches, renal and musculoskeletal ADRs were more frequent with rasagiline.No conflict of interest.

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EVALUATION OF RASAGILINE IN THE TREATMENT OF SLEEP DISORDERS IN PARKINSON’S DISEASE (PD)M. Melone1,*, G. Capaldo1, C. Dato1, D. Saracino1, M. Fratta1, C. Coppola1, G. Lus1

1Department of Clinical and Experimental Medicine and Surgery Division of Neurology, Second University, Naples, Italy

Objectives: To evaluate the effects of levodopa–rasagiline combination therapy versus levodopa therapy alone in the treatment of sleep disorders in PD.Methods: We performed a 12-weeks study in 38 patients, (mean age: 63–64 years; mean disease duration: 1.92–2.15 years; Schwab and England activities of daily living scores: approximately 90%). Patients were randomly assigned to levodopa (200–300 mg daily) (A) or levodopa–rasagiline (200–300 mg + 1 mg) group (B). Sleep parameters were recorded by means of PD sleep scale (PDSS) and sleep diaries.Results: At baseline almost all patients reported difficulties in falling and stay-ing asleep. Mean total PDSS was 104.7 ± 21.5 correlating with Hoehn and Yahr score (p = 0.004). After 12 weeks, parameters significantly improved in B group compared with A group (p = 0.019). Sleep latency, 2.6 h [95% confi-dence intervals (CI) 2.28–2.93] at baseline, was 1.91 h (95% CI 1.78–2.03) in A group and 1.06 h (95% CI 0.98–1.13) in B group. Night awakenings, 0.35 (95% CI 0.18–0.53) at baseline, were 0.26 (95% CI 0.20–0.34) in A group and 0.08 (95% CI 0.04–0.12) in B group. Total sleep duration, 6.05 h (95% CI 6.65–6.44) at baseline, was 6.75 h (95% CI 6.56–6.98) in A group and 6.84 h (95% CI 6.68–6.99) in B group.Conclusions: Our monocentric study, though small-sized, demonstrates the effectiveness of levodopa–rasagiline therapy in PD sleep disorders, which will hopefully be confirmed by larger studies.No conflict of interest.

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COMMUNITY PRACTICE EXPERIENCE IN PARKINSON’S DISEASE MANAGEMENT WITH RASAGILINE (AZILECT®): A RETROSPECTIVE CHART REVIEWD.J. Stewart1,*, P.L. O’Brien1, M.M. Harris1, C.A. Stewart1

1Clinical Services, Cambridge Neurology, Cambridge, Canada

Objectives: Rasagiline (Azilect®) has a beneficial symptomatic effect in PD but there is limited clinical information on the value of this drug with when used long term.Methods: A retrospective chart review was undertaken to assess benefits of rasagiline therapy over time. PD patients were divided into rasagiline naive and rasagiline experienced groups. Patients were seen between 1999 and 2013. A total of 417 charts were reviewed (271 male, 146 female). Of these 254 patients were rasagiline naïve and 163 had some experience with rasagil-ine. Of the rasagiline experienced, 120 continued treatment (range 1–6 years) while 43 stopped treatment. Reasons for stopping rasagiline were postural hypotension, nausea, mood disturbance, bradycardia, dizziness, cost con-cerns and lack of clinical efficacy.Results: In rasagiline experienced patients continuing drug 72% had PD for more than 5 years while 68.4% of rasagiline naïve patients had similar duration PD. Patients discontinuing rasagiline were predominantly those with greater than 5 years duration of PD (95%). There was no difference between the two groups on the usage of levodopa, dopamine agonists or anticholinergic medi-cations. There was a slightly lower incidence of dyskinesia in patients con-tinuing rasagiline (16.7%) compared to patients stopping rasagiline (34.9%) or rasagiline naïve patients (30.3%). Freezing was less common in patients continuing rasagiline treatment (3.3%) compared to those stopping rasagiline (18.6%) and rasagiline naïve patients (8.3%).Conclusions: The results indicate rasagiline is well tolerated, simple to use and can have a positive impact on PD treatment over time.Acknowledgment This study was supported by an unrestricted educational grant from Teva Canada Innovation.

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MULTIDISCIPLINARY INTENSIVE REHABILITATION TREATMENT AND RASAGILINE IN THE EARLY STAGES OF PARKINSON’S DISEASE: A RANDOMIZED CONTROLLED STUDY WITH A TWO-YEAR FOLLOW-UPG. Frazzitta1,*, R. Maestri2, G. Bertotti3, N. Boveri3, G. Riboldazzi4, M. Perini5, D. Uccellini6, M. Turla7, C. Comi8, G. Pezzoli9, M.F. Ghilardi10

1Parkinson Disease Rehabilitation, “Moriggia-Pelascini” Hospital, Gravedona ed Uniti, Italy, 2Department of Biomedical Engineering, “S. Maugeri” Foundation, Montescano, Italy, 3Department of Neurorehabilitation, “S. Maugeri” Foundation, Montescano, Italy, 4Department of Neurorehabilitation, Macchi Foundation and “Le Terrazze” Hospital, Varese, Italy, 5Department of Neurology, Gallarate Hospital, Gallarate, Italy, 6Department of Neurology, Tradate Hospital, Tradate, Italy, 7Department of Neurology, Valle Camonica Hospital, Esine, Italy, 8Department of Neurology, University of the Eastern Piedmont, Novara, Italy, 9Parkinson Institute, Istituti Clinici di Perfezionamento, Milano, Italy, 10Department of Physiology and Pharmacology, CUNY Medical School, New York, USA

Objectives: Although physical exercise improves motor aspects of Parkinson’s disease (PD), it is not clear whether it might also have a neuroprotective effect. In this two-year follow-up study, we determined whether intensive exercise in the disease’s early stages slows down PD progression.Methods: Forty newly diagnosed patients with PD were treated with rasagil-ine and randomly assigned two groups: Group_1 (two 28-day multidisciplinary intensive rehabilitation treatment, MIRT, at one-year interval) and Group_2 (control group). In both groups, UPDRS II, UPDRS III, six-minute walking test (6MWT), Timed-up-and-go test (TUG); PD disability scale (PDDS) and Ldopa equivalents were assessed at baseline (T0), 6 months (T2), 1 year, 18 months (T5) and 2 years (T6) later. Acute effect of MIRT was measured in Group_1 after the first (T1) and second MIRT (T4).Results: In Group_1, after both MIRTs, scores of the different outcome vari-ables acutely improved. Over 2 years, UPDRS II, UPDRS III, TUG and PDDS differentially progressed in the two groups: in Group_1, all scores at T6 were better than at T0 (all: p < 0.03). No changes were noted in Group_2. L-dopa equivalent dosages increased significantly only in Group_2 (p = 0.0015), with a decrease in the percentages of patients in monotherapy (T2: 40%, T3, T5 and T6: 20%). In Group_1, the percentages of such patients remained higher (T2 and T3: 100%, T5: 89%, T6: 75%).Conclusions: These results suggest that MIRT might slow down the progres-sion of motor decay, might delay the need for increasing drug treatment, and thus, might have a neuroprotective effect.No conflict of interest.

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COMPARISON BETWEEN OPICAPONE AND ENTACAPONE EFFECT ON LEVODOPA PHARMACOKINETICS WHEN ADMINISTERED WITH IMMEDIATE RELEASE 100/25MG LEVODOPA/CARBIDOPA IN HEALTHY SUBJECTSJ. Rocha1,*, A. Falcao2, N. Lopes1, T. Nunes1, R. Pinto1, P. Soares-da-Silva1

1R&D, BIAL – Portela & Co. S.A., S. Mamede Coronado, Portugal, 2Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal

Objectives: Investigate a once-daily 25, 50 and 75 mg opicapone (OPC) effect on levodopa pharmacokinetics (PK), in comparison to placebo and 200 mg entacapone (ENT).Methods: Single-centre, randomized, double-blind, placebo-controlled study in 4-groups of 20 (10 male and 10 female) subjects each. The study consisted of an once-daily administration of OPC or placebo for 11-days followed by 100/25 mg levodopa/carbidopa (LC), 200 mg ENT or placebo three times per day on Day 12.Results: Levodopa-AUC was significantly increased up to 78.9% and 73.74% with 75 mg-OPC in comparison to placebo and ENT, respec-tively. Levodopa-AUC0–24 was higher when LC was administered with any OPC dose than when administered concomitantly with ENT. Peak expo-sure (Cmax) to levodopa increased (>30%) with 75 mg-OPC following LC administrations. A significantly long-lasting and sustained S-COMT inhibi-tion occurred with OPC. Maximum S-COMT inhibition ranged from 67.1% (200 mg-ENT) to 94.2% (75 mg-OPC) and was higher than ENT for all OPC doses. The 50 and 75 mg-OPC were somehow similar (75 mg was slightly superior), thus, the 75 mg-OPC may not bring a significant advantage to 50 mg-OPC with regard to S-COMT inhibition. The tolerability profile of OPC was favorable.Conclusions: OPC may offer a therapeutic advantage in relation to ENT in patients with Parkinson’s disease receiving levodopa therapy. The dosages of 25 and 50 mg-OPC likely provide the most adequate enhancement in levo-dopa availability as adjunct to levodopa/carbidopa therapy.No conflict of interest.



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EFFICACY AND SAFETY OF OPICAPONE, A NEW COMT-INHIBITOR, FOR THE TREATMENT OF MOTOR FLUCTUATIONS IN PARKINSON’S DISEASE: BIPARK-II STUDYA. Lees1, J. Ferreira2, R. Costa3, J. Rocha3*, C. Oliveira3, N. Lopes3, T. Nunes3, P. Soares-da-Silva3

1Neurology, National Hospital for Neurology and Neurosurgery, London, United Kingdom, 2Neurological Clinical Research Unit, Medicina Molecular, Lisbon, Portugal, 3R&D, BIAL – Portela & Co. S.A., S. Mamede Coronado, Portugal

Objectives: Investigate the efficacy and safety of opicapone (OPC) adminis-tered once-daily, compared with placebo, in patients with Parkinson’s Disease (PD) on levodopa treatment and with end-of-dose motor fluctuations.Methods: Pivotal phase-III, multinational, multicenter, double-blind (DB), pla-cebo-controlled and parallel-group study. Subjects were randomized to placebo (n = 135), 25 mg-OPC (n = 125) or 50 mg-OPC (n = 147) on a 14–15 weeks DB-phase. Primary efficacy variable was the change from baseline in OFF-time, based on patient diaries. Secondary endpoints include proportion of responders, course of OFF/ON-time, UPDRS-III, PDQ-39, NMSS, PDSS and safety (including mMIDI, C-SSRS and clinical laboratory tests) assessments.Results: Mean reduction in absolute OFF-time in both 25 and 50 mg-OPC groups was considerably greater than in placebo (1.7, 2.0 and 1.1 h, respec-tively). Despite the high placebo response, 50 mg-OPC was significantly better than placebo (p = 0.0084). Significantly more patients receiving either 25 or 50 mg-OPC achieved the OFF-time responder endpoint than with pla-cebo (62.4%-[p = 0.0405], 66.0%-[p = 0.0088] and 50.4%, respectively), and also achieved greater OFF-time reductions (11.0%-[p = 0.0297], 12.1%-[p = 0.0044] and 6.7%, respectively). Furthermore, mean increase in abso-lute ON-time without or with non-troublesome dyskinesias was considerably greater in both 25 and 50 mg-OPC groups than in placebo (1.4, 1.43 and 0.8 h, respectively). Opicapone was safe and well tolerated.Conclusions: OPC once-daily was safe, well tolerated, and effective in reducing the OFF-time in patients with PD on levodopa treatment and with motor fluctuations.No conflict of interest.

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ZONISAMIDE OPEN-LABEL TRIAL IN EARLY PARKINSON’S DISEASET. Maeda1,*, D. Takano1, T. Yamazaki1, Y. Satoh1, K. Nagata1

1Department of Neurology, Research Institute for Brain and Blood Vessels-Akita, Akita, Japan

Objectives: Zonisamide (ZNS) is approved as an anti-parkinsonian agent in advanced Parkinson’s disease (PD) in Japan. The aim of this study is to evalu-ate ZNS in early PD.Methods: We consecutively recruited 13 PD patients satisfied less than 3 years of disease duration and 300 mg or less of L-dopa only or additional small amounts of any dopamine agonists in this prospective study. We evalu-ated motor severities with Hoehn and Yahr stage and unified PD rating scale and non-motor severities with nonmotor symptom scale. Health related quality of daily life was evaluated with the 39 item PD questionnaire (PDQ-39). Serum ZNS levels were monitored. Patients evaluated their condition by themselves with patient’s global impression of improvement (PGI-I). Following the first evaluation, patients received open-label 25 mg of ZNS and visited us 4 times for 28 weeks.Results: We could enroll 13 patients including 8 females and 5 males (mean age; 71.2, disease duration; 22.9 months, L-DOPA; 361.5 mg/day). Mean H&Y stage, UPDRS part III, PDQ-39 and NMSS were 2.2, 22.6, 17.2 and 14.0, respectively. Two female patients could not complete due to adverse events. Additional ZNS improved UPDRS part III score at 20 weeks (p = 0.009) and 28 weeks (p = 0.008). PGI-I also significantly improve at 12 weeks (p = 0.045), 20 weeks (p = 0.009) and 28 weeks (p = 0.015). PDQ-39 and NMSS showed no significant changes. Mean plasma ZNS levels were stable from 2.0 to 2.4 μg/ml.Conclusions: ZNS may be expected to be beneficial to motor symptoms in early PD as well as in advanced PD.

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ROTIGOTINE TRANSDERMAL PATCH FOR PARKINSON’S DISEASE IN ROUTINE CLINICAL PRACTICEI. CImas1,*, A. Pato1, I. Rodriguez-Constenla1, J.R. Lorenzo1

1Neurology, Povisa, Vigo, Spain

Objectives: To investigate the safety and tolerability of transdermal rotigotine, a non-ergoline dopamine agonist, in patients with PD being treated during routine clinical practice.Methods: (1) Study design: Prospective, observational, single-centre. (2) Setting: Hospital outpatient clinic. (3) Intervention: Transdermal rotigotine. Drug dosages were at the discretion of the treating physician.

Results: One hundred fourteen patients were enrolled, and evaluable for adverse events over a 12–24 months period. Adverse events occurred in 33 patients (28.94%). Twenty-three patients (20.17%) reported application site reactions (dermatitis, erythema, itching), and 10 (8.77%) had systemic adverse events, including hallucinations 3 patients (2.63%) and depression, dizziness,, head-ache and sleep disorders (1 patient each [0.87%)], syncope 2 patients (1.75%) and impulse control disorder in 2 patients (1.75%). Adverse events necessitated the discontinuation of rotigotine in 20 patients (17.54%); reasons for discontinu-ation were application site reactions in 10 patients (8.77%), hallucinations in 3 patients (2.63%), and depression and dizziness, headache in 1 patient each and sleep disorder (0.87%) and impulse control disorder in 2 (1.75%).Conclusions: Rotigotine is safe and well tolerated when used to treat PD in routine clinical practiceReferences1. Elmer LW, Surmann E, Boroojerdi B, et al. Long-term safety and toler-

ability of rotigotine transdermal system in patients with early-stage idi-opathic Parkinson’s disease: a prospective, open-label extension study. Parkinsonism and related disorders. 2012; 18(5):488–93.

2. Wingo TS, Evatt M, Scott B, et al. Impulse control disorders arising in 3 patients treated with rotigotine. Clin Neuropharmacol. 2009; 32(2):59–62.

3. Ceballos-Baumann A, Hack HJ. Rotigotine transdermal patch in combina-tion therapy for Parkinson’s disease--observations in routine clinical prac-tice. Curr Med Res Opin. 2011; 27(10):1899–905.


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ROTIGOTINE IMPROVES SLEEP FRAGMENTATION IN PARKINSON’S DISEASEJ. Pagonabarraga1,*, P. Sanz2, V. Puente3, E. Balaguer4, G. Piñol5, A. Cardozo5, I. Legarda6, T. Delgado7, P. Otermín8, C. Serrano9, M. Aguirregomozcorta10, R. Álvarez11

1Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, 2Neurology, Hospital de Mataró, Barcelona, Spain, 3Neurology, Hospital del Mar, Barcelona, Spain, 4Neurology, Capio Hospital General de Catalunya, Barcelona, Spain, 5Neurology, Hospital Santa Maria de Lleida, Lleida, Spain, 6Neurology, Hospital Son Espases, Mallorca, Spain, 7Neurology, Corporació Sanitària Parc Taulí, Sabadell, Spain, 8Neurology, Hospital de Granollers, Granollers, Spain, 9Neurology, Hospital de Martorell, Martorell, Spain, 10Neurology, Hospital de Figueres, Figueres, Spain, 11Neurology, Hospital Germans Trias i Pujol, Badalona, Spain

Objectives: Sleep fragmentation (SF) is a frequent complaint in Parkinson’s disease (PD) that impacts on quality of life. In the RECOVER study rotigo-tine improved sleep quality, but no significant changes were observed in SF. These could be explained by a heterogeneous sample of patients with and without sleep problems. We aimed to assess the efficacy of rotigotine on SF in a sample of PD patients with subjective complaints of unsatisfactory nocturnal awakenings. Relationships between SF and the different aspects of sleep dis-turbance assessed by the Parkinson’s-Disease-Sleep-Scale-2 (PDSS-2), and the response of these aspects to rotigotine were explored.Methods: Prospective, observational, multicentric study. Rotigotine effects on SF were assessed by change at 3 months in the item 3 (sleep maintenance) of the PDSS-2. A more specific questionnaire for SF was designed (PD-SFQ) to describe in more detail the phenomenology of SF, and the changes observed after rotigotine. The UPDRS-III and Geriatric-Depression-Scale (GDS) were administered to control for confounding factors.Results: Sixty-two patients with SF were recruited (age 70 ± 7 years, disease duration 5.7 ± 4 years). Rotigotine onset (8.5 ± 3 mg/day) resulted in significant improvements of SF by the PDSS-2 (p = 0.001) and PD-SFQ (p < 0.001). Total PDSS-2 (p < 0.001) and UPDRS-III (p = 0.01) scores improved. No changes on the GDS (p = 0.11) appeared. Univariate and regression analyses showed improve-ments in SF to independently correlate with improvements in motor nocturnal symptoms (p = 0.01), restless legs symptoms (p = 0.02), and nocturia (p = 0.04).Conclusions: Treatment with rotigotine was associated with significant improvement of sleep fragmentation, by amelioration of nocturnal motor symp-toms, restless legs symptoms, and nocturia.No conflict of interest.

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OBSERVATIONAL SURVEY ON THE USE OF ROPINIROLE PROLONGED RELEASE (PR) TABLETS IN CLINICAL PRACTICES. Zagury1,*, P. Kleist1

1Medical Department, GlaxoSmithKline AG, Münchenbuchsee, Switzerland

Objectives: The main objectives of this observational survey were to obtain information on how ropinirole PR is used in clinical practice and on how Parkinson’s Disease is managed in clinical practice in Switzerland.



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Methods: This was an open label, uncontrolled survey based on non-influ-enced prescriptions of ropinirole PR by neurologists. The Physicians treated the patients in line with the prescribing information. Anonymized patient-related information was documented using a questionnaire and an explorative data analysis of prescription patterns conducted.Results: 116 patients were assessed. Mean age: 68 years (range 45–91 years); 37% were women. The main reasons for using ropinirole PR were: once daily dosing and unsatisfactory effect of previous treatment (details, see Table 1).

Table 1. Reasons for treatment choice, n (%) (multiple selections possible).

One dose daily 79 (68)

Unsatisfactory effect of previous treatment 68 (59)

Improved relief from nocturnal symptoms 39 (34)

Simple titration when starting treatment 35 (30)

Flexibility in time of medication intake 31 (27)

Improvement of compliance 29 (25)

Unsatisfactory tolerance of previous treatment 21 (18)

Patient desire 10 (9)

The mean dose of ropinirole PR at the end of the survey was 9.2 mg/day (dose range: 2–24 mg/day).Adverse events were infrequent and in line with the prescribing information. 4 patients reported serious adverse events and 6 patients withdrew from treat-ment due to an adverse event. Safety results are shown in Table 2.

Table 2Subjects with any AE(s) reported during treatment with ropinirole PR, n (%)*.

Intervention group (N = 116, treatment duration up to 3 months)

Hallucinations 3 (2.6)Lack of efficacy 2 (1.7)Ankle oedema 1 (0.9)Confusion 1 (0.9)

Death unrelated to applied drug 1 (0.9)Dizziness 1 (0.9)Dyskinesia 1 (0.9)Dystonia 1 (0.9)Erythema 1 (0.9)Pruritus 1 (0.9)Patients with SAE, n (%) 4 (3.5)Total number of patients withdrawn, n (%)

11 (9.5)

Withdrawal due to adverse event (including lack of efficacy), n (%)

6 (5.2)

Withdrawal for other reasons, n (%) 5 (4.3)*These adverse events reflect both the documentation of adverse events on the questionnaire and spontaneous adverse events reporting.Conclusions: The use of ropinirole in clinical practice seems to be consistent with the use during clinical trials.Acknowledgment Project funded by GlaxoSmithKline (Project ID: 111905).

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ARE BRANDED AND GENERIC EXTENDED-RELEASE ROPINIROLE FORMULATIONS EQUALLY EFFICACIOUS? A RATER-BLINDED, SWITCH-OVER, MULTICENTER STUDYN. Kovács1,*, M. Herceg2, F. Nagy2, S. Komoly1, Z. Aschermann1, J. Janszky1, I. Késmárki3, K. Karádi1, T. Dóczi1, E. Pál1, E. Bosnyák1

1Department of Neurology, University of Pécs, Pécs, Hungary, 2Department of Neurology, Kaposi Mór County Hospital, Kaposvár, Hungary, 3Department of Neurology, EEI, Pécs, Hungary

Objectives: The aim of this rater-blinded multicenter study was to compare the efficacy of the branded and a generic extended-release ropinirole formula-tion in the treatment of advanced Parkinson’s disease (PD).

Methods: Of 22 enrolled patients 21 completed the study. A rater blinded to treatment evaluated Unified Parkinson’s Disease Rating Scale, Fahn-Tolosa-Marin Tremor Rating Scale, timed up-and-go test, Non-motor Symptom Assessment Scale, a structured questionnaire on ropinirole side-effects. Besides, the patients self-administered EQ-5D, Parkinson’s disease Sleep Scale-2 and Beck Depression Inventories.Results: Branded and generic ropinirole treatment achieved similar scores on all tests measuring severity of motor symptoms (primary endpoint, UPDRS motor examination: 27.0 vs 28.0 points, p = 0.505). Analysis of patient diaries revealed that the lengths of “good time periods” were comparable (10.5 and 10 h for branded and generic ropinirole, respectively, p = 0.670). However, generic ropinirole therapy achieved almost 3.0 h shorter ON time without dys-kinesia (6.5 vs. 9.5 h, p < 0.05) and 2.5 h longer ON time with slight dyskinesia (3.5 vs. 1.0 h, respectively, p < 0.05) than the branded ropinirole did. Except for gastrointestinal problems, non-motor symptoms were similarly controlled, and both medications had comparable side-effects profile. Patients did not prefer either formulation. After completion of the study, twelve subjects chose branded and 9 patients preferred generic ropinirole therapy for continuation (p = 0.513).Conclusions: Although this study has to be interpreted with limitations, our findings demonstrated that both generic and branded ropinirole usage can achieve similar control on most motor and non-motor symptoms of PD.References1. Parkinsonism Relat Disord 2011; 17(5):308–312.2. BMC Pharmacol Toxicol 2013; 14(1):24.

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ISOLATED APRAXIA OF LID OPENING CAUSED BY ROPINIROLE WITHDRAWALH. Kim1,*, H.J. Kang2, S.H. Han1

1Department of Neurology, Konkuk University Medical Center, Seoul, Korea, 2Department of Neurology, Senam Hospital, Seoul, Korea

Objectives: Apraxia of lid opening (ALO) is defined as a nonparalytic motor abnormality characterized by difficulty in initiating the act of eyelid elevation. However, the pathogenesis of ALO is not well understood.Methods: We report on one patient who suffered from disabling ALO after dopamine agonist withdrawal.Results: An 80-year-old woman with a history of Parkinson’s disease and dementia was referred for evaluation of decreased mentality. She was diag-nosed with hypoglycemia and regained alertness following glycemic control. Although she was on 4 mg of ropinirole per day for Parkinson’s disease, par-kinsonian feature was not found. Thus, we withdraw ropinirole. On the third day after withdrawal of ropinirole, we noticed that she had difficulty in lifting her eyelids despites frontalis muscle contraction. There was no evidence of pto-sis. Abnormal contraction of orbicularis oculi muscles or parkinsonian features was not seen. Diffusion-weighted magnetic resonance imaging was negative. Based on previous literatures reporting levodopa responsive ALO, we put her on levodopa/benserazide 100/25 mg three times a day, which dramatically improved inability to open her eyelids on that day. And the remission was sus-tained when she restarted ropinirole instead of taking levodopa/benserazide.Conclusions: The reversible eyelid opening difficulty in our patients was con-sistent with ALO. Our case suggests the importance of considering changes in dopaminergic medications when dealing with ALO and possible role of dopa-minergic pathways in the pathogenesis of ALO.Reference1. Dewey RB Jr, Maraganore DM. Isolated eyelid-opening apraxia: report of

a new levodopa-responsive syndrome. Neurology. 1994; 44(9):1752–4.No conflict of interest.

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MORNING ALINEKIA TREATMENT WITH APOMORPHINE INJECTIONS. Isaacson1,*, S. Am Impakt Investigators1

1Director, Parkinson’s Disease and Movement Disorders Center, Boca Raton, USA

Objectives: Parkinson’s patients often experience unreliable onset of thera-peutic effect after taking a dose of oral medication resulting in ‘morning aki-nesia’. The primary objective of this study will assess the effect of APOKYN (apomorphine HCl injection) in Parkinson’s disease (PD) patients with morn-ing akinesia resulting from delayed or unreliable onset of effect of first morning dose of L-dopa.Methods: This study will enroll approximately 100 PD subjects across 12 sites. Subjects complete a Baseline Period recording daily TTO following their regular L-Dopa morning dose for 7 days. Once optimal dose is identified, subjects self-inject APOKYN at regularly scheduled L-Dopa morning dose time during a 7-day APOKYN Treatment Period and record TTO following APOKYN injection.



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Results: Interim analysis is presented. Treated patients had average of 4 years of morning akinesia, and had duration of PD for 5–20 years. Mean delay of onset of first levodopa dose was 55 min, and after apomorphine injec-tion was mean 18 min. EQ-5D, VAS, PGI, and CGI scales were all significantly improved. Apomorphine treatment was well tolerated.Conclusion: Subcutaneous injection of apomorphine improves morning aki-nesia with rapid and reliable turning-ON effect.

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PARKINSON’S DISEASE: THERAPY’S NEW OPPORTUNITIESS. Turuspekova1,*, A. Ospanov2, A. Seydanova2, Z. Zheldybaeva1

1Neurology Institute of Graduate Studies, Kazakh National Medical University, Almaty, Kazakhstan, 2Neurology and Neurorehabilitation, City Clinical Hospital, Almaty, Kazakhstan

Objectives: Parkinson’s disease remains one of the most disabling and topical problem significantly reducing life quality of patients and their rela-tives. To evaluate efficacy of Liposome-Forte and PK-Merz application in correcting motor and cognitive impairments in patients with Parkinson’s disease.Methods: 59 patients studied: 36 men and 23 women; age: 53 to 75; disease duration: 8,1 ± 2,2 years; Hoehn and Yahr scale points – 2,4 ± 0,4. In deter-mining motor impairment degree Tinetti scale was used; cognitive disorders – mini-mental state examination (MMSE), scales of Wechsler (WMS, WAIS) and Matisse; life quality – measured by McDowell index. Patients were admin-istered Liposome-Forte 2.0 intramuscularly (20 days) and PK-Merz 200 mg intravenously (5–7 days). 17 patients treated by protocol composed control group.Results: Motor activity’s improvements and decrease in rigidity, tremor and hypokinesia were noted in patients receiving combined Liposome-Forte and PK-Merz treatment. Patients’ static and dynamic balance abili-ties (the Tinetti test) improved significantly by 18.9%. McDowell’s disability index fell to 44 (opposite to initial 90). Neurodynamic and operational func-tions improved firmly. MMSE cognitive impairment degree showed positive trend with 22,9 ± 1,5 reaching 26,7 ± 1,5; Matisse scale indexes increased to 5.2% (p < 0.01). Logical, visual memory, account and thinking tests’ results improved.Conclusions: Research’s dynamics demonstrates Liposome-Forte and PK-Merz combined treatment’s positive impact on motor and cognitive func-tion in patients with Parkinson’s disease.No conflict of interest.

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STUDY OF THE ANXIOLYTIC EFFECT AND INFLUENCE UPON SLEEP-WAKE ACTIVITY OF THE NOVEL ANTIPARKINSONIAN DRUG HEMANTANEE. Valdman1,*, I. Kokshenev1, I. Kapitsa1, E. Ivanova1, L. Nerobkova1, S. Seredenin1

1Psychopharmacology, Zakusov Institute of Pharmacology of the RAMS, Moscow, Russia

Objectives: Novel antiparkinsonian drug Hemantane (N-2-adamantyl hexa-methyleneimine hydrochloride) (H) was shown to reduce parkinsonian symp-toms in animal models. In clinical trials efficacy and safety of mono therapy by H in patients with early stages of Parkinson’s disease was proved. Also antidepressant activity of H was revealed in patients [1]. The aim of the study was to evaluate anxiolytic effect of H and its influence upon sleep cycles in animals.Methods: Anxiolytic effect of H was registered in BALB/c mice in elevated plus-maze. Time spend in open arms and on central platform was assessed as a parameter of anxiolytic effect. H. was administered orally 10–20 mg/kg 40 min before testing. Electroencephalograpy (EEG) analysis of sleep cycles was performed in freely moving rats with implanted electrodes. The sleep-wake cycles and the structure of the sleep periods were registered before and after H 10 mg/kg injection during 5 h.Results: H did not influence spontaneous motor activity. H. significantly increased time spend in open arms in BALB/c mice. H did not cause any changes in sleep-wake cycles. There was no difference in latency of slow-wave sleep before and after H administration. H also did not change the num-ber of quick and slow sleep episodes.Conclusions: The results obtained testify that H has anxiolytic activity and does not disturb normal sleep structure. This data should be taken into con-sideration in further clinical trials of H.Reference1. Katunina E. et al. Zh Nevrol Psikhiatr Im S S Korsakova. 2008; 108(6):

24–7. Russian. PMID: 18577930.No conflict of interest.

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COMPARISON OF DONEPEZIL’S EFFECTIVENESS IN PARKINSON’S DISEASE COUPLED WITH DEMENTIA AND IN VASCULAR DEMENTIA ONLYL. Kuanova1,*1Neurology, Republican Scientific Research Center for Emergency Care, Astana, Kazakhstan

Objectives: Evaluation of cholinesterase inhibitor donepezil’s effectiveness in Parkinson’s disease coupled with dementia and vascular dementia only.Methods: 2 groups were formed out of 65 patients to compare the efficiency of donepezil in an open study: 32 patients with vascular dementia (VD) and 35 with parkinsonism and dementia (PD). Results assessment was carried out at the start, after 12 and 24 weeks using the Mini-Mental State Examination (MMSE).Results: Gender differences were not observed in two study groups (p = 0.61). At the time of diagnosis verification, patients with VD were younger than PD patients (72.3 vs 75.8 years respectively, p < 0.001). A significantly higher inci-dence of patients with a score MMSE ≤ 24 was observed in the group VD (77.4% vs. 64,9%, p = 0,028). By twenty-forth week, MMSE mean score increased by 3.5 points in the group VD and by 3.2 points in PD. These therapeutic effects were a significant change compared to the baseline (p < 0.001), but there was no sig-nificant intergroup treatment differences (MMSE p = 0.49). 61 patients (91.8%) completed the study. Four patients, all with PD, had adverse side effects.Conclusions: Donepezil may delay the cognitive functions degradation at least for 6 months. Patients with Parkinson’s disease suffer from more severe side effects.No conflict of interest.

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EFFECT OF ARIPIPRAZOLE ON HALLUCINATIONS AND DELUSIONS IN PATIENTS WITH PARKINSON’S DISEASE: RESULTS OF AN OPEN-LABELED MULTICENTER STUDYK. Kashihara1,*, T. Maeda2, K. Yoshida3, M. Yamamoto4

1Neurology, Okayama Kyokuto Hospital, Okayama, Japan, 2Neurology, Research Institute for Brain and Blood Vessels-Akita, Akita, Japan, 3Neurology, Japanese Red Cross Asahikawa Hospital, Hokkaido, Japan, 4Neurology, Takamatsu Neurology Clinic, Takamatsu, Japan

Objectives: To evaluate the effect of aripiprazole on psychosis and motor function in patients with Parkinson’s disease (PD).Methods: Twenty-four PD patients with psychosis (13 male and 11 female, the mean age of 73) were enrolled in the study. These patients were started on aripiprazole 3 mg/day and increased or reduced the dose as needed. Subjects were evaluated on the Unified Parkinson’s Disease Rating Scale (UPDRS) parts I-IV, the Mini-Mental State Examinations (MMSE), the Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Impression – Severity scale (CGI-S) before, 2,4, and 12 weeks after open-label aripiprazole.Results: Nine patients discontinued the study due to worsened Parkinsonism (eight) or psychosis (one). Except for the discontinued patients, total score of UPDRS part I and Part II + III did not change significantly. Whereas, significant improvement in BPRS and CGI-S scores occurred with aripiprazole in patients who continued aripiprazole. There were no differences of the age, disease duration, disease sever-ity, and MMSE score between patients who continued and discontinued the study.Conclusions: Although aripiprazole may aggravate motor symptoms of PD patients [1], significant improvement of hallucinations and delusions can be expected. Aripiprazole may be useful for the psychosis of PD patients who do not aggravate Parkinsonism on dosing.Reference1. Friedman JH, et al. Mov Disord 2006; 21:2078–81.No conflict of interest.

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ANTIPSYCHOTIC EFFICACY AND MOTOR TOLERABILITY IN A PHASE III PLACEBO-CONTROLLED STUDY OF PIMAVANSERIN IN PATIENTS WITH PARKINSON’S DISEASE PSYCHOSIS (ACP-103-020)J. Cummings1, S. Isaacson2, R. Mills3*, H. Williams3, K. Chi-Burris3, R. Dhall4, C. Ballard5

1Lou Ruvo Center for Brain Health, Cleveland Clinic, Las Vegas, USA, 2Parkinson’s Disease and Movement Disorders Center of Boca Raton, Boca Raton, USA, 3ACADIA Pharmaceuticals Inc., San Diego, USA, 4Barrow Neurology Institute, Phoenix, USA, 5Wolfson Center for Age Related Diseases, Kings College London, London, United Kingdom

Objectives: A PhIII outpatient study, optimized to reduce placebo response, was conducted to assess the efficacy and safety of pimavanserin in PD psychosis (PDP). PDP is frequent, distressing and a leading cause of institutionalization.



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It complicates PD management and is linked to increased morbidity, incident dementia and mortality. Current antipsychotics lack efficacy and/or have serious tolerability and safety concerns. Pimavanserin, a selective non-dopaminergic 5-HT2A antagonist, has shown antipsychotic effects and good tolerability in pre-vious PhIII trials, but a robust placebo effect precluded statistical separation.Methods: Following screening, in which brief (non-pharmacologic) psycho-social therapy (BPST-PD) was offered, 199 non-demented patients with moderate-severe psychosis (on stable PD medication) were randomized to pimavanserin 40 mg or placebo (oral qd) for 6 weeks.Results: Pimavanserin met the primary endpoint using SAPS-PD (PD-adapted Scale for Assessment of Positive Symptoms, assessed by inde-pendent raters): −5.79 PIM vs −2.73 PBO change from Baseline at Day 43 (LSM∆ = −3.06; p = 0.001). These results were supported by highly signifi-cant improvement in the secondary efficacy measure, CGI-I (LSM∆ = −0.67; p = 0.001), assessed by Investigators blind to the SAPS-PD. Clinical benefits were also seen in all exploratory measures for nighttime sleep, daytime wake-fulness, and caregiver burden. Consistent with previous studies, pimavanserin met the key secondary endpoint for noninferiority to placebo on motor function (UPDRS II + III) and was otherwise safe and well tolerated. Most common AEs were UTI (11.7% PBO, 13.5% PIM) and falls (8.5% PBO, 10.6% PIM). SAEs in >1 patient were UTI (1-PBO, 3-PIM) and psychotic disorder (0-PBO, 2-PIM).Conclusions: Pimavanserin appears effective, safe and well-tolerated for PDP.

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COMPARATIVE EFFICACY AND SAFETY OF BOTULINUM TOXIN TYPE A AND B IN TREATING PARKINSON’S DISEASE-RELATED SIALORRHEA: A PRE-TEST POST-TEST STUDY.M. Capecci1,*, E. Sordoni1, L. Di Biagio1, E. Andrenelli1, M. Millevolte1, M.G. Ceravolo1

1Department of Experimental and Clinical Medicine, Università Politecnica Marche, Ancona, Italy

Objectives: To compare the efficacy and safety of botulinum toxin type A (BTX-A) and B (BTX-B) in Parkinson’s Disease (PD) patients suffering from disabling drooling.Methods: 44 PD patients (age: 72.3 ± 5.1 years, disease duration : 14.8 + 6.6 years) with severe drooling were randomized into two groups, either receiving BTX-A (50U Botox in each side) or BTX-B injections (2000U Neurobloc in each side) in the parotid glands. Outcome measures: visual analogue scale for the assessment of drooling-related family (VAS-FD) and social (VAS-SD) distress; Sialorrhea Scoring Scale (SDS). UPDRS-ADL scores of speech and dysphagia items were rated to appraise side effects. Assessment timing: imme-diately before treatment and after 1 month. The analysis of variance (ANOVA) for repeated measures was applied to quantify time and treatment effects.Results: At 1 month, all subjects reported an improvement of family (time effect: F = 82.7, p <.0001) and social (F = 74.5, p <.0001) distress follow-ing drooling reduction; the SSS score improved by 60% (F = 197, p <.0001). A greater impact of BTX-B was appreciated for both the VAS-SD score (time x treatment effect: F = 8.1, p =.005) and the SSS score (F = 17.2; p <.0001). Neither swallow ability nor speech worsened after treatment.Conclusions: Bilateral botulinum toxin injection at the parotid level is a safe and effective treatment for severe sialorrhea in PD subjects. Serotype B pro-vides larger effects, while being as safe as serotype A.No conflict of interest.

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TDCS TO TREAT FREEZING OF GAIT: A CASE REPORTM. Capecci1,*, E. Adrenelli1, C. Orni1, L. Provinciali1, M.G. Ceravolo1

1Department of Experimental and Clinical Medicine, Università Politecnica Marche, Ancona, Italy

Objectives: To investigate the effects of transcranial Direct Current Stimulation (tDCS) in a 50-years-old subject suffering from parkin disease, complicated by drug-resistant FOG.Methods: Three sessions of 2.0 mA cathodal tDCS were realized, 30 days apart from each other. In the first session, tDCS was delivered to the prefrontal cortex, in the second one to the parietal cortex, while in the last, a sham-stimulation of the prefrontal cortex was done. In each session, both the right and left hemispheres were separately stimulated, for 20 min each. Outcome measures: performance time and number of FOG events during TUG (carried out both as single and dual task), UPRDS-III, forward and backward Corsi’s and digit span, phonological fluency, Stroop test. At each session, measures were taken before, after right and, again, after left hemisphere stimulation.Results: Prefrontal stimulation reduced significantly FOG events (90%), though providing a lower effect on TUG time than parietal stimulation. Parietal cortex tDCS improved single-TUG time up to 34%, with minor impact on dual-task time, and negligible effect on FOG events. UPDRS-III decreased after both prefrontal and parietal stimulation (by 31% and 36% respectively).

Cognitive task scores increased after prefrontal stimulation (memory perfor-mances improving by about 20%), though not after parietal stimulation. No changes in motor or cognitive outcomes resulted after sham stimulation.Conclusions: In this selected subject, prefrontal cortex tDCS was effective at improving specific motor and cognitive performances. The role of parietal cortex stimulation needs further investigation.No conflict of interest.

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EFFECTS OF TRANSCRANIAL DIRECT CURRENT STIMULATION (TDCS) ON HANDWRITING IN PARKINSON’S DISEASES. Asaadi1,*, R. Soleiman zadeh Ardebili2, M. Omrani3, A. Abbassian2, F. Ashrafi41Neurosurgery, Functional Neurosurgery Research Center, Tehran, Iran, 2Cognitive Sciences, Institute for Research in Fundamental Sciences, Tehran, Iran, 3Laboratory of integrative Motor Behaviour, Queen’s University, Ontario, Canada, 4Neurology, Functional Neurosurgery Research Center, Tehran, Iran

Objectives: The basal ganglia and cerebellum are two groups of subcorti-cal nuclei that damage to these brain regions produces alterations in motor function (1,2,3,4). On other hand supplementary motor area (SMA) has been described as a cortical motor area on the brain cortex that receives the strong inputs from basal ganglia (5,6). it’s believed that Basal Ganglia can play impor-tant role in function of SMA (7). The aim of this study was to better understand between superficial and deep motor structures of the brain.Methods: We tested transcranial Direct Cortical Stimulation (tDCS) using dif-ferent stimulation of supplementary motor area (anodal, cathodal and sham) and evaluated it’s effects on handwriting in 17 patients with micrographia after held of antiparkinsonian medications for 12 h prior to the experiment and investigated of motor function by Unified Parkinson’s Disease Rating Scale(part III).Results: We assessed the effect of tDCS on micrographia improvement by increase in amplitude and wave length and decrease in the slope of amplitude decrement in patients handwriting. In 40% of the patients micrographia improved by anodal, 10% with cathodal and 7% with sham stimulation. Also in some cases tremor improved significantly after anodal stimulation.Conclusions: Our hypothesis states that there is a loop between SMA-basal ganglia-cerebellum that affect in Parkinson’s disease and anodal stimulation of SMA by tDSC can cause gain in negative feedback of this loop and can effects on micrographia as a sign of Parkinson’s disease.References1. K.P. Bhatia, et al. 1994.2. V.B. Brooks, et al. 1981.3. M.R. DeLong, et al. 1981.4. O. Hikosaka, et al. 1993.5. Penfield, 1951.6. Strick, 1985.7. Jenkins, et al. 2000.No conflict of interest.

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CUMULATIVE RTMS ON FREEZING OF GAIT IN PARKINSONISMW.H. Chang1,*, J.Y. Youn2, J.W. Cho2, S. Kim1, Y.H. Kim1

1Physical and Rehabilitation Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea, 2Neurology, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea

Objectives: To evaluate a therapeutic effect of multisession 10 Hz rTMS on Freezing of gait (FOG) in patients with Parkinsonism.Methods: Seven patients with Parkinsonism (3, idiopathic Parkinson’s disease; 3, vascular Parkinsonism; 1, Parkinson plus syndrome) were included. This study was performed with the double-blind random-order crossover design. Each patient completed two rTMS protocols (real vs. sham), and each protocol included 5 consecutive session with 10 Hz rTMS over their leg area of primary motor cortex. Timed 10 m walk test, Standing start 180° turn test (SS-180° turn test), self-assessment scale of FOG, and motor cortical excitability using motor evoked potentials amplitude were evaluated before treatment, day 1, day 5, and day 12 in each real and sham rTMS protocol.Results: The time in SS-180° turn test showed a significant improvement at day 5 in the real rTMS (p < 0.05) and this effect lasted up to day 12, whereas no significant improvement was seen in the sham rTMS. Gait speed tended to improve at day 5 and day 12 in the real rTMS, even though there was no sta-tistically significant difference from the sham rTMS. Change of FOG-Q score was not significant in both real and sham rTMS.Conclusions: A cumulative effect of multisession 10 Hz rTMS on primary leg motor cortex was beneficial for patients with Parkinsonism in improving FOG. Further study is invited to develop this method as a new treatment intervention



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in patients with Parkinsonism (Supported by Samsung Medical Center grant [#CRO112051] and by the National Research Foundation of Korea grant (No. 2011-0016960)).

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OUTCOME OF UNILATERAL POSTEROVENTRAL PALLIDOTOMY IN THE TREATMENT OF LEVODOPA INDUCED DYSKINESIA IN ADVANCED PARKINSON’S DISEASEZ. Fayed1,*, H. Anwar1

1Neurosurgery, Ain Shams University, Cairo, Egypt

Objectives: Dyskinesias are common complication of Levodopa therapy in patients with Parkinson’s disease and are difficult to treat. Unilateral pal-lidotomy has been effectively used to treat parkinsonism and reduce levo-dopa induced dyskinesia (LID) the aim of this study is to assess the effect of unilateral posteroventral pallidotomy in the treatment of LID in patients with Parkinson’s disease.Methods: We sought to determine the effects of unilateral posteroventral pal-lidotomy (right sided or contralateral to the more affected side if asymmetri-cal) in 12 patients with advanced Parkinson’s disease having LID, The unified Dyskinesia Rating Scale (UDysRS) was used to rate and quantify LID in a blinded fashion.Results: The mean UDysRS for the patients was 70.1, the mean handwriting score was 4.8, the mean walking score was 2.7 and the mean eating tasks score was 3.2, at 18 months following unilateral posteroventral pallidotomy the mean scores were 36.7, 1.9, 1.4, 1.5, respectively, all the 12 patients showed reduction in their UDysRS score up to 80%.Conclusions: Ablative surgery of the globus pallidus internus is a safe and effective therapy providing sustained benefit for disabling LID in patients with Parkinson’s disease.References1. Fine J, Duff J, Chen R, et al. Long-term follow-up of unilateral pallidotomy

in advanced Parkinson’s disease. N Engl J Med 2000; 342:1708–1714.2. Lang AE, Lozano AM, Montgomery E, Duff J, Tasker R, Hutchison W:

Posteroventral pallidotomy in advanced Parkinson’s disease. N Engl J Med 337:1036–1042, 1997.

3. Kleiner-Fisman G, Lozano M, Moro E, Lang A: Long term effect of pos-teroventral pallidotmy on Levodopa-induced dyskinesia. Movement Disorders, Vol. 25, No. 10, 2010.


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MR-GUIDED HIGH INTENSITY FOCUSED ULTRASOUND ABLATION OF THE CEREBELLOTHALAMIC TRACT FOR TREATMENT OF TREMOR-DOMINANT PARKINSON’S DISEASES. Schreglmann1,*, O. Sürücü2, C.R. Baumann1, R. O’Gormann3, R. Kocian4, B. Werner3, E. Martin3

1Department of Neurology, University Hospital of Zurich, Zurich, Switzerland, 2Department of Neurosurgery, University Hospital of Zurich, Zurich, Switzerland, 3Centre of MR research, University Children’s Hospital, Zurich, Switzerland, 4Department of Anaesthesiology, University Hospital of Zurich, Zurich, Switzerland

Objectives: MR-guided high intensity focused ultrasound (MRgFUS) delivers acoustic energy through the intact human skull to create thermocoagulations at sub-millimeter precision under real-time MR-thermometry control. There is first evidence for the safe application of MRgFUS in essential tremor1,2 (ET). However, experience in other movement disorders, including Parkinson’s dis-ease (PD), is scarce3.Methods: One tremor-dominant idiopathic PD patient (m, 71 years, UPDRSIII OFF 48/ON 20, MOCA 14/30, MMSE 25) with treatment-resistant rest tremor and contraindications for deep brain stimulation (DBS) was treated with MRgFUS (ExAblate Neuro, InSightec, Israel) of the cerebellothalamic tract caudal to the ventral intermediate nucleus (Vim) contralateral to the affected side. Patient-tailored targeting was based on an approach combining anatomical landmarks visualized on 3T MRI images, atlas-based tract coordinates and ACPC-based calculated Vim coordinates.Results: The lesion was precisely placed and measured max. 4.8 mm/2.8 mm diameter on T1-weighed MRI at 2 days/1 month post intervention. Clinically, the tremor was immediately and completely suppressed but partially reap-peared during the following 3 weeks. At 1 month follow up tremor severity was 50% of baseline. No adverse events occurred.Conclusions: Preliminary experience suggests MRgFUS to be a safe and effective procedure for tremor-dominant PD patients with contraindications to DBS. The evolution of and relationship between lesion size and clinical response needs to be studied further.

References1. Lipsman et al., Lancet Neurology, 2013.2. Elias et al., NEJM, 2013.3. Bauer R. et al., International Conference on DBS; Düsseldorf, 2013.No conflict of interest.

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MR-GUIDED HIGH INTENSITY FOCUSED ULTRASOUND FOR THE TREATMENT OF TREMOR-DOMINANT PARKINSON’S DISEASE – FIRST EXPERIENCER. Bauer1,*, B. Werner2, S. Haegele-Link3, G. Kägi3, S. Nitschke3, F. Brugger3, M. von Specht4, E. Martin2

1Neurosurgery, Cantonal Hospital St. Gallen, St. Gallen, Switzerland, 2Department of MR Research, University Children’s Hospital Zurich, Zurich, Switzerland, 3Neurology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland, 4Department of Anaesthesiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

Objectives: MR-guided high intensity focused ultrasound (MRgFUS) is a novel, noninvasive technique for the treatment of functional brain disorders through the intact human skull at millimeter precision.Methods: MRgFUS was successfully used for the treatment of therapy-resistant rest tremor of the arm and the hand in a high risk patient (m, 44), with tremor-dominant idiopathic Parkinson’s disease, who showed contraindication to DBS. During interventions the target was visually focused by MR-image guidance. In a first step, the correct focal location was verified with low, non-ablative energy, and targeted in the pallido-thalamic tract (fasciculus thalamicus) of the subtha-lamic area, contralateral to the dominant resting tremor. Continuous sonications lasting 15–25 s each were delivered with stepwise increased acoustic energy up to 13200 J to create thermocoagulations under real-time MR-thermometry. The sonications resulted in heating to 60°C at the focal point producing a ther-mal lesion. Circulating de-gassed water between the helmet shaped transducer and the patient’s head provided acoustic coupling and head cooling.Results: Clinically, MRgFUS intervention resulted in a prompt and complete suppression of the tremor, both at rest and under provocation, which remains to date. No adverse effects were noted.Conclusions: MRgFUS is a novel technique for the treatment of neurological disorders that is non-invasive. First experience with MRgFUS suggests it to be a safe and potentially effective alternative to standard DBS implantation for the treatment of tremor-dominant Parkinson’s disease.Reference1. Elias J, Huss D, Voss T, et al. A pilot study of focused ultrasound thalam-

otomy for essential tremor. N Engl J Med 2013; 369:640–8.No conflict of interest.

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RADIOFREQUENCY ABLATIVE NEUROSURGICAL PROCEDURES [PALLIDOTOMY AND SUBTHALAMOTOMY] A COST EFFECTIVE APPROACH FOR PATIENTS HAVING MOVEMENT DISORDER IN DEVELOPING COUNTRIESD. Ruikar1,*, S. Jayalakshmi2, M. Surath2, M. Panigrahi31Neurology, Krishna Institute of Medical Sciences, Hyderabad, India, 2Neurology, Krishna Institute of Medical Sciences, Hyderabad, India, 3Neurosurgery, Krishna Institute of Medical Sciences, Hyderabad, India

Objectives: To study and to compare the outcomes following DBS and Pallidotomy/subthalamotomy procedures for movement disorders in resource poor country.Methods: Very few centers in India do functional neurosurgery.

• Prospective study.• Study period: 2 years.• Study group : DBS group (10), Ablative group (9).• All patients selected after a thorough presurgical evaluation and standard

criterias.• Pre-op and post-op UPDRS and UDRS were done for all patients and also

used at follow up.• Lesion is created by radiofrequency probe which leads to thermocoagula-

tion of the structure.

Results: Improvement noted in all the cardinal symptoms of the disease and functional status of patient, 9 DBS were done for PD and one for dystonia. In ablative group 9 procedures done 5 for dystonia and 4 for non PD patients on evaluation there was approximately more than 50% improvement in UPDRS and UDRS scales. Both the groups done well at the end of 1 year follow up. There was significant cost difference in the two groups. bilateral DBS costs 12000USD while ablative procedures costs 1600 USD approximately at India. Most of patients were not able to afford DBS.Conclusions: There were sustained clinical benefits by both the proce-dures. For ablative neurosurgery cost of the procedure was significantly less [six times] than DBS. Ablative neurosurgery is affordable option in selected patients in resource poor country like India.



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Reference1. Hooper, AK; Okun, MS; Foote, KD; Fernandez, HH; Jacobson, C; Zeilman, P;

Romrell, J; Rodriguez, RL (2008). Clinical cases where lesion therapy was chosen over deep brain stimulation. Stereotactic and functional neurosur-gery 86 (3): 147–52.


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CONTRALATERAL AND IPSILATERAL EFFECT OF STN DBS ON MOTOR PERFORMANCE IN PARKINSON’S DISEASEC. Lavigne-Pelletier1,*, J.F. Daneault2, B. Carignan3, A.F. Sadikot2, C. Duval11Kinanthropologie, Université du Québec à Montréal, Montreal, Canada, 2Neurology and Neurosurgery, Montreal Neurological Institute McGill University, Montreal, Canada, 3Sciences Biologiques, Université du Québec à Montréal, Montreal, Canada

Objectives: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an invaluable treatment for refractory motor symptoms in Parkinson’s dis-ease (PD). However, its mechanisms of action are not fully understood. For instance, previous studies demonstrated an important contralateral, and a marginal ipsilateral effect of STN DBS on motor symptoms in PD. The objec-tive was to assess the contralateral and ipsilateral effect of STN DBS on motor performance of a diadochokinesis task in PD.Methods: Sixteen patients diagnosed with idiopathic PD had undergone successful bilateral STN DBS surgery and were deemed in stable clinical condition by their treating physician. Patients were asked to perform prona-tion-supination movements of the forearm with maximal amplitude and as fast as possible. This task was performed with the dominant and non-dominant hand; and was repeated three times for each hand. Patients were tested after a minimum of 10 h of medication withdrawal with both stimulators off, with only the right stimulator on, and with only the left stimulator on.Results: Overall, movement characteristics, such as amplitude, mean veloc-ity and maximal velocity, were only statistically significantly improved by con-tralateral STN stimulation. However, we identified that for each movement characteristic, a sub-group of PD patients did exhibit statistically significant ipsilateral improvements.Conclusions: These results indicate that STN DBS systematically improves contralateral motor performance and that a sub-group of PD patients may also gain ipsilateral benefits from this intervention. We hypothesize that the ipsilat-eral effect of STN DBS is related to lead placement and stimulation parameters.No conflict of interest.

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SUBTHALAMOTOMY VS. PALLIDOTOMY. RETROSPECTIVE, BLINDED EVALUATION OF 50 PATIENTS WITH PARKINSON’S DISEASEA. Mario1,*1Movement Disorders Clinic, International Center for Neurological Restoration (CIREN), Havana, Cuba

Objectives: To compare the effectiveness and safety of unilateral Pallidotomy vs. unilateral Subthalamotomy as a target of functional surgery in the treat-ment of Parkinson’s diseaseMethods: We conducted a retrospective review of our database and selected 50 patients diagnosed with Parkinson’s disease who had undergone func-tional surgery: 25 patients undergoing unilateral subthalamotomy and 25 patients undergoing unilateral Pallidotomy. Then look for the results of pre and postoperative assessments that included neuropsychological tests and motor skills. These assessments were made blind to the type of intervention. In this way we compare the outcome of surgery as a group and the difference when comparing the effect of unilateral pallidotomy and subthalamotomy.Results: There are significant differences in the assessments made before and after surgery. There are also differences between the group receiving sub-thalamotomy and Pallidotomy group, both in motor performance tests and in the neuropsychological variables.Conclusions: Pallidotomy and subthalamotomy are safe and effective treat-ments. There are significant differences when comparing the clinical effect of both procedures.No conflict of interest.

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CONTRIBUTION OF LOCAL FIELD POTENTIAL TO SUBTHALAMIC NUCLEUS DEEP BRAIN STIMULATION IN PARKINSON’S DISEASEJ. Coste1,*, P. Derost2, A. Mulliez3, J. Gabrillargues4, B. Pereira5, J.J. Lemaire1

1IGCNC EA 7282 Université d’Auvergne, Service de Neurochirurgie A CHU Clermont-Ferrand, Clermont-Ferrand, France, 2NPsy-Sydo EA 7280 Université d’Auvergne, Service de Neurologie CHU Clermont-Ferrand,

Clermont-Ferrand, France, 3Délégation Recherche Clinique et Innovation, CHU Clermont-Ferrand, Clermont-Ferrand, France, 4IGCNC EA 7282 Université d’Auvergne, Service de Radiologie A Unité de Neuroradiologie CHU Clermont-Ferrand, Clermont-Ferrand, France, 5IGCNC EA 7282 Université d’Auvergne, Délégation Recherche Clinique et Innovation CHU Clermont-Ferrand, Clermont-Ferrand, France

Objectives: The subthalamic nucleus (STN) is the main target for deep brain stimulation (DBS) in Parkinson’s disease. We analyzed the relationships between magnetic resonance imaging (MRI) anatomy and electrophysiology (local field potential, LFP) done during surgery. We hypothesized that the con-tribution of LFP to neuronal firing rate with detailed MRI anatomy should allow to explore finely anatomo-electrophysiological relationships and also to deter-mine precisely functional surgical targets.Methods: Ten patients with Parkinson’s disease (5F; mean age: 62 ± 4 years; 11 ± 3 years disease duration) underwent bilateral STN DBS surgical pro-cedure. Electrophysiology: 693 LFP recordings in MRI-outlined anatomical structures (Thalamus [Thal], Zona Incerta [ZI], Forel Field [Forel] and STN) were analyzed: Power spectral densities (PSD) from 0 to 100 Hz; 1024 fre-quency values; Normalization: percent of total PSD; Calculation for delta (0–4 Hz), theta (4–7 Hz), alpha (7–13 Hz), beta (13–30 Hz), gamma (30–50 Hz, 50–100 Hz) frequency range. Non-parametric Kruskal-Wallis ANOVA tests were performed followed by pairwise comparisons with adjusted p-value.Results: Percentage of power spectral density for main physiological LFP frequency range was considered for thalamus, ZI, STN and Forel (Figure).

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Figure. Local field potential power spectral density analysis.

Conclusions: This study suggests the interest of LFP to discriminate between structures in the subthalamic region using exploration electrode with patient at rest during DBS surgery. Another part of this study will consist in correlating extracellular neuronal activity and LFP, and analyzing modulations on LFP during voluntary movements of patients.No conflict of interest.

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ELECTROPHYSIOLOGICAL ACTIVITY OF THE SUBTHALAMIC NUCLEUS IN RESPONSE TO EMOTIONAL PROSODY: AN INTRACRANIAL ERP STUDY IN PARKINSON’S DISEASEJ. Péron1,*, C. Haegelen2, P. Sauleau3, L. Tamarit4, V. Milesi1, J.F. Houvenaghel5, T. Dondaine6, M. Vérin5, D. Gandjean1

1Psychology and NCCR Affective Sciences, University of Geneva, Geneva, Switzerland, 2Neurosurgery, ‘Behavior and BG’ Research Unit (EA 4712), University of Rennes 1, University Hospital of Rennes rue Henri Le Guilloux 35033, Rennes, France, 3Neurophysiology, ‘Behavior and BG’ Research unit (EA 4712), University of Rennes 1, University Hospital of Rennes rue Henri Le Guilloux 35033, Rennes, France, 4NCCR Affective Sciences, University of Geneva, Geneva, Switzerland, 5Neurology, ‘Behavior and BG’ Research Unit (EA 4712), University of Rennes 1, University Hospital of Rennes rue Henri Le Guilloux 35033, Rennes, France, 6Neurology and Psychiatry, ‘Behavior and BG’ Research Unit (EA 4712), University of Rennes 1, University Hospital of Rennes rue Henri Le Guilloux 35033, Rennes, France

Objectives: Using intracranial recordings (LFP) in DBS PD patients, previ-ous studies have consistently reported event-related desynchronization in the



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alpha frequency band within the STN in response to emotional stimuli (e.g., Kühn et al., 2005) suggesting that the STN is involved in emotional processing (see, for a review Péron et al., 2013). However, these studies have focused on the influence of visual stimuli and it has yet to be determined whether these STN electrophysiological changes in response to emotional stimuli are modal-ity-specific or supramodal. In this context, the aim of the present study was to explore the electrophysiological activity of the STN in response to emotional stimuli in the auditory modality, i.e., emotional prosody.Methods: LFP were recorded from the STN in 4 PD patients with bilateral STN DBS PD in response to anger, happiness, and neutral prosodies but also non-human auditory synthesized stimuli.Results: We observed i) a specific modulation of the right STN in response to human voice in comparison to synthesized stimuli occurring early but also later after onset, ii) a specific modulation of the STN in response to both anger and happiness prosodies in comparison to neutral ones occurring early but also later after onset.Conclusions: The present results seem confirm that the STN would be involved in emotional processing, irrespective of stimulus valence (positive or negative) and sensory-modality (visual or auditory), arguing for an involve-ment of the STN in emotional processing.Reference1. Kühn et al. (2005). Neurology, 65(5), 707–713.2. Péron et al. (2013). Neurosci Biobehav Rev, 37(3), 358–373.No conflict of interest.

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MICROELECTRODE-GUIDED UNILATERAL FOREL H1CAMPOTOMY FOR PARKINSON’S DISEASE: SHORT-TERM RESULTS OF NINE PATIENTSM.S. Rocha1, N.E. Marinho1,*, R.G. Kuark1, A.T. Neves1, P.R. Terzian2, O.J. Moraes2, F.L. Godinho2

1Neurology, Hospital Santa Marcelina, Sao Paulo, Brazil, 2Neurosurgery, Hospital Santa Marcelina, Sao Paulo, Brazil

Objectives: To describe the motor outcome in Parkinson’s Disease patients in the short-term surgical follow-up of microelectrode-guided unilateral Forel H1 campotomy in nine PD patients.Methods: We studied nine consecutive PD patients who underwent unilat-eral Forel H1 campotomy. Patients were assessed preoperatively and post-operatively (6 months). At inclusion, all patients had sustained response to levodopa with motor complications. Exclusion criteria were: unstable drug regimen, severe cognitive impairment, ongoing psychiatric symptoms, prior brain surgery, and unsatisfactory general condition. Unilateral campotomy was performed using: anatomical targeting based on stereotactic tomography and non-stereotactic MRI, single-unit microelectrode recordings, and intraop-erative macrostimulation.Results: Mean age and disease duration were 55.9 years and 8.5 years, respectively. Mean total UPDRS was 82.9. Mean Hoehn and Yahr was 3.1. Mean score on dyskinesia scale was 76.6. Mean baseline PDQ-39 was 60.9. Most motor features improved after surgery: rigidity and tremor showed remarkable improvement (64.3%, p < 0.001), followed by bradykinesia (57%, p < 0.001), and gait (54.5%, p < 0.001). UPDRS part III declined 63.5% (p = 0,013), and total score on UPDRS showed a reduction of 62.8% (p = 0.01). A reduction of 72.1% on dyskinesia scale score was noted (p = 0.012). Quality of life, measured by PDQ-39 scale, showed improvement of 79.8% (p < 00001). We observed significant improvement on ipsilateral bradykinesia (p = 0.005) and rigidity (p = 0.025). No effect upon freezing was observed.Conclusions: Short-term evaluation showed a considerable improvement on all motor outcomes after unilateral Forel H1 campotomy, and striking improve-ment on quality of life after surgery.Reference1. Aufenberg, C. et al. Thalamus and Related Systems 3(02):121–132,2005.No conflict of interest.

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DISTANCE BETWEEN ANODE AND CATHODE CONTACTS ALTERS PULSE GENERATOR LONGEVITY IN PATIENTS WITH DEEP BRAIN STIMULATIONL. Almeida1,*, B. Ditty2, P.V. Rawal1, L.B. Smelser1, H. Huang1, W. Fisher2, B.L. Guthrie2, H.C. Walker1

1Department of Neurology, University of Alabama at Birmingham, Birmingham, USA, 2Department of Surgery Division of Neurosurgery, University of Alabama at Birmingham, Birmingham, USA

Objectives: To evaluate whether the distance between the anode and cathode contacts used in the deep brain stimulation (DBS) electrode array alters bat-tery longevity in patients with movement disorders.Methods: We assembled a database of stimulation parameters in patients who underwent subthalamic and thalamic DBS for essential tremor and Parkinson’s disease. Based on the distance between anode and cathode

electrode contacts used for routine care, the batteries were subdivided into four categories: bipolar mode with contacts separated by 3, 6, and 9 mm and monopolar mode. We estimated IPG longevity across these groups using Kaplan Meier survival analyses, with statistical significance defined at p = 0.05.Results: In a sample of 267 patients, median battery longevity with bipolar DBS were 44.1 [31.1,62.6], 58.1 [43.4,60.9], and 86.6 [70.8,104.6] months for anode and cathode contacts separated by 3, 6, and 9 mm, respectively (median and 95% confidence interval, p = 0.02, log rank test). Regardless of the distance between anode and cathode contacts, bipolar stimulation was associated with greater pulse generator longevity than monopolar stimulation (59.0 [50.2,71.5] versus 45.1 [35.3,48.9] months, p < 0.001, log rank test).Conclusions: Bipolar DBS with more widely spaced anode and cathode contacts was associated with greater battery longevity than both bipolar mode with narrowly spaced adjacent contacts and monopolar stimulation. Optimization of DBS programming strategies and electrode design could be applied to decrease morbidity and expense associated with surgical replace-ment of expired pulse generator batteries.No conflict of interest.

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PATIENT SELECTION FOR DBS IN PARKINSON’S DISEASE: CLINICAL EXPERIENCE WITH 33 CONSECUTIVE PATIENTSD. Aygun1,*, E. Kocabiçak2, O. Yildiz1, M.K. Onar1, O. Boke3

1Neurology, Ondokuz Mayis University Medical Faculty, Samsun, Turkey, 2Neurosurgery, Ondokuz Mayis University Medical Faculty, Samsun, Turkey, 3Psychiatry, Ondokuz Mayis University Medical Faculty, Samsun, Turkey

Objectives: In advanced Parkinson’s disease (PD), deep brain stimulation (DBS) may be an alternative option for the treatment of motor symptoms. The success of DBS is mainly dependent on patient selection. The purpose of this paper is to discuss the preoperative data of our patients evaluated for DBS.Methods: From August 2011 to August 2013, 33 consecutive patients with advanced PD [disease duration (DD) of more than 5 years] evaluated for DBS were recruited. Their clinical motor symptoms were assessed by UPDRS III in both OFF and ON medication states. Thus, levodopa response (LR) rates of the patients were determined. Both Core Assessment Program for Surgical Interventional Therapies in PD (CAPSIT-PD) and Florida Surgical Questionnaire for PD were used to select patient for DBS.Results: STN DBS was applied bilaterally in 19 of 33 patients with PD (17 men and 16 women). Nine patients (27,2 %) were excluded for one item of the CAPSIT-PD. Mean age was 54,93 ± 9,2 years. Mean disease duration was 12,0 ± 5,8 years (5,5–30). LR rates ranged between 0,9 % and 81,8 % with an average of 46,92 ± 20,7 percent. There was no significant correlation with preoperative LR of DD and age. The effect of DBS in all patients after surgery was over 50%.Conclusions: Approximately one fourth of the patients with PD were not eli-gible for DBS. In all of the patients eligible for DBS, this therapy (DBS) was effective. Neither age nor DD had an effect on the response to LR.Reference1. Morgante L, et al. Parkinsonism Relat Disord 2007; 13:528–531.No conflict of interest.

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THE P300 EVOKED RELATED POTENTIALS AS A SELECTION TOOL FOR SUITABLE CANDIDATES OF DBS SURGERY IN PARKINSON’S DISEASEM. Balaz1,*, I. Rektor1, A. Hluckova1

1Neurology, St Anne University Hospital in Brno, Brno, Czech Republic

Objectives: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective long-term treatment for motor symptoms in advanced Parkinson’s disease (PD). However, it is evident that at least in some patients the change in cognitive functions after STN-DBS may have a clinical impor-tance. Thorough neuropsychological examination is an established part of preoperative assessment of candidates for DBS surgery. We studied whether scalp P300 wave can be used as an additional tool that would improve the selection process.Methods: 32 patients with Parkinson’s disease who had been implanted with DBS STN were included in the pilot study. They were examined by neu-ropsychologist before the DBS and year after the DBS. The latencies and amplitudes of P300 wave measured before the operation and again 1 year after the DBS STN.Results: Latencies of preoperative P300 inversely correlated with neuropsy-chological status 1 year after the operation. We have observed that patients with longer latencies of preoperative P300 tended to present with more psychiatric side effects and worse neuropsychological performance 1 year after the DBS.Conclusions: Scalp P300 can be proposed as a tool for selection of suitable candidates for the DBS STN surgery in PD for further study.No conflict of interest.



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THE “CLOVEN” WOMAN – SOMATOTOPIC ORGANIZATION OF STN AND DBS IMPLICATIONS IN PARKINSON’S DISEASED. Alimonti1,*, M. Poloni11Neurosciences – Neurology Unit, Papa Giovanni XXIII Hospital, Bergamo, Italy

Objectives: To describe an unusual side effect of subthalamic nucleus deep brain stimulation (STN-DBS).Methods: We report in the clinical observations made in a 72-year-old female patient affected by Parkinson’s disease who underwent bilateral STN-DBS and had ‘split’ in two halves by the effects of stimulation.Results: After surgery, the most effective contacts were at the beneath dorsal-most level of STN in both hemispheres. However, soon after observing that the motor response to stimulation was optimal in the lower limbs, we noticed hyperkinetic movements in the upper limbs, head and face. Variation of depth and parameters of stimulation were ineffective. Finally, a bipolar and asym-metric modality resulted to be optimal in balancing the effects on the upper and the lower halves of the body, though a clear difference between the lower limbs and the upper limbs / face persisted.Conclusions: The effects of STN-DBS in this patient seemed not to respect the known somatotopic organization of the STN, which assumes the presence of a representation of upper and lower limbs in the dorsolateral part of the nucleus – with lower limbs located centromedially and upper limbs located more laterally, with the addition of a representation of head and face move-ments more ventrally.References1. MC Rodriguez-Oroz, et al. Brain (2001), 124,1777–1790.2. PV Theodosopoulos, et al. Movement Disorders (2003), 18(7), 791–798.No conflict of interest.

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DBS STN FOR ADVANCED PARKINSON’S DISEASE: IMPACT OF THE INTRAOPERATIVE MICROELECTRODE RECORDINGA. Gamaleya1,*, A. Tomskiy1, E. Bril2, A. Dekopov1, E. Salova1, N. Fedorova2, V. Shabalov1

1Functional Neurosurgery Group, Burdenko Neurosurgical Institute RAMS, Moscow, Russia, 2Department of Neurology, Russian Medical Academy of Postgraduate Education, Moscow, Russia

Objectives: Precise placement of electrodes into sensorimotor part of STN is crucial for successful DBS in Parkinson’s disease. Microelectrode recording (MER) of neuronal activity is widely used to improve targeting of basal nuclei during DBS-surgery. We aimed to assess the influence of MER on intraopera-tive tactics and outcome in DBS STN for advanced PD.Methods: Since 2008, 86 PD patients were operated for DBS STN: 38 using intraoperative MER and 48 without (100 and 76 electrodes implanted, respectively). Disease duration was 12.2 ± 4.3 years, age at surgery – 54.5 ± 9.1 years. Surgical strategy and short-term clinical outcome were investigated.Results: In patients with MER, 1 to 5 microelectrodes were used per side (2.4 ± 0.8). Final electrode placing corresponded to the image-defined track only in 63.2%. In 25%, the medial trajectory was chosen, in 7.9% – the lateral. Placement depth was corrected in 75% of implantations. Postoperatively, no electrode replacement was needed and one case of stimulation-related dysarthria was observed. Symptomatic intracranial hemorrhage occurred in one case. In patients without MER, the central trajectory was used in 95%, depth adjustments – in 9%. In 7 patients, cor-rection of electrode position was required in early or long-term follow-up. Stimulation-induced dysarthria occurred in 8 patients. In analysis of motor improvement after 6 months of DBS STN, no significant difference was found between two groups.Conclusions: MER seems to optimize the accuracy of electrode placement and decrease side effects in DBS STN. Considering higher surgical risks and expenses, overall impact of MER on clinical outcome in PD still remains unclear.No conflict of interest.

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STEERING DEEP BRAIN STIMULATION: AN EXPLORATORY STUDY WITH A NEW 32-CONTACT LEADM.F. Contarino1,*, L.J. Bour1, R.M. de Bie1, P. van den Munckhof2, P.R. Schuurman2

1Neurology, Academic Medical Center, Amsterdam, Netherlands, 2Neurosurgery, Academic Medical Center, Amsterdam, Netherlands

Objectives: 1) To confirm that stimulation through a new 32-contact lead is safe and can produce equivalent effects as stimulation through currently available DBS leads with 4 large annular contacts. 2) To establish whether stimulation with directional steering can modulate the thresholds of stimula-tion-induced clinical effects and side effects, thus providing the option to opti-mize the therapeutic window.

Methods: Eight patients with Parkinson’s disease were included in the study. The new 32-contact lead was temporarily inserted during surgery. Double blind intraoperative test was performed to evaluate the threshold for benefit and the threshold for side effects in a “ring mode” and in 4 different rand-omized steering directions with the 32-contact electrode (Sapiens Steering Brain Stimulation B.V., Eindhoven, The Netherlands), and in monopolar mode with the 3389 electrode (Medtronic, Minneapolis, MN).Results: There were no adverse events related to the experimental device. Sixteen out of 18 observed effects (88.9%) occurred at comparable threshold between the 32-contact lead in ring mode and the 3389 lead. In 13 out of 15 side effects (87%) thresholds obtained with ring mode stimulation were differ-ent (≥1 mA) than those obtained in at least one steering direction.Conclusions: Stimulation through the new 32-contact lead is safe and able to reproduce the clinical effects of the existing DBS leads. In addition it provides effective directional steering of the stimulation field, which can potentially improve the therapeutic window.

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IMPROVED THERAPEUTIC WINDOW WITH DIRECTIONAL DBS ELECTRODES COMPARED TO OMNIDIRECTIONAL DBSC. Pollo1,*, M. Oertel1, L. Stieglitz1, A. Kaelin-Lang2, M. Schüpbach2

1Neurosurgery, Inselspital Universitätsspital Bern, Bern, Switzerland, 2Neurology, Inselspital Universitätsspital Bern, Bern, Switzerland

Objectives: DBS is currently carried in all directions around the lead. Directional leads may improve focalization of stimulation in the brain but their clinical effect has not yet been investigated in human. The objective of this study is to compare the Therapeutic Window (TW) using directionalDBS and omnidirectional DBSMethods: Eight patients with PD underwent STN DBS and two patients with ET underwent Vim DBS. Directional stimulation was assessed intra opera-tively using a novel lead design (direct STIMTM, Aleva Neurotherapeutics). It features two rings of three independent electrodes. TW is defined as the current threshold for side effects minus threshold for a significant therapeutic effect. TW was measured in each direction and best TWdir was compared to omnidirectional stimulation (TWomni).Results: A best TWdir was observed in 9/10 patients. The mean TWdir was 1.88 mA, compared to 1.2 mA for TWomni (p = 0.05). The mean current for significant positive effect was 0.66 mA compared with 1.14 mA in omnidirec-tional DBS (p = 0.006). In the STN as well as Vim, motor side effects (dysar-thria, muscle contractions) were observed in the direction of internal capsule, and sensitive side effects (sustained paresthesias) were seen in the direction of the Lemniscus medialis/VPL.Conclusions: This intraoperative study showed that TW is increased com-pared to omnidirectional TW and benefits of directional DBS were observed in the STN and Vim and suggest an increased effectiveness of Directional DBS Furthermore, in each target, the observed side effects were consistent with the spatial location of the surrounding anatomical structures. Further studies are needed to confirm these results in chronic implanted patients.

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LONG TERM FOLLOW-UP OF PARKINSON’S DISEASE TREATED WITH MRI-GUIDED IMPLANTED GPI-DBSA. Zacharia1,*, I. Sastre-Bataller1, J. Candelario1, Z. Kosutzka1, I. Aviles-Olmos1, Z. Kefalopoulou1, T. Foltynie1, L. Zrinzo1, M. Jahanshahi1, M. Hariz1, P. Limousin1

1Unit of Functional Neurosurgery, UCL Institute of Neurology, London, United Kingdom

Objectives: Deep Brain Stimulation in the Globus Pallidus internus (GPi) is considered as an effective treatment for dyskinesias and motor fluctuations of advanced Parkinson’s disease. Nevertheless long term data are still limited. We present results of GPi-DBS up to 7 years after surgery.Methods: 16 patients who were not deemed suitable for STN-DBS (either because of advanced age, concerns with cognitive function, or considerable brain atrophy on imaging) received MRI-guided and MRI-verified GPi-DBS. Patients with at least two follow-ups 1 year apart were included. The data were obtained from the functional neurosurgery’s database as well as from the medical notes. Assessments tools are Unified Parkinson Disease Rating Scale (UPDRS), levodopa equivalent doses (LED), dyskinesia scores and Parkinson Disease questionnaire PDQ-39 preoperatively and up to 7 years (3 patients).Results: The on-drug scores of motor UPDRS (part III) was unchanged after surgery and did not deteriorate over time. The LED were also stable over time. The improvements in dyskinesias and the PDQ39 were maintained over time. There was, however, some inter-patients variability.Conclusions: GPi-DBS resulted in a stable evolution of the clinical state and the quality of life up to 7 years after surgery. Patients with advanced PD who do not fulfill the strict selection criteria for STN-DBS can still benefit from GPi-DBSNo conflict of interest.



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LONG-TERM OUTCOME ON NON-MOTOR SYMPTOMS OF PARKINSON’S DISEASE AFTER SUBTHALAMIC NUCLEUS STIMULATIONI. Sastre-Bataller1,*, A. Zacharia1, I. Aviles-Olmos1, T. Foltynie1, L. Zrinzo1, M. Hariz1, P. Limousin1

1Unit of Functional Neurosurgery, Sobell Department of Motor Neurosciences, University College London, London, United Kingdom

Objectives: Non-motor symptoms (NMS) of Parkinson’s Disease (PD) have a deep impact in the quality of life of patients. So far, the effect of subthalamic nucleus stimulation (STN-DBS) on NMS is not well elucidated. We aim to investigate the long-term effect of STN-DBS on NMS.Methods: Seventeen patients with a median of 11 years of disease duration were implanted with STN-DBS with MRI-guided technique. Pre-surgical clini-cal data were obtained from the functional neurosurgery’s database as well as from the medical notes. UPDRS, NMS questionnaire, SCOPA autonomic, SCOPA sleep and PDQ39 scores were collected. We compared preoperative scores to post operative scores after 3 years.Results: NMS questionnaire, SCOPA autonomic and SCOPA sleep scores were not significantly changed more than 3 years after surgery. Nocturia, insomnia and sexual dysfunction were the most frequent NMS referred pre and post-surgery. Overall, quality of sleep, pains and excess of saliva were referred to improve after surgery whilst falls and cognitive functioning were referred to worse. Motor UPDRS and PDQ39 subscores, particularly activities of daily life, stigma and discomfort, showed statistically significant improvement.Conclusions: Overall NMS scores are stable after 3 years of STN-DBS. Sleep disturbances, pains and excess of saliva show a tendency towards improvement. Motor and quality of life subscores durably improved.No conflict of interest.

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PREDICTIVE FACTORS FOR THE 10-YEARS’ OUTCOME WITH DBS-STN IN PARKINSON’S DISEASEN. Meier1,*, G. Serra2, V. Czernecki2, E. Bardinet2, N. Chastan2, S. Navarro3, M. Schüpbach1, D. Dormont2, C. Karachi2, L. Mallet2, M. Vidailhet2, B. Pidoux4, P. Cornu3, J. Yelnik2, Y. Agid2, M.L. Welter2

1Department of Neurology, Inselspital University Hospital Bern, Bern, Switzerland, 2Centre de Recherche de l’Institut du Cerveau et de la Moelle épin-ière (CRICM), Université Pierre et Marie Curie-Paris 6, Paris, France, 3Service de Neurochirurgie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France, 4Service de Neurologie/Neurophysiologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France

Objectives: Deep brain stimulation of the subthalamic nucleus (DBS-STN) is an efficient treatment for advanced forms of Parkinson’s disease. The long-term efficacy is heterogeneously reported, and some patients showed marked degradation, with dementia and/or gait and balance disorders. The objective was to identify predictors for long-term efficacy of DBS-STN.Methods: Motor and cognitive evaluation before and 1, 2, 5 and 10 years after DBS-STN in 84 consecutive PD patients (mean age: 57 ± 8 years, disease duration: 14 ± 5 years).Results: Twenty-four patients died during the follow-up period, 11 could not be evaluated (loss to follow-up n = 7, electrode removal n = 2, very severe dis-ease n = 2), and 49 completed the 10-years’ assessment. Ten years after sur-gery, the motor disability was reduced by 30% with DBS-STN alone and 45% with DBS-STN and levodopa treatment. The Mattis Dementia Rating Scale score significantly decreased (138 ± 8 vs. 127 ± 15). Higher age and disease duration at time of surgery were predictive of cognitive decline and severe axial signs with DBS-STN. The long-term efficacy of DBS-STN on motor dis-ability and activities of daily living was related to the preoperative levodopa treatment efficacy, with the main predictive factor being the residual preop-erative axial score. Cognition depended upon both the preoperative cognitive status and residual axial score.Conclusions: Ten years after surgery, the efficacy of DBS-STN was still dependent upon the preoperative clinical features, in particular cognition and axial signs. Some patients showed a very long survival suggesting decreased mortality with DBS-STN.No conflict of interest.

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BIMANUAL COORDINATION IN PARKINSON’S DISEASE: IMPACT OF DOPAMINERGIC MEDICATION AND DEEP BRAIN STIMULATIONJ.F. Daneault1,*, A.F. Sadikot1, B. Carignan2, M. Lauzé3, S. Sens3, C. Duval41Neurology and Neurosurgery, Montreal Neurological Hospital and Institute McGill University, Montreal, Canada, 2Sciences Biologiques, Université du Québec à Montréal, Montreal, Canada, 3Kinanthropologie, Université du Québec à Montréal, Montreal, Canada, 4Movement Disorders Laboratory, Centre de Recherche de l’Institut Universitaire de Gériatrie de Montréal, Montreal, Canada

Objectives: Parkinson’s disease (PD) patients develop severe motor and non-motor symptoms associated with dysfunctions of sub-cortical and cortical structures. These neuro-anatomical dysfunctions also lead to impaired motor performance such as during bimanual tasks. We characterized deficits in per-formance during bimanual diadochokinesis and assess the impact of medica-tion and deep brain stimulation (DBS) on bimanual coordination.Methods: (i) We examined bimanual synchronization during diadochokinesis and assessed the impact of medication and DBS. (ii) We compared spatial and temporal assimilation during bimanual diadochokinesis between PD and Huntington’s patients, and controls. (iii) We examined the effect of medication and DBS on spatial and temporal assimilation.Results: (i) PD patients did not exhibit deficits in bimanual synchroniza-tion and, medication and DBS did not modify this synchronization. (ii) PD and Huntington’s patients did not display deficits in temporal assimilation. However, they had significant deficits in spatial assimilation. (iii) Medication and DBS did not alter the temporal assimilation seen in PD patients, and did not improve the deficits in spatial assimilation.Conclusions: Our results demonstrate that the basal ganglia and corti-cal structures are not playing a significant role in the temporal aspects of bimanual synchronization in PD, suggesting that is mediated possibly by the cerebellum. Our results also demonstrate that the basal ganglia are not sig-nificantly involved in spatial aspect of bimanual coordination suggesting the involvement of cortical motor areas or the corpus callosum. These results also suggest that current treatments do not alter or improve the characteristics of bimanual coordination in PD.No conflict of interest.

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INFLUENCE OF DEEP BRAIN STIMULATION ON VERBAL LEARNING IN PARKINSON’S DISEASE: A 1 YEAR FOLLOW-UP STURDYR. Tsuboi1,*, K. Okita2, M. Miyata3, S. Fujii1, Y. Shimizu1, I. Wada1, N. Matsukawa2, Y. Oka4, A. Umemura5, M. Mimura6

1Department of Rehabilitation, Nagoya City University Hospital, Nagoya, Japan, 2Department of Neurology, Nagoya City University School of Medicine, Nagoya, Japan, 3Faculty of Health Sciences, Nihon Fukushi University, Handa, Japan, 4Department of Neurosurgery, Nagoya City University School of Medicine, Nagoya, Japan, 5Department of Neurosurgery, Juntendo University, Tokyo, Japan, 6Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan

Objectives: The subthalamic nucleus deep brain stimulation (STN-DBS) is known to potentially impair various cognitive activities. Effect of STN-DBS on verbal learning was investigated Parkinson’s disease.Methods: The participants were 31 patients with Parkinson’s disease who received bilateral STN-DBS. Neuropsychological assessments included Mini-mental state examination (MMSE), Rey Auditory Verbal Learning Test (RAVLT), Modified Stroop Test and Digit span. Only the patients with MMSE scores of 24 or above were included. The performance on these tests was compared before and 1 year after STN-DBS.Results: The MMSE, digit span and delayed recall of RAVLT did not show significant change. However, the serial learning curve of RAVLT demonstrated some deterioration before and after 1 year after STN-DBS (p < 0.01). Executive functions, as indexed by Modified Stroop Test, also deteriorated after 1 year (p < 0.05). Changes in cognitive function tests did not relate to L-dopa dosage.Conclusions: The results suggest that STN-DBS did not impair long-term learning capacity per se, but did impair mnemonic activities presumably sec-ondary to attention/executive impairment caused by STN-DBS.Reference1. Neural correlates of STN-DBS induced cognitive variability in Parkinson dis-

ease. Campbell MC, Karimi M, Weaver PM, Wu J, Perantie DC, Golchin NA, Tabbal SD, Perlmutter JS, Hershey T. Neuropsychologia. 2008 Nov; 46(13).

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“I CAN’T WHISTLE ANYMORE” – FACIAL INVOLVEMENT BY STN-DBS IN PARKINSON’S DISEASED. Alimonti1,*, M. Poloni11Neurosciences – Neurology Unit, Papa Giovanni XXIII Hospital, Bergamo, Italy

Objectives: To describe an unusual side effect of subthalamic nucleus deep brain stimulation (STN-DBS) and formulating an anatomical consideration on the somatotopic organization of STN.Methods: Reporting the clinical observation of STN-DBS modulation in a 67-year-old male patient affected by Parkinson’s Disease who experienced an odd and unreported side effect.Results: The patient obtained satisfying motor control with activation of the caudal contacts with the exception of paresthesia and increased movements in the orofacial region, which were interpreted as dyskinesia. The activation of the adjacent, more cranial, contacts reduced these hyperkinetic movements, though his familiars noticed a ‘different’ facial expression, and the patient reported a sudden inability to whistle. The activation of further cranial contacts



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attenuated these side effects, yet not completely. A bipolar modality of stimula-tion was tried which did not changed the side effect, but worsened the efficacy on motor symptoms.Conclusions: The sensorimotor region of STN is located in the dorsolateral part of the nucleus. Neurons corresponding to the head and face are distrib-uted in its ventral part. This deep localization of facial-corresponding neurons may explain the loss of fine-movement control of oro-buccal muscles in the present case.References1. MC Rodriguez-Oroz, et al. Brain (2001), 124,1777–1790.2. PV Theodosopoulos, et al. Movement Disorders (2003), 18(7), 791–798.No conflict of interest.

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VERTICAL SUPRANUCLEAR GAZE PALSY INDUCED BY DEEP BRAIN STIMULATIONV. Fleury1,*, S. Spielberger2, E. Wolf2, J. Yelnik3, V. Fraix4, J.F. Lebas5, A.L. Benabid6, W. Eisner7, P. Krack4, W. Poewe2, P. Pollak1

1Neurology, Geneva University Hospital, Geneva, Switzerland, 2Neurology, Medical University Innsbruck, Innsbruck, Austria, 3Neurology, Centre de Recherche de l’Institut du cerveau et de la Moelle épinière, Paris, France, 4Neurology, Grenoble University Hospital, Grenoble, France, 5Neuroradiology, Grenoble University Hospital, Grenoble, France, 6Neurosurgery, Grenoble University Hospital, Grenoble, France, 7Neurosurgery, Medical University Innsbruck, Innsbruck, Austria

Objectives: To describe reversible vertical supranuclear gaze palsy (SGP) resulting from deep brain stimulation (DBS).Methods: We studied patients who developed vertical SGP induced by DBS during a postoperative evaluation of quadripolar electrodes with DBS param-eters of 60 ms pulse width and 130 Hz frequency. An anatomical localiza-tion of the DBS contacts was performed, using a 3D atlas-MRI coregistration method.Results: Two patients experienced vertical SGP. Patient 1 was treated with subthalamic nucleus (STN) DBS for Parkinson’s disease and patient 2 with ventral intermediate nucleus of the thalamus (VIM) DBS for essential tremor. When the second most proximal contact of the left STN-DBS was turned on, patient 1 experienced vertical SGP from 2.3 V. Patient 2 experienced vertical SGP from 3.0 V, on the left most distal contact, or on the right most distal contact. In both patients, the SGP resolved when the neurostimulation was turned off. The anatomical localization of the electrodes showed that the con-tact inducing SGP was situated in the zona incerta for patient 1, medial and posterior to the STN, and for patient 2, in the zona incerta for the right contact and in the junction between the fields of Forel H and H1 for the left contact, anterior to the Vim.Conclusions: Vertical SGP developed in these patients due to incorrect elec-trode positioning. It was probably induced by DBS diffusion to the rostral inter-stitial nucleus of the medial longitudinal fasciculus and the interstitial nucleus of Cajal, two critical structures involved in the control of vertical gaze.No conflict of interest.

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SUBACUTE FRONTAL SYNDROME AFTER SUBTHALAMIC NUCLEUS DEEP BRAIN STIMULATION – A CASE REPORTM. Gregoric Kramberger1,*, N. Zupancic Kriznar1, R. Rajnar1, L. Ocepek1, K. Boetzel2, J.H. Mehrkens3, B. Meglic1, M. Trost1

1Department of Neurology, University Medical Centre, Ljubljana, Slovenia, 2Department of Neurology, Ludwig-Maximilians-Universität München, Muenchen, Germany, 3Department of Neurosurgery, Ludwig-Maximilians-Universität München, Muenchen, Germany

Objectives: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is highly effective in relieving symptoms of Parkinson’s disease (PD). However several psychiatric side effects have been reported after chronic DBS.Methods: CASE DESCRIPTION: 67 years old male with 17 years history of PD was referred for DBS due to severe motor complications. He had no his-tory of psychiatric condition.Results: A postoperative computer tomography (CT) yielded the correct position of the electrodes in STN and excluded postoperative intracranial hemorrhage or edema. The stimulation was started on day 8 and on day 10 he became increasingly anxious, hypomanic, paranoid and agitated. Motor improvement was very good. The repeated CT, basic laboratory studies and lumbar puncture were all unremarkable. The stimulation was turned off for 24 h but he continued to decline and was deferred to a closed psychiatric ward, moderate remission was reached with quetiapine 150 mg bid in 7 days, later the effect faded away. Therefore switching from second highest to the uppermost active contact on the right STN electrode (in the STN motor area)

was done which resulted in moderate improvement of psychiatric and marked worsening of motor symptoms.Conclusions: This case describes very rare tempo of subacute post DBS syndrome in which despite the correct electrode position the symptoms of frontal dysfunction improved only partially. We suggest this is an effect of local tissue reaction to lead implantation and stimulation spreading to associative and limbic regions of STN.No conflict of interest.

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ACUTE MANIC PSYCHOSIS AS A LATE SUBTHALAMIC DEEP BRAIN STIMULATION SYNDROMEA. Corell1,*, E. Kurca1, M. Grofik1, E. Kantorova1, M. Galanda2

1Neurology Clinic, Jessenius Medical Faculty, Martin, Slovakia, 2Department of Neurosurgery, Rosevelt Hospital, Banska Bystrica, Slovakia

Objectives: Subthalamic nucleus deep brain stimulation (STN-DBS) for Parkinson’s disease (PD) improves all symptoms of PD and reduces the need of dopaminergic medication. However, early postoperative complications can include psychiatric side effects. Neurologist and psychiatrists are in need of treatment strategies.Methods: Case study.Results: 46-year-old woman with early onset of PD was indicated to bilateral STN-DBS when pharmacological treatment became ineffective. The course of operation was without complications and first days after intervention she was in good condition. The patient developed acute severe manic psycho-ses 11 days later, before activation of stimulation (overactivity, aggression, affective liability, and hallucinations). No new lesion impairment was found in performed CT scan. Patient was requiring recurrent treatment with first-generation and atypical neuroleptics for 3 weeks.Conclusions: The symptoms of Parkinson’s disease were only mildly influenced. In contrary to reported cases, the manic episode has not yet been repeated after the stimulation was activated. The patient’s case showed rare post-STN DBS syndrome in which local reaction to implanted electrodes provoked manic psy-chosis even without electrical stimulation. The treatment of this complication also appeared to have minimal impact on the symptoms of PD. This experience can have implications for management of post-STN-DBS PD patients.No conflict of interest.

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TOTAL HIP ARTHROPLASTY IN PATIENTS UNDER A DEEP BRAIN STIMULATION THERAPY FOR PARKINSON’S DISEASES. Murakami1,*, I. Wada2, H. Iguchi3, M. Kobayashi4, R. Tsuboi5, T. Otsuka4

1Department of Orthopaedic Surgery and Rehabilitation Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, 2Department of Orthopaedic Surgery and Rehabilitaion Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, 3Department of Arthroplastic Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, 4Department of Orthopaedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, 5Department of Rehabilitation Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

Objectives: Total hip arthroplasty (THA) in patients under Parkinson’s disease (PD) has been avoided because of the risk of loosening and dislocation. Deep brain stimulation (DBS) introduced to control PD symptoms don’t respond to drugs, and those patients could be candidates for THA. The purpose of this paper is to review and analyze our experiences of THA in patients under a DBS treatment.Methods: We reviewed hospital record of two female PD patients who under-went THA after a subthalamic nucleus-DBS. Information was obtained from patients’ PD status, body morphologic status, radiologic evaluation and histo-ries of postoperative dislocation of the hip.Results: THA was performed on three hips out of two patients because of osteoarthritis developed after DBS. DBS was successful in one patient, whereas walking disability of another patient was not improved by DBS, pri-mary THA and three revision surgeries following to recurrent dislocations. One patient had a history of developmental dislocation of the hip and underwent THA of both hips. Her right hip dislocated two times during 3.5-year-follow up while no dislocation was reported in left side.Conclusions: Even PD symptoms was controlled well by DBS, weight gain after DBS contributed to the progression of hip osteoarthritis and cognitive problems (MMSE 21/30) prevented to understand contraindicate posture to dislocation during her rehabilitation. After unsuccessful DBS, repeated minor falling may relate acute progression of osteoarthritis and following recurrent dislocation.No conflict of interest.



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VERBAL FLUENCY PERFORMANCE AFTER DEEP BRAIN STIMULATION: EFFECTS OF AGEN. Schwarz1,*, U. Gschwandtner1, R. Zimmermann1, N. Benz1, M. Ehrensperger2, E. Taub3, H. Bousleiman4, P. Fuhr1

1Department of Neurology, Hospital of the University of Basel, Basel, Switzerland, 2Memory Clinic, Felix Platter Spital, Basel, Switzerland, 3Neurosurgery, Hospital of the University of Basel, Basel, Switzerland, 4Swiss Tropical and Public Health Institute, Hospital of the University of Basel, Basel, Switzerland

Objectives: Literature indicates impairment of verbal fluency after deep brain stimulation (DBS) surgery in Parkinson’s disease (PD) patients while global cognition remains stable. We investigated the effect of age on changes in verbal fluency in relation to DBS.Methods: The study included 21 patients who underwent DBS and 19 PD control patients. The groups were matched for age, gender and education and evaluated with semantic and phonemic verbal fluency tasks at baseline and after the operation or at follow-up (FU). A time corrected change score was calculated, resulting in a verbal fluency change per month. A between-time-points and between groups analysis was carried out.Results: No significant changes were seen between the two groups. A within-group comparison highlighted significant deterioration over time in semantic fluency (T-test, p <.003) in the DBS group. Linear regression revealed changes in semantic fluency performance were independent of age, gender, education, and disease duration but not group.Conclusions: A significant change in semantic performance over time was only found within the DBS group. Age appears to have no modulating influ-ence on verbal fluency outcome. Our sample consisted of elderly PD patients, (mean age 67, control group 70) an age group so far not assessed in the literature. Even so, no significant change in verbal fluency in relation to age was found. We conclude that impaired verbal fluency is not related to age but rather to the DBS intervention.No conflict of interest.

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THE EFFECTS OF BILATERAL SUBTHALAMIC NUCLEUS STIMULATION ON COGNITIVE AND NEUROPSYCHIATRIC FUNCTIONS IN PARKINSON’S DISEASE: A CASE-CONTROL STUDYR. Mahdavi1,*, S. Malakouti1, G. Shahidi2, M. Parvaresh-Rizi2, M.I.N.A. Asadi11Psychiatry, Tehran University of Medical Science, Tehran, Iran, 2Neurology, Tehran University of Medical Science, Tehran, Iran

Objectives: Parkinson’s disease is one of the most disabling neurological diseases; however, much progress has been made in the treatment of drug resistant patients through electrode implantation and stimulation of the sub-thalamic nucleus (STN). This new neurosurgical method may lead to some neuropsychological side effects in patients. The main aim of this study was to evaluate the neuropsychiatric effects of this treatment.Methods: This case-control study was designed to compare two groups of patients with Parkinson’s disease. Thirty patients who underwent electrode implantation and deep brain stimulation were compared with 60 patients treated with antipar-kinson drugs. These two groups were matched for age, sex, duration and sever-ity of Parkinson’s disease. Measurements: The UPDRS was used to assess the severity of Parkinson’s disease. The Beck Depression Inventory questionnaire and the Hamilton Anxiety Rating Scale were used to evaluate depression and anxiety as a consequence of DBS. The Mini Mental Status Examination and Clock Drawing Test (CDT) were used to evaluate the cognitive and executive function.Results: Thirty months after STN stimulation, a lower level of anxiety and depres-sion were seen in the DBS patients compared with drug treated subjects, but the differences were not significant. However, cognitive status deteriorated to a greater extent in study subjects compared to the control group. The MMSE results were not significantly different, but the differences in CDT scores were significant.Conclusions: Patients who have undergone DBS surgery must be followed up for neuropsychiatric symptoms, particularly for subcortical cognitive dete-rioration in the long term.Reference1. The functional role of the subthalamic nucleus in cognitive and limbic circuits.No conflict of interest.



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Section 3 – Related Disorders

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INFECTIOUS MOVEMENT DISORDERS IN CHILDHOODA. Nasri1, H. Benrhouma1,*, I. Kraoua1, H. Klaa1, A. Rouissi1, I. Turki11Child and Adolescent Department of Neurology, Institute Mongi Ben Hmida of Neurology, Tunis, Tunisia

Objectives: To describe clinical, paraclinical and therapeutic features in chil-dren with infectious movement disorders (IMD).Methods: We conducted a retrospective study over a 9-year period including all patients diagnosed with IMD. Clinical characteristics, etiologies and man-agement were analyzed.Results: 16 patients were included (sex-ratio: 0.6, mean age: 8.5 years, mean age of onset: 4.9 years, mean delay between infection and onset of IMD: 32.2 days). Main features of IMD were acute onset (50%) and generali-zation (75%). Main movement disorders observed were: chorea (43.7%), dys-tonia (18.7%), myoclonus (18.7%) and Parkinsonism (18.7%). Responsible agents were identified in half of cases (streptococcus 50%, herpes virus sim-plex, meningococcal and plasmodium falciparum). Brain MRI performed in all patients was abnormal in 43.7%, showing basal ganglia abnormalities in 71.4%. Main treatments were acyclovir (43.7%), antibiotics (31.2%) and corti-costeroids (18.7%) with improvement in 80% of patients.Conclusions: Few studies reported IMD in childhood. It should be evoked in every child with acute movement disorder with fever. Brain MRI and serologi-cal testing should be performed in patients with acute and febrile movement disorders. The management of IMD is based on the use of symptomatic drugs and etiopathogenic treatment such as acyclovir or antibiotics.No conflict of interest

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COMPARISON OF NON-MOTOR SYMPTOMS IN PARKINSON’S DISEASE AND PARKINSON PLUS SYNDROMER. Verma1,*, K.S. Anand2, V. Verma2

1Department of Psychiatry, Lady Hardinge Medical College and Associated Hospitals, Delhi, India, 2Department of Neurology, PGIMER Dr RML Hospital, Delhi, India

Objectives: Our study aimed to investigate and compare the spectrum of non-motor symptoms (NMS) in Parkinson’s disease (PD) and Parkinson plus syndrome (PPS).Methods: Forty patients with PD and 40 with PPS were included consecutively from movement disorder clinic of a tertiary care centre over a period of 1 year. Severity of disease was assessed by Unified Parkinson’s Disease Rating Scale and Modified Hoehn & Yahr staging. Autonomic dysfunction, sleep and pain prob-lems were assessed by Scales for outcomes in Parkinson’s Disease- Autonomic, Parkinson’s disease sleep scale and pain analogue scale respectively.Results: The mean age of PD and PPS were 55.02 ± 13.56 and 62.65 ± 10.52 years respectively. Autonomic function impairment was observed in 87% and 95% of PD and PPS subjects. Common symptoms observed were constipation (62% vs 65%), sialorrhea (67% vs 60%), urinary urgency (65% vs 85%), nocturia (67% vs 75%), increased urinary frequency (40% vs 65%) and sleep disturbances (50% vs 55%). Pain was significantly more often complained of in PD patients. NMS in PD were significantly correlated with duration and severity of disease (p < 0.05) but not in PPS subjects.Conclusions: NMS are commonly present in patients with PD or PPS and are observed in more frequency with the increasing duration and severity of disease in subjects with PD but not in PPS.Reference1. Chaudhuri KR, Yates L, Martinez-Martin P. The non-motor symptom com-

plex of Parkinson’s disease: a comprehensive assessment is essential. Curr Neurol Neurosci Rep. 2005;5:275–283.


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FAMILIAL AGGREGATION OF SYNUCLEINOPATHIESS. Fujioka1,*, A.J. Strongosky1, K. Ogaki2, O.A. Ross2, Z.K. Wszolek1

1Neurology, Mayo Clinic, Jacksonville Florida, USA, 2Neuroscience, Mayo Clinic, Jacksonville Florida, USA

Objectives: Multiple system atrophy (MSA) was originally thought to be a spo-radic condition. However, several kindreds with affected family members diag-nosed as MSA and/or Parkinson’s disease (PD) have been reported. Recently the Multiple-System Atrophy Research Collaboration group identified COQ2 mutations in sporadic and familial MSA [1]. The objective of this study is to identify MSA families in our collection of more than 850 kindreds and to evalu-ate their clinical characteristics.

Methods: We reviewed the Mayo Clinic Florida Movement Disorders data-base for clinically diagnosed MSA cases.Results: We identified 74 MSA cases. After applying recent stringent MSA criteria [2], 11 cases were excluded from further analysis. In the remaining 63 cases, 12 index cases had positive family history of other family members suf-fering either from MSA (2), PD (10), and dementia (1). The MSA diagnosis was probable in 7 cases and possible in 4. All cases except one had parkinsonian variant of MSA (MSA-P). L-dopa responsiveness was poor in all probands except two. The mean age at onset was 65 years.Conclusions: In our cohort, approximately 17% of clinically probable or pos-sible MSA cases had positive family history thus implicating the genetic factors in the disease causation. We are conducting further genealogical and genetic studies including a molecular genetic study on these kindreds.ZKW, AJS, and OAR are supported by the NIH/NINDS P50NS072187.References1. Mutations in COQ2 in familial and sporadic multiple-system atrophy. N

Engl J Med. 2013;369:233–44. 2. Gilman S, et al. Second consensus statement on the diagnosis of multiple

system atrophy. Neurology. 2008;71:670–6.No conflict of interest

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MULTIPLE SYSTEM ATROPHY PRESENTING WITH INTERNAL TREMORE. Coon1,*, J.E. Ahlskog1, M.D. Suarez1, P.A. Low1, W. Singer1

1Neurology, Mayo Clinic, Rochester, USA

Objectives: The non-motor symptom of internal tremor is frequent in Parkinson’s disease (PD)1 but has not been reported in multiple system atro-phy (MSA). We sought to evaluate the frequency and clinical characteristics of this phenomenon in MSA.Methods: A retrospective review of the Mayo Clinic electronic medical records between 1998 to 2012 was performed. We identified MSA cases with the ini-tial complaint of internal tremor, and extracted clinical characteristics and response to medications.Results: A total of 731 patients with MSA were identified; 630 met consensus criteria for probable and 101 for possible MSA. Three of these patients (0.41%) presented with internal tremor. On exam, no visible tremor was apparent and surface electromyography in one patient confirmed absence of detectable tremor. All patients had probable MSA with Parkinsonism (MSA-P). Mean age at presentation was 64 years (range 56–75) and mean MSA symptom dura-tion was 24 months (range 18–28). All patients were distressed by the internal tremor. Depression was present in 2 patients with comorbid anxiety in 1. None had improvement of internal tremor nor sustained motor response to levodopa (maximum dose 600–750 mg daily). One patient had partial response to a selective serotonin reuptake inhibitor and benzodiazepine.Conclusions: Internal tremor can be the presenting symptom of MSA, but in contrast to PD is a rare complaint. Although observed only in patients with MSA-P, it does not respond to dopaminergic medication, which may argue for internal tremor being a non-motor rather than motor phenomenon.Reference1. Shulman, L.M., et al., Internal tremor in patients with Parkinson’s disease.

Movement disorders. 1996. 11(1): p. 3–7.No conflict of interest

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THE DIAGNOSTIC ANALYSIS OF PATIENT WITH MSA TYPE CZ. Kovacsova1,*, G. Krastev1

1Neurology, Faculty Hospital Trnava, Trnava, Slovakia

Objectives: MSA is a progressive neurodegenerative disease of unde-termined etiology, which appears in adulthood and affects more men than women. The prognosis is unfavorable and leads to a complete loss of mobility in the end. This rare disorder can manifest as Parkinson’s or cerebellar syn-drome. MSA is classified into: MSA-P with predominant striatonigral degen-eration and MSA-C with atrophy of olivopontocerebellar tracts, both types are accompanied by autonomic and urogenital dysfunction (1).Methods: We report a patient who was admitted to the Department of Neurology with the history of progressive deterioration of the gait and speech lasting 6 months. The clinical examination revealed the presence of dysar-thria, neocerebellar syndrome on the left side and paleocerebellar syndrome. Initial 1,5T MRI of the brain was negative. The gluten ataxia, tyreopathy, Wilson’s disease, withdrawal and paraneoplastic etiology were excluded, there was no peripheral neurogenic or myogenic lesion on EMG. CSF examina-tion except of hyperalbuminorachia was negative, the infection of CNS and Creutzfels- Jacob’s disease were ruled out. MRI of cervical and thoracic spinal cord was without myelopathy. MEP excluded damage of corticospinal tract. Posturographic examination confirmed disability of cerebellum as well as extrapyramidal system. According to this result, 3T MRI of the brain was indi-cated and the atrophy of pons, medulla oblongata and cerebellum was verified.

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Results: On the basis of the clinical picture and results of paraclinical exami-nations, the diagnosis of MSA- C was stated.Conclusions: For the last year of the monotoring the patient, the stage reached the significant progression.Reference1. André Dietrich, MD, PhD. Multiple system atrophy [online], http://emedi-

cine.medscape.com/article/1154583-overviewNo conflict of interest

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EVIDENCE FOR LIPID DYSTROPHY IN MULTIPLE SYSTEM ATROPHY BRAINW. Kim1,*, G. Halliday1

1Ageing and Neurodegeneration, Neuroscience Research Australia, Sydney, Australia

Objectives: Multiple system atrophy (MSA) is a fatal neurodegenerative dis-ease of unknown aetiology characterised by the accumulation of insoluble α-synuclein (α-syn) aggregates in the cytoplasm of myelin-producing oligo-dendrocytes. Dysfunction of the lipid-rich myelin membrane may precede α-syn pathology in MSA pathogenesis. ATP-binding cassette transporter A8 (ABCA8) is a little-known lipid transporter, which has recently been found to be highly expressed in oligodendrocyte-rich white matter regions of the human brain. ABCA8 expression promotes sphingomyelin production in oli-godendrocytes in vitro, suggesting a role in myelin formation and mainte-nance. We hypothesise that the function of ABCA8 is dysregulated in MSA brain.Methods: We measured the mRNA expression of ABCA8 in MSA brains (n = 8) and age- and gender-matched control brains (n = 10) in disease-affected grey matter (GM, putamen and cerebellum), disease-affected white matter (WM, under the motor cortex) and an unaffected brain region (visual cortex) by quantitative PCR. We also measured the level of different sphingomyelin spe-cies in the same regions by liquid chromatography-mass spectrometry.Results: ABCA8 expression was significantly increased (7 fold, p < 0.01) in the disease-affected GM and WM with no significant change in the unaf-fected brain region. The level of sphingomyelin species was either significantly decreased (39–54%, p < 0.05) or showed non-significant trend for decrease in both disease-affected GM and WM with no significant change in the unaf-fected brain region.Conclusions: Increased ABCA8 expression in α-syn-positive regions could be in response to decreased sphingomyelin levels in MSA brain, indicating possibly lipid dystrophy underlying MSA pathology.No conflict of interest

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MULTIPLE SYSTEM ATROPHY-CEREBELLAR WITH CRUCIFORM HYPERINTENSITY IN THE PONS: A CASE PRESENTATIONM. Xifaras1, A. Pasioti1,*, E. Poulimenou1, E. Kerezoudi11Neurology, Pammakaristos Hospital, Athens, Greece

Objectives: Multiple system atrophy (MSA) is an adult onset sporadic, rare, progressive neurodegenerative disorder characterized by various combina-tions of autonomic, parkinsonian, cerebellar or pyramidal symptoms or signs. The annual incidence rate is 3 new cases per 100000 person years. According to the predominant characteristics, there are three clinical syndromes included under MSA: MSA-P, when parkinsonian features predominate; MSA-C, when cerebellar features predominate; and MSA-A when autonomic failure predominates.Methods: A 60-year-old male with a 2-year history of progressive postural instability and 6 months of urinary incontinence was admitted in the depart-ment of Neurology. Examination revealed hypomimia, dysarthria, akinetic-rigid Parkinsonism, instability due to ataxic gait and pyramidal signs (generalized hyperreflexia and bilateral extensor plantar responses without limb weak-ness). The patient met diagnostic criteria for probable cerebellar-type MSA. Brain T2-weighted MR image showed cruciform signal hyperintensity in pons (“hot cross bun” sign).Results: MSA is a condition often confused with Parkinson’s disease (PD). Clinically, cardinal features include Parkinsonism, cerebellar ataxia, autonomic failure and pyramidal signs, in any combination. In MSA-C the degenerative changes predominantly affect the infratentorial structures. On T2-weighted MR images, the typical hyperintense “hot cross bun” sign in the pons are seen.Conclusions: The pontine cruciform hyperintensity is not pathognomonic to MSA-C; it has also been observed in more than one disorder. However, the “hot cross bun” sign can provide evidence to support a clinical diagnosis of MSA-C. These MRI signs are not seen in Parkinson’s disease and have been helpful to differentiate MSA from PD, as the treatment and prognosis vary.No conflict of interest

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THE PROBLEM OF DIAGNOSTICS AND MANAGEMENT OF PROGRESSIVE SUPRANUCLEAR PALSY (PSP) IN ARMENIAK. Harutyunyan1,*, I. Gabrielyan1, A. Voskanyan1, H. Amirjanyan1, L. Khachatryan1, A. Avetisyan1, A. Sahakyan1, G. Avagyan1, A. Karapetyan1, H. Manvelyan1

1Neurology, Yerevan State Medical University, Yerevan, Armenia

Objectives: PSP is a Neurodegenerative disease first described in 1963. It affects cognition, extrapyramidal system, eye movements. Only few years ago diagnosing PSP was a serious problem in Armenia, because of low level of diagnostics and it’s similarity with other Neurodegenerative diseases (e.g. PD, MSA).Currently we notice an observable increase of this problem in Armenia. During last 3 years in our clinic we had more than 60 patients, who were previously diagnosed with Parkinson’s disease (PD) and considered as therapy-resistant. The characteristics for PSP include primarily vertical gaze dysfunction accom-panied by extrapyramidal symptoms and cognitive dysfunction, the disease usually starts with dizziness and depression; these patients have a history of multiple falls, which isn’t phenotypical for PD.Methods: There are no specific methods for diagnosis of this syndrome; MRI scan could be performed, because in patients with PSP we can observe mid-brain atrophy, which is, however, not 100% specific for diagnosis. The diagnosis is based on clinical features, neuroimagining and laboratory tests, which are more likely to be performed to eliminate other entities in the differential diagnosis.Results: After Neurological and technical investigation, the diagnosis of PSP was established, new pharmacological management and physical treatment was applied.Conclusions: PSP, despite of distinct clinical features, still omitted with Parkinson disease. PSP must be suspected in all motility disorder patients over 50 years who have a Parkinson syndrome with the onset of vertical gaze palsy, early cognitive dysfunction, instability and dizziness, and appropriate management must be initiated.No conflict of interest

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GAIT IN PROGRESSIVE SUPRANUCLEAR PALSY – IS GAIT PATTERN DIFFERENTLY AFFECTED IN DIFFERENT DISEASE TYPES?S. Radovanovic1,*, M. Jecmenica-Lukic2, N. Dragasevic2, M. Svetel2, V. Kostic2

1Department of Neurophysiology, Institute for Medical Research University of Belgrade, Belgrade, Serbia, 2Clinic for Neurology, School of Medicine University of Belgrade, Belgrade, Serbia

Objectives: Progressive Supranuclear Palsy (PSP), with rapidly progressive postural instability and slow, unsteady gait, vertical gaze palsy, Parkinsonism unresponsive to levodopa, may be difficult to differentiate from Parkinson’s disease in its early stages. Gait analysis of two mayor clinical types of PSP, Steele-Richardson-Olszewski syndrome (RSO) and PD-like form (PSP-P) may help to differentiate and improve accuracy of early diagnosis and dif-ferentiate PSP subtypes.Aim was to compare gait patterns in PSP patients during demanding dual-tasking (DT) while walking.Methods: Dual-Task walking was performed and gait analyzed in 30 PSP patients, 20 with PSP-RSO and 10 patients with PSP-P. Patients performed simple walking task, dual-motor task, dual-mental task, and combined motor-mental task. Measurement of spatiotemporal gait characteristics was per-formed on the GAITRite walkway system. Calculated parameters were cycle time, stride length, double support time, swing time and variability (CV) of those four parameters.Results: Results show that RSO patients have higher variability of gait parameters then PSP-P and control subjects. Concerning changes during motor task, the significant changes were found only for stride length. The effect of mental task was present for all parameters and all groups except for swing time. Variability of these parameters increases with more demanding parallel tasks.Conclusions: It could be concluded that differences in gait patterns between RSO and PSP-P types could separate RSO from PSP-P concerning postural instability during gait and warn for possible falls in complex walking situations.No conflict of interest

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CASE OF FAMILIAL OPCAA. Voskanyan1,*, K. Harutyunyan1, I. Gabrielyan1, A. Avetisyan1, H. Amirjanyan1, L. Khachatryan1, G. Avagyan1, A. Sahakyan1, A. Karapetyan1, H. Manvelyan1

1Neurology, Yerevan State Medical University after M. Heratsi, Yerevan, Armenia

Objectives: Olivopontocerebellar atrophy (OPCA) is a neurodegenerative disease associated with the degeneration of nerve cells in specific areas of



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the brain: cerebellum, pons and olives. OPCA could be sporadic and genetic, that has certain criteria, but clinically is often misdiagnosed.45 year old male presented with progressive gait ataxia, intentional tremor, slurred speech, dysarthria and horizontal nystagmus within 3 years. The MRI scan approved the atrophy of cerebellum and pons, the diagnosis of OPCA was established.A year later patient’s sibling presented with dysarthria, balance impairment and intentional tremor. On performed MRI scan similar changes were observed.After thoughtful interview it was found, that patient has another, older brother, who was diagnosed with Multisystem Atrophy.Methods: Complete neurological examination, otoneurology, neuroimaging and common blood tests were performed.Results: Despite the fact that only two brothers of three siblings underwent investigations in our clinic, it seems that all of them were suffering of hereditary type OPCA.Conclusions: Since clinical signs of MSA-C and OPCA are similar, each case need thoughtful investigation to prove or deny hereditary origin of the disease, and development of the best plan of management.Reference1. Adams and Victor’s Principles of NeurologyNo conflict of interest

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ATYPICAL FORMS OF PARKINSONISM PLUS SYNDROMESN. Bouzidi1,*, E.M.N.A. Turki1, F. Hamza2, H.E.N.D. Hachicha3, M. Damak1, I. Bouchhima1, H. Masmoudi3, F. Guermazi2, C. Mhiri11Neurology, Habib Bourguiba Hospital, SFAX, Tunisia, 2Nuclear Medecine, Habib Bourguiba Hospital, SFAX, Tunisia, 3Immunological Laboratory, Habib Bourguiba Hospital, SFAX, Tunisia

Objectives: Parkinsonism plus syndrome (PPS) is a group of heterogeneous degenerative neurological disorders. In some cases, early diagnosis may be difficult and needs more complementary examinations.We describe atypical cases of PPS in young adult (onset before the age of 50 years).Methods: Two patients were followed up in our department for PPS. We report new clinical signs, CSF markers and SPECT imagining aspects of the disorders.Results: They were 2 males respectively aged of 38 and 37 years. They had Parkinson syndrome with poor levodopa response, dementia and fronto- executive dysfunction. The first patient was suffering from erectile dysfunction and urinary incontinence and his neurological examination revealed dysarthria, cerebellar ataxia and pyramidal signs. The clinical diagnosis of multiple system atrophy was evoked. MRI showed cerebellar atrophy. SPECT study revealed severe hypoperfusion in the cerebellar. CSF Aβ42 levels were reduced and CSF t-tau levels were increased. In the second case, the diagnosis of cortico-basal degeneration was made by physical examination (dystonia, apraxia of limbs, progressive apraxia of speech and non-fluent aphasia), MRI (atrophy in the right hemisphere) and SPECT (asymmetric striatal hypoperfusion).Conclusions: Patients with PPS represent a relatively small portion of Parkinsonism patients and a broad spectrum of disease phenotypes. The analysis of CSF proteins (Aβ42 and tau) and advancement of nuclear imagin-ing may provide a better understanding of some of these rare syndromes.Reference1. Holmberg B. Cerebrospinal fluid Abeta42 is reduced in multiple system

atrophy but normal in Parkinson’s disease and progressive supranuclear palsy; Mov Disord. 2003, Feb;18(2):186–90.


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SPECTRUM OF CORTICOBASAL SYNDROME IN A TUNISIAN COHORTM. Ben Djebara1,*, A. Nasri1, I. Kacem1, L. Sellami1, Y. Hizem1, A. Gargouri1, R. Gouider1

1Neurology, Razi Hospital, Tunis, Tunisia

Objectives: To determine characteristic features in Tunisian patients with corticobasal syndrome (CBS).Methods: We conducted a retrospective study over a 10-year period includ-ing all patients diagnosed with CBS according to the international proposed criteria. Clinical and paraclinical data were analyzed.Results: Thirty-five patients with CBS were identified (mean age of onset at 62.4, mean age at diagnosis of 65.9 years and sex-ratio of 1.9). Consanguinity rate was 68% and a family history of neurological disorders (Parkinsonism or demen-tia) was found in 60%. Presenting symptom was mainly Parkinsonism in 45.7%. It was asymmetrical in 91.4%, akinetic-rigid in 68.5% and responding to acute levodopa test in only 33.3%. At examination, dystonia was found in 74.3%, myo-clonus in 40%, apraxia in 82.9%, dysarthria in 42.8%, frontal syndrome in 54.3% and dementia in 58.8%. Clinical picture included also dysautonomy (54.9%), gait disturbance (51.4%), sleep disorders (34.9%) and alien limb (34.3%). Electro-oculographic recordings showed abnormalities in 80%. Corticobasal

Degeneration (CBD) was diagnosed in 18 cases (51.4%). CBS was related to other neurodegenerative diseases in 13 patients (5 PSP, 3 MSA, 3 DLB and 2 AD), ischemic lesions in 3 patients and cerebral meningiomatosis in one.Conclusions: Only half patients responded to the criteria of DCB denoting the overlap of CBS with various underlying pathologies. Atypical features such as cognitive, dysautonomic and oculomotor signs orientate to a different pathol-ogy than CBD. The high frequency of familial neurological history in our series may suggest a genetic substratum.No conflict of interest

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CLINICO-NEUROIMAGING PROFILE OF VASCULAR PARKINSONISMT. Cardoso Vale1, P. Caramelli2, F. Cardoso2,*1Neurology, Federal University of Minas Gerais, Belo Horizonte, Brazil, 2Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil

Objectives: To compare clinico-neuroimaging findings between Vascular Parkinsonism (VP) and Parkinson’s disease (PD).Methods: 15 patients with VP were compared to 30 patients with PD using motor, cognitive and neuroimaging tests and scales.Results: 17 PD patients were male (56.7%), mean age of 67.3 years, and 8 VP patients were male (53.3%), mean age of 75.7 years. All VP patients had arterial hypertension and they were on the average 8.4 years older and presented with a sudden onset of Parkinsonism (80%) and a rapidly progres-sive clinical course (53.3%). VP patients had significantly more lower body Parkinsonism (80% PV, none PD), postural instability (86.7% VP, 40% PD) with falls (80% VP, 20% PD), urinary incontinence (80% of VP, 13.3% PD) and pyramidal signs (73.3% VP, 6.7% PD). Tremor (90% PD, 6.7% VP) and psychotic symptoms (23.3% PD, none VP) were statistically more common in the PD group. Freezing of gait was more common in VP (93.3%) than in PD (50%) and the former group had higher scores on the UPDRS scale with statistical significance. VP patients had greater cognitive impairment and 12 (80%) fulfilled criteria for vascular dementia. Most VP patients had multiple lacunar infarcts (66.7%) and extensive white matter disease (26.7%).Conclusions: VP should be distinguished from PD based on an older age of onset with Parkinsonism characterized by lower body predominance, urinary incontinence, pyramidal signs, postural instability with freezing of gait and falls and dementia.Reference1. Kalra S, Grosset DG, Benamer HT. Differentiating vascular Parkinsonism

from idiopathic Parkinson’s disease. Mov Disord 2010;25:149–156.No conflict of interest

383

TRIPLE STIMULATION TECHNIQUE MAY BE A USEFUL METHOD TO DIFFERENTIATE BETWEEN VASCULAR PARKINSONISM AND PARKINSON’S DISEASEW. Jang1,*, J. Yoon2

1Neurology, Gangneung Asan Hospital, Gangneung, Korea, 2Emergency Medicine, Dong-In Hospital, Gangneung, Korea

Objectives: One of the predominant clinical features differentiating VP from PD is the pyramidal sign. The triple stimulation technique (TST) is one of the most sensitive methods to compare upper motor neuron involvement between VP and PD. This study aimed to evaluate the usefulness of TST as a diagnos-tic tool for VP.Methods: This study enrolled 13 VP patients, 18 PD patients, and 10 age-matched healthy controls. We obtained the patients’ basic demographic infor-mation, and TMS, including the TST amplitude ratio, was performed on all participants. We compared the TMS parameters between the patients in the VP, PD, and control groups.Results: The TST amplitude ratio was significantly lower in the VP group com-pared to the PD and control groups (71.59 ± 11.86 versus 96.42 ± 5.11 and 97.70 ± 3.82, and p < 0.01, respectively). The TST amplitude ratio showed a positive correlation with the UPDRS-III, which reflects motor function.Conclusions: TST is an effective and easy technique used to improve the diagnostic sensitivity of VP by assessing UMN involvement. TST might also represent a useful monitoring tool to evaluate disease progression.References1. Buhler R, Magistris MR, Truffert A, Hess CW, Rosler KM. The triple stimu-

lation technique to study central motor conduction to the lower limbs. Clin Neurophysiol 2001;112:938–949.

2. Eusebio A, Azulay JP, Witjas T, Rico A, Attarian S. Assessment of cortico-spinal tract impairment in multiple system atrophy using transcranial mag-netic stimulation. Clin Neurophysiol 2007;118:815–823.

3. Zijlmans JC, Daniel SE, Hughes AJ, Revesz T, Lees AJ. Clinicopathological investigation of vascular Parkinsonism, including clinical criteria for diag-nosis. Mov Disord 2004;19:630–640.




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MOVEMENT DISORDERS AFTER STROKEA. Chahidi1,*, M. Chraa2, N. Kissani21ED268, Sorbonne University & Moroccan AMCEP Society, Marrakech, Morocco, 2Neurology, University Hospital Ibn Tofail, Marrakech, Morocco

Objectives: To describe clinical, paraclinical and evolutive features of patients having suffered movement disorder in aftermath of ischemic stroke.Methods: Authors report retrospective study from January 2000 to December 2009. Data collected 442 patient’s folders who hospitalized for ischemic stroke in Neurology Department, UH Marrakesh, Morocco. Our department is third level structure which covers much of southern Morocco. Ischemic stroke diagnostic was established in base of clinical and CT scan criteria. Only patients who presented with movement disorders in aftermath of stroke were included.Results: Of 442 patients with ischemic stroke, 18 presented movement dis-orders. There was 10 man and 8 women. The mean age was 59. Patients presented this complication 3 days to 1 year after acute episode. We had 8 patients who developed Parkinsonism syndrome, 4 patients had chorea, 3 others had an isolated tremor and 3 presented dystonia. Parkinsonism was later to develop in our patients whereas chorea developed whiting days after the stroke. CT scan showed subcortical ischemic stroke interesting basal gan-glia in all cases. Finally, evolution was marked by resolution of all cases of dystonia and chorea, in other hand patients who had Parkinsonism were being followed in our department for up to 6 years without any major improvement.Conclusions: The present series report clinical, paraclinical and patients outcomes who presented movement disorder after ischemic stroke. Even with small patient number in our work, many finding and suggestions may be developedReference1. Siniscalchi A, Gallelli L, et al. Post-stroke Movement Disorders: Clinical

Manifestations and Pharmacological Management. Curr Neuropharmacol. 2012;10(3):254–62


385

POST STROKE PARKINSONISM AT THE NEUROLOGY DEPARTMENT OF FANN TEACHING HOSPITALP. Sounga Bandzouzi1,*, Y. Fogang1, D.H. Motoula1, Z. Kone1, K. Toure1

1Neurology Fann teaching Hospital, University of Cheikh Anta Diop, Dakar, Senegal

Objectives: We report the case of post stroke parkinsonian syndromes at the neurology department of Fann teaching hospital.Methods: We conducted a prospective study from 1 June 2012 to 31 June 2013. We included cases of post-stroke parkinsonian syndromes in patients aged 65 years or more. Patients with prior Parkinsonism before stroke(s) onset.Results: We included 17 patients, aged 65 to 75 years. The average age was 70.23 years and the sex ratio:7.5. The frequency was 0.57% in outpa-tient neurology. Quinz of our patients were male and two were female. Of the 17 cases, 41.17% had tremors, 29.41% of akinésies, and 17.65% rigidity. 58.82% had Parkinsonism hemisyndrome. All patients had dysarthria (100%). We had 2 cases of Parkinsonism post hemorrhagic stroke (11.76%) and 15 cases of Parkinsonism post ischemic stroke (88.24%) of all strokes. The time of symptoms occurred was 10 ± 1.2 months. The evolution of our patients was favorable in L-dopa (70.58%), dopamine agonist (17.65%) and combina-tion L-dopa and dopamine agonist (11.76%) with satisfying outcomes.Conclusions: Post stroke Parkinsonism stroke is quite common especially among the elderly. It appears most often in lesions of the basal ganglia. Ischemic strokes are the most common causes. The main treatment is L-dopa.References1. Journées de Neurologie de Langue Française. Les spécificités du

Parkinson du sujet âgé. Nice. 3 au 6 avril 20122. Diederich NJ, Moore CG, et coll. Parkinson disease with old-age onset: a

comparative study with subjects with middle-age onset. Arch Neurol. 2003 Apr;60(4):529–33.


386

CLINICAL FACTORS RELATED TO THE SIZE OF CAROTID ARTERIAL PLAQUE IN PATIENTS WITH VASCULAR PARKINSONISMJ.H. Lee1,*, S.H. Hwang2

1Neurology, National Health Insurance Service Ilsan Hospital, Goyang, Korea, 2Neurology, Hallym University Hospital, Seoul, Korea

Objectives: Carotid arterial stenosis becomes more common and important risk factor for stroke patients in Asian area, also can be a risk factor for vascu-lar Parkinsonism. We reviewed stroke database to investigate clinical factors

related to carotid arterial stenosis, including intracranial arterial stenosis and peripheral arterial disease which reflects advanced atherosclerosis in patients with vascular Parkinsonism.Methods: The patients with vascular Parkinsonism whose stroke onset were within 6 months from January 2008 to December 2012 with available carotid ultrasound study, transcranial Doppler (TCD) examination and ankle-bra-chial indexes (ABI) formed the analysis cohorts. Retrospective review was performed.Results: A total of 104 patients were included during that period. By duplex ultrasound, 3 groups of carotid arterial plaques are defined: diameter is less than 2 mm (37%), 2–4 mm (57%) and greater than 4 mm (6%). As the size of carotid arterial plaques increased, ABI is decreased (P = 0.000) and the number of intracranial arterial stenosis is increased (P = 0.008). Among the risk factors, Age, diabetes, male patients are increased (P = 0.000, P = 0.047, P = 0.004) and smoking history showed tendency of increase (P = 0.057) as diameter of carotid arterial plaque increase. However hypertension, total cho-lesterol, LDL cholesterol, HDL cholesterol, triglyceride and past stroke history are not correlated with carotid arterial stenosis.Conclusions: Among the patients with vascular Parkinsonism, more than a half of them have carotid arterial plaque which diameters are greater than 2 mm and these patients tend to have higher burden of advanced atheroscle-rosis as evidenced by a higher prevalence of diabetes, intracranial arterial stenosis and peripheral arterial occlusive disease.Reference1. Precursors of extracranial carotid atherosclerosis in the Framingham

Study. Neurology 1994;44: 1046–1050No conflict of interest

387

PROINFLAMMATORY CYTOKINES OF CHRONIC BRAIN ISCHEMIAD. Usmanova1,*, Y. Madjidova2

1Chair of Neurology, Tashkent Medical Institute of Postgraduate Education, Tashkent, Uzbekistan, 2Chair of Neurology, Tashkent Medical Pediatric Institute, Tashkent, Uzbekistan

Objectives: Immunological mechanisms have significant value in the patho-genesis of chronic brain ischemia (CBI).The purpose of investigation was to study immunological status and efficiency of cortexin in the treatment of the patients with CBI.Methods: We examined 187 patients with CBI. The patients were divided into 2 groups: I group included 98 patients who were treated with cortexin, group II consisted of 89 patients receiving therapy without cortexin. The levels of IL 1β and TNF-α in blood serum were determined by immunoenzymatic analysis. Cortexin was injected in dose 10 mg during 10 days.Results: The level IL1β α in patients of group I before treatment was 18.4 ± 0.8 pgml, after 14.0 ± 0.5 pgml (P < 0.05). In patients of group II the level of IL1β before treatment was 17.9 ± 0.6 pgml, after 16.8 ± 0.5 pgml. The level of TNFα in patients of group I before treatment was 13.2 ± 0.7 pgml, after decreased in 1.5 times. In group II before treatment the level of TNFα was 12.8 ± 0.7 pgml, after 11.9 ± 0.6 pgml.Conclusions: Cortexin resulted in decrease of the levels of proinflammatory cytokines that specifies its ability to reduce activity of immune inflammation.Reference1. CBI – chronic brain ischemia

388

NEUROPROTECTIVE ROLE OF WITHANIA SOMNIFERA SUPPLEMENTATION IN EXPERIMENTAL MODEL OF FOCAL CEREBRAL ISCHEMIA: IMPLICATIONS IN STROKEA. Sood1,*, R. Sandhir1

1Biochemistry, Punjab University Chandigarh, Chandigarh, India

Objectives: To investigate the neuroprotective efficacy of WS supplementa-tion in focal cerebral ischemia induced damage with the help of SPECT scan, TTC staining, blood brain barrier permeability and histological analysis.Methods: The progression of cerebral ischemia was assessed by SPECT imaging and preventive effect of WS supplementation on cerebral ischemia was analysed via TTC staining and histopathological studies. Neurobehavioral tasks including, actophotom-eter, rota-rod treadmill for grip strength and Morris water maze were evaluated using Anymaze tracking software. Brain water content and Blood-brain barrier integrity was evaluated using Evans blue dye.Results: WS supplementation restored cerebral blood flow as observed in in vivo SPECT scanning and reduced infarct size, aided in improving the neurological deficit score, improved performance in Morris water maze test, improved grip strength on the rota rod trendmill. Enhanced blood brain bar-rier leakage and brain edema caused by ischemia reperfusion injury was also found to be significantly attenuated in WS supple-mented group. WS sup-plemented rats also displayed only slight extravasation of Evans blue dye at the surface of the ipsilateral hemisphere, which was slightly higher than that



106

of control animals but was found to be significantly restored in comparison to the MCAO operated group.Conclusions: Ws supplementation can be engaged in prevention and man-agement of stroke.Reference1. Scheibe et al., 2012No conflict of interest

389

REVASCULARIZATION OF THE BRAIN IN THE TREATMENT OF ATHEROSCLEROTIC PARKINSONISMI. Maksimovich1,*1Iterventional Neuroangiology, Clinic of Cardiovascular Diseases Named After Most Holy John Tobolsky, Moscow, Russia

Objectives: Atherosclerotic Parkinsonism is becoming more common among American and European population. Aims – application of brain endovascular laser revascularization in atherosclerotic Parkinsonism treatment.Methods: 37 patients aged 52–80 (average age 74) with severe forms of spe-cific movement disorders, 28 male (75.68%), 9 female (24.32%), diagnosed with atherosclerotic Parkinsonism, were examined and operated on. Research plan included CT, MRI, SG, REG, MUGA of the brain.31 (83.78%) patients had intracranial type of atherosclerotic lesions, 6 (16.22%) patients – a mixed type. 33 (89.19%) patients showed numerous signs of calcium salt deposits on the walls of brain arteries (anterior inferior, posterior inferior, superior cerebellar, paramedien and circumflex, posterior and anterior communicating, basilar, and middle cerebral arteries, the central branch of posterior and anterior cerebral artery). 31 (83.78%) patients had signs of involutive changes with subarachnoid space extension.Endovascular laser interventions were conducted in a 2–8 years period after the manifestation of the disease symptoms.Results: Good immediate angiographic outcome manifested in the recon-struction of intracranial vessels angioarchitectonics was obtained in 35 (94.59%) cases.29 (78.38%) patients showed decline of involutive brain changes in 6–12 months.Good clinical outcome followed by total cancellation of antiparkinsonian drugs was observed in 9 (24.32%) cases.Satisfactory clinical outcome – a significant reduction in antiparkinsonian drugs doses -was observed in 26 (70.27%) cases.Lack of pronounced effect after the treatment was observed in 2 (5.40%) cases.Conclusions: The results obtained demonstrate the high efficacy of brain endovascular laser revascularization in the treatment of patients with athero-sclerotic Parkinsonism.Reference1. Endovascular RevascularizationNo conflict of interest

390

PREDICTORS OF PERCUTANEOUS ENDOSCOPIC GASTROSTOMY TUBE PLACEMENT AFTER STROKEL. Jian1,*, H. Hu1

1Neurology, Chaoyang Hospital, Beijing, China

Objectives: The goal of this study was to identify important prognostic vari-ables affecting placement of a percutaneous endoscopic gastrostomy (PEG) tube after acute stroke.Methods: We retrospectively reviewed our patient database to identify acute ischemic stroke patients who placed PEG or nasogastric tube (NGT) tube, but were free of other confounding conditions affecting swallowing. A total of 340 patients were involved in our study. We assessed the influence of age, National Institutes of Health Stroke Scale (NIHSS) score, infarct volume, stroke subtype based on the TOAST criteria, swallowing disorders, bilateral lesions in cerebrum and length of stay (LOS) in a logistic regression analysis.Results: In univariate analysis, age (p = 0.048), NIHSS score (p < 0.0001), lesion volume (p < 0.0001), LOS (p < 0.0001), stroke location (p = 0.045), and swallowing disorders (p < 0.0001) were found to be the primary predictors of placing PEG. The presence of lesions in bilateral cerebral was included in the final model based on clinical considerations. After multivariate adjust-ment, only NIHSS score (odds ratio [OR], 4.055; 95% confidence interval [CI], 2.398–6.857; p = 0.0001), lesion volume (OR, 1.69; 95% CI, 1.09–4.39; p = 0.014), swallowing disorders (OR, 1.151; 95% CI, 1.02–1.294; p = 0.047), LOS (OR, 0.955; 95% CI, 0.914–0.998; p = 0.0415) and bilateral lesions (OR, 2.8; 95% CI, 1.666–4.705; p = 0.0001) remained significant.Conclusions: Our data shows that NIHSS score, lesion volume, swallowing disorders, LOS and bilateral lesions in cerebrum can predict the requiring of PEG tube insertion in patients after stroke.No conflict of interest

391

THE EFFECTS OF A MODIFIED ANKLE FOOT ORTHOSIS ON THE CORRECTION OF GAIT KINEMATICS OF TWO CHILDREN WITH HEMIPLEGIC CEREBRAL PALSYN. Chehrehnegar1,*, L. Abbasi2, S. Sayadi3, S. Zandi41Occupational Therapy, Shiraz University of Medical Sciences, Shiraz, Iran, 2Physical Therapy, Shiraz University of Medical Sciences, Shiraz, Iran, 3Occupational Therapy, Shiraz University of Medical Sciences, Shiraz, Iran, 4Physical Therapy, Tehran university of Medical Sciences, Shiraz, Iran

Objectives: Hemiplegic cerebral palsy causes unilateral involvement and different patterns like genurecurvatum and ankle plantar flexion. This study designed an Ankle Foot Orthosis (AFO) to prevent a fixed wrong pattern in two hemiplegic children who walked with hip abduction, ankle plantar flexion and knee genurecurvatum.Methods: Two hemiplegic cerebral palsy children, who were able to walk with parallel bar and wall support, were evaluated. They had a tendency to walk with hip abduction, ankle plantar flexion and knee genurecurvatum without weight bearing on the affected heel. A modified AFO with 2.5 cm heel height and 1.5 cm height beneath metatarses was used for the affected sides with-out any shoes. The orthosis was prescribed for home use. Electrogoniameter and foot switches were used for gait kinematic analysis. Walking kinematics was evaluated before the intervention and reevaluated after 6 months.Results: Data showed that after 6 months intervention ankle plantar flex-ion angel in heel strike for one child changed from 25 degree to 3 and from 20 degree to 4 for the other child. Peak knee extension in stance phase changed from 3 degree to 1 and it changed from 4 to 0.5 degree i.Hip abduc-tion angel in heel strike for one of the children changed from 10 to 3 degree and from 10 to 5 degree in the another child.Conclusions: With AFO prescription which was modified with 2.5 cm heel height the wrong gait pattern will be moderated in the affected side. Besides after walking independently, children walked much more normally.No conflict of interest

392

COMBINATION OF PARKINSONISM, DEMENTIA AND MOTOR NEURON DISEASE: FOUR CASES OF GUAM SYNDROME IN ARMENIA?I. Gabrielyan1,*, K. Harutyunyan1, A. Voskanyan1, A. Avetisyan1, G. Avagyan1, A. Sahakyan1, H. Hambadzumyan1, A. Karapetyan1, H. Manvelyan1

1Neurology, Yerevan State Medical University, Yerevan, Armenia

Objectives: Guam syndrome is a rare endemic neurodegenerative condition, which has been described mostly on the islands of Guam archipelago.Four patients (1 male and 3 female) of Armenian (Caucasian) origin with a mean age of disease onset of 60 ± 6 years were reviewed. Two patients were primary diagnosed Parkinson disease with polyneuropathy, one was diagnosed Alzheimer’s disease and last one was with Amyotrophic Lateral Sclerosis (ALS). Disease gradually progressed within a year and combination of symptoms of these diseases was developed in each case. The objective is comprehensive understanding of neurodegenerative disorder, presented in these patients with the complex syndrome of Parkinsonism, ALS-syndrome and Dementia.Methods: The clinical presentation of each patient corresponded to the complex of symptoms of Parkinsonism, ALS-syndrome and cogni-tive deficit (to the level of dementia). On brain MRI-scan basal ganglia degeneration was observed. By ENMG examination the motor neuron disease signs were described. Cognitive impairment was assessed by MMSE (the mean score was 15). Other routine analyses were in a range of norms.Results: Thorough neurological examination, neuroimaging studies, labora-tory analyses and cognitive tests established the simultaneous presence of Parkinsonism, ALS-syndrome and dementia in each of four patients, and other possible neurodegenerative disorder was excluded, which is evident for Guam syndrome.Conclusions: Armenia is a country in Caucasus, and is not endemic region for Guam syndrome, but the appearance of these three syndromes in our patients does not exclude the possibility of Guam syndrome.Reference1. Parkinson plus syndromes: Adams and Victor’s principles of neurologyNo conflict of interest

393

PERRY SYNDROME: MORE COMMON THAN PREVIOUSLY THOUGHT AND ASSOCIATED WITH EARLY COGNITIVE IMPAIRMENTB.M. Aji1,*, L. Fratalia1, S.H. Alusi1, A.J. Larner1

1Cognitive Function Clinic, The Walton Centre, Liverpool, United Kingdom

Objectives: To report patients with Perry syndrome diagnosed at a regional neuroscience centre in the north-west United Kingdom.



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Methods: Case series.Results: We identified four patients with clinical findings compatible with Perry syndrome with diagnosis confirmed by neurogenetic testing. One developed progressive depression and Parkinsonism with mild levodopa responsiveness in his mid-forties. Following a respiratory arrest, Perry syndrome was considered, and a novel dynactin-1 gene point mutation (p.Gly67Asp) identified, although there was no family history.1 The other three patients were from a large pedigree with autosomal dominant Parkinsonism. The proband presented in her mid-sixties with Parkinsonism which proved moderately levodopa-responsive; she had a prior history of depression. Two younger half-sisters had a similar phenotype, although presenting in their mid-fifties, and one showed no meaningful response to levodopa. This family was found to carry a dynactin-1 gene point mutation (p.Lys68Glu). Of the three patients who underwent cognitive testing at neu-rological presentation, all had evidence of cognitive impairment.Conclusions: The autosomal dominant syndrome of depression, sleep dis-turbance, Parkinsonism, and respiratory failure, first described by Perry et al., 2 has been considered extremely rare: a 2008 review identified only seven families worldwide. Four patients with Perry syndrome have been identified at this centre, one without a family history, all with genetic confirmation of diagnosis (OMIM#168605). The availability of genetic testing for dynactin-1 gene mutations may demonstrate that Perry syndrome is more common than was previously thought.References1. J Neurol Sci 2013;330:117–8.2. Arch Neurol 1975;32:108–13.No conflict of interest

394

MOVEMENT DISORDERS INDUCED BY MANGANESE: CORRELATION BETWEEN CLINICAL COURSE AND HYPERINTENSIVITY OF THE BASAL GANGLIA ON THE T1-WEIGHTED MRI IMAGESN. Lobjanidze1,*, M. Janelidze1, L. Chinchaladze1, K. Esartia1, N. Akiashvili1, S. Kapianidze1, T. Maisuradze1

1Neuromedicine, S. Khechinashvili Medical University Hospital, Tbilisi, Georgia

Objectives: To find correlation between the clinical course and radiological abnormalities in patients with Manganese-Induced Encephalopathy (MIE). MIE is caused by hand-made drug “ephedrone”, containing manganese. According the current publications the development of neurological distur-bances is different in separate cases as conflicting to MRI pictures.Methods: We evaluated clinical and MRI records of 22 patients with MIEResults: Clinical symptoms of 22 patients with MIE were investigated as well as their MRIs. The mean length of “ephedrone” abuse was about 1 year. The T1-weighted MRI images were divided in 4 groups: I group: increased signal intensity in basal ganglia (globus pallidus, substantia nigra), II group: hyperintensity in basal ganglia and cerebellar nuclei, III group (3 patients): hyperintensity of basal ganglia and pyramidal tract, VI group: normal MRI. I group includes 11patients with hypokinesia, hypomimia, dystonic smile, spas-tic- hypokinetic dysarthria, gait disturbances with postural unsteadiness, falls. The symptoms were characterised by “stepwise progression II group includes 5 patients with moderate stable Parkinsonism symptoms and more prominent apathy, depression, and executive dysfunction. III group includes 3 patients with clinical and ENMG findings of lower motor neuron dysfunction, repre-sented by Parkinsonism and ALS-syndrome. VI group includes 3 patients with severe Parkinsonism, prominent postural instability with falls and muscle rigid-ity, which were stable and didn’t changed during the time.Conclusions: Despite the symptoms of MIE is quite stereotypical, it is pos-sible to outline the subgroups of patients with peculiar MRI and clinical data.Reference1. Manganese-Induced Encephalopathy, neuroimagingNo conflict of interest

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RE-EMERGENT TREMOR RE-VISITEDZ. Ayturk1, M.C. Akbostanci1,*1Neurology, Ankara Üniversity Faculty of Medicine, Ankara, Turkey

Objectives: We aim to test the hypothesis that says re-emergent tremor (RET) is brought out by the same mechanisms that generates rest tremor (RT), so both types of tremor should have similar clinical and electrophysiological properties.Methods: Fifty-six patients (28 females) with Parkinson’s disease (PD) were separated into three groups. Group 1 consisted of patients with both RT and RET (18 cases), the Group 2 had RT without RET (24 patients), and the Group 3 had no tremor (14 cases).We obtained following data from accelerometric recordings: Lantency of RET, peak frequency; amplitude at peak frequency; root mean square amplitude and mean power value of tremor signal. Clinical variables were UPDRS total score, scores of parts I, II, III, and IV; the age, gender, age at onset of PD, disease duration, and, Hoehn-Yahr stage.

Results: None of the clinical and accelerometric variables (Table) showed significant differences between groups.

Group 1 Group 2

VariableRest

tremor Re-emergent

tremorRest

tremor

Peak frequency (Hz) 4.92 (1.20) 5.25 (1.03) 4.80 (0.76)

Amplitude at peak frequency (mg2)

5.68 (18.58) 18.32 (47.47) 2.21 (4.00)

RMS amplitude (g) 0.09 (0.08) 0.16 (0.19) 0.07 (0.06)

(Standard deviation in parantheses)Conclusions: Since all electrophysiologic and clinical properties of RT and RET are similar both within Group 1, and between Group 1 and 2, re-emergent tremor, as proposed before, is probably just a manisfestation of RT.Reference1. Jankovic J, Schwartz KS, Ondo W. Re-emergent tremor of Parkinson’s

disease. J Neurol Neurosurg Psychiatry 1999;67:646–650.No conflict of interest

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PREVALENCE OF TREMOR AMONG FREQUENT CELLULAR PHONE USERSN. Kumar1,*1DCSE, Shri Ramswaroop Memorial University, Barabanki, India

Objectives: Tremor, an unintentional, rhythmic muscle movement that affects only the hand or fingers, is often seen in patients with Parkinson’s disease. In some people, tremor is a symptom of a neurological disorder or appears as a side effect of certain drugs. But still a relation could not be established between frequent usage of cellular phone and tremor. The objective of this study is to investigate the risk of tremor among the frequent cellular phone users.Methods: The modified methodology of Interphone study [1] and Balikci et al. [2] was followed for this study. Prevalence of tremor was observed in 94 respondents out of 659 cellular phone users.Results: The risk for tremor symptom was found higher in individual groups of NU (p < 0.05), MU (p < 0.05) and HU (p < 0.001), when compared to LU. There was 1.9 fold risk of tremor in NU (OR: 1.943; CI: 1.009–3.740), 1.18 fold in MU (OR: 1.184; CI: 1.031–3.442) and this risk was above 3 times greater in HU (OR: 3.039; CI: 1.545–5.980) when compared to LU. However, risk of tremor in adult mobile phone user was observed at significant higher in NU (p < 0.05), MU (p < 0.05) and HU (p < 0.05) when compared to LU. This risk was higher by 2 fold in NU (OR: 2.052; CI: 1.054–3.996), 1.8 fold in MU (OR: 1.876; CI: 1.012–3.478) and 2.9 fold in HU (OR: 2.965; CI: 1.493–5.889).Conclusions: Mobile phone’s frequent use can be one of the causes for tremor.ReferencesPrevalence of Tremor (Table-1).References (Methodology):1. Lakhola, A., Salminen, T., Raitanen, J., Heinavaara, S., Schoemaker, M.J.,

Christensen, H. C., Feychting, M., Johansen, C., C., Klaeboe, L., Lonn, S., Swerdlow, A.J., Tynes, T., Auvinen, A.: Meningiome and mobile phone use-a collaborative case-control study in five North European countries. Int J Epidemiol 37 (2008) 1304–1313

2. Balikci, K., Cem Ozcan, L., Turgut-Balik, D., Balik, H.H.: A survey study on some neurological symptoms and sensations experienced by term users of mobile phone. Pathol Biol (Paris) 53 (2005)30–34.


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ASSESSMENT OF TREMOR AND ABNORMAL MOVEMENTS USING A MARKERLESS MOTION TRACKING SYSTEMB. Carignan1,*, J.F. Daneault2, C. Lavigne-Pelletier3, M. Lauzé3, S. Sens3, L. Frossard3, C. Duval31Sciences Biologiques, Universite du Quebec a Montreal, Montreal, Canada, 2Neurology and Neurosurgery, McGill University, Montreal, Canada, 3Kinanthropologie, Universite du Quebec a Montreal, Montreal, Canada

Objectives: In clinics, tremor and abnormal movements such as dyskine-sia are usually assessed using clinical scales, because of their efficiency. In laboratory, these types of movement can be measured with motion capture systems such as accelerometers or optical motion tracking. Although labora-tory equipments can be more precise, their use is more complex and time consuming. A markerless motion capture system (MMOCAP) should merge advantages of both types of assessment. Our objective is to assess the poten-tial of using MMOCAP to detect and measure tremor and dyskinesia.



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Methods: The MMOCAP to be assessed is the Biostage system (Organic Motion, NY). First, the smallest detectable oscillatory movement was evalu-ated while a healthy participant was simulating different tremor amplitudes. Second, the Biostage was compared to an optoelectric motion capture sys-tem with active markers (VisualeyezTM VZ4000, PhoeniX Technologies Incorporated). Two healthy participants performed predetermined move-ments while they were captured by both systems simultaneously. Finally, a Parkinson’s patient presenting with tremor (off meds) and mild dyskinesia (on meds) was captured by the Biostage system.Results: Our preliminary results show that the smallest simulated tremor detected by the Biostage is approximately 1.2 mm, which represents the reso-lution of the system. Subtle dyskinesia above the aforementioned threshold were detected by the Biostage system which allowed differentiation from a healthy control participant.Conclusions: The Biostage system has sufficient precision to detect motor symptoms of Parkinson’s disease, such as tremor and dyskinesia. These results demonstrate the potential in using such a system for the automatic assessment of patients presenting with motor deficits.No conflict of interest

398

POSTURAL TREMOR AFTER ENDOVASCULAR EMBOLISATION OF CEREBRAL ARTERIOVENOUS MALFORMATIONC. Falup-Pecurariu1,*, R. Mircea2, M. Moarcas3, G. Sica1, M. Bustan3, R. Chiperi31Department of Neurology, Faculty of Medicine Transilvania University, Brasov, Romania, 2Department of Neurosurgery, Emergency County University Hospital, Brasov, Romania, 3Department of Neurology, Emergency County University Hospital, Brasov, Romania

Objectives: Movement disorders associated with cerebral arteriovenous mal-formations (AVM) both before and after endovascular treatment are infrequent.Methods: We report the case of a 62 years old man with a right parietal com-plex arteriovenous malformation who developed a postural tremor of the right hand. The patient was diagnosed by angio- MRI and cerebral vessels arteriog-raphy with the AVM in 2007. He underwent partial endovascular embolisation of the arteriovenous malformation in 2008. The tremor onset was at 6 months after endovascular embolisation.Results: Neurological examination reveals in the present a left hemiparesis and a postural, high amplitude tremor of right hand. The tremor has intentional component and it is not accompanied by extrapiramidal rigidity.Brain angio-MRI did not reveal complications or modifications in the aspect of the cerebral arteriovenous malformation that contains aberant vessels from branches of anterior and middle cerebral arteries and the venous part drains in the superior sagital sinus.Treatment trials with different drugs were used, with partial benefit of Clonazepam and Propranolol.Conclusions: Postural tremor in a patient with cerebral arteriovenous malfor-mation is rare and treating it is a clinical challenge.No conflict of interest

399

A CASE OF TREMOR ASSOCIATED WITH CHRONIC INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHYM. Krommyda1,*, J. Deeb2, A. Misbahuddin1

1Essex Neurosciences Centre Department of Neurology, Queen’s Hospital, Romford, United Kingdom, 2Essex Neurosciences Centre Department of Neurophysiology, Queen’s Hospital, Romford, United Kingdom

396 – Table I Prevalence of Tremor

LU NU mm HU

Overall CP users (659) 217 (32.9%) 140 (21.2%) 209 (31.7%) 93 (14.1%)

Cases of Tremor (94) 19 (8.8%) 22 (15.7%) 32 (15.3%) 21 (22.6%)

P-value - 0.047 0.039 0.001

OR (9S% CI) Reference 1.943 (1.009–3.740) 1.184 (1.031–3.442) 3.039 (1.545–5.980)

Male CP users (460) 145 (31.5%) 93 (20.2%) 155 (33.7%) 67 (14.6%)

Cases of Tremor (71) 13 (9.0%) 15 (16.1%) 29 (18.7%) 14 (20.9%)

P-value - 0.098 0.017 0.018

OR (95% CI) Reference 1.953 (0.883–4.318) 2.337 (1.163–4.698) 2.682 (1.182–6.086)

Female CP users (199) 72 (36.2%) 47 (23.6%) 54 (27.1%) 26 (13.1%)

Cases of Tremor (23) 6 (8.3%) 7 (14.9%) 3 (5.6%) 7 (26.9%)

P-value - 0.268 0.552 0.023

OR (95% CI) Reference 1.925 (0.604–6.134) 0.647 (0.154–2.713) 4.053 (1.216–13.51)

Children CP users (35) 16 (45.7%) 9 (25.7%) 10 (28.6%) NF

Cases of Tremor (2) 1 (6.3%) NF 1 NF

P value - - 0.729 -

OR (9S% CI) Reference - 1.667 (0.092–30.06) -

Adult CP users (624) 201 (32.2%) 131 (21.0%) 199 (31.09%) 93 (14.9%)

Cases of Tremor (92) 18 (9.0%) 22 (16.8%) 31 (15.6%) 21 (22.6%)

P-value - 0.035 0.046 0.002

OR (95% CI) Reference 2.52 (1.054–3.996) 1.876 (1.012–3.478) 2.965 (1.493–5.889)

Urban CP users (489) 159 (32.5%) 97 (19 8%) 160 (32.7%) 73 (14.9%)

Cases of Tremor (70) 13 (8.2%) 16 (16.5%) 22 (13.8%) 19 (26 0%)

P-value - 0.045 0.115 0.000

OR (95% CI) Reference 2.218 (1.016–4.842) 1.790 (0.868–3.693) 3.952 (1.827–8.547)

Rural CP users (170) 58 (34.1%) 43 (25.3%) 49 (28.8%) 20 (11.8%)

Cases of Tremor (24) 6 (10.3%) 6 (14.0%) 10 (20.4%) 2 (10.0%)

P-value - 0.581 1.153 0.965

OR (95% CI) Reference 1.405 (0.420–4.701) 2.222 (0.744–6.636) 0.963 (0.178–5.207)

N.B.-LU: Low Users (≤500 hours); NU (>500 and ≤1000 Hours); MU (>1000 and ≤5000 Hours); HU (>5000 Hours); CP: cell phone, NF: Not Found cases, Data was analyzed using binary logistic regression test. P-value < 0.05 was considered as significant. OR: odds ratio, CI: confidence interval.



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Objectives: To present a case of prominent tremor related to CIDP.Methods: A 63 year-old female with a previous history of repeated lum-bar spine operations and bilateral total hip replacement presented with a longstanding history of dysaesthesiae of gradual onset in her upper and lower limbs, progressive rest, postural and eventually kinetic tremor in both upper limbs and more so on the left, combined with mild nodding head and lower limb tremor. The initial neurological examination had revealed normal power examination, symmetrically present reflexes without any signs of rigidity or bradykinesia.Results: The patient had previously undergone an MRI of the brain and cervical spine without any significant pathological findings. Due to the initially atypical features of her tremor, surface EMG and accelerometry recording were performed which characterized the tremor as being ‚organic with an ele-ment of functional overlay’.The follow-up neurological examination after 1 year revealed additionally to the previous findings distal sensory impairment in all modalities. A nerve conduction/EMG study was performed, which showed evidence of a severe, demyelinating, sensory-motor, inflammatory polyneuropathy. Blood and CSF investigations supported the diagnosis of CIDP. The patient received a course of intravenous IVIG treatment with mild improvement of her symptoms accord-ing to the clinical rating scale for tremor.Conclusions: Tremor can be a prominent and disabling symptom in CIDP phenotypes1. Clinical awareness of this manifestation is very important in order to avoid delays in treatment.Reference1. Eftimov F., Schaik IV. CIDP: update on clinical features, phenotypes and

treatment options. Curr Opin Neurol. 2013 Jul 11.No conflict of interest

400

DOPAMINE RESPONSIVE PATTERN IN TREMOR PATIENTSL.L. Imbach1,*, M. Sommerauer1, K. Leuenberger2, S. Schreglmann1, O. Maier1, R. Gassert2, C.R. Baumann1

1Neurology, University Hospital Zurich, Zurich, Switzerland, 2Department of Health Sciences and Technology, ETH Zurich Rehabilitation Engineering Laboratory, Zurich, Switzerland

Objectives: Diagnosis and treatment of tremor patients is largely based on clinical assessment. From a clinical perspective, it is crucial to distin-guish Parkinsonian tremor from other tremor entities, because patients with Parkinson’s disease (PD) may respond to dopaminergic treat-ment. However, L-Dopa response varies considerably even within PD patients and it remains unclear which patients may respond to dopamine. Considering the growing evidence that higher harmonic oscillations in cerebello-thalamo-cortical networks are linked to tremor generation in PD patients, we hypothesize that harmonic oscillations correlate with L-Dopa response in tremor patients.Methods: We assessed 60 consecutive tremor patients and performed a quantitative tremor analysis with an Inertial Measurement Unit (combined 3D-accelerometer/3D-gyroscope). L-Dopa challenge tests were performed in 19 patients, and tremor response to L-Dopa was compared to the amount of higher harmonic oscillations.Results: In general, PD patients had significantly more higher harmonics as compared to patients with essential tremor (p < 0.005). Furthermore, we found a strong correlation between higher harmonic tremor oscillations and L-Dopa response (R = 0.66, p = 0.002, n = 19). Similarly, higher harmonics were sig-nificantly greater in patients with positive response to L-Dopa (tremor reduc-tion by >50%) as compared to non-responders (p < 0.005). This correlation was not restricted to PD patients, but applied to all tested patients.Conclusions: We conclude that higher harmonic oscillations are a measure for L-Dopa response of tremor. Because of the observational character of the study a causal relation between higher harmonics and L-Dopa response still remains speculative. Nevertheless, we propose a novel, non-invasive and rapid approach to assess L-Dopa response in tremor patients.No conflict of interest

401

PARKINSON’S DISEASE IN SENEGAL: EPIDEMIOLOGIC, CLINICAL AND THERAPEUTIC ASPECTSN.M. Gaye1,*, S.O.M. Lemine1, L.B. Seck1, O. Cissé1, M. Ba1, A.D. SOW1, M.S. Diop1, N. Diagne1, A. Bass1, K. Touré1, M. Ndiaye1, A.G. Diop1, M.M. Ndiaye1

1Neurological Clinic Service, CHNU Fann, Dakar, Senegal

Objectives: The study aimed to determine the epidemiologic, clinical and therapeutic aspects of patients treated for Parkinson’s disease (PD).Methods: This was a prospective and transversal study conducted on 19 patients aged between 52 and 79 years and treated for PD at the Neurology department of Fann teaching hospital. The data have been collected using a form of a pre-established survey.

Results: Sex ratio was 12/7 and the mean age was 65.26 ± years. 68.42% were married. 21.05% were farmers and 63.15% had achieved the primary level education. Notion of consanguinity was found in 42.10% cases and the use of pesticides was noted in 15.78% of our patients. The average age of onset was around 60.52 ± years. Tremor was the first functional sign (68.42%) and this sign was present in 84.21% of patients. Rigidity was found in 94.73% of them. The other signs were represented by motor fluctuations (78.94%), painful syndrome (73.68%), mood disorder (52.63%), hallucinations (42.10%), insomnia (31.57%), falls (10.52%) and orthostatic hypotension (5.26%). Brain CT was available in five patients and was normal in four of them. 36.84% of the patients were receiving (Levodopa + benserazide), (Levodopa + carbi-dopa) or Piribedil and 52.63% in association with Trihexyphenidyl.Conclusions: PD diagnosis is clinical. Frequency of PD signs in our setting are not different from those in western countries. It is important to educate general practitioners and people for early recognition of PD signs for a better management.Reference1. L. Defebvre. Parkinson’s disease and other parkinsonian syndromes.

Médecine Nucléaire 2007; 31: 304–313.No conflict of interest

402

LONG-TERM OUTCOME OF THALAMIC DEEP BRAIN STIMULATION FOR ESSENTIAL TREMOR: ANALYSIS OF CLINICAL EFFICACY AND STIMULATION PARAMETERSP.M. Rodriguez Cruz1,*, A. Vargas2, C. Fernandez Carballal2, J. Garbizu2, B. De La Casa- Fages1, F. Grandas1

1Neurology, Movement disorders deep brain stimulation group, Hospital General Universitario Gregorio Marañón, Madrid, Spain, 2Neurosurgery, Movement disorders deep brain stimulation group, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Objectives: To analyze the long-term results of deep brain stimulation of the ventral intermediate nucleus of the thalamus (VIM-DBS) for essential tremor (ET), according to DBS parameters (DBSP) and clinical response.Methods: Retrospective study of patients with medication-refractory ET who underwent VIM-DBS surgery at our center. DBSP (contacts, voltage, fre-quency, pulse width, total electrical energy delivered [TEED1sec]) and the Fahn-Tolosa-Marin rating tremor scale (FTM-TRS) were recorded at each follow-up visit. Potential changes along the follow-up period in DBSP and FTM-RT scores were assessed using Wilcoxon signed-rank test, curve fitting models and Spearman correlation.Results: 14 patients (12 men, 6 women; mean age 61 years) were treated and 25 VIM-DBS electrodes were implanted (3 unilateral, 11 bilateral). Mean fol-low-up after DBS-surgery was 7.71 (range 2.25–16.17) years. Compared with pre-surgery evaluation, FTM-TRS scores at the last visit showed a reduction of 50.1% (p < 0.001). Tremor improvement was sustained along the observa-tional period (Figure 1). DBSP adjustments determined a statistically significant increase in voltage (p = 0.012), pulse width (p = 0.008) and TEED1sec (p = 0.008), the latter fitting a polynomial curve model (Figure 2). There was a significant cor-relation between FTM-TRS and DBPS, especially with TEED1sec (p < 0.0001).

0FTM-A

PRE-SURGERY FIRST ADJUSTMENT 10 YEARS AFTER SURGERY

FTM-TRS TEMPORAL EVOLUTION

FTM-B FTM-C FTM-T

10

20

30

40

50

60

70

Figure 1. Evolution of FTM-TRS total score and subscores.

Conclusions: VIM-DBS is an effective long-term treatment for ET. However, to obtain a sustained benefit in tremor control, TEED1sec should be progressively increased. This finding can be related to the development of DBS tolerance, disease progression or local gliosis surrounding the electrode placement.References1. Koss AM, et al. Ann Neurol 2005;58:168; author reply 168–169.2. Favilla CG, et al. Brain 2012;135:1455–1462.No conflict of interest



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00 2 4

FOLLOW-UP PERIOD (YEARS)

FTM

-TR

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TEE

D (j

ubos

)

6 8 10

5

10

15

20

25

30

35

40

45

50

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20

40

60

80

100

120

140

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Figure 2. temporal evolution of TEED1sec and FTM-TRS

403

STATUS DYSTONICUS IN CHILDHOODN. Touati1, H. Benrhouma1,*, I. Kraoua1, H. Klaa1, A. Rouissi1, I. Turki11Child and Adolescent Department of Neurolgy, Institute Mongi Ben Hmida of Neurology, Tunis, Tunisia

Objectives: To describe clinical features, management and follow up children with status dystonicus (SD).Methods: We conducted a prospective study over an 8-year period including all patients diagnosed with SD. Clinical characteristics, etiologies and man-agement were analyzed.Results: 6 patients were included (4 boys and 2 girls, mean age: 12.1 years, mean age of onset: 8.8 years). Main features of SD were a severe generalized dystonia with vegetative signs. Laryngeal spasm and swallowing disorders were observed in one case. Five of them had secondary dystonia (anoxia) and one had primary dystonia (DYT1).Several treatments such as Levodopa, Anticholinergics, Baclofen, Benzodiazepines and Neuroleptics were tried. Mechanical ventilation was required in 3 cases. Two patients died due to rhabdomyolysis and respiratory failure. Others returned to their pre-SD.Conclusions: SD is a life threatening condition that needs an urgent manage-ment on an intensive care unit. In fact, patients with SD can develop respira-tory failure and metabolic complications.On the basis of our experience, we delineated a therapeutic approach in which the patient with SD needs supportive care, specific therapy of dystonia and intravenous sedative treatment.References1. Mariotti P, Fasano A, Contarino MF, Della Marca G, Piastra M, Genovese

O, et al. Management of status dystonicus: our experience and review of the literature. Mov Disord 2007 May 15;22(7):963–8.

2. Mishra D, Singhal S, Juneja M. Status dystonicus a rare complication of dystonia. Indian Pediatr 2010 Oct;47(10):883–5.

3. Grosso S, Verrotti A, Messina M, Sacchini M, Balestri P. Management of status dystonicus in children. Eur J Paediatr Neurol. 2012 Jul;16(4):390–5.


404

20 YEARS OF EXPERIENCE IN THE TREATMENT OF BLEPHAROSPASM WITH ONABOTULINUM TOXIN AA. Rodriguez Sanz1,*, F. Vivancos-Matellano1, I. Ybot Gorrín1, E. Díez-Tejedor1

1Neurology, University Hospital La Paz, Madrid, Spain

Objectives: Blepharospasm (BS) is the most prevalent focal dystoni. The bot-ulinum toxin (BT) is a more effective therapeutic alternative than oral drugs. The aim of this study is to analyze the response to BT and its adverse effects in 161patients with BS in the long term.Methods: Consecutive patients with BS who have attended to the Movement Disorders Unit for treatment with BT for 20 years were prospectively included. The following variables were analyzed: demographic data, aetiology, associa-tion with oromandibular or cervical dystonia, duration of BS and treatment, BT dose, number of sessions, technique of administration, response to treatment, degree of patient’s satisfaction, need for association of oral drugs or orbicular myectomy and adverse effects.Results: 161patients were included. 111 (68%) were women. Age:66 (SD12). Duration of BS:13 years. In 18 patients (11%), BS was secondary. In18 (11%), was associated with oromandibular dystonia and in12 (7%) with cervical dystonia. They were treated with BT during 9 years (SD5), range: 0–20, and required 20 sessions (SD13), range: 2–57. The minimum and maximum doses of BT were: 27IU (SD9), range: 15–45 and 40IU (SD12), range: 20–80, respectively. 30

(18%) required pretarsal technique. 157 (97%) responded adequately. Degree of patient’s satisfaction was high in 138 cases (86%).18 (11%) needed oral drugs and 3 (1.9%) orbicular myectomy. 63 (32%) presented infrequent and reversible adverse events at some time during follow-up, 53 (22%) mild and 10 (6%) serious.Conclusions: To our knowledge, the sample size of our study is one of the biggest ever published. Our results confirm that BS usually begins in the sixth decade of life and affects women more frequently. Most of the cases are essen-tial. BT treatment maintains its efficacy and safety during long-term follow-up.References1. Aquino CC. Clinical features and treatment with botulinum toxin in blepha-

rospasm: a 17-year experience. Arq Neuropsiquiatr2. Vivancos F.A 17-year experience of abobotulinumtoxinA in cervical dysto-

nia. Int J Neurosci

405

BOTULINUM TOXIN IMPROVE QUALITY OF LIFE IN MEIGE’S SYNDROME WITH LINGUAL DYSTONIAS. Ochudlo1,*1Neurology, Central Clinical Hospital of Medical University of Silesia, Katowice, Poland

Objectives: Lingual dystonic disorders can exist as isolated forms like primary lingual dystonia, and more frequently as Meige’s syndrome (MS). MS is physi-cally and socially disabling, which can lead to social isolation.Methods: 16 MS patients with abnormal tongue movement were treated with intra-lingual injections of Botox every 3 m. over a period of 12–78 m. The treatment effectiveness was measured with Voice Related Quality of Life Questionaire, and subjective questionnaire, using a scale from 1–5 score. A direct injection into the tongue was given approximately 5 mm deep on their side upon the anterior surface of the tongue in 2 to 4 points, in total dose 20 to 50 U. 12 patients received Botox in at least one other oromandibular or neck muscles group. 4 patients received Botox only in tongue muscles.Results: All patients in this series experienced improvement in their abnormal tongue movements with intra-lingual Botox treatment. VRQL was significantly better 4 weeks after BTX injections in all patients, and was observed during 8 to 12 weeks after treatment. Adverse events included dysphagia was observed in two patients, were reversible, short in duration, mild intensity, and reversible.Conclusions: Direct injections of Botox into tongue may be an effective and safe method in improvement QoL in lingual dystonic disorders associated with MS.No conflict of interest

406

ELECTROPHYSIOLOGIC INVESTIGATION DURING FACIAL MOTOR NEURON SUPPRESSION IN PATIENTS WITH HEMIFACIAL SPASM; POSSIBLE PATHOPHYSIOLOGY OF HEMIFACIAL SPASM: A PILOT STUDYM.W. Kim1,*, D.H. Jang1, S.I. Choi1, Y.M. Han2

1Rehabilitation Medicine, The Catholic University of Korea Incheon St. Mary’s Hospital, Incheon, Korea, 2Neurosurgery, The Catholic University of Korea Incheon St. Mary’s Hospital, Incheon, Korea

Objectives: To evaluate the pathophysiological mechanism of hemifacial spasm (HFS), we performed electrophysiological examinations such as supraorbital nerve stimulation with orbicularis oris muscle recording and lat-eral spread tests, after suppressing the patient’s central nervous system by administering intravenous diazepam.Methods: Six patients with HFS were recruited into this study. Supraorbital nerve stimulation with orbicularis oris muscle recording and the lateral spread test were performed, followed by the intravenous application of 10 mg of diaz-epam to achieve facial motor neuron suppression. Subsequently, we repeated the 2 electrophysiological experiments mentioned above at 10 and 20 min after the patients had received diazepam intravenously.Results: Orbicularis oris muscle responses were observed in all patients after the supraorbital nerve stimulation and lateral spread tests. After diazepam injections, there was no orbicularis oris muscle response to supraorbital nerve stimulation in 1 patient, and the latencies of this response were evident as a slowing tendency with time in the remaining 5 patients. However, in the lateral spread test, the latencies of the orbicularis oris muscle responses were observed consistently in all patients.Conclusions: Our results suggest that ectopic excitation/ephaptic transmis-sion contributes to the pathophysiological mechanisms of hemifacial spasm. This is because, in a lateral spread test, the latencies of the orbicularis oris muscle responses were observed consistently in the suppressed motor neu-ron in our current series of patients.No conflict of interest



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MANAGEMENT OF HEMIFACIAL SPASM: A TUNISIAN EXPERIENCEH. Benrhouma1,*, A. Ben mahmoud1, I. Rebai1, H. Touaiti1, N. Gouider-Khouja1, I. Turki11Movement Disorders and Botulinum Toxin clinic, Institute Mongi Ben Hmida of Neurology, Tunis, Tunisia

Objectives: To describe demographic, clinical and therapeutic characteristics of Tunisian patients with hemifacial spasm (HFS) treated with botulinum toxin type A (Bt A).Methods: We conducted a retrospective study over a 18-year period including all patients diagnosed with HFS and treated with BtA. Clinical characteristics, etiologies and management were analyzed.Results: Fifty one patients were included (sex ratio 0.7, mean age: 59.6 years; mean age of onset: 48.3 years). Main clinical features were a clonic spasm in left side of the face. Main etiologies were: compressive lesion (52.9%), Bell’s palsy (43.1%), idiopathic (4%). Main BTA dose was 60U. A good response to treatment was observed in 51.9% of patients with a satisfactory return to daily activities and work. Average total duration of therapeutic response was 11.5 weeks. Local side effects observed were: ptosis (7.8%), drooping of the labial commissure (5.8%) and tearing (1.9%).Conclusions: HFS is usually caused by vascular compression of cranial nerve VII. Bt A provides effective results in the treatment of HFS. It should be performed in every patient with HFS whatever its etiology.References1. Hemifacial spasm: conservative and surgical treatment options.

Rosenstengel C, Matthes M, Baldauf J, Fleck S, Schroeder H. Dtsch Arztebl Int. 2012 Oct;109(41):667–73

2. Botulinum toxin in hemifacial spasm: Revisited. Singh S. Indian J Plast Surg. 2013 Jan;46(1):159–60

3. Safety and efficacy of botulinum toxin in hemifacial spasm. Mazlout H, Kamoun Gargouri H, Triki W, Kéfi S, Brour J, El Afrit MA, Chéour M, Kraiem A. J Fr Ophtalmol. 2013 Mar;36(3):242–6


408

COMPARISON OF DOUBLE MONOPOLAR AND INTERLEAVING STIMULATION MODES IN THE TREATMENT OF PRIMARY DYSTONIAN. Kovács1,*, E. Bosnyák2, G. Deli2, I. Balás2, T. Dóczi1, J. Janszky1, S. Komoly2

1MTA-PTE MR Research Group, University of Pécs, Pécs, Hungary, 2Department of Neurology, University of Pécs, Pécs, Hungary

Objectives: To systematically compare the efficacy and side-effect profile of double monopolar stimulation mode to those of interleaving stimulation mode in a prospective, randomized, double-blind and cross-over study.Methods: This randomized, cross-over, double-blind study was initiated in 2012 and is expected to be completed by 2015. An estimation of 20 patients with primary generalized or segmental dystonia is planned to be enrolled.Design: double-blind, cross-over.Results: The interim analysis of 9 patients is presented. Average age was 33.5 ± 16.2 years. The size of improvement during the double monopolar phase was 43.7 ± 9.3%, whereas in the interleaving phase it was 55.6 ± 7.5% (p = 0.13).Conclusions: For the treatment of drug-refractory dystonia, bilateral pallidal deep brain stimulation (GPi-DBS) is proven to be an efficient option. On aver-age, 40–55% improvement on dystonia rating scales (DRS) could be achieved according to the results of multicenter trials lasting for years. However, a considerable portion (10–25%) of patients experience minimal alleviation despite of good electrode placement. These patients can be regarded as non-responders to GPi-DBS defined as having either limited improvement (less than 25% on DRS) or worsening.Although our preliminary findings are promising, more data is required to reach the statistical power and draw the conclusion that interleaving stimulation might be superior to double monopolar stimulation in the treatment of primary dystonia.References1. Deli G et al. Ideggyogy Sz 2012;65(7–8):249–260.2. Kovacs N et al. Mov Disord 2012;27(1):163–165.

409

ACUTE POSITIONAL DYSTONIA AFTER ANTIPSYCHOTIC DRUG ADMINISTRATION IN A PATIENT WITH POSTTRAUMATIC INTRACEREBRAL HEMATOMAC. Falup-Pecurariu1,*, R. Mircea2, M. Moarcas3, O. Falup-Pecurariu4, R. Alexandru1, R. Chiperi31Department of Neurology, Faculty of Medicine Transilvania University, Brasov, Romania, 2Department of Neurosurgery, Emergency County University Hospital, Brasov, Romania, 3Department of Neurology, Emergency County

University Hospital, Brasov, Romania, 4Department of Pediatrics, Faculty of Medicine Transilvania University, Brasov, Romania

Objectives: Acute dystonia can appear shortly after administration of typical antipsychotic drugs in a dose dependant fashion, more frequently in males and in younger ages.Methods: We report the case of a 69 year old male who had been admitted for a head trauma with loss of consciousness following a car accident. Brain CT scan showed left temporal and right parietal intraparenchimal hematomas and minimal subarachnoid hemorrhage.Results: Three days after admittance, the patient had nocturnal episodes of psychomotor agitation for which there was administered Haloperidole. At 7 hours after that, he developed acute dystonia of left limbs triggered by dor-sal decubitus position. The episodes were painfull, lasted between 30 and 120 seconds and were very frequent (50–200/day). Administration of Haloperidole was stopped and there was prescribed Carbamazepine. After 12 days the patient did not present any dystonia. The patient presented left hemiparesis that aggravated in the 5th day after onset. The motor deficit got better in time with conservatory treatment, remaining a mild left hemiparesis.Conclusions: Acute dystonia may appear following intracranial hematoma, but also secondary to administration of typical antypsychotics.No conflict of interest

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CASE REPORT ON WILSON’S DISEASE:HOW FAR THE WRONG DIAGNOSIS COULD GO?A. Avetisyan1,*, K. Harutyunyan1, A. Voskanyan1, I. Gabrielyan1, A. Karapetyan1, E. Gevorgyan1, H. Manvelyan1

1Neurology, Yerevan State Medical University after M. Heratsi, Yerevan, Armenia

Objectives: 27 years old female patient with 7 months history of difficulty in motility and speech was seen in several clinics. Diagnosis of Parkinson+ syn-drome, hysteria, encephalitis, early dementia were proposed. She underwent brain MRI scan which despite the presence of hyperintensive depatchments in basal ganglia and phenotypical changes in pons (‘giant panda face’) was described as normal.Methods: Thoughtful neurological investigation found extrapyramidal syn-drome with increased muscle tone, slurred speech, cognitive impairment and mild rest tremor. Serum ceruloplasmine level was 0.08 g/L, blood copper was 6.3 μmol/l. 24 hours urinary copper excretion was 124 μg/day. Bilateral Kayser-Fleischer rings were present.Results: Clinical features and MRI findings prove the diagnoses of Wilson’s disease and treatment with zinc acetate was initiated.Conclusions: The lack of knowledge in Wilson’s disease’s presentation leads to delay in intime diagnostics of Wilson’s disease, whereas treatment delay could be paramount for the management of copper induced degeneration.Reference1. Allan H. Ropper, Martin A. Samuels. Adams & Victor’s Principles of

Neurology, 9e.No conflict of interest

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HEMORRHAGIC SYNDROME IN WILSON’S DISEASE PATIENTSM. Melnikova1,*, T. Fedorova1, S. Lobzin1, E. Panina1, K. Raikhelson1, L. Tarkovskaya2, N. Silina2, O. Smirnova2

1Neurology, North-Western State Medical University named after I.I. Mechnikov, Saint-Petersburg, Russia, 2Neurology, Russian Research Institute of Hematology and Transfusiology, Saint-Petersburg, Russia

Objectives: To investigate the incidence of hemorrhagic syndrome (HS) and disturbances of platelet and plasma coagulation hemostasis in patients with Wilson’s disease (WD).Methods: 68 patients (27 ± 13 years) with WD and 65 patients with other liver diseases (LDG) were examined retrospectively about different spontaneous or easy provoked signs of HS they had in anamnesis. The time interval, included in the test, was since the birth till the time when diagnosis was established and chelating treatment was started. 65 normal individuals were examined as the control group (CG). Parameters of platelet and plasma coagulation hemosta-sis were evaluated in 48 patients with WD.Results: The percentage of patients with WD, who presented hemorrhagic signs, was 52% at the age of 3–9 years and increased to 77% at the time when diagnosis was established. It was significantly higher than in the CG and LDG (p < 0.05). The most typical hemorrhagic signs were nasal and gin-gival bleeding and bruises (petechial type of bleeding) and in 68% of patients they repeated daily or weekly. 95% of patients with WD had abnormal labora-tory parameters of hemostasis: thrombocytopenia, increase of intravascular



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platelet activation and aggregation, increased vWF activity (p < 0.01), prolongation of APTT, decrease of PT (because of reduced activity of factors V, VII and X) (p < 0.01), decreased activity of AT (p < 0.01) and plasmino-gen level (p = 0.05) and diminished time of factor XII-dependent fibrinolysis, elevated level of D-dimer (p < 0.01).Conclusions: Patients with WD demonstrate the high incidence of HS in com-parison with patients with other liver disorders.Reference1. Wilson’s disease, hemorrhagic syndromeNo conflict of interest

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POLYCYTHEMIA VERA, A TREATABLE CAUSE OF CHOREA IN THE ELDERLYH. Kim1,*, H. Lee2, H.J. Kang3, S.H. Han1

1Department of Neurology, Konkuk University Medical Center, Seoul, Korea, 2Department of Hematology, Konkuk University Medical Center, Seoul, Korea, 3Department of Neurology, Seonam Hospital, Seoul, Korea

Objectives: Chorea is an involuntary movement disorder characterized by continuous, abrupt, rapid, and irregular movement. The differential diagno-sis of chorea is broad including vascular, hereditary, metabolic, autoimmune, infectious or drug induced cases. Polycythemia vera is also a well known, but rare cause of chorea.Methods: We report on a patient with sudden onset chorea associated with polycythemia vera.Results: A 76-year-old woman presented our outpatient clinic with sud-den onset chorea which developed 1 month before her visit. Chorea was generalized, but prominent in lower face and upper limbs. Physical exami-nation showed reddish coloration of the skin. Laboratory findings showed increased levels of hemoglobin at 22.1 g/dl and hematocrit at 66.1%. Brain magnetic resonance imaging showed high signal intensity along the cortical vessels on FLAIR and T1-weighted images with nonspecific T2 high sig-nal intensity in the cerebral deep white matter. A diagnosis of polycytemia vera-associated chorea was obtained. After repeated phlebotomy and treat-ment with hydroxyurea, hemoglobin level was normalized and chorea was disappeared.Conclusions: This case emphasizes that in elderly patients with chorea, poly-cythemia vera should be considered as one of the treatable causes.References1. Midi I, Dib H, Köseoglu M, Afsar N, Günal DI. Hemichorea associated with

polycythaemia vera. Neurol Sci. 2006;27(6):439–41.2. Kim W, Kim JS, Lee KS, Kim YI, Park CW, Chung YA. No evidence of

perfusion abnormalities in the basal ganglia of a patient with general-ized chorea-ballism and polycythaemia vera: analysis using subtraction SPECT co-registered to MRI. Neurol Sci. 2008;29(5):351–4.


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DRUGS RELATED TO TOURETTE-LIKE SYNDROME: A CASE/NON-CASE STUDY IN THE FRENCH PHARMACOVIGILANCE DATABASE AND A COMPARISON WITH CASES REPORTED IN THE LITERATURES. Perez Lloret1,*, M.V. Rey1, E. Bondon-Guitton1, O. Rascol1, J.L. Montastruc1, French Network of Regional Pharmacovigilance Centers1

1Pharmacology department, Paul Sabatier University, Toulouse, France

Objectives: The objective of this study was to detect alert signals of drugs potentially connected with Tourette-like syndrome in the French Pharmacovigilance Database (FPVD) and to compare these reports with cases published in general medical literature.Methods: We selected all reports of Adverse Drug Reactions from 1st January 1984 to 31st December 2010 coded by MeDRA as “tics” or “Tourette syndrome”. Reporting Odds Ratios (ROR) and their 95% confidence intervals were calculated for “suspected” drugs. We performed a search in Pubmed cov-ering the same period of drug-induced Tourette syndrome or tics. Suspected drugs were extracted from articles found.Results: 36 reports were found (66% were females, median age was 14 years). Alert signals were detected for hidden neuroleptics such as metoclopramide, oxatomide or niaprazine (ROR = 11.65 [3.57–38.01]), vaccines against Influenza H1N1 Virus (2 cases; 51.06 [12.23–213.11]) or Hepatitis B virus (4 cases; 15.65 [5.53–44.28]), tramadol (3 cases; 9.64 [2.96–31.45]), methylphe-nidate (6 cases; 541.62 [222.25–1319.88]) or serotoninergic antidepressants such as fluoxetine, fluvoxamine, mirtazapine, venlafaxine or agomelatine (10.47 [4.07–26.94]). We found 157 case reports in the literature. Cases with psychostimulants or neuroleptics were more frequent in the literature. Conversely, cases with hidden neuroleptics, vaccines or opioids were more frequent in the FPVD, whereas cases with antiepileptics or antidepressants were equally represented in both sources.

Conclusions: We found alert signals of tourette-like syndrome in connection with hidden neuroleptics, tramadol, methylphenidate or serotoninergic anti-depressants. Reports of drugs classically connected to Tourette were more frequent in the Literature, whereas “unexpected” cases were more frequently reported to the FPVD.No conflict of interest

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COMPARISON OF EFFECTS OF A PHYSIOTHERAPIST-SUPERVISED EXERCISE PROGRAM WITH A SELF AND CAREGIVERS SUPERVISED ON THE MOTOR SYMPTONS OF HUNTINGTON’S DISEASE (HD).T.T.C. Capato1,*, M.S. Haddad2, E. Gonçalves1, P. Avila3, M.E.P. Piemonte1, E.R. Barbosa2

1Physiotherapy, University of Sao Paulo, Sao Paulo, Brazil, 2Neurology, University of Sao Paulo, Sao Paulo, Brazil, 3Physicaltherapy, University of Sao Paulo, Sao Paulo, Brazil

Objectives: The objective was verify the comparison of effects of Physiotherapist-Supervised (PTS) with Exercise Program and a Self (SS) and Caregiver (CS) -Supervised on the motor Symptoms of Huntington’s Disease patients.Methods: A single-blinded trial, 35 HD patients divided on 3 groups, were examiner before and after 10 training sessions (once in a week during 45 min) and after 60 days of the end of the training. Balance was assessed by BBS and Mini BESTest and gait by TUG. Mobility was evaluated by FIM. Through interviews independence to AVDs was assessed; motor performance through UHDRS and FC. The cognition was assessed to MOCA and MEEM. All sub-jects have HD diagnosis genetically confirmed and they were expected to understand tests and exercises sequences according to inclusion criteria. During the study period there wasn’t medication changing. The first Group PTS, comprised generalized exercises with external cues Warming (10 m, stretching, mobility and motor control); Main Part (30 m gait cues, balance and functional, activities, attention strategies; Relaxation (5 m breathing exercises and trunk control). The second group (SS) receives a book for to do exercises at home alone and the last one (CS) did the same exercises with their family. The control group receives orientations and no exercises.Results: The results showed a significant improvement after treatment in all groups, to gait, balance and mobility improvement. After 60 days there are scores maintenance. There were significant differences for the PTSConclusions: A SS and CS improve motor Symptoms of HD patients, the effects of the training were a significant difference with the PTSNo conflict of interest

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MITOCHONDRIA TARGETED THERAPY IMPROVES LOCOMOTOR AND COGNITIVE DEFICITS OBSERVED IN EXPERIMENTAL MODEL OF HUNTINGTON’S DISEASEM. Arpit1,*1Biochemistry, Punjab University Chandigarh, Chandigarh, India

Objectives: The present study was carried out to evaluate the beneficial effect of mitochondrial antioxidants supplementation to animals on various locomo-tor and cognitive deficits using automatic Anymaze video tracking system and whether these alterations were related to striatal degeneration.Methods: Animal model of HD was developed by administering rats with sub-chronic dosage of 3-NP twice daily for 17 days and later subjecting to test their behavioural performance using Anymaze software for testing their locomo-tor abilities & cognitive deficits. HD treated animals received mitochondrial antioxidants supplementation for 21 days. Initially, before the start of 3-NP exposure, animals in all groups were trained extensively for each task for their better performance.Results: At the end of the study, 3-NP treated animals showed a significant impairment in motor functions including decreased stride length, increased distance between inner toes, increased gait angle and increased transfer latency on elevated plus maze task, which correlated with increased histo-pathological changes in terms of enhanced gliosis in neurons. The cognitive ability of animals on performing morris water maze task for assessing spatial memory was poorly reflected by 3-NP induced HD animals. However, sup-plementing HD treated animals with combination of mitochondrial antioxidants improved locomotor and cognitive performance.Conclusions: The study thus concluded that, analysis of disturbed walking pattern and poor cognitive ability are sensitive indicators to correlate behav-ioural changes with respect to striatal degeneration induced by 3-NP expo-sure. However, combined supplementation to 3-NP administered animals with mitochondrial antioxidants efficiently improved behavioural performance and histological changes.



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References1. Sandhir et al, 2010, 2012.2. Sandhir & Mehrotra, 20133. Beal et al., 1993No conflict of interest

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ROLE OF NEUROSTEROIDS IN EXPERIMENTAL 3-NITROPROPIONIC ACID INDUCED HUNTINGTON’S DISEASE IN RATS: POSSIBLE ROLE OXIDATIVE STRESS AND NEUROINFLAMMATIONP. Bansal1,*, K. Pusphender2, R. Deshmukh2, P.L. Sharma2

1Pharmacology, University Institute of Pharmacy Baba Farid University of Health Sciences, Barnala, India, 2Pharmacology, ISF College of Pharmacy, Moga, India

Objectives: Huntington’s disease is an fatal neurodegenerative disease char-acterized by progressively worsening chorea and psychiatric disturbance. Systemic administration of 3-Nitropropionic acid (3-NP), a complex II inhibitor of the electron transport chain induces selective striatal lesions in rodents and a well established model for HD. Neurosteroids are synthesized in nervous system, able to modulate GABAA receptor function and has been reported to have neuroprotective action.The present study explore the role neurosteroids such as progesterone (PROG) positive and pregnenolone (PREG) negative modulators of GABA against 3-NP induced experimental HD.Methods: Systemic administration of 3- NP (10 mg/kg i.p) for 14 days sig-nificantly reduced body weight, locomotor activity, grip strength, balance beam walk performance, % memory retention, antioxidant defense enzymes significantly increase oxidative stress markers in striatum and cortex. 3-NP treatment also increases pro-inflammatory cytokines (TNF-α and IL-1β) level in striatum.Results: Progesterone (10, 20, mg/kg/day i.p) treatments for 14 days sig-nificantly restore the behavioral, antioxidant defense enzymes, and attenu-ate oxidative defense and pro-inflammatory cytokines as compared to the 3-NP treated group. PREG (1 and 2 mg/kg i.p) pretreatment significantly reversed the protective effect of PROG on behavioral and biochemical parameters.Conclusions: The results of the present study suggest that the positive GABAergic modulation may be beneficial for the treatment of motor disorderReferences1. Modulatory effect of neurosteroids in haloperidol-induced vacuous chew-

ing movements and related behaviors. Psychopharmacology (Berl) 196, 243–254.

2. Role of LOX/COX pathways in 3-nitropropionic acid-induced Huntington’s disease-like symptoms in rats: protective effect of licofelone. Br J Pharmacol 164 (2b):644–654


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PAROXYSMAL HYPNOGENIC DYSKINESIA: A CASE REPORT AND BRIEF REVIEWL. Almeida1,*, L.S. Dure2

1Department of Neurology, University of Alabama at Birmingham, Birmingham, USA, 2Department of Pediatrics Division of Pediatric Neurology, University of Alabama at Birmingham, Birmingham, USA

Objectives: To report a case of a patient diagnosed with paroxysmal hypno-genic dyskinesia (PHD) and provide a review of the literature.Methods: With informed consent, we report the clinical presentation for the patient and the treatment proposed. Through an online database search we reviewed the current literature on clinical aspects of PHD and anecdotal expe-riences from other authors.Results: We present a 13-year old female with no significant previous his-tory presenting for evaluation of abnormal movements occurring during sleep, consisting of stiffening of the limbs bilaterally and random flailing of the arms and legs lasting less than 1 minute, occurring several times per night. Daytime episodes were reported, but were rare. She could interact and follow commands during the spells and remember the ones occurring during the day. Outside of the spells, there were no other complaints and she had no cognitive abnormalities. She is adopted, so there was no clear family history available.After extensive workup she was given a diagnosis of PHD and started on oxcarbazepine 300 mg at bedtime in addition to clonazepam, and on subse-quent follow up visits patient and family deny any further episodes.Conclusions: PHD typically occurs during non-REM sleep, and episodes are short in duration, and typically result in fragmented sleep. Little is known about PHD and there is no established treatment. Most of the experience is

shared through case reports, and medical management is based on treatment of other more common paroxysmal dyskinesias.Reference1. M. Demirkiran and J. Jankovic, “Paroxysmal Dyskinesias : Clinical

Features and Classlfication,” Ann Neurol 38: 571–579, 1995No conflict of interest

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PAROXYSMAL NON-KINESIGENIC DYSKINESIA IN A PATIENT WITH SPASTIC PARAPARESISC. Falup-Pecurariu1,*, R. Mircea2, M. Moarcas3, R. Chiperi3, R. Alexandru1

1Department of Neurology, Faculty of Medicine Transilvania University, Brasov, Romania, 2Department of Neurosurgery, Emergency County University Hospital, Brasov, Romania, 3Department of Neurology, Emergency County University Hospital, Brasov, Romania

Objectives: Paroxysmal non-kinesigenic dyskinesia (PKND) is a rare group of hyperkinetic movement disorders.Methods: We report the case of a 41 year old woman without significant past medical history who was initially admitted for acute onset paraparesis. Cranial and spinal MRI were normal. The symptomatology progressed over months. The patient complains also of pain in all limbs.Results: The patient started to present attacks of paroxysmal non-kinesigenic dyskinesia manifested as chorea and dystonia at 8 months after diagnoses of disease. In the first month there were 1 attack per week, after 3 months there were 1–2 per day and in present 7–8 severe attackes per day. The attacks are lasting 2–10 minutes, are very painful and are precipitated by fatigue and stress. Sometimes the attack occur without any precipitating factors. There are no aura-like symptoms before the attacks.Episodes are encountered only when the patient is awake. There are no loss of conscious during the attack. After that the patient is polyuric. Between attacks the patient presents paraparesis and important spasticity in lower limbs.There were no response to benzodiazepines, carbamazepin, valproic acide, but partial response to acetazolamide.Conclusions: Paroxysmal non-kinesigenic dyskinesia is difficult to treat and could worsening during a short time.No conflict of interest

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CLINICAL CHARACTERISTICS OF PSYCHOGENIC TICSN. Szejko1,*, L. Milanowski1, P. Janik1

1Department of Neurology, Medical University of Warsaw, Warsaw, Poland

Objectives: To determine clinical characteristics and prevalence of PT.Methods: 268 consecutive patients (221 males, 82.5%), aged 4–54 years (mean: 18.4 ± 8.4), presenting with different phenotypes of tics were analyzed: Gilles de la Tourette syndrome (GTS, n = 255), chronic motor tics (n = 6), chronic vocal tics (n = 1), transient tics (n = 1), unclassified tics (n = 2), PT (n = 5).Results: PT were found in 5 patients (1.9%). Age at onset varied from 17 to 51 years (mean: 34.0 ± 16.6). Two patients with the onset of PT at 17 were diagnosed with GTS in childhood, in two adult patients mental disor-ders atypical for GTS were observed. In all of these patients administration of high doses of neuroleptics was ineffective. The clinical phenotype of PT included vocalizations (n = 3), arching the body (n = 1), tensing the whole body (n = 1), lack of suppressibility of tics (n = 5), severe intensity mak-ing the daily activity impossible (n = 5), constant intensity and localization (n = 5); subsiding in unpredictable situations (in recumbent position n = 1, while smoking cigarettes n = 1), lack of simple tics involving the head and the neck (n = 3).Conclusions: PT are rare and may appear in patients with GTS. The most reliable features differentiating PT from organic tics are: onset in adulthood, appearance at the time when organic tics decline in severity, complete inability to suppress, invariability in time and severity, disappearing in unpredictable positions.No conflict of interest

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PANDAS AND TIC DISORDERSS. Munasipova1,*, Z.A. Zalyalova1

1Neurology and Rehabilitation, Kazan State Medical University, Kazan, Russia

Objectives: Most of hyperkinetic syndromes that occur during childhood is an autoimmune caused by sensitization of the β-hemolytic streptococcus group A (BGSGA) and known as PANDAS.



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Methods: We examined 69 patients with tics in age from 6 to 29 years includ-ing 51% males and 49% female. The study’s design included a comparison of clinical and laboratory findings (ASL-O, swab to the BGSGA, ANA, JgA, JgM, JgG, CD4+, CD8+).Results Significant differences were observed in patients with a positive BGSGA (p < 0.01); with reduced CD4+ (p < 0.03); with reduced of JgA (p < 0.03).Conclusions BGSGA, CD4+, Jg A – according to our study are reliable diag-nostic value in the differentiation of idiopathic tic disorders and autoimmune nature and these characteristics can meet PANDAS.No conflict of interest

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OCULOGYRIC CRISIS DYSKINESIA IN PATIENTS WITH GILLES DE LA TOURETTE SYNDROMEM. Figura1,*, A. Jaskowiak1, P. Janik1

1Department of Neurology, Medical University of Warsaw, Warsaw, Poland

Objectives: Oculogyric crisis (OGC) is characterized by spasmodic devia-tions of the eyes, most commonly upwards, and is not frequently encountered complication from antidopaminergic medications in patients with Gilles de la Tourette syndrome (GTS).The aim of the study was to describe clinical phenotype of antidopaminergic-induced OGC dyskinesia in patients with GTS.Methods: 290 consecutive patients, aged 6 to 54 years, were analyzed. The duration of illness varied from 1 to 44 years.Results: OGC was characterized by recurrent episodes of upward gaze lasting from 1 to 4 hours per day and was found in three males. All patients were previ-ously exposed to other neuroleptics. Acute OGC (n = 1) was induced by the use of tetrabenazine at the dose of 62.5 mg daily and tardive OGC (n = 2) was related to haloperidol and risperidone at the dose of 6 mg and 4 mg, resp. per day. The age of OGC onset varied from 16 to 18 years. Acute OGC was devel-oped after 8 days of therapy with tetrabenazine. Exposure to neuroleptic was 2 and 3 years in case of tardive OGC. Duration of the disease was 7 years in the patient with acute OGC and 10 and 4 years in cases with tardive OGC. Acute OGC resolved after decrease of tetrabenazine dose to 37.5 mg daily. Tardive OGC resolved after 2 and 3 months after the discontinuation of neuroleptics.Conclusions: Ocular dystonia may occur as a complication from treatment with antidopaminergic medications in patients with GTS. Clinical outcome is good in non-adult patients.Reference1. Tardive and chronically recurrent oculogyric crises, P. Sachdev, Movement

Disorders, Volume 8, 1993No conflict of interest

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ORTHOSTATIC MYOCLONUS: A CLINICAL AND ELECTROPHYS-IOLOGICAL REVIEW OF 32 CONSECUTIVE PATIENTSJ.A. van Gerpen1,*1Neurology, Mayo Clinic, Jacksonville, USA

Objectives: To review the electrophysiological and clinical characteristics of 32 consecutive orthostatic myoclonus (OM) patients diagnosed at Mayo Clinic in Florida over 30 months.Methods: The database of the Mayo Clinic Florida Movement Disorder Laboratory was searched for all patients referred for possible OM or orthos-tatic tremor (OT) from 6/2010–12/2012. All clinical records and archived sur-face electromyographical data of these patients were reviewed and analyzed.Results: 32 patients were diagnosed with OM, 8 with OT, and 55 patients with neither were identified.Conclusions: OM, a relatively recently recognized disorder, has some similarities to OT, including causing “shaky legs.” Novel data from this study include the following: 1) As in OT, OM is alleviated by leaning forward on an object while standing, taking the majority of their weight off their legs; 2) OM may be a more common cause of “shaky legs” than OT; 3) Given that many patients without OM have similar gait and balance complaints and probable neurological disorders to those with it, OM is likely a pathological phenom-enon. This condition is potentially under-recognized and may contribute to gait instability in older patients.References1. Glass GA, Ahlskog JE, Matsumoto JY. Orthostatic myoclonus: a contribu-

tor to gait decline in selected elderly. Neurology 2007;68:1826–1830.2. Mestre TA, Lang AE, Ferreira JJ, et al. Associated movement disorders in

orthostatic tremor. J Neurol Neurosurg Psychiatry 2012;83:725–729.3. Shibasaki H, Hallett M. Electrophysiological studies of myoclonus. Muscle

Nerve 2005;31:157–174No conflict of interest

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SIMILAR PHENOTYPE AND GOOD RESPONSE OF MYOCLONIC JERKS TO LEVETIRACETAM IN THREE MITOCHONDRIAL DISEASESM. Schinwelski1,*, M. Krygier2, E.J. Sitek1, J. Kondracka3, J. Slawek1

1Neurological and Psychiatric Nursing, Medical University of Gdansk, Gdansk, Poland, 2Biology and Genetics, Medical University of Gdansk, Gdansk, Poland, 3Developmental Neurology, Medical University of Gdansk, Gdansk, Poland

Objectives: Mitochondrial diseases (MD) are associated with broad phe-notypic spectrum and a growing number of mitochondrial DNA (mt-DNA) mutations. We present three patients sharing phenotype characteristic for myoclonic epilepsy with red ragged fibers (MERRF), albeit caused by different mitochondrial mutations.Methods: Three patients: 26-y.o male (Patient no.1), 19-y.o. female (Patient no.2) and 23-y.o. female (Patient no.3) with unremarkable family history, asymptomatic until adolescence (18, 14 and 12 y.o. respectively) when multi-focal myoclonus appeared followed by generalized seizures and ataxia. In all cases symptoms did not respond to but even exacerbated after valproate. In Patients no. 1 and no. 3 headache, nausea and vomiting were also observed. In all patients administration of levetiracetam (LVT) resulted in significant improvement in myoclonus.Results: In Patient no.1 genotyping for common mt-DNA mutations was nega-tive. However, further testing evidenced very rare 13042G>A in ND5 gene mutation. In Patient no. 2 8344 A>G mt-DNA mutation, most common for MERRF, was detected. In Patient no.3 the sequencing of POLG gene evi-denced W748S point mutation associated with mitochondrial recessive ataxia syndrome (MIRAS).Conclusions: It is widely known that myoclonus and seizures in young patients could be associated with MD. However, our case series shows that MERRF phenotype may be caused by different mutations. Thus, care-ful genetic examination is needed before MD is excluded. Furthermore, LVT seems to be the treatment of choice for myoclonic jerks in MD.No conflict of interest

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CREUTZFELDT-JACOB DISEASE: A CASE REPORTD. Imamovic1,*, N. Subasic1, J. Djelilovic1, E. Suljic1

1Neurology Clinic, University Clinical Center of Sarajevo, Sarajevo, Bosnia and Herzegovina

Objectives:Introduction: Classic CJD is a human prion disease. This disease is rapidly progressive and always fatal. Infection with this disease leads to death usually within 1 year of onset of illness. Typically, onset of symptoms occurs at about age 60. There is currently no single diagnostic test for CJD.Methods:Results:Case presentation: 63 years old female patient referred with complaints of weak-ness and anxiety, insomnia, depression, lack of coordination, failing memory.Neurological exam: right cerebral hemiparesis. CT were with hipodense area in left parietal lobe. Illness progresses rapidly, with myoclonic contractions of various muscle groups appear, at first unilaterally, later becoming generalized. In general, the myoclonic jerks are evocable by sensory stimuli of all sorts, but they occure spontaneously as well. Hypertonus extrapyramidal and pyramidal tipe, caracteristic pathways. CSF with slow elevation gama globulin (IgG), but could not be tested for 14-3-3 protein, as facility is not available in Bosnia and Herzegovina.EEG: electroencephalography followed longitudinaly, and shous characteristic changes indicating Creutzfeldt Jakob disease.MRI: In T2 weighted MR images discret hiperintense basal ganglia, left pari-etal lobe with ischemic lesion, about 1 cm.The pacient became afonic, anartric, with afagia, and cortical blind.She was dismissed at social helth care, later at home, and illness was contin-ued for about 3 month.Conclusions: Final dg: Encephalopathia spongiformis. Magnetic resonance imaging (MRI) brain scans with characteristic patterns of brain degeneration in this case was helped to clinical diagnosis. Autopsy was not done.No conflict of interest

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EVALUATION OF STOCHASTIC VIBRATION THERAPY IN SPINOCER-EBELLAR ATAXIAS 1, 2, 3 AND 6O. Kaut1,*, A. Prochnicki1, H. Jacobi1, C. Coch2, M. Minnerop3, T. Klockgether1, U. Wüllner1

1Neurology, University Hospital of Bonn, Bonn, Germany, 2CSSC (Clinical Study Support Core), Pharmacology, Bonn, Germany, 3Institute of Neurosciences and Medicine (INM-1), Research Centre Jülich, Jülich, Germany



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Objectives: Spinocerebellar ataxias (SCAs) are a group of inherited dis-eases characterized by progressive imbalance and incoordination as well as speech problems. Treating ataxia is still a major challenge in clinical neurol-ogy. Stochastic whole body vibration (sWBV) is a biomechanical treatment used widely in rehabilitation. Since sWBV has been found to mitigate symp-toms in Parkinson’s disease, it might also have positive effects in the case of SCA.Methods: We examined the effect of sWBV on ataxia in SCA 1, 2, 3 and 6 in a single-center double-blind sham-controlled study. SWBV was applied on 4 days, each treatment consisting of 5 stimulus trains of 60 seconds at a fre-quency 6.5 Hz and 60 seconds resting time between stimuli (verum, n = 17). Patients allocated to the sham group received the same treatment with 1 Hz (n = 15). Patients were rated at baseline and after the last treatment using clinical scores (SARA, SCAFI, INAS).Results: After treatment we found significant improvement of functional gains in gait and posture (SARA subitems 1, 2, 3; p = 0.023), speed of walking (8 MW; p = 0.02) and speed of speech (PATA; p = 0.02) in com-parison to sham. While scores of limb kinetics and ataxia of speech did not respond.Conclusions: Stochastic sWBV might act on proprioceptive mechanisms and could also stimulate non-cerebellar/compensatory mechanisms. Although the involved neuronal loops cannot be deciphered at present, the use of sWBV seems to provide a novel functional relevant supplementation for treating ataxia.No conflict of interest

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COGNITIVE IMPAIRMENTS AS DIAGNOSTIC MARKERS FOR ADHD: AN OVERVIEWR. Gupta1,*1Centre of Behavioural and Cognitive Sciences, University of Allahabad, Allahabad, India

Objectives: The present study evaluated the diagnostic capabilities of certain measures based on cognitive-motivational tests that were chosen with respect to the specific cognitive deficits in Attention Deficit Hyperactivity Disorder (ADHD).Methods: A total of 240 children (120 with ADHD and 120 healthy controls) in the age range of 6–9 years and 32 children with Oppositional Defiant Disorder (ODD) (aged 9 years) participated in the study. Stop-signal, attentional- disengagement, attentional-network, and choice-delay test were administered to all the participants. A total of nineteen parameters were derived from the four tests. Receiver operating characteristic (ROC) analysis and multinomial logistic regression (MLR) was performed to examine the diagnostic efficiency of each parameter.Results: Data fusion produced improved overall diagnostic accuracy and a combination of stop-signal reaction time, post-error-slowing, mean delay, switch costs, and %LDR produced overall classification accuracy of 97.8% and with internal validation, the overall accuracy was 92.2%.Conclusions: Combining performance from different tests enabled an accurate classification of ADHD children from healthy controls and those with ODD. The present study provides markers based on neuro-cognitive measures for the diagnosis of ADHD with higher sensitivity and specific-ity in classification. The study has theoretical and clinical implications for the theories of executive control mechanisms that underlie the pathology of ADHD.Reference1. Barkley, R.A. (1997). Behavioral inhibition, sustained attention, and executive

functions: Constructing a unifying theory of AD/HD. Psychol Bull, 121, 65–94.No conflict of interest

427

PREVALENCE OF DEMENTIA-CAUSED DISABILITY AMONG CHINESE OLDER ADULTS: A NATIONAL POPULATION BASED SURVEYX.Y. Zheng1,*, N. Li11Institute of Population Research, Peking University, Beijing, China

Objectives: In this study, using a population based survey data we aimed to describe the prevalence rate of dementia-caused disability, its associated fac-tors, and daily activities and social functions of people with dementia-caused disability in Chinese elderly people.Methods: We used the second China National Sample Survey on Disability, comprising 2,526,145 persons from 771,797 households. Identification for dementia was based on consensus manuals. Standard weighting procedures were employed to construct sample weights considering the multistage strati-fied cluster sampling survey scheme. Population weighted numbers, weighted prevalence, and the Odd Ratios (OR) were calculated.

Results: The prevalence rate of dementia-caused disability was 4.64‰ (95% CI = 4.26–5.01) and it accounted for 41.03% of mental disability among Chinese elderly people. Urban residence (OR = 1.33 [1.12–1.57]), older age (80+) (OR = 4.12 [3.38–5.03]), illiterate (OR = 1.79 [1.27–2.53]), and cur-rently not married (OR = 1.15 [1.00–1.32]) were associated with increased risk of dementia-caused disability. Compared with those with mental disability of other causes and those with other disabilities, older adults with dementia-caused disability were more likely to have severe or extreme difficulty in daily activities and social functions.Conclusions: Countermeasures are warranted to obtain a more precise overview of dementia in China, and strategies on enhancing early identi-fication, treatment, and rehabilitation should be developed for people with dementia.Reference1. Due to rapid population aging and a tidal wave of dementia in China, de-

mentia has become an urgent public health issue. Few large-scale sur-veys on dementia were conducted in China and little was known about the magnitude of dysfunction and disability caused by dementia.


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AN INVESTIGATION ON POTENTIAL BIOMARKERS IN THE SERUM OF PATIENTS WITH ALZHEIMER’S DISEASEL.J. Zuo1,*, S.Y. Yu1, C.J. Cao1, F. Wang1, Y. Hu1, Z.J. Chen1, X.Y. Huang1, L. Sun1, Z. Liu1, W. Zhang1


Objectives: To investigate potential biomarkers in the serum of patients with Alzheimer’s disease (AD).Methods: (1) 20 AD patients and 30 healthy controls were evaluated by MMSE, MoCA and clinical dementia rating (CDR) scales;(2) Blood were col-lected and detected the levels of β-amyloid protion (Aβ)1–42 oligomer, iron and its metabolism-related proteins including ferritin (Fer), transferrin (Tf) and lactoferrin (Lf), neuroinflammatory factors including nitric oxide (NO), interleukin-1β (IL-1β), prostaglandin E2 and tumor necrosis factor-α, and anti-oxidative factor of total superoxide dismutase (tSOD);(3) The levels of above factors were analyzed between AD and control subjects.Results: (1) The level of Aβ1–42 oligomer was significantly decreased, which might be results from the increased Aβ1–42 deposition in brain;(2) Abnomal iron metabolism was shown by the dramatically increased levels of Fer, Tf and Lf, which might lead to excessively deposited iron in brain and subsequently reduced iron level in serum;(3) The levels of NO and IL-1β in serum of patients were remarkably elevated, revealing a pivotal role of neuroinflammation in AD;(4) tSOD level in serum of patients was markedly declined, suggesting an obviously compromised anti-oxidative ability in AD.Conclusions: Aβ1–42 oligomer, iron and its metabolism-related proteins (Fer, Tf and Lf), neuroinflammatory factors (NO and IL-1β) and anti-oxidative factor (tSOD) in serum might serve as the potential biomarkers of AD.No conflict of interest

429

A BOTULINUM TOXIN TYPE-A TOPICAL GEL IS EFFECTIVE FOR CHRONIC MIGRAINE HEADACHE PROPHYLAXIS IN ADULTS. RESULTS OF A PHASE 2, DOUBLE-BLIND, PLACEBO-CONTROLLED PILOT STUDYE. Lim1,*, L.L. Yeo2, A.W. Chow1, J. Waugh3

1Medicine, National University of Singapore, Singapore, Singapore, 2Medicine, National University Hospital Singapore, Singapore, Singapore, 3Revance, Revance Therapeutics, San Francisco, USA

Objectives: Injections of botulinum toxin type-A (BoNTA) are effective for chronic migraine prophylaxis. RT001 is a topical gel containing puri-fied 150 kDa BoNTA and an absorption-enhancing peptide, enabling the percutaneous delivery of botulinum toxin to underlying muscles. To evaluate the safety and efficacy of RT001 for chronic migraine headache prophylaxis in adults, thereby avoiding the need for injections.Methods: The study enrolled 40 adult male and female patients who suffered from episodic migraine (approximately 6 per month) without aura during the preceding 3 months but who were otherwise healthy. Patients were rand-omized to undergo a single treatment with RT001 gel containing RT001 or placebo. Both products were applied to six specific sites on the head and neck areas, left on the skin for 30 minutes, and then removed. The primary endpoint was the proportion of patients achieving a ≥50% improvement in a composite of the Headache Impact Test (HIT); the number of migraines and intensity of migraines at Week 4 following treatment.Results: Among RT001-treated patients, 43.8% achieved a ≥50% improve-ment in composite score vs. 10.5% placebo-treated patients (p < 0.05). The



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mean change in baseline HIT scores were −5.4 and −2.1 for RT001- and pla-cebo-treated patients, respectively. RT001 decreased migraine frequency by a mean of 48.8% and peak intensity by 25% vs. 19.7% (p = 0.052) and 4.7% (p = 0.067) for placebo-treated patients, respectively. Adverse events were similar in both groups.Conclusions: RT001 appears to be safe and effective for chronic migraine headache prophylaxis in adults.

DAY 3, WEDNESDAY, DECEMBER 11, 2013

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THE EFFECTS OF NEUROTROPHIC FACTORS CDNF AND MANF ON STRIATAL DOPAMINE – MICRODIALYSIS STUDY IN RATSJ.M. Renko1,*, S. Bäck1, M.H. Voutilainen1, T.P. Piepponen1, M. Saarma2, R.K. Tuominen1

1Division of Pharmacology and Toxicology Faculty of Pharmacy, University of Helsinki, Helsinki, Finland, 2Institute of Biotechnology, University of Helsinki, Helsinki, Finland

Objectives: Neurotrophic factors are secreted proteins which promote the survival of neurons. They might be beneficial for the treatment of neurodegen-erative disorders like Parkinson’s disease. The aim of the study was to clarify the effects of CDNF, MANF and GDNF on dopaminergic neurotransmission within the striatum of freely moving rats.Methods: Neurotrophic factors (10 μg) or PBS were injected stereotaxically into the left striatum of intact male Wistar rats. Microdialysis experiments were performed one and 3 weeks after the treatment. During the experiments neu-rotransmission was stimulated by replacing perfusion solution with K+-solution (100 mM) and with amphetamine solution (100 μM), respectively. The concen-tration of dopamine, DOPAC, HVA and 5-HIAA was measured from dialysates with HPLC.Results: The stimulus-evoked release of dopamine increased in MANF and CDNF groups compared to GDNF and PBS groups 1 week after the treatment. Three weeks after the treatment the release of dopamine was still increased in MANF group. Also dopamine-turnover was increased in MANF group com-pared to GDNF and PBS groups 1 week after the treatment. DOPAC/HVA-ratio was significantly smaller in GDNF group than in the other groups 1 week after the treatment. The baseline concentrations of dopamine and metabolites did not differ between the treatment groups.Conclusions: These findings suggest that MANF and CDNF potentiate dopaminergic neurotransmission. Their effect seems to be stronger than that of GDNF. MANF also increases the metabolism of dopamine. The potentiation of neurotransmission could be e.g. due to increased biosynthesis of dopa-mine, increased sprouting or potentiation of the function of nerve terminals.No conflict of interest.

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SELECTIVE D2 RECEPTOR AGONIST PIRIBEDIL PREVENTS MEMORY DEFICITS INDUCED BY PEDUNCULOPONTINE TEGMENTAL NUCLEUS LESION IN THE OBJECT RECOGNITION TESTA. Targa1, L. Rodrigues1, A. Noseda1, M. Fortes1, M. Lima1,*1Physiology, Federal University of Paraná, Curitiba, Brazil

Objectives: The aim of this study was to investigate the cognitive effects of a selective lesion of the pedunculopontine tegmental nucleus (PPT) associated to a pharmacological and paradoxical sleep (dopaminergic-induced supersen-sitivity) modulation of the striatal D2 receptor.Methods: The Wistar rats underwent stereotaxic surgery for bilateral can-nula implantation within the striatum and direct infusion of ibotenic acid or phosphate buffer in the PPT. Seven days after, the animals were exposed to the paradoxical sleep deprivation (PSP), followed by D2 receptor agonist (piribedil, 3 mg/ml), antagonist (Raclopride, 10 mg/ml) or vehicle (DMSO) administration. The cognitive task employed was the object recognition test (performed 30 min after the infusions).Results: These concentrations were determined by a concentration-response curve, which revealed that piribedil and, surprisingly, raclopride improved cog-nitive parameters. The PPT-lesioned group spent less time exploring the novel object, compared to sham animals, indicating a memory deficit. While provid-ing an improved memory performance in the sham PSP group, the PSP modu-lation was not able to provide the same effect in the PPT-lesioned animals, with the exception of the piribedil PPT-lesioned group. After the sleep rebound period the effect of PSP appeared to be diminished.Conclusions: The lesion with ibotenic acid in the PPT generated an important deficit, not reverted by the PSP, in the object recognition memory. Furthermore, we suggest a mutual involvement of the striatal D2 receptors and the PPT in this particular cognitive function.No conflict of interest.



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CELECOXIB AS A NEUROPROTECTIVE AGENT IN CHRONIC CEREBRAL HYPOPERFUSION-INDUCED NEURODEGENERATION IN RATSA. Saxena1,*, F. Mohd Fadly1, A. Norlelawati11Basic Medical Sciences, International Islamic University Malaysia, Kuantan, Malaysia

Objectives: Reduced cerebral blood flow (CBF) has been associated with neurodegenerative disorders. Since neuroinflammation is thought to play a significant role in chronic degenerative neurological disorders like Alzheimer’s disease, the present study was planned to assess the neuroprotective role of celecoxib in Alzheimer’s model of rats (2VO).Methods: Experimentally, a condition of chronic cerebral hypoperfusion due to reduced CBF can be induced by permanent bilateral occlusion of common carotid arteries (2VO) in rats. After 1 week of acclimatization, fifteen Sprague Dawley rats weighing 200–250 g were equally divided into three groups. Group A served as – sham control, Group B – 2VO, and Group C – 2VO-C (treated daily with celecoxib 50 mg/kg, orally following 2VO). On 8th week, all the rats were euthanized and the hippocampi were isolated. Viable neuronal cells in the hippocampal CA-1 region were counted and hippocampal COX-2 mRNA expression and prostaglandin E2 (PGE-2) levels were estimated.Results: There was a significant difference in neuronal cell death, increase in COX-2 mRNA expression and PGE-2 levels in 2VO group as compared to sham control group. In celecoxib-treated 2VO-C rats, the viable neuronal cell count of the hippocampal CA-1 region was significantly higher as com-pared to the untreated 2VO group. The hippocampal COX-2 mRNA expres-sion and hippocampal PGE-2 levels were found to be significantly lower in the celecoxib-treated 2VO rats as compared to untreated 2VO rats.Conclusions: The results indicate that celecoxib could be successfully used in the management of Alzheimer’s disease.No conflict of interest.

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FERROUS CITRATE INDUCED OXIDATIVE INJURY TO RAT NIGROSTRIATAL SYSTEM – IN VIVO RELEVANCE TO PARKINSON’S DISEASE MODEL.B. Aryal1,*1Department of Clinical Pharmacology, Chitwan Medical College, Bharatpur-10 Chitwan, Nepal

Objectives: The present study was undertaken to investigate the effect of intranigral infusion of ferrous citrate on tetrahydrobiopterin (BH4) and GTP-CH I turnover in rat nigrostriatal system.Methods: Ferrous citrate solution (8 nmole) was infused through microdialysis probe at the rate of 0.8 μL/min to the right substantianigra using stereotaxic coordinates; AP: 3.2 mm, L: 2.1 mm and DV: 2.0 mm. Animals were decapi-tated at different time intervals, 0 hr, 12 hr, 24 hr, 48 hr, 96 hr, and 1 week using guillotine cutter and corpus striatum was analyzed using liquid chromatogra-phy tendam mass spectroscopy and Real time PCR technique.Results: The results showed that intranigral ferrous citrate infusion caused sig-nificant increase in striatal BH4 levels during 12 to 24 hr after stereotaxic proce-dure and subsequently led to severe depletion of BH4 levels measured during 48 hr to 1 week due to auto-oxidation of overloaded BH4 produced in response to ferrous citrate injection after 12 hr of surgery. The oxidative injury to nigrostri-atal system in response to ferrous citrate injection was confirmed by measuring the expression levels of GTP-CHI during 12 hr to 1 week, which was found to be in increasing order in response to oxidative damage in nigrostriatal system.Conclusions: In conclusion, intranigral infusion of ferrous citrate provides good animal model for studying oxidative stress and Parkinson’s disease, which is in vivo relevance to Parkinson’s disease.No conflict of interest.

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THE OLIGOMER MODULATOR ANLE138B INHIBITS DISEASE PROGRESSION IN A MOUSE MODEL OF PARKINSON’S DISEASE EVEN WITH LATE TREATMENT STARTED AROUND CLINICAL DISEASE ONSET.J. Levin1,*, F. Schmidt1, C. Boehm2, C. Prix2, K. Bötzel1, S. Ryazanov3, A. Leonov3, C. Griesinger3, A. Giese2

1Neurologische Klinik, Ludwig-Maximilians Universität, München, Germany, 2Zentrum für Neuropathologie und Prionforschung, Ludwig-Maximilians Universität, München, Germany, 3NMR-basierte Strukturbiologie, Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany

Objectives: Parkinson’s disease (PD) is characterized by the deposition of aggre-gated α-synuclein (aSyn). Recent evidences suggest that oligomers formed in the

aggregation process constitute the main toxic species causing neurodegeneration. Recently, we demonstrated that the novel oligomer modulator anle138b blocked formation and accumulation of aSyn oligomers, reduced disease-associated motor deficits, and lead to prolonged disease-free survival in mouse models of PD1. However, so far it has not been investigated if anle138b is also effective when treatment is started when signs of disease become detectable.Methods: The disease modifying effect of anle138b, a novel compound de-rived from a systematic drug-discovery project, was tested in a transgenic PD mouse model based on neuronal expression of human A30P-aSyn. Anle138b was given orally twice daily. Disease onset was monitored by measurements of rotarod performance.Results: In control mice, deposits of aSyn in the brainstem and fluctuations of rotarod performance (e.g. disease onset) became apparent around the 50th week of life. Thus, oral treatment with anle138b was administered start-ing from this age. Anle138b-treated mice showed a significantly prolonged disease-free and overall survival. The effect size was comparable to previous results obtained with early start of treatment at 8 weeks of age.Conclusions: The oligomer modulator anle138b has a strong effect on dis-ease progression and survival also after disease onset, which is a key prereq-uisite for disease-modifying therapy in PD patients.Reference1. Wagner et al., Anle138b: a novel oligomer modulator for disease-modify-

ing therapy of neurodegenerative diseases such as prion and Parkinson’s disease. Acta Neuropathol. 2013;125(6):795–813.


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CLINICAL SIGNIFICANCE OF METALLOTHIONEINS IN PARKINSON’S DISEASES. Sharma1,*, A. Chabenne1, A.Z.Z.A. Khogali1, C. Moon1, C. Ojo1, M. Ebadi11Pharmacology, Saint James School of Medicine, Kralendijk, Netherlands Antilles

Objectives: Metallothioneins (MTs) are cysteine-rich, zinc-binding proteins that are induced by metal nanoparticles (NPs). MTs provide neuroprotection as antioxidant, anti-inflammatory, and anti-apoptotic agents by augmenting zinc-mediated transcriptional regulation of genes involved in cell proliferation and differentiation. Liposome-encapsulated MT-1 promoter has been used to induce anti-apoptotic genes.

We discovered therapeutic potential of MTs in inhibiting Charnoly body (CB) formation and α-synucleinopathies for effective treatment of Parkinson’s disease (PD).Methods: We employed MTs gene manipulated cultured cells and animals, digital fluorescence imaging, E.M, ICP-MS, microPET imaging, and molec-ular neurobiological procedures to discover that MTs enhance Ubiquinone-(NADH)-Oxidoreductase (complex-1), a rate-limiting enzyme involved in oxidative phosphorylation.Results: CBs are electron-dense multi-lamellar structures formed by mito-chondrial degeneration due to free radical overproduction. MTs as free radical scavengers inhibit CB formation and α-synucleinopathies before Lewy body formation. Selegiline also inhibits α-synuclein nitration, implicated in Lewy body formation. Furthermore, it inhibits 1-methyl, 4-phenylpyridinium and 3-morpholinosydnonimine apoptosis in SK-N-SH and mesencephalic fetal stem cells.Conclusions: (i) CB and α-Synuclein Index (SI) may be used as sensitive PD biomarkers; (ii) MTs transgenic fetal stem cells may be transplanted in the stri-atal region of weaver mice exhibiting neurodegeneration and Parkinsonism; (iii) MTs may facilitate theranostic potential of NPs-labeled cells as thera-peutic agents in PD; (iv) MTs could facilitate the synthesis, characterization, and functionalization of NPs for theranostic applications of PD and related disorders.Reference1. Sharma S, Rais A, Sandhu R, Nel W, Ebadi M (2013) Clinical Significance

of Metallothioneins in Cell Therapy and nanomedicine. International Journal of Nanomedicine. 8:1–12.


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DOES THE LRRK2*R1441G PD MUTATION MODULATE THE IMMUNE REACTION IN THE BRAIN?E. Kozina1,*, Y. Jiao1, Y. Dou1, R.J. Smeyne1

1Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, USA

Objectives: Missense mutations in LRRK2 gene cause late-onset Parkinson’s disease (PD) with clinical and pathological phenotypes similar to idiopathic

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PD. Although PD’s etiology is multifaceted, studies of PD brains support a critical role for neuroinflammation. Since LRRK2 is expressed in macrophages and B-lymphocytes, we examined the inflammatory response in brain and blood of mice carrying a LRRK2 mutation.Methods: 3 and 12 month FVB/N and LRRK2*R1441G mice were injected with saline or LPS (5 mg/kg, i.p.). Blood and brain tissue were collected 4, 9, 24 hours, 7 days and 2 months after LPS injection. Cytokines/chemokines, LRRK2 protein expression and SNpc TH+ neurons were analyzed at each timepoint.Results: 4–24 h after LPS in young LRRK2*R1441G mice, IL-6, KC, and MCP-1 levels were higher in the SN while IFN-g and KC were higher in stria-tum compared to WT. These changes were absent in the SN and striatum of older LRRK2*R1441G mice. LPS upregulated LRRK2 protein in the SN of young LRRK2*R1441G mice, but not in older LRRK2*R1441G or FVB mice. LPS injection transiently reduced the number of SNpc TH+ neurons in young LRRK2*R1441G mice. In serum, different patterns of cytokine changes were observed: IL-13, IFN-g, IP-10, KC, MCP-1 levels in young LRRK2*R1441G mice were higher than controls 1–9 h after LPS, returning to baseline by 24 h.Conclusions: LPS-stimulated LRRK2*R1441G mice show higher expression of cytokines and LRRK2, and transitory decrease of TH expression in the SN.No conflict of interest.

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A MODEL OF PARKINSON’S DISEASE IN PIG AND PRIMATE BY REPEATED INTRAVENTRICULAR ADMINISTRATION OF AN INHIBITOR OF THE UBIQUITIN PROTEASOME SYSTEM (UPS)D. Doudet1,*, S. Jakobsen1, A.K.O. Alstrup1, A. Moller1, J.C. Sorensen2, A.M. Landau1

1PET Center, Aarhus University Hospital, Århus C, Denmark, 2Neurosurgery, Aarhus University Hospital, Århus C, Denmark

Objectives: Parkinson’s disease (PD) is characterized by both motor and non-motor symptoms and widespread neurochemical pathologies including loss of dopamine and noradrenergic neurons. Dysfunction of the UPS is prominent in aging and has been implicated in PD. We repeatedly administered a UPS inhibitor in the CSF of 2 large animal species often used as animal models of PD and used non invasive PET imaging with dopaminergic and noradrenergic tracers to investigate the effects of chronic exposure to UPS inhibition on the brain neuropharmacology.Methods: 4 Gottingen minipigs and one rhesus monkey received mul-tiple intraventricular injections of lactacystin, a UPS inhibitor, over sev-eral weeks. Baseline scans were obtained with [11C]DTBZ, a tracer of the VMAT2, and [11C]yohimbine, a tracer of the alpha2 adrenergic receptors. The animals were scanned before the appearance of clear, unambiguous motor symptoms. A third series of scans was conducted after development of motor symptoms. PET data yielded the total volume of distribution for yohim-bine and the binding potential for DTBZ.Results: In the presymptomatic phase, only yohimbine binding was increased by 15–25% in various cortical regions. In addition, in the symptomatic stage, striatal DTBZ binding was also decreased by 35%.Conclusions: Increased yohimbine binding suggests early upregulation of the adrenergic receptors in response to loss of noradrenergic terminals from brainstem and provide the first in vivo evidence for early NA deficits preceding motor and dopaminergic deficits.No conflict of interest.

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RNAI-MEDIATED KNOCKDOWN OF VPS35 IMPAIRS α-SYNUCLEIN DEGRADATION BY INHIBITING THE MATURATION OF CATHEPSIN DT. Hasegawa1,*, E. Miura1, M. Konno1, N. Sugeno1, Y. Nagai2, N. Fujikake2, M. Suzuki2, R. Oshima1, A. Kikuchi1, M. Aoki1, A. Takeda1

1Neurology, Tohoku University, Sendai, Japan, 2Degenerative Neurological Diseases, National Center for Neurology and Psychiatry, Tokyo, Japan

Objectives: Mutations in Vacuolar protein sorting 35 (VPS35) have recently been identified in families with autosomal dominant familial Parkinson’s disease (PD). VPS35, a key component of the retromer cargo-sorting ma-chinery, is thought to mediate retrograde transport of proteins from the endosome to the trans-Golgi network. It is known that the depletion of retromer increases the lysosomal turnover of the mannose 6-phosphate receptor, thereby decreases the level of lysosomal hydrolases includ-ing cathepsin D (CTSD). Becasuse CTSD is the main lysosomal enzyme involved in the degradation of α-synuclein (a-syn), a principal culprit for Lewy pathology in PD, the pathogenic mutation in VPS35 may cause the malfunction of retrograde transport and thus contribute to the pathological metabolism of a-syn.

Methods: In order to better define the molecular mechanisms of how retromer malfunction affects on the a-syn pathology and subsequent motor symptoms, RNAi-mediated silencing of VPS35 was performed using cultured cellular and in vivo fly models.Results: We showed that the retromer disruption by VPS35 downregulation impairs the processing of CTSD, which leads to the accumulation of intracel-lular a-syn. Furthermore, we confirmed that the RNAi-mediated knockdown of VPS35 promotes compound eye degeneration as well as locomotor abnor-malities observed in transgenic Drosophila overexpressing human wild-type a-syn.Conclusions: These findings suggest that the functional disruption of retromer machinery may be implicated in a-syn-related neurodegenerative process leading to PD.References1. Vilariño-Güell C, et al., AJHG 2011, 89, 162–7.2. Zimprich A, et al., AJHG 2011, 89, 168–75.3. Arighi CN, et al., JCB 2004, 165, 123–33.4. MacLeod DA, et al., Neuron 2013, 77, 425–439.No conflict of interest.

439

LATE-ONSET PARKINSONISM IN NF-KB/C-REL-DEFICIENT MICE: INSIGHTS INTO NOVEL DRUGABLE TARGETSM. Pizzi1,*, C. Baiguera1, A. Bellucci1, A. Pinna2, M.A. De Luca2, M. Morelli2, P.F. Fabene3, M. Pellitteri3, M.G. Spillantini4, P.F. Spano1

1Department of Molecular and Translational Medicine and National Institute of Neuroscience, University of Brescia, Brescia, Italy, 2Department of Biomedical Science and National Institute of Neuroscience, University of Cagliari, Cagliari, Italy, 3Department of Neurological Neuropsychological Morphological and Motor Sciences, University of Verona, Verona, Italy, 4Department of Clinical Neurosciences Brain Repair Centre, University of Cambridge, Cambridge, United Kingdom

Objectives: NF-kB factors are cardinal players of the neurodegenerative pro-cess, with dual effect on inflammation and apoptosis. While aberrantly acet-ylated NF-kB/RelA is responsible for the commencement of apoptotic gene expression, NF-kB/c-Rel factor promotes transcription of anti-apototic genes MnSOD, Bcl-xL and UCP4. We investigated possible age-associated neuro-degeneration in c-Rel−/− mice.Methods: WT and c-Rel−/− mice were analyzed at 2, 12 and 18 months for motor behavior, brain neurochemistry and pathologyResults: c-Rel−/− mice displayed age-dependent deficits in locomotor activity and various gait-related deficits associated with bradykinesia and muscle rigid-ity. Motor deficits recovered after treatment with L-DOPA. 18-month-old c-Rel−/− mice exhibited a significant loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). SNc degeneration was accompanied by a significant loss of DA terminals and reduction of DA and HVA levels in the striatum. Rel−/− mice exhibited a marked immunoreactivity for fibrillary α-synuclein in the SNc, DMT1 and iron. Aged c-Rel−/− brain showed increased microglial reactivity, but no astro-cytic reaction. Preliminary data show that, as observed in premotor PD, c-Rel−/− mice display early loss of DAT in the caudatum putamen at a presymptomatic age. Furthermore, PBMC of selected PD patients display reduced c-Rel activityConclusions: c-Rel factor is a regulator of SNc resilience to aging. It dis-closes a new therapeutic target deserving further investigation in PD patients. c-Rel−/−mice represent an innovative animal tool to study pathological pro-gression of PD and also model PD preclinical phase of dopamine deficiency.Reference1. Baiguera et al., Brain 135:2750–65 2012No conflict of interest.

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EFFECTS OF TRIPTOLIDE ON THE NEURONAL LOSS IN LC AND NE FIBERS DEGENERATION IN HIPPOCAMPUS OF RAT INDUCE BY DSP4D. Lei1,*, J.M. Li1, X.H. Deng1

1Anatomy and Neurobiology, School of Basic Medical Science Central South University, Changsha, China

Objectives: To investigate the protective roles of triptolide (T10) on the Norepinephrine (NE) neuronal loss in locus coeruleus and the NE fibers de-generation in hippocampus of adult SD rat induced by DSP4.Methods: 24 SD rats were randomly divided into DSP4 group, DSP4 + T10 group and NS group. Rats in DSP4 and DSP4 + T10 group were injected in-traperitoneally DSP4 (25 μg/kg) on the day 1 and day 30. The rats in the NS group were injected intraperitoneally the equal volume of double wateras that of DSP4 solution. Then the rats in group DSP4 + T10 were administrated intra-gastricly T10 (10 μg/kg.d) for 45 days from the 1st day, the rats in group NS and DSP4 were given the same volume of the normal saline. Tyrosine hydroxylase (TH) immunohistochemical stainig to show the NE neurons in Locus coeruleus (LC) and NE nerve fibers in hippocampus. Quantitative analysis for the neu-ronal numbers in the LC, and gray value of TH fibers in the hippocampus.



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Results: The results showed that the NE fiber in the hippocampus of group NS was longer and continuous, while in group DSP4 was fewer and incon-secutive, and the continuity of NE nerve fibers in the group DSP4 + T10 is much better than that of DSP4 group. TH-positive neuronal number in the Locus coeruleus of group DSP4 (504 ± 24) was lower than that of group NS (1069 ± 49) and group DSP4 + T10 (996 ± 63) (P < 0.05).Conclusions: T10 possess of neuronal protective roles for the NE neuronal loss in locus coeruleus and the NE fibers degeneration in hippocampus in-duced by DSP4.References1. Selkoe DJ. Folding proteins in fatal ways. Nature, 2003;426:900–9042. Akiyama H, Barger S, Barnum S, et al. Inflammation and Alzheimer?

Disease. Neurobiol Aging, 2000;21:383–4213. Sastre M, Klockgether T, Heneka MT etal. Contribution of inflamma-

tory processes to Alzheimer’s disease molecular mechanisms. Int J Dev Neurosc, 2006;24:167–176

4. Michael T, Heneka, I Mutiah Ramanathan, et al. Locus Ceruleus degen-eration promotes Alzheimer pathogenesis in Amyloid Precursor Protein 23 transgenicmic. J Neurosc, 2006;26:1343–1354


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STUDIES ON DELIVERY OF DOPAMINE IN RAT BRAIN VIA NASAL ADMINISTRATION THROUGH OLFACTORY PATHWAY BYPASSING BLOOD BRAIN BARRIERV. Vibhu1,*, R.N. Saha1

1Pharmacy, Birla Institue of Technology and Sciences, Pilani, India

Objectives: Better delivery of DA to brain is a challenge to formulation phar-macist. Thus, it is planned to study possibility and determine extent of delivery of DA through nasal route. For this study DA depleted rats, by pretreatment with reserpine (RES), was used for determining extent of delivery of DA.Methods: Three groups (n = 5) of animal (Wistar rats) were taken for this study. First group of control animals, were administered 5% glucose solution i.p. Second group rats were treated with RES solution injected i.p. at a concentration of 5 mg/kg for 5 consecutive days to generate acute DA depletion. In third group same RES treatment were given to rats for 5 consecutive days and after this 50 μL DA (10 mg/kg) in buffer of pH 5.0 was delivered through nasal route via polypropyl-ene tube of internal diameter 0.8 mm. In all the groups DA level in brain were estimated in house developed & validated HPLC method using PDA detector.Results: Amount of DA, in control animals brain, found to be 2.06 μg/g ± 0.7 of brain. DA in case of RES treated group depleted to almost zero level. In group 3 a very high level of DA (1.56 mg/g ± 0.3 of brain) found, after 4 hr, suggesting very high extent of delivery of DA to brain via nasal route (Figure).

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0.0 2.5 5.0 7.5 min

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Figure 2. Representative chromatograms of brain samples analyzed using HPLC-PDA detector show-ing Dopamine (DA) level a) brain sample from control group, b) RES treated group c) nasally administered DA after RES treatment.

Conclusions: The results will be useful not only to validate the reserpine rat model but also to study extent of delivery of DA to brain through nasal route to deliver formulations like nanoparticles, liposomes, gels etc.No conflict of interest.

442

DOPAMINERGIC D2 RECEPTOR IS A KEY PLAYER IN THE NEURONAL ACTIVATION MEDIATED BY REM SLEEP DEPRIVATIONM. Proença1, M. Lima1,*1Physiology, Federal University of Paraná, Curitiba, Brazil

Objectives: Currently, several studies addresses the novel link between sleep and dopaminergic neurotransmission, focusing most closely on the mechanisms by which Parkinson’s disease (PD) and sleep may be inter-twined (Lima, 2013). In light of this relationship it was reported that dopamin-ergic D2 blockade may produce the reduction of REM sleep after REM sleep deprivation.Methods: Accordingly, we performed striatal and hippocampal neurochemi-cal quantifications of DA, serotonin (5-HT) and metabolites of rats intraperito-neally treated with haloperidol (1.5 mg/kg) or piribedil (8 mg/kg) and submitted to REM sleep deprivation (REMSD) and sleep rebound (REB). Also, we evaluated the effects of REMSD on motor and cognitive parameters and SNpc c-Fos neuronal immunoreactivity.Results: The results indicated that DA release was strongly enhanced by pir-ibedil in the REMSD group. In opposite, haloperidol prevented that alteration. A c-Fos activation characteristic of REMSD was affected in a synergic man-ner by piribedil, indicating a strong positive correlation between striatal DA levels and nigral c-Fos activation. Hence, we suggest that memory process is severely impacted by both D2 blockade and REMSD and was even more by its combination. Conversely, the activation of D2 receptor counteracted such memory impairment.Conclusions: Therefore, the present evidence reinforce that the D2 receptor is a key player in the SNpc neuronal activation mediated by REMSD, as a consequence these changes may have direct impact for cognitive and sleep abnormalities found in patients with PD.Reference1. Lima, M. M. S., 2013. Sleep disturbances in Parkinson’s disease: The con-

tribution of dopamine in REM sleep regulation. Sleep Medicine Reviews 17(5), 367–375.


443

NEUROTOXIC EFFECT OF SYNEDRELLA NODIFLORA (L.) GAERTN. ON THE CENTRAL NERVOUS SYSTEM OF ALBINO MICE: A BANGLADESHI MEDICINAL PLANTM.A.H. Mollik1,*1Biological Sciences, Peoples Integrated Alliance, Dhaka, Bangladesh

Objectives: Synedrella nodiflora (L.) Gaertn. is a Bangladeshi plant which has long being used medicinally in traditional systems of medicine. Extract of Synedrella nodiflora (L.) Gaertn. exhibited high antioxidant properties with hydrophilic-oxygen radical absorbance capacity, and 2,2-diphenyl-1-picryl-hydrazyl scavenging activity being 342.81 ± 1.48, and 38.13 ± 2.69 μmol Trolox equivalent/gram of dry weight (TE/g DW), respectively. The extract also showed to be neurotoxic to the animal especially on central nervous system.Methods: Albino mice of the five experimental groups (AF1, AF2, AF3, AF4, and AF5) were treated for 10 days, with an aqueous fraction of Synedrella nodiflora (L.) Gaertn. extract diluted in normal saline water in order to obtain doses of 5 g/kg, 10 g/kg, 20 g/kg, and 25 g/kg.Results: Neurotoxic behaviors were observed in the experimental groups such as behavioral response of movement, unconsciousness, loss of ap-petite resulting in weight loss at the high dose concentration, symmetrical ataxia as compared to control. Histopathological lesions increasing with dose concentrations were observed in the brain of exposed animals. Dose dependent cellular vacuolation, a centric nucleus, edema, spongy degen-eration, cellular necrosis, lipodosis, and hyper chromatic nuclei were ob-served. Histopathological lesions such as degeneration neurons are more prevalent in the higher dose groups AF3, AF4 as compared to AF1, AF2 groups.Conclusions: The results suggested that Synedrella nodiflora (L.) Gaertn.extract is a potent neurotoxic agent affecting the central nervous system of albino mice brain. So, this biological agent has drastic effect on brain tissue. Research implicates that Synedrella nodiflora (L.) Gaertn. may be considered as bio-pesticide for future use.No conflict of interest.



120

444

INDUCTION OF BASAL GANGLIA INFLAMMATION AFTER INFECTION WITH THE NON-NEUROTROPIC A/CA/04/2009 H1N1 INFLUENZA VIRUS IS DEPENDENT ON CD8+ T-CELLSS. Sadasivan1, M. Zanin2, K. O’Brien2, S. Schultz-Cherry2, R. Smeyne1,*1Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, USA, 2Infectious Disease, St. Jude Children’s Research Hospital, Memphis, USA

Objectives: Influenza viruses, including H5N1 (A/VN/1203-04) and the pan-demic A/California/04/2009 (CA/09), are capable of inducing encephalitis and Parkinsonism. Based on previous work showing that the highly pathogenic H5N1 Avian Influenza virus was neurotropic and induced an associated CNS inflammation, we examined the neurotropic and inflammatory potential of the pandemic A/California/04/2009 H1N1 (CA/09) virus in mice, specifically exam-ining the substantia nigra.Methods: Mice were intranasally infected with CA/09. At 3, 7, 10, 21 and 60 dpi we examined the ENS, PNS and CNS for neurotropism. Additionally, brains were examined to determine if CA/09 induced TH+ DA neuron loss, alterations in CD-3+ T-cells, and resting and activated Iba-1+ microglial num-bers. Mice were subjected to immunodepletion using antibodies directed against CD4 and CD8 T-cells to determine if these cells signaled microglial inflammation.Results: We found no evidence for neurotropism in the enteric, peripheral or central nervous systems. We did not detect any loss of TH+ DA neurons in the SNpc, nor any qualitative increase in CD-3 T-cells. Despite the lack of CA/09 virus in the brain, we did observe a robust neuroinflammation in the brain characterized by an increase in the number of Iba-1+ activated micro-glia. Immunodepletion studies showed that the induction of CNS microgliosis was dependent upon circulating CD8+ T-cells.Conclusions: Given that neuroinflammation contributes to generation and progression of a number of neurodegenerative disorders, it is possible that an influenza-induced CNS inflammatory response may contribute to the patho-genesis of these neurological disorders.Reference1. Jang et al. Proc Natl Acad Sci USA 106:14063–14068, 2009.No conflict of interest.

445

A NOVEL PROGRESSIVE MODEL OF PARKINSON’S DISEASE WITH COGNITIVE DEFICITSJ. Van Kampen1,*, C.A. Shaw2, D.G. Kay3

1Biomedical Science, University of Prince Edward Island, Charlottetown, Canada, 2Opthalmology, University of British Columbia, Vancouver, Canada, 3Biochemistry, University of Prince Edward Island, Charlottetown, Canada

Objectives: Progress in the development of PD therapies is hampered by the paucity of animal models capable of recapitualting, not only the progressive nature of the disease, but also the appearance of non-motor features such as dementia. Indeed, there is a pressing need to identify an effective therapy for Parkinson’s Disease Dementia (PDD). However, no appropriate animal mod-els are available for screening such potential therapies. Here, we describe a novel progressive model of PD, which also displays late-stage cognitive defi-cits and cortical pathology.Methods: Male Sprague Dawley rats were fed 3 mg/kg β-sitosterol-βD glu-coside (BSSG) daily for the first 16 weeks. Animals were tested for deficits in locomotor activity and coordination as well as cognitive deficits. Tissue was assessed for markers of inflammation, apoptosis, cell loss, abnormal protein aggregation and synaptic atrophy at 16, 24, 32, and 40 weeks following first exposure to the toxin.Results: Following the termination of toxin consumption, animals dis-played the progressive development of locomotor deficits followed by the appearance of deficits in spatial working memory at 40 weeks, as assessed by their performance in the radial arm maze. This time point was also marked by the spread of inflammatory markers and abnormal protein aggregates from the nigrostriatal pathway to regions of the cortex and hippocampus.Conclusions: The BSSG model of PD may offer a novel means of screening not only neuroprotective candidates, but also therapies targeting PDD.Reference1. Shen et al., 2010, Annals of Neurology 68(1): 70–80.No conflict of interest.

446

SESAMOL, A LIPID LOWERING AGENT AMELIORATES ALUMINIUM CHLORIDE INDUCED COGNITIVE DYSFUNCTION IN RATSM. Nampoothiri1,*, J. Jessy1, C.M. Rao1, K. Nitesh1, M. Jayesh1

1Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal, India

Objectives: Emerging epidemiological data has suggested hypercholester-olemia and abnormal cholesterol homeostasis as predisposing factors for neurodegenerative disorders. Sesamol a constituent of sesame oil is a potent antioxidant and anti-inflammatory molecule. In our previous study the anti-dyslipidemic effect of sesamol was established.Objectives: 1. To assess the effect of sesamol in aluminium chloride induced cognitive dysfunction 2. To evaluate the hypolipidemic potentials of sesamol and to correlate its effects to neuroprotective potential.Methods: Aluminium chloride (AlCI3) was administered orally once daily at a dose of 175 mg/kg from day 6 onwards for 60 days. Sesamol (10 mg/kg, 20 mg/kg) and rivastigmine (1 mg/kg) were administered 45 minutes be-fore administration of aluminium chloride orally for 60 days. Animals were randomized based on escape latency on day 5 and divided in to 6 groups (n = 8) as follows: Group 1- Normal control- Received distilled water (5 ml/kg p.o.) Group 2-Vehicle control-Receives 0.5% CMC (5 ml/kg p.o.), Group 3- AlCI3, Group 4- Rivastigmine + AlCI3, Group 5- Sesamol + AlCI3, Group 6- Sesamol + AlCI3. Spatial memory was assessed using morris water maze. Serum samples were analysed for triglycerides, total cholesterol, LDL and HDL levels.Results:

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)

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30

20

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eAlC

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**

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erol

(mg/

dl)

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AlCl 3+ S

ML(10m

g/kg)

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g)

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g/kg)

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20

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B

Data presented as mean ± S.E.M. (n = 8). *p < 0.05 as compared to control group and ap < 0.05as compared to AlCl3 treated group.Conclusions: Sesamol may be considered as a potential candudate to con-trol cognitive deficits associated with hyperlipidemia.No conflict of interest.

447

DOPAMINERGIC NEUROTOXICITY DUE TO DEVELOPMENTAL EXPOSURE TO ARSENIC IN RATSL. Chandavanshi1,*, R. Shukla1, A. Pant1, V. Khanna1

1Developmental Toxicology Division, CSIR-Indian Institute of Toxicology Research, Lucknow, India

Objectives: The study has therefore been carried out to assess the impact of arsenic exposure from post-lactational day (PD)22 to PD59 on selected behavioral and neurochemical endpoints and investigate the changes im-mediately after exposure on PD60 and 30 days after withdrawal of arsenic exposure on PD90Methods: Rats were exposed to arsenic (2 or 4 mg/kg b.w, p.o) from PD22 to PD59. Behavioural studies were deliberate by using selected behavioural pa-rameters which are associated with dopaminergic dysfunctions. Assay of DA-D2 receptors by radioligand receptor binding. Expression of TH protein and apoptosis linked selected proteins was carried out by Western blotting. Pro-oxidant and antioxidant defense mechanism analysis by different biochemical assays. mRNA expression of DA-D2 was studied by RT- PCR. Arsenic levels were estimated through AAS.Results: Arsenic caused a significant increase in locomotor activity was ob-served in rats treated with arsenic. A increase in the binding of dopaminergic



121

receptors, enhanced DA-D2 mRNA levels and expression of TH. Enhance the oxidative stress and increase and decrease in the expression of key protein of pro-apoptotic anti-apoptotic proteins of apoptosis respectively. The arsenic treated rats also exhibited a increased arsenic levels in brain regions was associated with differential effects were observed in arsenic treated rats com-pared to controls.Conclusions: The results exhibit vulnerability of developing rats to ar-senic and suggest that most of these changes were persisted at higher dose 30 days withdrawal of exposure in dopaminergic system of develop-ing brainReferences1. Bardullas et al., 20092. Calderon et al., 20013. Luo et al., 20134. Rodriguez et al., 2010No conflict of interest.

448

DECIPHERING THE MOLECULAR MECHANISMS OF NEUROPROTECTIVE EFFICACY OF CURCUMIN IN ARSENIC INDUCED BRAIN DOPAMINERGIC ALTERATIONS IN RATSP. Srivastava1,*, R.S. Yadav1, R.K. Shukla1, Y. Dhuriya1, A.B. Pant2, V.K. Khanna1

1Developmental Toxicology Division, CSIR-Indian Institute of Toxicology Research, Lucknow, India, 2In Vitro Toxicology, CSIR-Indian Institute of Toxicology Research, Lucknow, India

Objectives: Studies have been carried out to investigate molecular targets associated with protective potential of curcumin in arsenic induced brain dopaminergic alterations in rats.Methods: Rats were exposed to arsenic (20 mg/kg b.w, p.o) or curcumin (100 mg/kg b.w, p.o) or simultaneously with arsenic and curcumin for 28 days. Assay of mitochondrial complexes and membrane potential was carried out in corpus striatum (CS) to assess the integrity of mitochondria. Expression of molecular proteins associated with dopaminergic pathway including tyrosine hydroxylase (TH) and dopamine transporter (DAT) and those associated in PI3K-Akt survival pathway, apoptosis and antioxidant potential was assessed in CS by Western blotting and ultrastructural changes by transmission electron microscopy.Results: Exposure to arsenic resulted to decrease the expression of TH and DAT proteins, impaired activity of mitochondrial complexes I, II-III, IV

associated with enhanced apoptosis and affected anti oxidant potential in CS. Distorted mitochondrial cristae with loss of myelin sheath in arse-nic treated rats were also distinct in ultrastructural images. Simultaneous treatment with arsenic and curcumin caused significant protection via in-volvement of PI3K-Akt pathway and preventing arsenic induced dopamin-ergic alterations, mitochondrial dysfunctions, apoptosis and ultrastructural changes.Conclusions: Arsenic induced brain dopaminergic alterations appear to be associated with enhanced apoptosis and mitochondrial dysfunctions and are protected by curcumin by modulating specific molecular targets.No conflict of interest.

449

NEUROPROTECTION SEEN BY WATER SOLUBLE FORMULATION OF COQ10 IN PARAQUAT INDUCED ENVIRONMENTAL RAT MODEL AND MPTP INDUCED DJ-1 MOUSE MODEL OF PARKINSON’S DISEASEK. Muthukumaran1,*, S. Leahy1, J. Smith1, H. Jasra1, K. Harrison1, M. Sikorska2, J. Sandhu2, J. Cohen3, D. Lopatin3, S. Pandey1

1Chemistry and Biochemistry, University of Windsor, Windsor, Canada, 2Institute for Biological Sciences, National Research Council, Ottawa, Canada, 3Psychology, University of Windsor, Windsor, Canada

Objectives: Parkinson’s disease (PD) is the second most common neurode-generative motor disorder caused by a lack of dopamine due to the death of dopaminergic neurons (DN) in the substantia nigra region of the brain. Recent research suggests that most cases of PD arise as a result of a combination of environmental and genetic risk factors. Unfortunately, an effective therapeutic that can halt the progression of the disease is not available. We work with a water soluble formulation of CoQ10 and test its efficacy in both environmental and genetic animal models of PD.Methods: We evaluated the neuroprotective effects in terms of behavioural recovery and the number of tyrosine hydroxylase positive neurons in the sub-stantia nigra region of the brain.Results: In this study we have shown that the formulation is effective in protecting neurons in the environmental toxin (paraquat) induced rat model of PD. Many genes in which a loss-of-function mutation can increase the susceptibility to PD have been identified and among them is the DJ-1 gene. We have also shown that prophylactic treatment with the formulation is able to prevent neurodegeneration of DN in a genetic mice model where we

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122

combine DJ-1 deficiency and MPTP toxicity to create a more representative model of PD.Conclusions: This formulation of CoQ10 is effective at lower doses than the other formulations of CoQ10 currently available in the market and crosses the blood brain barrier. It is already FDA GRAS approved and can be produced for testing in human clinical trials.Reference1. Somayajulu-Nitu et al, BMC Neuroscience.2009, 10(88).No conflict of interest.

450

A CROSSTALK BETWEEN THE BASAL GANGLIA AS AN ANATOMICAL BASIS OF IPSILATERAL MOVEMENT DISORDERD. Lee1,*, T. Ahn1

1Department of Neurology, School of Medicine Kyung Hee University, Seoul, Korea

Objectives: 1) To report two cases of ipsilateral movement disorder (IpMD).2) To show a plastic change in crossed nigrostriatal pathway (CNSP) after

intracerebral hemorrhage (ICH) in the unilateral striatum (STR) for the in-vestigation of the pathomechanim of IpMD.

Methods: 1) Case reports: One case with ipsilateral Parkinsonism and the other with

ispilateral hemichorea was described.2) Animal experiment: At the baseline, flourogold (FG) was injected into the

unilateral STR of SD rat. Staining was done to detect FG immunoreac-tive (FG+) cells in the bilateral substantia nigra (SN), confirming CNSP. To study a change in CNSP, we made an animal model of ICH in unilateral STR using collagenase type 4. After 30 and 90 days after ICH model, FG was injected into healthy STR and staining was repeated to find FG+ cells in the SN.

Results: 1) Cases: In the first case, 3rd nerve injury and decreased uptake of dopa-

mine transporter ligand was present in the same side with Parkinsonism. In the second case, subdural hemorrhage (SDH) was found in the same side with hemichorea. 2) Animal experiment: At the baseline, there was a small fraction of FG+ neurons (<1%) in the contralateral SN to FG-injected STR. The fraction increased 30 days after ICH and returned to the baseline 90 days after ICH.

Conclusions: In human cases, clinical features and neuroimaging studies were compatible with IpMD. In the animals, the transient increase of FG+ neu-rons in the contralateral SN could be a plastic response, which was a crosstalk between BG. It remains to be further studied whether a crosstalk could be present in human, especially in IpMD.No conflict of interest.

451

SYSTEMIC LEVODOPA PHARMACOKINETICS IN THE CYNOMOLGUS MONKEY AFTER OPICAPONE DOSINGM.J. Bonifácio1,*, L. Torrão1, L.C. Wright1, P. Soares-da-Silva1

1LIF, BIAL – Portela & Co, S. Mamede do Coronado, Portugal

Objectives: Opicapone is a novel catechol-O-methyltransferase (COMT) inhibitor developed for the use as an adjunct therapy with levodopa/aromatic aminoacid decarboxylase inhibitors in Parkinson’s disease. This study evalu-ated the effect of opicapone on levodopa pharmacokinetics and COMT activity in cynomolgus monkeys (Macaca fascicularis).Methods: The study comprised two experimental parts, each with two phases: in each phase, 4 monkeys were given either vehicle or opicapone (30 mg/kg in Part I, and 100 mg/kg in Part II) and 24 h later levodopa/bens-erazide (12/3 mg/kg). Blood collection was performed at various time points. Plasma and erythrocytes were separated and used for the quantification of plasma levodopa and 3-O-methyldopa and the assay of COMT activity in erythrocytes.Results: Oral administration of levodopa/benserazide 24 h after 30 mg/kg or 100 mg/kg opicapone resulted in significant increases in the area under the concentration-time curve of plasma levodopa and significant decreases in the area under the concentration-time curve of plasma 3-OMD, as compared to the vehicle. The decrease in 3-OMD levels was proportional to the dose of opicapone administered, with the largest decrease being observed at 100 mg/kg. The increase in levodopa levels was similar with either dose of opicapone.

COMT activity of erythrocytes, was similarly inhibited with either dose of opi-capone over the course of the experiment.Conclusions: In non-human primates, pretreatment with opicapone 24 h before levodopa/benserazide results in a significant increase in levodopa bioavailability and a significant reduction in plasma 3-OMD levels and in sus-tained inhibition of erythrocyte COMT.No conflict of interest.

452

MONOCROTOPHOS INDUCED DOPAMINERGIC DEFICITS AND PROTECTIVE EFFICAY OF BACOPA MONNIERI IN RATSR.S. Yadav1,*, M.L. Sankhwar2, P. Srivastava2, V.K. Khanna2

1Department of Criminology and Forensic Science, Dr. Hari Singh Gour Central University, Sagar, India, 2Neurotoxicology Laboratory Developmental Toxicology Division, CSIR-Indian Institute of Toxicology Research, Lucknow, India

Objectives: In view of increasing human health risk following exposure to monocrotophos, an organophosphate insecticide, studies have been carried out to investigate the neuroprotective effect of Bacopa monnieri (BM) in mono-crotophos induced dopaminergic deficits associated with oxidative stress and muscle weakness in rats.Methods: Rats were exposed to monocrotophos (1.0 mg/kg body weight, p.o.), BM (50 mg/kg body weight, p.o.) or simultaneously with monocrotophos and BM for 28 days. The motor activity and motor co-ordination were moni-tored using automatic computerized systems. The neurochemical end points including assay of dopamine receptors, mRNA expression of DA-D2 receptor gene and expression of signaling proteins was measured following standard protocols.Results: Monocrotophos exposure in rats caused a decrease in motor behav-ior, muscle co-ordination (64%) linked with decreased binding of dopamine (DA)-D2 receptors (20%), mRNA expression of DA-D2 receptor gene, expres-sion of TH protein (1.51 fold) and levels of nitric oxide (1.45 fold) in striatum as compared to controls. Altered motor behavior and motor co-ordination were found to be protected in rats co-treated with monocrotophos and BM. Increase in the binding of DA-D2 receptor in striatum (21%), mRNA expression of DA-D2 receptor gene, expression of TH protein (1.33 fold) and levels of nitric oxide (1.19 fold) in corpus striatum were also observed in rats co-treated with monocrotophos and BM as compared to those exposed to monocrotophos alone.Conclusions: The results indicate that dopaminergic dysfunctions induced by monocrotophos could be significantly protected by simultaneous treatment with BM possibly due to its strong anti-oxidant potential.No conflict of interest.

453

MONOCROTOPHOS, AN ORGANOPHOSPHORUS INSECTICIDE ELICITS NEUROTOXICITY AND ALTERS THE STRIATAL DOPAMINERGIC SYSTEM IN A MOUSE MODEL OF PARKINSON’S DISEASEP. Rajini1,*, S.J. Ali11Food Protectants & Infestation Control, Central Food Technological Research Institute, Mysore, India

Objectives: The present study was aimed at understanding the potential of Monocrotophos (MCP), an organophosphorus insecticide (OPI), to elicit or augment parkinsonian features on the striatal dopamine circuitry in mouse model.Methods: Swiss albino mice (5 wks, 25–30 g) were administered mul-tiple doses of MCP (1/20 and 1/40 of their established LD50:12 mg/kg b.w) for 7 days, either alone or in conjunction with 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) (at 14 mg/kg b.w, total of 4 i.p. injections every 2 h). Neurobehavioral deficits, dopamine content, histology, immunohistochemical localization of tyrosine hydroxylase (TH) and ratio of oxidized to reduced glu-tathione levels were analysed in the striatum.Results: A significant decrease in the dopamine content, along with neurobehavioral alterations was evident in mice administered MCP alone or along with MPTP. Ratio of oxidized to reduced glutathione lev-els were significantly decreased (P < 0.05) in the treated mice as com-pared to the control. A marked decrease in the number of TH-positive cells along with histopathological alterations was evident in striatum of mice treated with higher doses of MCP. These changes were compara-ble to that seen in mice administered lower doses of MCP co-treated with MPTP.



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CONTROL: Normal architecture. MPTP: Neuronal degenera-tion with shrinkage,necrosis of neuronal cells, presence of occasional apoptotic bodies. MCP 1/20: Varying degrees of neuronal degeneration with shrinkage, necrosis, apoptotic bodies. MCP1/20+MPTP: Disintegration, severe degree of neuronal degeneration with wearing of neuronal architecture, hypertrophy of neurons.

Effect of MPTP and MCP on TH staining in mice. Values represented are mean± S.E (n=5). Data analyzed by ANOVA followed by post-hoc analysis (Tukey Multiple Comparison Test) (P<0.05)a,b: MCP1/20 vs MPTP+1/20MCP treatment.

Conclusions: Based on the above findings we presume that MCP has the potential to cause degeneration of dopaminergic neurons and augment nigrostriatal injury.No conflict of interest.

454

EARLY ONSET CORTICO-CORTICAL SYNCHRONIZATION IN THE HEMIPARKINSONIAN RAT MODELB.N. Jávor-Duray1,*, M. van der Roest1, C.P.J. de Kock2, M. Vinck3, A.B. Mulder1, P. Voorn1

1Anatomy and Neurosciences, VU University Medical Center, Amsterdam, Netherlands, 2Integrative Neurophysiology, VU University, Amsterdam, Netherlands, 3Cognitive and Systems Neuroscience, University of Amsterdam, Amsterdam, Netherlands

Objectives: The aim was to investigate changes in (sub)cortico-cortical oscillatory activity, interregional synchronization and interregional directional-ity over the course of dopaminergic cell loss in the 6-OHDA hemiparkinsonian rat model for Parkinson’s disease.Methods: Local field potentials of freely moving rats were recorded in: motor cortex (M1ipsi) and subthalamic nucleus (STN) ipsilateral and motor cortex con-tralateral (M1contra) to the lesion. We performed serial recordings of behaving rats before and after a 6-OHDA injection in the medial forebrain bundle. Data was analysed with the Fieldtrip toolbox and custom-made Matlab programs. PLI1

was used to compute interelectrode coupling, PSI2 for assessing directionality.Results: Oscillatory activity showed an increase at 20–35 Hz that developed first in M1ipsi, next in STN and finally in M1contra. Synchronization was en-hanced between all 3 electrode pairs at 26–33 Hz. During development of dopa-minergic cell loss, increased synchronicity was seen at 10–20 Hz on post-lesion day (pld) 1–13 between M1ipsi and STN, and between M1ipsi and M1contra on pld1-2. In contrast to M1ipsi – M1contra, increased 10–20 Hz persisted into the fully lesioned state between M1ipsi and STN. Directionality showed frequency-specific, bidirectional changes between STN and the cortical areas.Conclusions: Synchronization increased early in the development of dopaminergic cell loss in two frequency bands. The transition between the different frequency bands showed different patterns in the cortico-cortical and

subthalamo-cortical axis. Directionality changed bidirectionally in a frequency-dependent manner.References1. Stam et al. (2007) Hum. Brain Mapp 28, 11782. Nolte et al. (2008) Phys Rev Lett. 100:234101No conflict of interest.

455

NEUROREGENERATIVE EFFECTS OF CDNF AND GDNF AFTER MILD UNILATERAL 6-OHDA LESIONS IN MARMOSET MONKEYSE. Garea Rodríguez1,*, C. Schlumbohm2, G. Helms3, P. Pulkkila4, J. Meller5, M. Saarma4, K. Krieglstein6, E. Fuchs7

1Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Freiburg, Germany, 2Preclinical Research and Development, Encepharm GmbH I.Gr., Göttingen, Germany, 3Cognitive Neurology, University Medical Center, Göttingen, Germany, 4Institute of Biotechnology, University of Helsinki, Helsinki, Finland, 5Department of Nuclear Medicine, University Medical Center, Göttingen, Germany, 6Department of Molecular Embryology, Institute of Anatomy and Cell Biology, Freiburg, Germany, 7Clinical Neurobiology Laboratory, German Primate Center, Göttingen, Germany

Objectives: Neurotrophic factors are considered potent drug candidates for treatment of neurodegenerative disorders such as Parkinson’s disease (PD). The newly discovered cerebral dopamine neurotrophic factor (CDNF) gained attention since it proved to restore function and survival of dopamin-ergic neurons in different lesion protocols and treatment regiments in rodent models of PD. The aim of the study was to test the therapeutic efficacy of CDNF and GDNF in a neurorestorative treatment approach in marmoset monkeys.Methods: Animals received unilateral 6-OHDA injections into the caudate nucleus. Three weeks after lesion induction 20 μg of either CDNF or GDNF were intracerebrally injected into the center of lesion. Lesions as well as treatment effects were monitored in vivo using 123I-FP-CIT SPECT. At the end of experiment immunohistochemistry was performed.Results: Reduced DAT binding was observed after mild 6-OHDA lesions were targeted to the caudate nucleus. After treatment, quantitative analysis of 123I-FP-CIT SPECT showed a significant increase of DAT binding (p = 0.037) in animals treated with CDNF. In the GDNF group single animals responded to the treatment with GDNF. However, no significant recovery was observed in the GDNF treated group.Conclusions: In the neurorestorative approach a clear but moderate increase of DAT binding was observed after treatment with neurotrophic factors. In di-rect comparison to GDNF, CDNF treatment was more effective. However, increased numbers of TH-positive neurons observed within the lesioned area of GDNF treated animals, indicate a strong regenerative potential of GDNF.No conflict of interest.

456

DIFFERENT SUBTYPES OF STRIATAL NEURONS ARE ENGAGED IN CORTICAL OSCILLATIONS IN ACUTE AND CHRONIC DOPAMINE DEPLETED ANIMALSC. Prosperetti1, A. Stefani2, C.J. Moeller1, S. Galati1,*1Neurology, Neurocenter of Southern Switzerland, Lugano, Switzerland, 2Neurology, University of Rome, Rome, Italy

Objectives: Degeneration of substantia nigra pars-compacta (SNc) is a hallmark of Parkinson’s disease (PD) pathology. The electrophysiological counterpart is an exaggerated oscillatory activity within the cortical-basal ganglia (BG)-thalamic loop. It was suggested that transmission of slow corti-cal rhythms through the BG involves the dopamine depleted striatum. Other evidences propose that cortical activity propagates via subthalamic nucleus. The aim of this study is to clarify how cortical activity spreads into the BG in PD.Methods: We recorded the striatal and the cortical activity in three animal groups: 1) control; 2) tetradotoxin injected (acute dopamine-depleted); 3) 6-OHDA-lesioned animals (chronic dopamine-depleted). On the basis of elec-trophysiological properties we divided the striatal neurons in different groups: medium spiny neurons (MSN); tonically active neurons (TAN) and fast spiking interneruons (FSI). We correlate the activity of the cortex with the single unit activity of these neurons for coherence analysis.Results: The magnitude of correlations varies with neuron type and dopamine level. The majority of pFSI and pMSN neurons were locked to cortical oscilla-tions in normal state while the pTAN did not shown any correlation with cortical oscillations. In dopamine depleted animals, instead, we observed a dispersion of the cortical signaling by the pMSN neurons.



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Conclusions: The acute and chronic deprivated striatum has probably lost the ability to convey messages through selective pathways. The timing dys-function of different striatum neurons might also alter the downstream network of BG enhancing the spread of cortical rhythms.No conflict of interest.

457

PHOTO-STIMULATING EFFECT OF LOW REACTIVE LEVEL LASER ON LOWER URINARY TRACT DYSFUNCTION IN PARKINSON DISEASE MODELT. Uchiyama1,*, T. Yamamoto2, C. Shibata-Yamaguchi1, H. Tateno3, M. Fuse1, T. Kamai4, T. Yamanishi1, R. Sakakibara5, S. Kuwabara2, K. Hirata3

1Neurourology and Continence Center, Dokkyo Medical University, Tochigi, Japan, 2Neurology, Chiba University Graduate School of Medicine, Chiba, Japan, 3Neurology, Dokkyo Medical University, Tochigi, Japan, 4Urology, Dokkyo Medical University, Tochigi, Japan, 5Neurology Division Department of Internal Medicine, Sakura Medical Center Toho University, Chiba, Japan

Objectives: Photo-stimulation using low reactive level laser was reported to have neurobiological effects. As these effects, inhibition of Aδ- and C- fibre nerve conductions, activation of central descending inhibitory system, and sup-pression of local synaptic neurotransmission were reported. Micturition reflex is constructed by activation of peripheral Aδ- and C- fibre afferent nerves, and which is controlled by central descending inhibitory system. Then, the photo-stimulation will be applicable to modulate these neural controls. Therefore, we investigate the photo-stimulating effect of low reactive level laser on lower urinary tract dysfunction (LUTD) in Parkinson disease (PD) model.Methods: Experiments were performed on adult male Sprague-Dawley rats with bilateral injections to substantia nigra of 6OHDA (PD model). Cystometric investigation was performed, and interval time between voids, urine volume per void, and maximum bladder pressure during voiding were investigated. After 30–60 minutes’ baseline recording, photo-stimulation using low reac-tive level laser or sham stimulation via prove was irradiated to bilateral L6/S1 intervertebral foramen via the probe contacted to body. Recording after the stimulation was continued for several hours until micturition cycle returned to baseline.Results: Compared with the baseline record, in sham-stimulated groups, interval time between voids and urine volume per void were not unchanged. In photo-stimulated groups, interval time between voids and urine volume per void was significantly increased. These changes were stimulation-time dependent. Maximum bladder pressure was unchanged.Conclusions: Photo-stimulation using low reactive level laser to bilateral L6/S1 root improved storage dysfunction without exacerbation of voiding dysfunc-tion in LUTD of PD model.No conflict of interest.

458

BETA AND GAMMA OSCILLATIONS PARALLEL THE EMERGING OF PARKINSONISM AND LEVODOPA-INDUCED DYSKINESIAA. Salvadè1, V. D’Angelo2, A. Stefani2, J.C. Moeller1, S. Galati1,*1Neurology, Neurocenter of Southern Switzerland, Lugano, Switzerland, 2Neurology, University of Rome Tor Vergata, Rome, Italy

Objectives: The relation between beta band oscillation (BBO) and Parkinsonism remains not elucidated. Although, the basal ganglia activity of Parkinson’s disease (PD) patients show an augmentation of BBO, recent findings suggest that parkinsonian symptoms are not directly related on this frequency. The direct causative relation of BBO was inferred by the worsen-ing of Parkinsonism given by stimulating the subthalamic nucleus with this frequency. In order to study the time course of oscillatory activity in relation to motor performance we performed a continuous monitoring of oscillatory activ-ity in animal model of PD.Methods: We performed our study in three animal groups: sham-lesioned; 6-OHDA-lesioned animals treated with levodopa; 6-OHDA-lesioned animals not treated with levodopa. Recordings were conducted continuously from the lesion day up to 2 weeks after the development of levodopa-induced dyski-nesia (LID). We daily recorded the local field potential from the frontal cortex and the pallidus.Results: The 6-OHDA animals showed a significant increase of the high beta band (20–30 Hz) 5 days after the toxin injection while no effects were ob-served in the low beta band range (10–20 Hz). The electrophysiological find-ing parallels the histological data, while the development of Parkinsonism was delayed of about another week. As far as the gamma activity is concerned, we observed a clear-cut increase during the development of LID.Conclusions: Our data suggest that the high beta band precedes the devel-opment of Parkinsonism reflecting the strict relation between BBO and dopa-mine deficit. The gamma band parallels the development of LID confirming its pro-kinetic nature.No conflict of interest.

459

SYNAPTIC HOMEOSTASIS IMPAIRMENT IN LEVODOPA-INDUCED DYSKINESIA: AN ELECTROPHYSIOLOGICAL STUDY IN PARKINSONIAN ANIMAL MODELA. Salvadè1, M. Pace2, F. Baracchi2, C. Bassetti2, C. Moeller1, P. Stanzione3, S. Galati1,*1Neurology, Neurocenter of Southern Switzerland, Lugano, Switzerland, 2Neurology, University of Bern, Bern, Switzerland, 3Neurology, University of Rome Tor Vergata, Rome, Italy

Objectives: Levodopa-induced dyskinesia (LID) represents a major complica-tion of the long term treatment of Parkinson’s disease (PD). Animal models of PD provide strong evidence that a hyper-plasticity underlies the development of dyskinesia. Evidences show that slow homeostatic adjustments of network excitability occurring during sleep are crucial for reducing plasticity thresholds. Assuming an association with LID, we measured these sleep process in a LID animal model.Methods: We studied five animal groups: (i) sham-lesioned drug-naive rats (sham/LD-), (ii) sham-lesioned levodopa-treated rats (sham/LD+); (iii) 6-OHDA-lesioned drug-naïve rats (PD/LD-), (iv) 6-OHDA-lesioned levodopa-treated rats w/o dyskinesias (PD/DYS−), (v) 6-OHDA-lesioned levodopa-treated rats with dyskinesias (PD/DYS+).Results: We found that PD/DYS− animals had a physiological sleep-induced reduction of synaptic strength, while PD/DYS+ animals do not manifest an adequate synaptic down-scaling during sleep in terms of electrophysiological (slow waves activity) and molecular (Arc protein) data analysis.Conclusions: Our results are consistent with an impaired synaptic homeostasis (SH) in animals showing dyskinesia.

460

CHANGES IN ITPR1 EXPRESSION IN RATS WITH A MODEL OF PARKINSON’S DISEASEO.A. Fedorenko1,*, S.M. Mamontov1, S.A. Talanov2

1Department of Brain Physiology, Bogomoletz Institute of Physiology, Kiev, Ukraine, 2Department of Blood Circulation Physiology, Bogomoletz Institute of Physiology, Kiev, Ukraine

Objectives: Our aim was to find out whether there are changes in the expres-sion of inositol-1,4,5-triphosphate receptors gene itpr1 in neurons in the brain of rats with experimental Parkinson’sdisease (PD).Methods: We used the 6-hydroxydopamine-induced rat model of unilateral PD and real time PCR.Results: We found that in rats with PD expression of itpr1 gene is increased in in neurons of the striatum, cerebellum and motor cortex.Conclusions: Our findings indicate that the level of itpr1 gene expression in neurons in thebrain of PD rats is higher than in healthy animals. This may be one of reasons for the excessive Ca2+ release from cell stores during neurode-generative processes in neurons.No conflict of interest.

461

REDUCTION OF MOTION DISABILITY IN MIGRAINOUS RATS WITH PARKINSON DISEASEA. Lotfinia1,*1Neuroscience, Shefa Neuroscience Research Center, Alborz, Iran

Objectives: Cortical spreading depression (CSD), a transient reversible phe-nomenon, which slowly propagates through the brain, is widely accepted in mi-graine aura pathophysiology as a headache trigger. On the other hand, it has been previously proved that dopaminergic system and brainstem mechanisms are involved in the pathogenesis of migraine and other related disease like Parkinson’s disease (PD), the paradigm of brainstem dopaminergic disease. SD-induced rats as a nearest animal model to migraine have been used for this purpose.Methods: 18 male Wistar rats (250 ± 5 gr) were anesthetized and two elec-trodes stereotaxically were implanted above the somatosensory neocortex. SD was induced by 3 M KCl and simultaneously electrophysiological record-ing continually was recorded from the cortex to confirm induction of SD. Unilateral injection of 6-hydroxydopamine (6-OHDA) in the lateral striatum was performed and open-field test were used for evaluation of movement disability.Results: Behavioral data showed significant decrease of movement disabil-ity in KCl-inducted rats with intrastriatal 6-OHDA lesions in comparison with Parkinson disease rats which have not received KCl in open-field test.Conclusions: Our studies suggest that dopaminergic receptor hypersensi-tivity followed by migraine attacks could reduce the clinical manifestation of Parkinson disease. Therefore, modulation of dopaminergic neurotransmission should be considered in the therapeutic management of Parkinson disease.



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References1. Akerman, S. and P. Goadsby (2007). ‘Dopamine and migraine: biology and

clinical implications.’ Cephalalgia 27(11): 1308–1314.2. Barbanti, P., G. Fabbrini, et al. (2000). ‘Dopamine and migraine: does

Parkinson’s disease modify migraine course?’ Cephalalgia 20(8): 720–723.No conflict of interest.

462

STUDY ON 6-OHDA-INDUCED RAT MODEL OF HEMIPARKINSONISM: BEHAVIOR, IMMUNOHISTOCHEMISTRY AND MICRODIALYSISY. Zhao1,*, Z.G. Liu2, S.D. Chen3

1Neurology, Shanghai Songjiang Central Hospital, Shanghai, China, 2Neurology, Shanghai Xinhua Hospital, Shanghai, China, 3Neurology, Shanghai Ruijin Hospital, Shanghai, China

Objectives: To evaluate the hemiparkinsonian rats induced by 6-OHDA.Methods: A rat model of hemiparkinsonism was induced by unilateral admin-istration of 6-hydroxydopamine (6-OHDA) into the substantia nigra. 6-OHDA-treated rats were tested for apomorphine (APO)-induced rotational asymmetry and TH immunohistochemistry analysis. Extracellular DA and its metabolites (DOPAC, HVA) in the striatum of hemiparkinsonian rat model were measured by microdialysis and high performance liquid chromatography with electro-chemical detection (HPLC-ECD).Results: 36 of the total 82 rats exhibiting the contralateral rotation (>7 turns/min) were selected for further study. Dopaminergic neurons were almost ab-sent in the lesioned nigra and TH-positive fibers were not observed in the denervated striatum. The levels of DA, DOPAC and HVA in thelesioned side were significantly decreased (p < 0.05, p < 0.01 and p < 0.01), as compared with those in the intact side.Conclusions: The hemiparkinsonian rat induced by 6-OHDA provides a very useful model for the study of human Parkinson disease.No conflict of interest.

463

COGNITIVE AND NEUROPSYCHIATRIC SYMPTOMS IN A MOUSE MODEL OF PARKINSON’S DISEASEA. Bonito Oliva1,*, M. Pignatelli2, G. Spigolon1, T. Yoshitake3, J. Kehr3, N.B. Mercuri2, R. Nisticò2, G. Fisone1

1Neuroscience, Karolinska Institute, Stockholm, Sweden, 2Neuroscience, IRCSS Santa Lucia Foundation, Rome, Italy, 3Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden

Objectives: Parkinson’s disease (PD) is accompanied by non-motor symptoms including cognitive (e.g. impaired spatial memory and object recognition abilities) and neuropsychiatric disturbances (e.g. anxiety and de-pression). To study these symptoms we used a mouse model characterized by partial lesion of the dopaminergic and noradrenergic inputs to striatum and hippocampus.Methods: In sham- and 6-OHDA-lesioned mice cognitive performances were tested using the novel object recognition test. Depression was examined us-ing tail suspension and forced swim tests and anxiety using open field and elevated plus maze tests.

Long-term potentiation (LTP) was determined in the hippocampal dentate gyrus and CA1 regions.Results: Bilateral 6-OHDA lesion reduced long-term, but not short-term, novel object recognition and decreased LTP in the dentate gyrus, which is critically involved in memory function. These abnormalities were abolished by admin-istration of L-DOPA, or by activation of dopamine D1-type, but not D2-type, receptors (D1R, D2R).

The 6-OHDA-lesion induced a depression- and anxiety-like phenotype, in-dependently of the partial loss of noradrenaline. These deficits were not responsive to L-DOPA treatment, but were reverted by the administration of a D2R agonist. Notably, we observed that the administration of selective in-hibitors of noradrenaline and serotonin transporters, was able to counteract depressed and anxious behaviors.Conclusions: Our findings show that experimental Parkinsonism leads to cognitive, memory deficits corrected by activation of D1R, but not D2R, whereas neuropsychiatric symptoms are reverted by a D2R agonist, as well as by noradrenaline and serotonin transporter inhibitors.References1. Braak, et al., Neurobiol Aging 2003.

2. Aarsland, et al., Arch Neurol 2004.3. Bonito-Oliva, et al., Biol Psy 2013.

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DECREASED SPREADING DEPRESSION SUSCEPTIBILITY IN PARKINSON RAT MODELM. Lotfinia1,*1Neuroscience, Shefa Neuroscience Research Center, Tehran, Iran

Objectives: Parkinson disease (PD) is known by a major loss of dopaminergic nigrostriatal neurons and by an increased turnover of neurotransmitter by sur-viving neurons of the nigrostriatal tract. The clinical diagnosis of PD is based on the identification of some combination of the cardinal motor signs of brad-ykinesia, rigidity, tremor, and postural instability. Spreading depression (SD) is a transient loss of spontaneous and evoked neuronal activity and changes in ionic, metabolic and hemodynamic characteristics of the brain. Pronounced release of dopamine during SD and the probable role of dopamine in SD pro-cess, suggests that disruption of dopaminergic pathway in PD may cause SD to behave differently.Methods: To test this possibility, we induced dopaminergic lesion by bilateral intracerebral stereotactic injection of 6 μL of 6-hydroxydopamine in the medial forebrain bundle (MFB). After 4 days, SD was induced by the injection of 3 M KCl and SD propagation was followed using two ion-sensitive microelectrodes placed in the parietal and occipital cortex.Results: Eliciting SD in rat model was associated with a significant increase in the threshold of SD and a decrease in the propagation velocity and duration of accompanying extracellular DC changes.Conclusions: The present data show that rat model of Parkinson’s disease are less prone to SD.References1. Gelb, D.J., E. Oliver, and S. Gilman, Diagnostic criteria for Parkinson dis-

ease. Archives of Neurology, 1999. 56(1): p. 33.2. Gorji, A., Spreading depression: a review of the clinical relevance. Brain

Research Reviews, 2001. 38(1–2): p. 33–60.No conflict of interest.

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COMPARATIVE STUDY OF BEHAVIORAL MODIFICATIONS IN PARKINSON’S AND ALZHEIMER’S DISEASE IN RAT MODELN. Mishra1,*, D. Sharma1

1School of Life Sciences, Jawaharlal Nehru Univarsity, Delhi, India

Objectives: Study of behavioral modifications in rat models of Parkinson’s and Alzheimer’s disease and their comparatively analysis.Methods: Stereotaxic surgery on male Wistar rats (6–8 months old) as follows:

Parkinson’s Disease

Alzheimer’s Disease

Amyloid β1-40 Amyloid β1-42

Test 1Hydroxydopaminebromide (6-OHDA) 20 μg in 4 μl saline

2 μl of 5 mg/ml 3 μl of 5nM

Control 0.9% Saline 0.9% Saline 16.7% DMSO

Stereotaxic coordinates

2Hippocampus 3Amygdala

Anterioposterior −1 mm −3.0 mm −3.0 mm

Mediolateral −3 mm −2.0 mm −4.6 mm

Dorsoventral −4.5 mm −3.3 mm −8.8 mm

The animals were given 2 weeks for recovery, after which behavioral tests were per formed. Each test was performed for 7 days with 6 trails each day for every animal.4Morris Water Maze: Spatial Memory; 5Open Field Test: Emotional State; 6Light and dark Chambered Test: Anxiety; 7Three Chambered Sociability Test: Social Behavior



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Results:

Park

inso

n’s

Test

Park

inso

n’s

Con

trol

Alz

heim

er’s

Te

st

Alz

heim

er’s

C

ontr

ol

Morris water maze

Average latency period (final day)

11.5 3.3 35.3 1.8

Open Field test

Average percentage ambulatory activity (centre)

3.0 44.2 11.2 36.2

Average rearing activity 2.8 13.3 5.6 21.3

Fecal index 4.1 0.91 1.3 0.3

Light and dark chamber

Mean percent time in dark chamber

74.0 95.1 59 80.2

Mean number of crossings 13.9 4.1 11.9 4.4

Three cham-ber social behavior

Mean percent social time 78.9 84.3 62.1 79.8

Average time: familiar unfamiliar

0.4 2.4 0.2 2.3

Mean crossings: familiar unfamiliar

0.9 1.8 0.8 1.5

Mean close contacts: familiar unfamiliar

0.6 2.5 0.7 2.3

Conclusions: 1. There are similar and comparable behavioral manifestations in the rat

models of both dementias in the fear, anxiety, emotional state and social parameters.

2. There is greater special cognitive impairment in the Alzheimer’s subjects as compared to Parkinson’s subjects.

3. There is greater ambulatory impairment in the Parkinson’s subjects as compared to Alzheimer’s subjects.

4. Point 2 and 3 elucidate the hallmarks of the respective dementias, i.e. there is greater cognitive decline in Alzheimer’s and there is motor activity deficit and rigidity associated with Parkinson’s.

5. One can thus inference from the common behavioral attributes (Point 1), plausibly there are overlapping and or inter-mingled pathways for these dementias which need to be studied.

6. Breakthroughs in one dementia could shed light on the other, if the com-mon mechanisms can be accomplished.

7. Animal models could possibly be applied to achieve greater understand-ing of behavioral modifications and improve the quality of life of dementia sufferers.

References1. H. Sauer and W. H. Oertel: Progressive Degeneration of Kigrostriatal

Dopamine Neurons Following Intrastriatal Terminal Lesions With 6-Hydroxydopamine: A Combined Retrograde Tracing And Immuno-cvtochemical Studv In The Rat. Neuroscience 1994. 59: 2:401–415.

2. Mei-Han. Yin Liu. Qi Tan. Bing Zhang. Wei Wang. Jian Liu. Xiao-Jun Zang. Yang-Yan Wang. Jin-Ming Jhang: Therapeutic efficacy of Stemazole in a P-amyloid injection rat model of Alzheimer’s disease. European Journal of Pharmacology 2011, 657:104–110.

3. Singurdsson. E.M.. Lee. J.M. Dong. X.W., Hejna. M.J. and Lovens. S.A.: Bilateral injections of Amyloid P25-35 into the amygdala of young fischer rats: Behavioral, neurochemical and time dependent histopathological ef-fects. Neurobiology of Aging 1997, 18:591–608.

4. Sethi P. Jyoti A. Hussain E. Sharma D.: Aluminium-induced electrophysi-ological, biochemical and cognitive modifications in the hippocampus of aging ratsw Neurotoxicology2008. 29:1069–1079.

5. Hall. C. S. Emotional behavior in the rat: Defecation and urination as measures of individual differences in emotionality. Journal of Comparative Psychology l934. IS: 385–403.

6. Bourin M.. Hascoet M.: The mouse light dark test. European Journal of Pharmacology 2003. 463:55–65.

7. Moy S.S. et al: Sociability and preference for social novelty in five inbred strains: an approach to assess autistic-like behavior in mice. Genes. Brain and Behavior 2004. 3: 287–302.


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LPA/LPA1 SIGNALING IS DOWN-REGULATED IN THE DYSFUNCTION OF DOPAMINERGIC NEURONS OF PARKINSON’S DISEASEX. Yang1,*, W. Fu2, F. Sun1, H. Han3, M. Qu3, X. Zeng4

1Biochemistry, Wei Fang Medical College, Weifang, China, 2Histology and Embryology, Wei Fang Medical College, Weifang, China, 3Key Lab of Applied Pharmacology, Wei Fang Medical College, Weifang, China, 4Neurosurgery, The Affiliated Hospital of Wei Fang Medical College, Weifang, China

Objectives: Previous studies implicated that Lysophosphatidic acid (LPA) sign-aling plays a crucial roles in the development of nervous system. LPA signaling could affect the central nervous system (CNS), and consequently influences the survival, proliferation, migration, differentiation, and morphology of CNS cell types, such as neurons, neuroblasts, astrocytes, and oligodendrocytes. However, the mechanism underlying the relationship between LPA and the do-paminergic system is incompletely understood. In this study we investigated the role of LPA/LPA1 signaling in the dysfunction of dopamine (DA) neurons.Methods: The studies were carried out in a Parkinson’s disease (PD) rat model. PD rat models induced with 6-OHDA that was microinjected into sub-stantia nigra and medial forebrain bundle on right side of the brain in adult Sprague-Dawley rats. The tissues of substantia nigra were lysed and detected by Western blotting assay. The expression of LPA1 in the substantia nigra in the 6-OHDA PD rat model was examined.Results: The level of LPA1 in the substantia nigra was significantly reduced rela-tive to control rats as by western blot (P < 0.01). These results suggest that LPA/LPA1 expression level and the consequent signaling effects may regulate DA neuron function and protect these cells from damage in the development of PD.Conclusions: LPA1 is a compelling candidate receptor for PD because it plays a pivotal role in the cell signal system, displays neuron-specific expression, and is involved in DA dysfunction, the neuropathologic hallmark of PD.Supported by Shandong Provincial Natural Science Foundation, China (No.ZR2009CL047, No.ZR2009DM024, No.Y2008C129).No conflict of interest.

467

SPATIAL AND TEMPORAL DISTRIBUTION OF 5-HYDROXYMETHYL CYTOSINE IN RAT BRAINT. Zheng1,*, Q. Lu1, B.R. Zhang2

1Neurosurgery, Zhejiang University, Hangzhou, China, 2Neurosurgery, The Second Affiliated Hospital of Zhejiang University, Hangzhou, China

Objectives: 5-hydroxymethyl cytosine (5hmC) has been recently found in higher organisms as a new kind of epigenetic modification factor, yet its exact role remains elusive. To reveal its role, a general screen on spatial and tem-poral distribution will be a reasonable start. Therefore, we investigated the distribution on different region of brain and explored the relationship between 5hmC level and animal age on rats. Additionally, we compared striatal 5hmC level in 6-OHDA treated rats with controls.Methods: 5hmC in each region including cerebral cortex, striatum, hip-pocampus, cerebellum and brainstem, and bilateral striatal 5hmC in differ-ent age were quantified with ELISA. The level of 5hmC on 6-OHDA induced Parkinsons disease (PD) models were also compared with healthy control with ELISA and Immunohistochemistry.Results: 5hmC is widely distributed in cerebral cortex (0.159%), striatum (0.058%), hippocampus (0.063%), cerebellum (0.032%) and brainstem (0.040%). The level of bilateral striatal 5hmC is significantly higher (P < 0.05) in adulthood (0.058%) compared to early postnatal stage (0.005%). No re-markable difference of striatal 5hmC was found in 6-OHDA induced PD model.Conclusions: 5hmC is widely distributed in cerebral cortex, striatum, hip-pocampus, cerebellum and brainstem with various amount in different re-gion. The level of 5 hmC may be related to the development of brain. In vivo 6-OHDA PD model, 5hmC might not change.No conflict of interest.

468

THE EFFECTS OF SHORT-TERM NICOTINE ADMINISTRATION ON BEHAVIORAL AND OXIDATIVE STRESS DEFICIENCIES INDUCED IN A RAT MODEL OF PARKINSON’S DISEASE.A. Ciobica1,*, M. Padurariu2, L. Hritcu1

1Molecular Biology, Alexandru Ioan Cuza University Iasi, Iasi, Romania, 2Psychiatry, UMF Iasi, Iasi, Romania

Objectives: We previously demonstrated that a 6-hydroxydopamine (6-OHDA) induced lesion of substantia nigra (SN), which is a very well



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known animal model of Parkinson’s disease, resulted in memory deficits and increased brain oxidative stress. Also, recent reports had suggested that nicotine from smoke may contribute, at least in some parts, to the apparent neuroprotective effect of tobacco use in Parkinson’s disease.Methods: In this way, in the present study we were interested to examine the effects of low-dose nicotine administration (5 days, 0.3 mg/kg/day) in a rat model of Parkinson’s disease, on behavioral parameters from Y-maze or shuttle-box task and also on the oxidative stress markers from the temporal lobe, which is one of the most vulnerable cortical area to oxidative stress effects.Results: The administration of nicotine resulted in significant improvements of short-term memory, as seen in the Y-maze task, as well an increase of conditioned avoidance responses and decreased number of escape failures in the shuttle-box task. Additionally, an increase in the specific activity of glu-tathione peroxidase and a decrease of the lipid peroxidation processes is reported. Moreover, we found a significant correlation between the behavio-ral results from the Y-maze and shuttle-box tasks and the levels of oxidative stress markers.Conclusions: Taken together our data suggest that short-term administration of low-dose nicotine facilitates memory processes and improves the oxidative stress status of the brain, after a 6-OHDA induced lesion of the SN.No conflict of interest.

469

CAFFEINE IMPROVES BEHAVIOR, RISES DOPAMINE AND DECREASES TNF-α AND IL-1β, IN A PARKINSON’S DISEASE MODELG. Viana1,*, J.A. Machado-Filho2, M.E. Nobre3, A. Correia3, G. Cerqueira1, K.R. Neves1, G.A. Brito4, E. Cavalheiro5, M.G. Naffah-Mazzacoratti61Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil, 2Neurology, Federal University of Ceará, Barbalha, Brazil, 3Biophysiology, Faculty of Medicine Estácio of Juazeiro do Norte, Juazeiro do Norte, Brazil, 4Morphology, Federal University of Ceará, Fortaleza, Brazil, 5Experimental Neurology, Federal University of São Paulo, São Paulo, Brazil, 6Biochemistry, Federal University of São Paulo, São Paulo, Brazil

Objectives: Caffeine is a methylxanthine, nonselective antagonist of A1 and A2A adenosine receptors. Evidences have shown a significant association between higher caffeine intake and lower incidence of Parkinson’s disease. The objectives were to study the neuroprotective actions of caffeine in a Parkinson’s disease model.Methods: Male Wistar rats were anesthetized with ketamine and xila-zine, and divided into sham-operated (SO), untreated (6-OHDA) and treated orally with caffeine (10 and 20 mg/kg: 6-OHDA + CAF10 and 6-OHDA + CAF 20). Except for the SO group, injected with saline, all the others were subjected to a unilateral injection of 6-OHDA into the right striatum. After 14 days, the apomorphine-induced rotation and open field tests were performed. The animals were euthanized for determinations of striatal DA and DOPAC, and hippocampus slices processed for immunohis-tochemical assays (TNF-α and IL-1β).Results:

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Figure 1. Caffeine decreases apomorphine-induced contralateral rota-tions, as related to the untreated 6-OHDA-lesioned rats, a, b. vs. the 6-OHDA group, with q = 4.290 and 5.673, respectively (One wayANO-VAand Newman-Keuls as the post-hoc test).

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Figure 2. Caffeine increases dopamine (DA) contents in striata of 6-OHDA-lesioned rats. a. p < 0.0014 and b. p < 0.0002 vs. 6-OHDA R; c. p < 0.0052 and d. p < 0.0036 vs. SO L (two-tailed unpaired t-test).

IL-1A

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S.nigra

Striatum

P. cortex

S.nigra

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DG

DG

TNF-α 6-OHDA 6-OHDA+CAF20SO

6-OHDA 6-OHDA+CAF20SO







Figure 3. Caffeine decreases IL-1β (A) and TNF-α (B) immunostaining in various brain areas: mainly in substantia nigra, striatum, pyriform cortex and dentate gyrus (DG), as related to 6-OHDA-lesioned rats.

The results showed that caffeine reversed behavioral changes and de-creased DA contents in the 6-OHDA group. While increased immunostaining for TNF-α and IL-1β were observed, mainly in the striatum, substantia nigra, pyriform cortex and DG in the 6-OHDA group, these were decreased in the 6-OHDA + CAF groups.Conclusions: In conclusion, caffeine exerts neuroprotective effects by im-proving behavior and decreasing pro-inflammatory cytokines, pointing out to the potential benefit of this drug as a therapeutic strategy for Parkinson’s disease.No conflict of interest.



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COMPARATIVE ANALYSIS OF THE EFFICACY OF DOPA-CONTAINING NANOPARTICLES AND STANDARD L-DOPA-BASED DRUGS NASAL ADMINISTRATION USING A PARKINSON’S DISEASE RAT MODELP.Y. Gambaryan1,*, I.G. Kondrasheva2, I.A. Tubashova2, E.S. Severin2, A.A. Guseva1, A.A. Kamensky1

1Biology Faculty, Moscow State University, Moscow, Russia, 2Neurochemistry Lab, Research Center of Molecular Diagnostics & Therapy, Moscow, Russia

Objectives: To compare the efficacy of L-DOPA-containing nanoparticles (nano-DOPA) and standard medicine during chronic nasal administration us-ing rat Parkinson’s Disease (PD) model.Methods: L-DOPA-containing PLGA nanoparticles (250 ± 50nm) were syn-thetized with double emulsion method. The therapy’s efficacy was examined using Wistar rats (420 ± 30 g) with 6-OHDA induced PD. Motion coordination and behavior were analyzed using forelimb placing, open field, etc tests during daily drug administration (0.35 mg/kg, by L-DOPA).Results: L-DOPA, L-DOPA + benserazide and nano-DOPA treated animals showed equal significant (p < 0.05) coordination performance improve-ment 30 minutes after the first drug administration – 80 ± 9%, 80 ± 13% and 79 ± 10% (by the healthy control) respectively, non-treated group got 69 ± 10%. After 4 weeks of treatment coordination performance was 89 ± 13% in nano-DOPA, 45 ± 12% in L-DOPA, 43 ± 22% in L-DOPA + bens-erazide and 45 ± 20% in non-treated group of animals. The effect of nano-DOPA was significantly higher and long-lasting (90 ± 13% 24 h after the administration).

030%

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100%

7 14 21 35 42Experimentday n1=n2=n3=n4=12

* p<0.05

The first day of drugadministration(4weeksafter 6-OHDA injection)

L-DOPA+benserazidetreated

nano-DOPA treated

L-DOPA treated

Non-treated

Coordination performance 30 min after drug administration

% b

y he

alth

y co

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up

28

Measured by ELISE after a single drug administration, the brain levels of DA (AUC1-4) were double higher after nano-DOPA than L-DOPA administration, blood levels did not differ.Conclusions: Nano-DOPA administration provides long-lasting motor func-tion recovery. In comparison with standard drugs it requires lower dose and suites for nasal administration.No conflict of interest.

471

THE EFFECTS OF PERGOLIDE ON MEMORY AND OXIDATIVE STRESS IN A RAT MODEL OF PARKINSON’S DISEASEM. Padurariu1,*, L. Hritcu2, R. Lefter2, A. Ciobica2

1Psychiatry, UMF “Gr.T.Popa” Iasi, Iasi, Romania, 2Molecular Biology, Alexandru Ioan Cuza University Iasi, Iasi, Romania

Objectives: One of the most widely used animal models of Parkinson’s dis-ease (PD) involves injecting 6-hydroxydopamine (6-OHDA) directly into the substantia nigra (SN). Some recent reports speculated that dopaminergic drugs may exert brain antioxidant activity, which could explain some of their protective actions. In this way, the aim of the present study was to examine the effects of low-dose pergolide on memory deficits and brain oxidative stress in a 6-OHDA-induced rat model of PD.Methods: Right-unilateral lesions of the SN were produced with 6-OHDA. Two weeks after neurosurgery, pergolide (0.3 mg/kg/day) was injected intraperi-toneally in the 6-OHDA + pergolide and sham-operated + pergolide groups, while sham-operated and 6-OHDA alone groups received saline. Radial-8-arm maze and Y-maze were used for memory assessment. We also determined some enzymatic antioxidant defenses like superoxide dismutase or glu-tathione peroxidase and a lipid peroxidation marker [malondialdehyde (MDA)], from the temporal lobe.Results: A reduced number of working/reference memory errors was ob-served in 6-OHDA + pergolide group, compared to sham-operated rats.

Additionally, post hoc analysis showed significant differences between 6-OHDA and 6-OHDA + pergolide groups in both Y-maze and radial-arm-maze tasks. We also noted a significant decrease of MDA level in the 6-OHDA + per-golide group, compared to sham-operated rats. Significant correlations were also found between behavioral parameters and MDA levels.Conclusions: Our data suggest that pergolide facilitates spatial memory and improves brain oxidative balance, after a 6-OHDA-induced model of PD. This could be useful for further investigations and clinical applications of pergolide.No conflict of interest.

472

EFFECT OF THE NOVEL ANTIPARKINSONIAN DRUG HEMANTANE ON RATS WITH 6-HYDROXYDOPAMINE-INDUCED HEMIPARKINSONISME. Ivanova1,*, I. Kapitsa1, A. Nepoklonov1, I. Kokshenev1, E. Valdman1, T. Voronina1

1Laboratory of Psychopharmacology, Zakusov Institute of Pharmacology of the RAMS, Moscow, Russia

Objectives: Hemantane has a complex mechanism of action that involves uncompetitive, low affinity NMDA receptor open-channel blocking, antiradical and immunotropic effects. This suggests that hemantane may have neuropro-tective effects on 6-hydroxydopamine-treated dopaminergic neurons.Methods: Rats were lesioned with 6-hydroxydopamine (12 μg) injected into the left medial forebrain bundle. Two weeks later, lesion severity was screened by forelimb use asymmetry using the cylinder test [1]. After the rats with sig-nificant forelimb use asymmetry were selected, they were orally administered 50 mg/kg levodopa (group 1), or 10 mg/kg hemantane (group 2), or saline (active control and sham operated groups) per day for 21 days. On days 21, 28 and 35 after the operation the animals’ behavior was evaluated using the cylinder test, footstep test [2] and curling test [3].Results: In the cylinder test and footstep test in groups 1 and 2 forelimb use asymmetry was not observed, whereas in the active control group right forelimb use dropped by 55% vs. sham operated animals. In the curling test hemantane-treated animals preferentially curled contralaterally to the lesion more than the active control group throughout the observation. The effect of levodopa was insignificant.Conclusions: Hemantane reversed the effects of 6-hydroxydopamine lesion and had a more pronounced effect than levodopa.References1. Schallert T., Jones T.A. J Neural Transplant Plast 1993;4:193–8.2. Olsson M., et al. J Neurosci 1995;15:3863–75.3. Borlongan C.V., Sanberg P.R. J Neurosci 1995;15:5372–5378.No conflict of interest.

473

SESAMIN INHIBITS INFLAMMATORY MARKERS AND MAPKINASE ACTIVATION IN 6-OHDA MICE MODELS. Ahmad1,*, A. Jamal1, M. Khan2, D. Katare3

1Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia, 2Neurology, Georgia Regents University, Augusta, USA, 3Biotechnology, Amity University, Noida, India

Objectives: Sesamin, a natural anti-oxidant found mainly in sesame seed oil, was evaluated as neuroprotective in 6-hydroxy dopamine (6-OHDA) induced brain damage. 6-OHDA is known to produce a mimic of Parkinson’s disease in animal model and causes dopaminergic neuronal cell death in brain (Ahmad et al., 2012, Khan et al., 2010).Methods: Mice were pretreated with sesamin 30 mg/kg Body weight for 15 days. 6-OHDA was injected into striatum and mice were sacrificed after 21 days of injection and brain was collected for biochemical, cellular and his-topathological studies.Results: Sesamin treatment significantly reduced the lipid peroxidation and el-evated glutathione level in straitum as compared to lesioned group. DHE staining showed increased superoxide production in lesioned group as compared to sham and sesamin treatment significantly reversed this process. SODs expression was low in lesioned group and sesamin treatment significantly attenuated its expres-sion. Furthermore, we investigated sesamin effect on inflammatory and oxidative stress markers (Iba1, Nox-2, Cox-2 and iNOS), and observed marked decrease in treated group as compared to lesioned group. mRNA level of TNF-a, iNOS and IL-6 were significantly increased in lesioned group and depleted remarkably in sesamin treated group. Immunfloroscence study revealed that sesamin inhibits mitogen activated protein kinase p-ERK and p-p38 activation in neurons.Conclusions: Based on our findings, sesamin may protect 6-OHDA induced neurotoxicity by inhibiting MAPKinase activation, and enhancing anti-oxidative and anti-inflammatory mechanism in the brain.References1. Ahmad et al., 2012, Neurochemical Research 37: 516–526.2. Khan et al., 2010, Brain Res 1328: 139–151.No conflict of interest.



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PURINERGIC P2X7 RECEPTOR ACTIVITY AND PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR? COACTIVATOR-1 ALPHA AS TARGET FOR THERAPEUTIC STRATEGIES STUDIED IN A RAT MODEL OF PARKINSON’S DISEASEE.G. Ferrazoli1,*, T.T. Schwindt2, H. Ulrich3

1Department of Physiology, Federal University of Sao Paulo, Sao Paulo, Brazil, 2Department of Cell Biology and Developments, Institute of Biomedical Sciences of University of Sao Paulo, Sao Paulo, Brazil, 3Department of Biochemistry, Institute of Chemistry of University of Sao Paulo, Sao Paulo, Brazil

Objectives: We have evaluated effects of Brilliant Blue-G (BBG), a spe-cific antagonist of the P2X7R, and fenofibrate, an activator of PGC-1α, in reverting cell death of dopaminergic neurons in a rat model of of Parkinson’s disease.Methods: For this purpose, unilateral hemisphere lesions of the nigrostriatal pathway of adult male Sprague-Dawley rats was achieved by stereotactic in-jection of 6-hydroxydopamine (6-OHDA). One week after lesion, the animals presented rotational behavior when challenged with apomorphine.Results: Treatment with BBG had a beneficial functional effect. Animals treated with 6-OHDA received BBG (n = 6) during 7 days at a 50 mg/kg dose showed a statistically significant decrease in the number of rotations per minute (13 to 4, p < 0.05) whereas animals receiving only saline did not reveal any significant improvement in rotational tests (11 to 8, p > 0.05). In agree-ment, the percentage of regeneration in BBG treated animals, as revealed by anti-tyrosine hydroxylase staining, was twice as high than that observed for the saline group. Lesioned animals, receiving 0.2% fenofibrate in their diet for 14 days (n = 5), did not reveal any reduction in apomorphine-induced rota-tions (11 to 14, p > 0.05) when compared to animals fed with common diets (n = 5) (12 to 17, p > 0.05). Accordingly, in the Fenofibrate group there was no evidence of recovery of the dopaminergic circuitry.Conclusions: In conclusion, BBG is a promising tool for developing novel strategies in the therapy of Parkinson’s disease.No conflict of interest.

475

PENTOXIFYLLINE (PTX) EXERTS NEUROPROTECTIVE EFFECTS, ON THE MODEL OF PARKINSON’S DISEASE IN RATSG.B. Viana1,*, K.R. Neves1, G.M. Andrade1, G.A. Brito2, M.G. Naffah-Mazzacoratti31Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil, 2Morphology, Federal University of Ceará, Fortaleza, Brazil, 3Biochemistry, Federal University of São Paulo, São Paulo, Brazil

Objectives: To evaluate PTX (a methylxantine derivative and phosphodiester-ase inhibitor) neuroprotection on a Parkinson’s disease (PD) modelMethods: Groups of Male Wistar rats (SO, 6-OHDA, and 6-OHDA treated with PTX at 10, 25 and 50 mg/kg, p.o.) were anesthetized and subjected to an injection of 6-OHDA into the right striatum. The SO group received an intra-striatal injection of saline. The groups were administered with water (SO and the untreated 6-OHDA groups) or with PTX (6-OHDA + PTX treated groups), for 2 weeks. After treatments, the animals were subjected to the apomorphine-induced rotation test. Then, they were euthanized for dissection of striatal tissues and neurochemical, histological and immunohistochemical assays.Results: PTX significantly decreased the number of rotations/h and in-creased striatal dopamine (ng/mg tissue), as related to the untreated 6-OHDA group. The cresyl violet and fluoro jade staining show a reduced number of viable neurons in the striatum, after the 6-OHDA lesion, and this effect was reversed by the PTX treatment. Furthermore, PTX also increased the number of immunostained cells for tyrosine hydroxylase (limiting enzyme for DA synthesis).

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Pentoxifylline (PTX) decreases the number of apomorphine-induced contralateral rotations, in the model of 6-OHDA-induced Parkinson’s disease in rats. ***p < 0.0001 vs. 6-OHDA (ANOVA and Newman-Keuls as the post hoc test).

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g tis

sue)

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Pentoxifylline (PTX) partially reverses the decreased dopamine (DA) levels in the right striatum of the untreated 6-OHDA groups, in the model of 6-OHDA-induced Parkinson’s disease in rats. ***p < 0.0125 vs. 6-OHDA R (ANOVA and Newman-Keuls as the post hoc test).

Pentoxifylline (PTX) reverses the decreased striatal tyrosine hydroxy-lase (TH) immunostaining of the untreated 6-OHDA group (right lesioned side), in the model of Parkinson’s disease in rats.

Conclusions: The results show a neuroprotective effect of PTX, probably re-lated to its anti-inflammatory and antioxidant effects, pointing out to the poten-tial benefit of PTX in the treatment of PD.No conflict of interest.

476

NEUROPROTECTIVE EFFECTS OF THE STANDARDIZED EXTRACT AND POLYPHENOLS FROM CAMELLIA SINENSIS (GREEN TEA), IN THE 6-OHDA MODEL OF PARKINSON’S DISEASEG.B. Viana1,*, N.B. Pinto1, R.M. Vieira2, B.S. Alexandre2, L.K. Leal31Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil, 2Biophysiology, Faculty of Medicine Estácio of Juazeiro do Norte, Juazeiro do Norte, Brazil, 3Pharmacy, Federal University of Ceará, Fortaleza, Brazil

Objectives: Parkinson’s disease is a neurodegenerative disorder character-ized by dopaminergic neurons loss in the substantia nigra. The purpose was to investigate the effects of a standardized extract from Camellia sinensis (CS) and its main catechins, epigallocatechin-3-gallate (EGCG) and epicatechin (EC), in a model of Parkinson’s disease.Methods: Wistar rats were injected daily orally with CS, EGCG and EC, 1 h after the 6-OHDA lesion. The sham-operated group (SO) was administered with water. Fourteen days later, body rotations induced by apomorphine were counted. The animals were euthanized and the striatum removed for determi-nations of nitrite, lipid peroxidation and monoamines.Results: The results showed that the drastic increase in body rotations induced by 6-OHDA was reversed by CS, EGCG and EC. The decrease of dopamine striatal levels, in the lesioned animals, was blocked by CS and catechins. CS, EGCG and EC were effective in reducing nitrite and TBARS.



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Effects of Camellia sinensis (CS) standardized extract and catechins (EC and EGCG), on the apomorphine-induced rotational behavior in rats, after 6-OHDA-induced striatal lesions. The results are expressed as means ± SEM (nmol/g tissue). *p < 0.05, **p < 0.01 and ***p < 0.001 vs. 6-OHDA group (ANOVA and Newman-Keuls as the post hoc test).

Sham op

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6-OHDA

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S 25

6-OHDA+C

S 50

6-OHDA+E

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GCG

Determination of lipid peroxidation (TBARS) in the striatum of rats le-sioned with 6-OHDA. The animals were treated for 14 days with the standardized green tea extract (CS), at the doses of 25 and 50 mg/kg, and catechins (epicatechin, EC and epigallocatechin-3 gallate, EGCG), at the dose of 10 mg/kg). The results are expressed as means ± SEM (nmol/g tissue). *p < 0.05, **p < 0.01 and ***p < 0.001 vs. 6-OHDA group (ANOVA and Newman-Keuls as the post hoc test).

Concentrations of DA and its metabolites (DOPAC and HVA), in the striatum of rats lesioned with 6-OHDA. The animals were treated for 14 days with the standardized green tea extract (CS), at the doses of 25 and 50 mg/kg, or cat-echins (epicatechin, EC and epigallocatechin-3 gallate, EGCG), at the dose of 10 mg/kg.

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+CS 25

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5.56.06.5

7.57.0

8.0

Determination of nitrite concentration (mM) in the striatum of rats le-sionecl with 6-OHDA. The animals were treated for 14 days with the standardized green tea extract (CS) at the doses of 25 and 50 mg/kg, and catechins (epicatechin, EC and epigallocatechin-3 gal I ate, EGCG) at the dose of 10 mg/kg. The results are expressed as meansiSEM. *p < 0.05, **p < 0.01 and ***p < 0.001 vs. 6-OHDA group, respectively (ANOVA and Newman-Keuls as the post hoc test).

GROUPS DOPAMINE DOPAC HVA

SHAM-OPERATED 1960 ± 96.6b 5993 ± 136.1b 2313 ± 706

6-OHDA 458.1 ± 95.6 910.6 ± 176.1 896.4 ± 414

6-OHDA + CS 25 1485 ± 86.7b 2890 ± 820.3 2684 ± 406.9

6-OHDA + CS 50 1 503 ± 195.8b 1966 ± 634a 1802 ± 170

6-OHDA + EC 10 1396 ± 232b 1178 ± 45.3a 3969 ± 813.9

6-OHDA + EGCG 10 1451 ± 139.5b 1244 ± 185.1ab 4748 ± 793b

The results are expressed as means ± SEM (ng/mg tissue). p < 0.05: avs. sham-operated, b vs. 6-OHDA, respectively (ANOVA and the post hoc Tukey’s test).

Conclusions: In conclusion, the standardized extract of CS and its cat-echins reversed behavior and biochemical alterations observed in the 6-OHDA-lesioned rats. CS can act as a neuroprotective agent, due to its antioxidant effect and the reduction of free radicals. Furthermore, this drug and its bioactive components may be an auxiliary tool in the treatment of Parkinson’s disease.No conflict of interest.

477

ACUTE AND LONG-TERM EFFECTS OF HUMAN ADIPOSE DERIVED MSC ON ENDOGENOUS NEUROGENESIS IN THE RAT SVZ FOLLOWING 6-HYDROXYDOPAMINE LESIONINGA. Schwerk1,*, J. Altschüler1, M. Roch2, M. Gossen3, C. Winter4, J. Berg5, A. Kurtz6, B. Steiner7

1Neurology, Charité University-Medicine Berlin, Berlin, Germany, 2Immunology, Charité University Medicine, Berlin, Germany, 3BCRT, Charité University Medicine, Berlin, Germany, 4Psychiatry, Technical University Dresden, Dresden, Germany, 5Neurology, Charité University Medicine, Berlin, Germany, 6Immunology, Charité University-Medicine Berlin, Berlin, Germany, 7Neurology, Charité University-Medicine Berlin, Berlin, Germany

Objectives: Adult human mesenchymal stem cells (MSC) can be eas-ily derived from many tissues, are non-carcinogenic, anti-inflammatory and secrete growth factors important for neuronal differentiation and survival. Consequently, they are ideal candidates to induce neurogenesis and repair in neurodegenerative disorders, as Parkinson’s disease (PD). Several animal studies showed such paracrine effects weeks after MSC transplantation, yet few is known about MSC effects and development right after and after very long-term transplantation. This knowledge is essential in order to understand the mechanisms of effect mediation and ensure their (therapeutic) usability as paracrine vehicles in neurodegenerative disorders.Methods: Here, the acute and long-term effects of adipose-derived MSC transplanted into the rat substantia nigra were assessed in the 6-hydroxydo-pamine (6-OHDA) model of PD.Results: Four days after transplantation, MSC were found in the region of the substantia nigra, showed a strong expression of the astrocytic marker S100β and brain-derived neurotrophic factor (BDNF) and enhanced neuro-genesis in the subventricular zone compared to non-transplanted animals. After 6 months, MSC were found almost exclusively in the arachnoid mater of the brain, expressing S100β and CD34. Neurogenesis was still elevated and dopaminergic decline was attenuated.Conclusions: Hence, adipose-derived MSC survive up to 6 months and seem to achieve their acute effect mediation by microenvironmental modulation in the 6-OHDA diseased rat brain.No conflict of interest.

478

THE EFFECT OF SUBTHALAMIC NUCLEUS MODULATION IN THE SURVIVAL OF DOPAMINERGIC GRAFTS IN A RAT MODEL OF PARKINSON’S DISEASEL. Furlanetti1,*, J.G. Cordeiro1, K.K. Cordeiro1, J. Garcia2, C. Winkler2, M.D. Döbrössy1, G. Nikkhah3

1Stereotactic and Functional Neurosurgery, University Medical Center Freiburg, Freiburg, Germany, 2Neurology, University Medical Center Freiburg, Freiburg, Germany, 3Stereotactic and Functional Neurosurgery, University Hospital Erlangen, Erlangen, Germany

Objectives: Current surgical treatment for Parkinson’s disease (PD) by neu-romodulation of the subthalamic nucleus (STN) can temporarily improve motor symptoms. Alternative regenerative approaches are under research to res-titute dopaminergic neurotransmission and offer a more extensive and long lasting repair. The aim of our project was to test whether the high frequency stimulation within the STN can act synergistically with dopaminergic grafts in reversing functional deficits.



131

Methods: Rats were rendered parkinsonian by unilateral injection of 6-OHDA into the right medial forebrain bundle (MFB). The MFB lesioned animals were assigned into two groups (STN-TX or TX-only). All animals were given stri-atal grafts of rat E14 ventral mesencephalic (VM) tissue into the ipsilateral striatum. Behavioral tests and post-mortem immunohistochemistry were performed.Results: Survival of transplanted VM cells and functional recovery were ob-served in both transplanted groups, however the STN-TX group presented a significant increment in the number of grafted TH positive cells in comparison to the TX-only group (p = 0.017).

Other than that, the STN-TX Group showed better outcome than the TX group in the Amphetamine-induced rotation test (p = 0.047), in the Cylinder test (p = 0.009), as well as in the Stepping test (p < 0.01).Conclusions: The read-outs as host re-innervation and behavioural recov-ery showed that dopaminergic grafts and DBS can act synergistically in the experimental model of PD. These findings suggest that cell therapy could be combined with STN neuromodulation. Further studies should be performed to confirm and extend these findings.No conflict of interest.

479

INTRACAROTID INFUSION OF MESENCHYMAL STEM CELLS IN AN ANIMAL MODEL OF PARKINSON’S DISEASEF. Blandini1,*, S. Cerri1, R. Greco1, A.S. Mangione1, C. Ghezzi1, G. Levandis1, M.T. Armentero1

1Neurobiology, National Neurological Institute C. Mondino, Pavia, Italy

Objectives: Current therapies for Parkinson’s disease (PD) are purely symptomatic and do not modify disease progression. Advances in the stem cell field have drawn considerable attention, particularly on mes-enchymal stem cells (MSCs), which show potent neurotrophic, im-mune-regulatory and anti- inflammatory properties. We have previously demonstrated MSC neuroprotective potential following intrastriatal trans-plantation in a rodent PD model (1). However, intra-cerebral injection represents a quite invasive method to be applied in patients. Alternative routes of administrations should be therefore explored. To this aim, we developed and validated a protocol for intra-arterial infusion of autolo-gous rat MSCs.Methods: Bone marrow-derived MSCs were co-labelled with Far Red and Near-Infrared fluorochromes (2) and infused into Wistar rats through the in-ternal carotid, at different time intervals after 6-hydroxydopamine intrastriatal injection, which causes PD-like neuronal degeneration. Hyperosmolar solution of mannitol was used to transiently permeabilize the blood-brain barrier. At designed times after cell infusion, brain and peripheral organs were excised and underwent Near-Infrared imaging to evaluate whole-body MSC distribu-tion. Microscopic analysis of organ sections was then executed, to assess cell localization.Results: MSC clusters were found in brain, spleen, liver and lungs. Surgery and cell distribution to peripheral organs did not affect long-term animal sur-vival and health, confirming safety and tolerability of the intra-arterial infusion.Conclusions: Evaluations of MSC neuroprotective and neuroreparative ef-fects are currently ongoing. Successful achievement of this work will set the ground for clinical trials employing intra-arterial MSC transplantation in PD patients.References1. Blandini et al., Cell Transplant 2010; 19: 203–2172. Bossolasco et al., Int J Nanomed 2012; 7: 435–447No conflict of interest.

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MODIFICATION TO BEHAVIOUR AND OXIDATIVE INDICES AFTER NEUROTOXIN INSULT TO THE DIENCEPHALIC DOPAMINERGIC NEURONS IN ZEBRAFISH LARVAEA. Norazit1,*, S. Noor1, V. Kanthasamy1, M. Dharmani2, A. Zubaidah3

1Department of Biomedical Science, University of Malaya, Kuala Lumpur, Malaysia, 2Department of Pharmacology, University of Malaya, Kuala Lumpur, Malaysia, 3Electron Microscopy Unit, University of Malaya, Kuala Lumpur, Malaysia

Objectives: To elucidate the pathophysiology of dopaminergic neuron dam-age in the diencephalon region of zebrafish embryos following induction with neurotoxins, namely 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and rotenone respectively.Methods: The effect of neurotoxins on dopaminergic neurons was observed concurrently with the development of the zebrafish larvae. This enabled both a faster method to study the effects of neurotoxins on the dopaminer-gic neurons and a prompt analysis to further study possible pathogenesis,

treatment and neuroprotective measures. Larvae [n = 3 (30 larvae per test)] were maintained in DMSO (control), 6-OHDA, MPTP or rotenone from 4 dpf up to 7 dpf. Locomotor activity was monitored daily and scored in accord-ance to increase or decrease in movement, tail touch response and motility. Morphological changes were also noted. Cellular damage and oxidative stress were assessed by analysing gene expression (th, gfap,sod2) and by immuno-florescent detection of th.Results: Larvae exposed to the neurotoxins showed marked differences (p ≤ 0.05) in movement indices compared to controls, and showed reduced response to tail touch and external stimuli. Twitching was also observed. Pathophysiological changes were detected at the cellular and molecular level.Conclusions: Neurotoxin-induced oxidative stress affected the dopaminergic neurons of the diencephalon region of the developing zebrafish larvae. Loss of these dopaminergic neurons would support the behavioural changes exhibited by the toxin-treated larvae. Such treatments could prove to be a useful tool in screening for potential neuroprotective and neuroregenerative strategies.No conflict of interest.

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A SELECTIVE NURR1/RXR ACTIVATOR FOR TREATING PARKINSON’S DISEASEM. Tallandier1,*, B. Boubia1, O. Lacombe1, O. Poupardin1, R. Steinschneider2, E. Bezard3

1Research, Inventiva, Daix, France, 2Research, Neuron Experts, Marseille, France, 3Research, Motac Neuroscience, Manchester, United Kingdom

Objectives: Nurr1 is a nuclear receptor strongly implicated in the growth, maintenance, and survival of dopaminergic neurons, and as such represents a promising therapeutic target for PD. Nurr1 forms functional heterodimers with RXR. In the absence of a ligand binding pocket in Nurr1, our strategy for an efficient Nurr1 activation was to find molecules that activate Nurr1/RXR heterodimers via binding the RXR.Methods: A functional screening on a proprietary library was performed to identify RXR ligands that selectively activate Nurr1/RXR heterodimers. Selected hit series were optimized. Functional activity was evaluated in vitro using primary neurons derived from embryonic rat mesencephalon. In vivo ac-tivity was evaluated in two animal models: the mouse MPTP sub-acute model and the 6-OHDA unilateral lesion model in rats.Results: IVA360 is a RXR ligand, that activates Nurr1/RXR heterodimers in a Nurr1-dependent manner. In vitro, IVA360 antagonized cell death induced by neurotoxins in mesencephalic primary cell cultures. IVA360 neuroprotec-tive activity is completely blocked by co-treatment with an RXR antagonist. In mice, the compound administered orally showed good brain penetration and was able to dose-dependently reverse the effects of sub-acute and acute MPTP on dopamine level in the striatum and TH-positive cell loss in the midbrain. Neuroprotection was also observed when IVA360 was adminis-tered after 6-OHDA intoxication in rats. Most interestingly, when administered after 6-OHDA, chronic treatment with IVA360 translates into full recovery of functional/motor activity.Conclusions: IVA360, a novel potent and selective Nurr1/RXR activator, rep-resents a promising disease modifying candidate in PD.No conflict of interest.

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A CELL-BASED PHENOTYPIC SCREEN FOR COMPOUNDS PROTECTING DOPAMINERGIC NEURONS FROM PROGRESSIVE DEGENERATIONM. Zhang1,*, X. Feng1, S. Ma1, Y. Zhou1, D. Tattersall11Neurodegeneration DPU, GlaxoSmithKline R&D China, Shanghai, China

Objectives: The phenotypic-based drug discovery approach is designed to look for drugs or targets modulating a disease-relevant characteristic (pheno-type). In an effort to identify neuroprotective agents for Parkinson’s disease, we developed a phenotypic-based assay to monitor progressive dopaminergic neuronal death and conducted a screen for compounds that could delay or halt neurodegeneration.Methods: A mixed cell culture containing rat primary dopaminergic neurons, glial cells and other types of neurons was grown in 384-well plate. Progressive dopaminergic neuronal death was induced by the neurotoxin MPP+. The cul-ture was then treated with a library of compounds with annotated targets at 24 hrs after the start of MPP+ treatment, at which time point the morphology of dopaminergic neurons was not affected but dopamine uptake activity was largely abolished. Hit compounds from the primary screen were further con-firmed in full dose response studies.Results: The screen was conducted with good assay quality (Z’ > 0.5, GDNF as positive control). Among 764 compounds screened, 8 hits were confirmed to be neuroprotective in full dose response study.Conclusions: In this study, we have described a phenotypic assay for pro-gressive cell death and subsequent compound screening. Since phenotypic



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screening does not require prior understanding of the disease mechanism, it is suitable for discovering theraputic agents for complex diseases, such as Parkinson’s disease.No conflict of interest.

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MECHANISMS OF NEURODEGENERATION AND RECOVERY IN A MPTP MARMOSET MODEL FOR IDIOPATHIC PARKINSON’S DISEASES.K. Tolboom1,*, I. Philippens2, R.E. van Kesteren1, A.B. Smit1

1Centre for Neurogenomics and Cognitive Research, VU University, Amsterdam, Netherlands, 2Neurodegeneration, Biomedical Primate Research Centre, Rijswijk, Netherlands

Objectives: Here we study the dynamics and progression of neurode-generation in a slow progressive model for idiopathic PD in non-human primates, with emphasis on 1) the timing of symptom expression, 2) the variation of sensitivity towards MPTP, a variation that is also ob-served in patients, 3) the mechanism of spontaneous recovery after MPTP-intoxication.Methods: Marmoset monkeys (Callitrix jacchus) were selected from five dif-ferent breeding families to obtain a genetically diverse group of animals and to be able to also investigate familial aspects of PD. The monkeys were weekly injected with low doses MPTP (0.5 mg/kg sc). Parkinsonism was monitored over time using a multilevel integrative approach, including observation of par-kinsonian signs, different levels of motor function, histology, biochemistry and immunology.Results: As expected, variation was observed in the onset and progres-sion of parkinsonian symptoms. However, a significant distinction could be made between high responders and low responders, and these dif-ferences correlated well with the animal’s genetic backgrounds. These findings strongly suggest a genetic component underlying MPTP-induced parkinsonian symptoms in marmosets, which will be further investigated using whole-genome sequencing. In addition, all tested animals showed improvement of PD-symptoms after stopping MPTP-treatment, which allows us to uniquely address molecular and cellular mechanisms of recovery.Conclusions: Our MPTP induction model provides a window of opportunity to test disease-modifying drugs on early progression and dynamics of PD. The integrative nature of the markers used and the human clinical validity of the marmoset model will contribute to a better understanding of the development of the disease.No conflict of interest.

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EFFECTS OF AGING AND RESPONSE TO MPTP IN THE SNPC OF C57BL/6 AND GSTPI−/− MICEY. Jiao1, Y. Dou1, R. Smeyne1,*1Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, USA

Objectives: The goal of this study was to stereologically assess the re-sponse to MPTP by counting DA neurons, astrocytes and microglia in the SNpc from in young (4–6 months) and aged (24 months) C57BL/6 and GSTpi−/− mice.Methods: At 4–6 months or 24 months, mice were injected with MPTP (2 × 20 mg/kg/day × 2 days). 7 days after MPTP, mice were transcardially perfused with 3% paraformaldehyde, sectioned at 10 microns and immu-nostained for TH (DA neurons), GFAP (astrocytes) and Iba-1 (microglia). Using design and methods based stereology, estimates of cell populations were attained.Results: We found no change in baseline DA neurons number in either mouse strain. Following administration of MPTP, we found a larger loss of TH+ neurons in mice lacking GSTpi. that was evident at 24 months. For as-trocytes, we found no difference in GFAP+ cell number at 4 months between C57BL/6 and GSTpi−/− mice. At 24 months, there is a significant increase in astroctye number in both strains, although GSTpi−/− mice have a signifi-cantly greater difference. For microglia, we do not see any change in baseline microglia number in C57BL/6 or GSTpi−/− mice through 24 months of aging. However, following MPTP administration, there is a significant increase in microglia number in C57BL/6 and GSTpi−/− mice at 4 and 24 months of age. Additionally, the response to MPTP is significantly greater at 24 months in GSTp−/− mice.Conclusions: Aging does not seem to have a significant effect on the num-ber of DA neurons, astrocytes and microglia in the SNpc of C57BL.6 or GSTpi−/− mice.No conflict of interest.

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CHANGES OF NICOTINIC ACETYLCHOLINE RECEPTORS AT EARLY STAGES OF PARKINSONISM IN MICEE. Kryukova1,*, I. Shelukhina1, A. Kolacheva2, I. Kasheverov1, M. Ugrumov2, V. Tsetlin1

1Department of Molecular Bases of Neurosignalization, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow, Russia, 2Laboratory of Hormonal Regulation, Koltsov Institute of Developmental Biology RAS, Moscow, Russia

Objectives: Neuronal nicotinic acetylcholine receptors (nAChRs) are widely rep-resented in the brain and some non-neuronal tissues, and their malfunctioning is associated with diverse pathologies. Parkinson’s disease (PD) is associated with significant decline of different subtypes of nAChRs in nigrostriatal area. The aim of this study was to develop models of early PD and to study changes in the content of individual nAChR subtypes at the transition from presymptomatic to clinical stage.Methods: The advanced presymptomatic or the early symptomatic stages of Parkinsonism were modeled in mice by respectively two- or four-fold subcutane-ous injections of 1-methyl-1,2,3,6-tetrahydropyridine (MPTP) at the individual dose of 12 mg/kg with 2-h intervals. After 15 days the animals were sacrificed and the striatum and substantia nigra homogenates were prepared. Quantification of individual nAChR subtypes in homogenates was performed by radioligand as-says using 125I-α-bungarotoxin, 125I-Y0-α-conotoxin MII or 3H-epibatidine.Results: In mice with presymptomatic stage of Parkinsonism the number of 3H-epibatidine sensitive nAChRs decreased in the striatum, but increased in the substantia nigra. These changes preceded the clinical manifestation of the disease. Level of α-conotoxin MII sensitive nAChRs containing α6-subunit in the striatum relatively increased per axonal terminal at presymptomatic stage and decreased with more severe lesion at symptomatic stage.Conclusions: The results indicate the possible involvement of heteromeric nAChRs containing α4β2 and α6-subunits in the mechanisms of plasticity un-der toxic brain injury.No conflict of interest.

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BEHAVIOURAL CHARACTERISATION OF A PROGRESSIVE MODEL OF PARKINSON’S DISEASE INDUCED BY CHRONIC CENTRAL DELIVERY OF MPP+ IN THE RATC. Muller1,*, B. Lapertot1, N. Violle2, J.F. Bisson3

1Aging and Neurodegenerative Diseases Department, Etap, Vandoeuvre-les-Nancy, France, 2Cerebrovascular Diseases Department, Etap, Vandoeuvre-les-Nancy, France, 3Human Pathologies Department, Etap, Vandoeuvre-les-Nancy, France

Objectives: The sporadic form of Parkinson’s disease has a long-lasting evo-lution over several decades, characterised by progressive death of dopamin-ergic neurons in Substantia Nigra (SN). New preclinical models that mimic such a progressive death are of interest. Unilateral intracerebroventricular infusion of small doses of MPP+ in rats during 28 days was showed to induce the progressive death of dopaminergic neurons in SN (Yasdani et al. 2006). The aim of our work was to perform a first assessment of the behavioural outcomes focused on motor function in this model.Methods: Male adult Sprague Dawley rats were stereotaxically implanted in the lateral cerebral ventricle in order to deliver MPP+ or its excipient with an osmotic pump. Behaviour of rats was evaluated through a battery of tests including sensorimotor coordination, spontaneous locomotor activity, apomor-phine induced rotation, limbs dexterity, before histological analysis of the SN.Results: Sensorimotor coordination deficits and akinesia were observed in MPP+ rats, but not in Shams, at the end of the infusion. Nevertheless, these troubles were not found 5 weeks later. Neuronal counting showed a 20% de-crease of SN dopaminergic neurons in the MPP+-group vs. Sham group.Conclusions: Our studies demonstrated that a MPP+ infusion during 28 days was able to induce temporary motor troubles suggesting the establishment of compensatory mechanisms. The increase of MPP+ dose should induced more permanent troubles. Another study under progress will complete these results.References1. Yazdani U, German DC, Liang CL, Manzino L, Sonsalla PK, Zeevalk GD

(2006). Rat model of Parkinson’s disease: chronic central delivery of 1-me-thyl-4-phenylpyridinium (MPP+). Exp. Neurol. 200(1):172–83


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BEHAVIORAL CHANGES RELATED TO INCREASED EMOTIONALITY IN THE CHRONIC MPTP-TREATED-MOUSE MODEL OF PARKINSONISMM. Mazurkiewicz1,*, E. Palasz1, M. Goras1, A. Gasiorowska2, W. Niewiadomski2, G. Niewiadomska1

1Laboratory of Preclinical Studies in Neurodegenerative Disease, Nencki Institute of Experimental Biology PAS, Warsaw, Poland, 2Department of Applied Physiology, Mossakowski Medical Research Centre, Warsaw, Poland



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Objectives: Nonmotor symptoms in Parkinson’s disease (PD) involving cogni-tion and emotionality have progressively received attention. There are studies that have indicated that PD patients score lower than controls on a personal-ity trait called novelty seeking (1), which according to some authors is the temperament trait primarily modulated by dopamine, whereas others denied dopamine involvement. The objective of the present study was to examine behavioral changes related to emotionality in the chronic MPTP-treated-mouse model of PD characterized by excessive loss of dopaminergic neurons.Methods: Three-months old, male C57BL/6 mice were injected with 10 doses of MPTP (12.5 mg/kg subcutaneously) in combination with probenecid (250 mg/kg, intraperitonealy) on 5 week schedule. Emotionality and explorative behav-ior were assessed both in circular (COF) and square open-field (SOF). In COF walking-distance in the central area and in the periphery was measured, whereas in SOF time spent in home cage and the walking-distance outside. Tests were performed before treatment and immediately and 4 weeks after treatment.Results: In comparison to before-treatment test, the MPTP-mice covered the shorter distance in COF central area and spent more time in home cage in SOF during test performed immediately and 4 weeks after treatment. Additionally they had longer latency to the first exit from the cage.Conclusions: The present results indicate on enhanced emotionality in mice with MPTP/probenecid induced Parkinsonism. These support hypothesis of the involvement of dopaminergic system impairment in reduction of novelty-seeking behavior, as it has been postulated in PD patients.Reference1. Kaasinen et al. PNAS 98, 2001.No conflict of interest.

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MOTOR LEARNING IN THE CHRONIC MPTP-TREATED-MOUSE MODEL OF PARKINSONISME. Palasz1,*, M. Goras1, A. Gasiorowska2, M. Mazurkiewicz1, W. Niewiadomski3, G. Niewiadomska1

1Laboratory of Preclinical Studies in Neurodegenerative Disease, Nencki Institute of Experimental Biology PAS, Warsaw, Poland, 2Laboratory of Preclinical Studies in Neurodegenerative Disease, Nencki Institute of Experimental Biology PAS, Department of Applied Physiology Mossakowski Medical Research Centre, Warsaw, Poland, 3Department of Applied Physiology, Mossakowski Medical Research Centre, Warsaw, Poland

Objectives: Motor therapy in animal models of Parkinson’s disease (PD) has neuroprotective and neuroregenerative effects. However, the mechanisms of motor therapy effects is unknown. Fundamental research relies on good animal models that demonstrate the hallmarks of PD. Chronic treatment with MPTP and probenecid in mice produced long-lasting dopamine cell loss and motor deficits. Overreaching aim of the present study was to examine efficacy of physical training on changes in the motor learning in MPTP model.Methods: Three-months old, male C57BL/6 mice were injected with 10 doses of MPTP (12.5 mg/kg subcutaneously) in combination with probenecid (250 mg/kg, intraperitonealy) on 5 week schedule. The motor learning was assessed in RotaRod and treadmill. Motor performance was assessed as maximal rpm sustained for each trial on RotaRod and number of electro foot-shocks on treadmill. Behavioral tests were performed before treatment and immediately and 4 weeks after treatment.Results: Before treatment mice doubled maximal sustained rpm during 4 con-secutive days of RotaRod training. Immediately after treatment MPTP-mice lowered the maximal learned speed and did not improve during training. Tested 4 weeks later MPTP-mice were able to increase their speed during learning and finally achieved the pre-treatment level. In contrast, the performance in treadmill training was unimpaired by MPTP treatment. Moreover, they significantly re-duced number of shocks when tested immediately and 4 weeks after treatment.Conclusions: Contrary to the claimed sustainability of motor impairment caused by MPTP/probenecid treatment in our study some forms of motor learning recovered spontaneously and some other were not affected at all.No conflict of interest.

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SLEEP DEPRIVATION EXACERBATES PARKINSON’S DISEASE PATHOLOGY IN A MOUSE MODEL. NEUROPROTECTIVE EFFECTS OF A POTENT ANTIOXIDANT COMPOUND H-290/51A. Sharma1,*, D. Muresanu2, R. Castellani3, R. Patnaik4, P. Sjoquist5, H. Sharma6

1Surgical Sciences Anesethesiology & Intensive Care Medicine, Uppsala University Hsopital, Uppsala, Sweden, 2Clinical Neurosciences, University Hospital University of Medicine & Pharmacy, Cluj-Napoca, Romania, 3Division of Neuropathology, University of Maryland School of Medicine, Baltimore, MD, USA, 4School of Biomedical Engineering, Indian Institute of Technology Banaras Hindu University, Varanasi UP, India, 5Division of Cardiology Department of Medicine, Karolinska Institute Karolinska University Hospital, Stockholm, Sweden, 6Surgical Sciences Anesthesiology & Intensive Care Medicine, Uppsala University Hospital Uppsala University, Uppsala, Sweden

Objectives: Stress and environmental factors affect Parkinson’s Diseases (PD) pathology involving oxidative stress. Since sleep deprivation (SD) is a profound stress in Military, we examined role of SD on PD pathology in a mouse model. Furthermore, neuroprotective effects of a chain-breaking anti-oxidant H-290/51 in PD were also investigated.Methods: SD was induced in mice using an inverted flowerpot model for 24 and 48 hours. The PD like symptoms were induced by four injections of METH (10 mg/kg, i.p.) or MPTP (20 mg/kg, i.p.) within two h intervals daily for 5 days. In separate groups H-290/51 (50 or 100 mg/kg, i.p.) was administered in iden-tical manner for 1 week and brain pathology was examined.Results: On the 8th day, METH or MPTP reduced DA in ST (control 26 ± 4 ng/mg protein to MPTP 5 ± 2 ng/mg protein; METH 6 ± 2 ng/mg protein, P < 0.01) and were further reduced (−30 to −50%) in SD mice. Pronounced activation of microglia, astrocytes and neuronal damages together with loss of tryptophan hydroxylase (TH) positive neurons in striatum (ST) and substantia niagra (SN) occurred in MPTP or METH treated mice that were further exacerbated in SD mice in a time dependent manner.

Treatment with H-290/51 significantly reduced these brain pathologies in normal mice but require higher dose of the compound for neuroprotection in SD mice.Conclusions: These observations are the first to show that the SD could ag-gravate PD pathology and antioxidants could be useful in attenuating brain pathology in PD.No conflict of interest.

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MPTP-INDUCED DOPAMINE NEURON DEGENERATION AND GLIA ACTIVATION IS POTENTIATED IN MDMA PRETREATED MICEG. Costa1,*, L. Frau1, J. Wardas2, A. Pinna1, A. Plumitallo3, M. Morelli11Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy, 2Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland, 3Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy

Objectives: Clinical observations report a higher propensity to develop Parkinson’s disease (PD) in amphetamine users. 3,4-Methy-lenedioxymethamphetamine (MDMA, ‘ecstasy’) is an amphetamine-related drug that is largely consumed by adolescents and young adults which may have neuroinflammatory and neurotoxic effects. The present study was aimed at evaluating in mice whether consumption of MDMA during adolescence might influence the neuroinflammatory and neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin known to induce PD in humans.Methods: Activation of astroglia and microglia by glial fibrillary acidic protein (GFAP) and complement type 3 receptor (CD11b) immunohistochemistry and degeneration of dopaminergic neurons by tyrosine hydroxylase (TH) immu-nohistochemistry was evaluated. MPTP (20 mg/kg × 4) was administered in mice treated from age 8 to 17 weeks with MDMA (10 mg/kg twice a day/twice a week).Results: In mice chronically treated with MDMA, administration of MPTP induced a higher microglial and astroglial response both in the striatum and substantia nigra pars compacta (SNc) compared with vehicle or vehi-cle + MPTP-treated mice. Inflammatory changes were associated with a de-crease in TH immunoreactivity in the SNc of MDMA-treated mice and with a further decrease in the striatum and SNc of MDMA + MPTP-treated mice compared with vehicle, MDMA or MPTP-treated mice.Conclusions: Results show that chronic administration of MDMA during late adolescence in mice exacerbates the neurodegeneration and neuroinflamma-tion caused by MPTP, suggesting that MDMA may constitute a risk factor for dopaminergic neuron degeneration.Reference1. Christine CW, Garwood ER, Schrock LE, Austin DE, McCulloch CE.

Parkinsonism in patients with a history of amphetamine exposure. Mov Disord 2010;25:228–31.


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SEMICARBAZIDE, A SEMICARBAZIDE-SENSITIVE AMINE OXIDASE (SSAO) INHIBITOR, ENHANCES MPP+ -INDUCED HYDROXYL RADICAL GENERATION IN RAT STRIATUMT. Obata1,*1Pharmacology, Yokkaichi Nursing and Medical Care University, Yokkaichi, Japan

Objectives: In the present study was examined whether or not semicar-bazide, a non-selective, but highly potent inhibitor, as a result of a carbonyl group at the cofactor site (such as in in semicarbazide-sensitive amine oxi-dase (SSAO) inhibitor), can increase 1-methyl-4-phenylpyridinium ion (MPP+) induced hydroxyl radical (•OH) generation in the rat striatum.Methods: Rats were anesthetized, and sodium salicylate (0.5 nmol/ml/min) was infused through a microdialysis probe to detect the generation of •OH



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as reflected by the non-enzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) in the striatum.Results: Induction of semicarbazide or 2-bromoethylamine (100 mM or 0.1 nmol/ml/min) into rat striatum drastically increased the formation of •OH re-sults, trapped as DHBA by the action of MPP+. When iron (II) was administered to the semicarbazide-pretreated rats, a marked elevation of DHBA was also observed, compared with MPP+-alone treated animals, that showed a posi-tive linear correlation between iron (II) and •OH formation trapped as DHBA (R2 = 0.988) in the dialysate.Conclusions: These results suggest that after inhibition of tissue bound and/or blood plasma SSAO activity, with consequent increases in amine levels, semicarbazide or 2-bromoethylamine enhances the formation of •OH products of efflux/oxidation due to MPP+.

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DISHEVELLED-1 MODULATES NEURODEGENERATION IN PARKINSON’S DISEASE MODELSA. Liou1,*, Z. Wang1, Y. Guo2, Y. Gao2, J. Chen1

1Neurology, University of Pittsburgh, Pittsburgh, USA, 2Medical Neurobiology, Fudan University, Shanghai, China

Objectives: In this study, we characterized the capacity of dishevelled-1 (DVL1) to modulate neuronal demise under MPTP toxicity and other toxin-induced and genetic models of PD.Methods: Cell death modulation of DVL1 level in MPP+ and other PD-related models in SHSY5Y cells was characterized using molecular and cell biology approaches. Meanwhile, the use of AAV delivery system, immunohistological and immunofluorescence staining together with stereology were used to verify the capacity of DVL1 to modulate dopaminergic neuronal demise in MPTP mice model.Results: Various PD-related insults (over-expression of α-synuclein wild-type and mutant, LRRK2 wild-type and mutant, rotenone and MPP+) elicited significant increase in cytosolic DVL1 and its knockdown attenuated cell death. A similar DVL1 response and modulation pattern was observed for dopaminergic neurons in MPTP treated mice resulting in an improvement of sensorimotor functions. Mechanistically, this increase of DVL1 was es-sentially due to its re-partitioning from mitochondria to cytosol, in turn ac-tivating JNK (independent of the Wnt pathway) to elicit a novel cell death program.Conclusions: Cytosolic DVL1 is capable of modulating cell death in vari-ous PD-related insults. Under MPTP toxicity, DVL1 initiated a novel cell death program mediated by JNK demonstrating its therapeutic candidacy for PD.No conflict of interest.

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PROTECTIVE EFFECT OF DIETARY SUPPLEMENTATION OF DATES ON MPTP INDUCED OXIDATIVE STRESS AND DOPAMINE DEPLETION IN A MOUSE MODEL OF PARKINSON’S DISEASES. Selvaraju1,*, M.M. Essa1, A. Ahood1, A. Kathyia1

1Food Science and Nutrition CAMS, Sultan Qaboos University, Muscat, Sultanate of Oman

Objectives: The sub chronic mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP) paradigm is one of the most widely used in vivo model for Parkinson’s disease (PD). We investigated the therapeutic effect of 4% dates supplementation in diet against MPTP neurotoxicity in Mouse.Methods: Mouse were treated with MPTP for 4 days to show neurochemical parameters and oxidative stress abnormalities similar to patients with PD. PD mice were treated with 4% dates for 28 days. Dopamine and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) by HPLC; antioxidants: catalase, superoxide dismutase (SOD) and glutathione peroxi-dase (GPx) activities, and reduced glutathione (GSH) and lipid peroxidation marker (TBARS) were analyzed in the dates treated and untreated PD mouse striatum.Results: Mouse treated with MPTP showed reduced levels of DA, DOPAC, HVA, catalase, GSH, SOD and GPx and induced TBARS level compared to the control. Dates rich in diet treatment of PD mouse 4% for 28 days increased DA, DOPAC, HVA, catalase, GSH, SOD and GPx levels and normalized TBARS levels in the striatum of the PD mouse.Conclusions: Dates significantly improve all the neurochemical parameters and oxidative stress abnormalities compared to PD mice and offer a promis-ing new strategy for the treatment of neurodegenerative disorders and PD in particular.Financial Source: This project was supported by a research grant from The Research Council, Oman (RC/AGR/FOOD/11/01).No conflict of interest.

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DIETARY SUPPLEMENTATION OF FIGS ON 1-METHYL-4-PHENYL-1, 2, 3, 6-TETRAHYDROPYRIDINE INDUCED MOUSE MODEL OF PARKINSON’S DISEASEM.M. Essa1,*, S. Selvaraju1, A. Ahood1, A. Kathyia1


Objectives: We investigated the therapeutic effect of 4% figs rich in diet against MPTP neurotoxicity in mice, by examining: (1) biochemical entities for PD, including the levels of dopamine and its metabolites dihydroxypheny-lacetic acid (DOPAC) and homovanillic acid (HVA), and (2) lipid peroxidation markers (TBARS) and endogenous antioxidant; catalase, SOD, GPx and GSH levels.Methods: The mice were divided into four groups. First group of mice were not treated and used as a control. Second group of mice were injected with MPTP 20 mg/kg body weight/day for 4 days to induce PD. Third group of mice were injected with MPTP for 4 days and treated with diet rich in 4% figs for 28 days. In addition group IV mice received only 4% figs in diet respec-tively. The animals were sacrificed after 28 days of the experiment, brain was dissected out and striatum was collected and above mentioned biochemical analyzed.Results: 4% figs rich in diet treatment of PD mouse for 28 days increased DA, DOPAC, HVA, catalase, GSH, SOD and GPx levels and normalized TBARS levels in the striatum of the PD mouse compared to the figs untreated PD mouse striatum.Conclusions: The results of our study confirmed that figs mediated its neu-roprotective action against experimental PD through its antioxidant and anti-inflammatory properties and also our results suggest that further studies are needed to validate and determine the mechanism of action of these fruits against PD.The project was supported in the form of research grant from The Research Council, Oman (Grant # RC/AGR/FOOD/11/01).No conflict of interest.

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POMEGRANATE RICH DIET IMPROVES CATECHOLAMINES AND PHYSIOLOGICAL ABNORMALITIES SEEN IN A PARKINSON’S DISEASE MODEL MOUSES. Selvaraju1,*, M.M. Essa1, A. Ahood1, A. Kathyia1


Objectives: The objective of the study was to examine effect of diet rich in 4% pomegranate on catecholamines and physiological abnormalities seen in Parkinson’s disease (PD) using PD model mouse.Methods: Mouse were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyri-dine (MPTP) for 4 days to show biochemical and physiological abnormalities similar to patients with PD. PD mice were treated with dietary supplementation of 4% pomegranate for 28 days. Catecholamines: dopamine (DA), 3,4-dihy-droxy-phenylacetic acid (DOPAC) and homovanillic acid (HVA); antioxidants: glutathione (GSH) and glutathione peroxidase (GPx); and lipid peroxidation marker (TBARS) were analyzed in the 4% pomegranate treated and untreated PD mouse striatum.Results: Mouse treated with MPTP showed reduced levels of DA, DOPAC, HVA, GSH and GPx and induced thiobarbituric acid reactive substance (TBARS) level compared to the control. Physiological abnormalities were seen in the mouse as determined by hang test and rotarod test. Dietary supplemen-tation of 4% pomegranate to PD mouse for 28 days increased DA, DOPAC and HVA levels and normalized TBARS levels in the corpus striatum of the PD mouse. 4% Pomegranate treated mice showed improved motor function as determined by hang test and rotarod test and increased GSH and GPx levels in the striatum compared to the pomegranate untreated PD mouse striatum.Conclusions: These data suggest that pomegranate is a potential drug in treating catecholamines, oxidative damage and physiological abnormalities seen in the PD mouse.The project was supported in the form of research grant from The Research Council, Oman (Grant # RC/AGR/FOOD/11/01).No conflict of interest.

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WALNUT REVERSES 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROP-YRIDIN (MPTP)-INDUCED NEURODEGENERATION IN A MOUSE MODEL FOR PARKINSON’S DISEASEM.M. Essa1,*, S. Selvaraju1, A. Kathyia1, A. Ahood1




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Objectives: In this study, we evaluated the neuroprotective effect of dietary sup-plementation of walnut against 1-methyl-4-phenyl-1, 2, 3, 6- tetrahydropyridine (MPTP) induced oxidative stress, behavioral deficits and dopamine depletion.Methods: First group of mice were not treated and used as a control. Second group of mice were injected with MPTP 20 mg/kg body weight/day for 4 days to induce PD. Third group of mice were injected with MPTP for 4 days and treated with diet rich in walnut for 28 days. The animals were sacrificed after 28 days of the experiment, brain was dissected out and striatum was col-lected. Dopamine and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) by HPLC; antioxidants: catalase, and glutathione peroxidase (GPx) activities, and reduced glutathione (GSH) and lipid peroxi-dation marker (TBARS) were analyzed.Results: Walnut rich in diet treatment of PD mouse for 28 days increased DA, DOPAC, HVA, catalase, GSH, and GPx levels and normalized TBARS levels in the striatum of the PD mouse. Behavioral analyses showed that walnut ameliorates MPTP-induced motor coordination.Conclusions: In this study suggest that in mice, walnut attenuates MPTP-induced neurotoxicity and that an antioxidant effect against oxidative stress may be partly responsible for its observed neuroprotective effects. However, further studies are necessary to better understand the mechanisms for the observed neuroprotection.This project was supported by a research grant from The Research Council, Oman (RC/AGR/FOOD/11/01).No conflict of interest.

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ENDURANCE TRAINING COUNTERACTS MPTP TREATMENT-RELATED CHANGES IN MIDBRAIN CONTENTS OF DOPAMINE AND DOPAMINE METABOLITES, AND IN PARVALBUMIN EXPRESSIONJ. Langfort1,*, M. Chalimoniuk2, D. Kania3, N. Lukacova4, S.J. Chrapusta5

1Department of Sports Training–The Jerzy Kukuczka Academy of Physical Education Katowice, Department of Experimental Pharmacology-Mossakowski Research Centre PAS, Warsaw, Poland, 2Faculty of Biology and Environmental Sciences–Cardinal Stefan Wyszynski University, Department of Cellular Signalling–PAS Mossakowski Medical Research Centre PAS, Warsaw, Poland, 3Department of Sports Training, The Jerzy Kukuczka Academy of Physical Education, Katowice, Poland, 4Department of Neurobiology, Institute of Neurobiology Slovak Academy of Sciences, Koscice, Slovakia, 5Department of Experimental Pharmacology, Mossakowski Research Centre PAS, Warsaw, Poland

Objectives: Degeneration of the nigrostriatal dopamine (DA) system and its related drop in DA are the causes of Parkinsonism neurological deficits. Pharmacological interventions include the use of DA receptor agonists and/or of the substrate for DA synthesis L-DOPA. We hypothesized that the desired increase in DA supply might be also achieved by stimulating DA synthesis with increased locomotor activity involving large skeletal muscle groups.Methods: We compared midbrain contents/expression of tyrosine hydroxy-lase (TH), DA and its metabolites, DA transporter and parvalbumin, be-tween healthy and MPTP-treated sedentary and endurance-trained (EnTr) male Wistar rats. EnTr consisted of treadmill running for 1 h daily, 5 days/week, for 6 weeks. MPTP was injected to the respective rats intraperitoneally (2 × 40 mg/kg, with a 2 h interval) 12 days before the completion of the train-ing. Rats were killed 48 h after the last bout of exercise.Results: MPTP alone significantly decreased midbrain TH and DA transporter expression and the contents of DA, but not of DA metabolites. EnTr elevated midbrain expression of TH and midbrain contents of DA, but not of DA me-tabolites, similarly in healthy and MPTP-treated rats. MPTP alone markedly elevated midbrain parvalbumin expression, whereas EnTr did not significantly affect midbrain parvalbumin expression in healthy rats, but partially counter-acted the effect of MPTP.Conclusions: These data indicate that enhanced physical activity involving large skeletal muscle groups counteracts MPTP-induced changes in midbrain DA system(s) and suggest that it may delay the emergence of or partially com-pensate the Parkinsonism-related midbrain degeneration changes.Supported by the NCN grant #2011/01/B/ZN5/01397No conflict of interest.

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ENDURANCE TRAINING DIFFERENTLY AFFECTS THE ACTIVITY OF THE NOS/GC/CGMP PATHWAY IN THE NIGROSTRIATAL SYSTEM IN HEALTHY AND ‘PARKINSONIAN’ (MPTP-TREATED) MALE WISTAR RATSM. Chalimoniuk1,*, N. Lukacova2, S.J. Chrapusta3, J. Langfort4

1Department of Cellular Signalling – PAS Mossakowski Medical Research Centre, Faculty of Biology and Environmental Sciences – Cardinal Stefan Wyszynski University, Warsaw, Poland, 2Institute of Neurobiology, Slovak Academy of Sciences, Kosice, Slovakia, 3Department of Experimental Pharmacology, PAS Mossakowski Medical Research Centre, Warsaw, Poland,

4Department of Experimental Pharmacology – PAS Mossakowski Medical Research Centre, Department of Sports Training – The Jerzy Kukuczka Academy of Physical Education – Katowice, Warsaw, Poland

Objectives: Perturbations in the activity of the nitric oxide synthase/guanylyl cyclase/cGMP (NOS/GC/cGMP) pathway in the midbrain and striatum may underlie the dying-out of nigrostriatal dopamine neurons in Parkinson’s dis-ease and rodent models of this clinical entity. The related motor deficits can be partly corrected by enhanced physical activity.Methods: We compared, between sedentary and endurance-trained healthy and MPTP-treated male Wistar rats, the effects of 7-week endurance train-ing (EnTr) on mRNA and/or protein levels and activity of Ca2+ -dependent endothelial (eNOS) and neuronal (nNOS) nitric oxide synthases, of the α1, α2 and β1 subunits of soluble guanylyl cyclase (GCα1, GCβα2 and GCβ1, re-spectively) and of the major CNS phosphodiesterase isoform (PDE10) levels in the striatum and midbrain. The trained rats were sacrificed 48 h after the last training session.Results: MPTP treatment alone enhanced nNOS but not eNOS expression. EnTr preferentially enhanced eNOS expression in healthy rats and enhanced eNOS and nNOS similarly in MPTP-treated rats in both the midbrain and stria-tum. GCβ1 expression was increased similarly by all treatments in these brain regions. EnTr increased GCα2 but not GCα1 expression in both the midbrain and striatum, whereas MPTP alone elevated GCα1 but not GCα2. MPTP alone decreased PDE10 expression in both the midbrain and striatum, while EnTr alone exerted an opposite effect and counteracted the effect of MPTP administered during the training process.Conclusions: These results suggest that EnTr may counteract the MPTP-induced degeneration of the nigrostriatal dopamine system by preferentially enhancing the expression of eNOS, and elevating α2β1 GC isoform.Supported by the NCN grant #2011/01/B/ZN5/01397No conflict of interest.

499

KNOCKDOWN OF TRKB RECEPTOR BLOCKS THE EXERCISE-MEDIATED NEUROPROTECTION IN THE MPP+-INDUCED PARKINSONIAN RATSJ. Chuang1,*, C.T. Shih1, S.H. Ching2

1Department of Physiology, National Cheng Kung University, Tainan, Taiwan, 2Department of Physical Therapy, National Cheng Kung University, Tainan, Taiwan

Objectives: Our previous studies have shown that treadmill exercise improved learning and memory in association with upregulation of brain-derived neuro-trophic factor and its receptor TrkB expression in the rat hippocampus. Partial deprivation of TrkB receptor induces selective nigrostriatal dopaminergic neu-rodegeneration, hallmark of Parkinson’s disease. Therefore, we hypothesized that TrkB signaling is involved in treadmill exercise-mediated neuroprotection in a 1-methyl-4-phenylpyridinium (MPP+)-induced parkinsonian rat model.Methods: Male Wistar rats (4-week-old) were subjected to treadmill exercise or non-exercise (sedentary) for 4 weeks. MPP+ was infused into right side of striatum 24 h after the cessation of 4-week exercise and brain samples were collected 72 h after the treatment.Results: We found that the protein expression of tyrosine hydroxylase (TH, a marker enzyme of dopamine neurons), total TrkB/Akt/ERK and phospho-rylated TrkB (p-TrkB)/p-ERK was decreased in the striatum 72 h after MPP+

injection. However, MPP+ treatment did not affect their activation (no change in the p-Akt/total Akt and p-TrkB/total TrkB and p-ERK/total ERK). Treadmill exercise training upregulated total TrkB expression and prevented the MPP+-induced downregulation of TH, TrkB, ERK and p-ERK protein expression. Moreover, we inhibited TrkB expression by lentivirus-carried shTrkB and found that knockdown of TrkB blocked exercise-mediated prevention of MPP+ -induced protein downregulation and neuroprotection against MPP+ -induced loss of nigral TH+ neurons and dopamine transporter immunoreactive nerve terminals in the striatum.Conclusions: These results reveal that treadmill exercise regulates TrkB signaling to protect nigrostiatal dopaminergic neurons from MPP+ toxicity.No conflict of interest.

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NEUROPROTECTIVE EFFECTS OF ROPINIROLE ON MPTP-INDUCED PARKINSON’ ANIMAL MODELSC. Cho1,*1Neurosurgery, St. Vincent’s Hospital Catholic University of Korea, Suwon, Korea

Objectives: The anti-Parkinsonian effects of ropinirole (4-[2-(dipropylamino) ethyl]-1,3-dihydro-2H-indol-2-one), a nonergoline dopamine receptor agonist with a high affinity for dopamine D2 receptors, was investigated using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesion mouse model



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Methods: To investigate the neuroprotective effects of ropiniroleon Parkin-sonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg with 2 h intervals, 4 times), were examined in behavioral tests and neurochemical analysis. Pole test, rotarod test, locomotor activity measure-ment and tyrosine hydroxylase (TH) immunohistochemistry were measured in MPTP-lesioned mouse modelResults: The behavioral results showed that treatment ropinirole (5 × 1 mg/kg with interval 24 h, 5 times) could improve the MPTP-induced PD mice mark-edly. In addition, administration of ropinirole provides neuroprotection against the loss of dopaminergic neurons and behavioral impairment caused by MPTP.Conclusions: Taken together, we demonstrate that protection of ropinirole against MPTP and suggest that ropinirole treatment might represent a neuro-protective treatment of PD.No conflict of interest.

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TESTOSTERONE SUPPLEMENTATION DOES NOT NORMALIZE THE ACTIVITY OF STRIATAL NITRIC OXIDE SYNTHASE/GUANYLYL CYCLASE/CGMP PATHWAY IN A RAT MODEL OF PARKINSON’S DISEASE (PD)S.J. Chrapusta1,*, J. Wesolowska-Waliszewska2, B. Brodacki2, A. Stepien2, J. Langfort3, M. Chalimoniuk4

1Department of Experimental Pharmacology, Polish Academy of Sciences Mossakowski Medical Research Centre, Warsaw, Poland, 2Department of Neurology, Military Institute of Medicine, Warsaw, Poland, 3Department of Experimental Pharmacology – Polish Academy of Sciences Mossakowski Medical Research Centre/Warsaw, Department of Sports Training – The Jerzy Kukuczka Academy of Physical Education, Katowice, Poland, 4Department of Cellular Signalling – Polish Academy of Sciences Mossakowski Medical Research Centre, Faculty of Biology and Environmental Sciences – Cardinal Stefan Wyszynski University, Warsaw, Poland

Objectives: Androgenemia is considered a risk factor in PD, and testoster-one supplementation alleviates various Parkinsonism symptoms. Dying-out of nigrostriatal dopamine neurons in PD and its rodent models is partly related to perturbed activity of the nigrostriatal nitric oxide synthase/guanylyl cyclase/cGMP (NOS/GC/cGMP) pathway. We hypothesized that these perturbations might be causally related to hypoandrogenemia and that compensation of the latter may restore proper functioning of the NOS/GC/cGMP pathway.Methods: We compared total striatal NOS activity and striatal mRNA and pro-tein levels of neuronal (nNOS) and endothelial (eNOS) NOS isoforms and of GCβ1 subunit, as well as striatal cGMP content and the effect of orchidectomy and testosterone propionate (TP) supplementation (8 mg/kg/week, for 6 weeks) on these variables, between healthy and MPTP-treated male Wistar rats.Results: Total NOS activity was significantly enhanced by orchidectomy, MPTP treatment and TP supplementation, either used alone or in combina-tion. nNOS expression was significantly enhanced by both MPTP treatment and orchidectomy, irrespective of TP supplementation, whereas the latter de-creased nNOS expression in intact rats. eNOS expression was unaffected by MPTP and orchidectomy, whereas TP supplementation markedly enhanced it irrespective of the other manipulations. GCβ1 expression was significantly enhanced by both MPTP treatment and orchidectomy, whereas TP supple-mentation increased it in intact rats but partially counteracted the effect of MPTP. Striatal cGMP content was significantly and similarly increased in all experimental groups compared to untreated control rats.Conclusions: The possible beneficial effects of testosterone supplementation in PD are unlikely to be mediated by the nigrostriatal NOS/GC/cGMP pathway.Supported by the NCN grant #2011/01/B/ZN5/0139No conflict of interest.

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NITRITE ADMINISTRATION AMELIORATES MITOCHONDRIAL BIOENERGETICS AND IS NEUROPROTECTIVE IN CELLULAR AND VERTEBRATE MODELS OF PARKINSON’S DISEASE.C. Milanese1,*, S. Sepe1, M.T. Gladwin2, S. Sruti3, P.G. Mastroberardino1

1Department of Genetics, Erasmus MC University, Rotterdam, Netherlands, 2Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA, 3Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA, USA

Objectives: Nitrite administration has been proposed as a therapeutic avenue in cardiac ischemia due to its ability to decrease mitochondrial production of reactive oxygen species (ROS), via transient inhibition of respiratory complex-I. Augmented ROS and mitochondrial complex-I dysfunction are also hallmarks of Parkinson’s disease (PD), a chronic neurodegenerative disorder. Here we aimed to explore the neuroprotective capacity of nitrite in cellular and animal models of PD.Methods: We used the parkinsonian toxin MPP+ to model PD in dopaminergic neuronal cell lines (SH-SY5Y) and in zebrafish embryos, and we used human fibroblasts derived from genetic PD patients harboring mutations in the LRRK2 gene. We pre-treated our specimens with nitrite and investigated its neuropro-tective effects on cell viability, mitochondrial bioenergetics and motor functions.

Results: In dopaminergic neurons, nitrite administration ameliorates MPP+ in-duced cell death. Bioenergetics analysis indicates that MPP+ perturbs mitochon-drial respiration and this defect is reversed by nitrite administration. In zebrafish nitrite pre-treatment ameliorates locomotor activity after MPP+ exposure, improves viability, and reduces dopaminergic neuron loss in the brain. At molecular level, the physiological effects of nitrite are mediated by nitrosation of cysteine residues in proteins, as evidenced by specific labeling with fluorescent maleimide deriva-tives after Cu++/ascorbate reduction of nitrosothiols. Finally, in PD patient human fibroblasts nitrite administration improves mitochondrial respiration efficiency by increasing mitochondrial membrane potential and reducing proton leakage.Conclusions: Nitrite administration constitutes an amenable neuroprotective strategy in PD. We provide evidence that nitrite mitigates neurodegeneration in PD models and ameliorates the mitochondrial respiratory profile in primary fibroblasts from genetic PD cases.No conflict of interest.

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CEREBROLYSIN DOWNREGULATES NEURONAL AND INDUCIBLE NITRIC OXIDE SYNTHASE EXPRESSION AND INDUCES NEUROPROTECTION IN A MOUSE MODEL OF PARKINSON’S DISEASEH. Sharma1,*, R. Castellani2, R. Patnaik3, A. Sharma4, H. Moessler5, D. Muresanu6

1Surgical Sciences Anesthesiology & Intensive Care Medicine, Uppsala University Hsopital, Uppsala, Sweden, 2Division of Neuropathology, University of Maryland School of Medicine, Baltimore MD, USA, 3School of Biomedical Engineering, Indian Institute of Technology Banaras Hindu University, Varanasi UP, India, 4Department of Surgical Sciences Anesthesiology & Intensive Care Medicine, University Hospital Uppsala University, Uppsala, Sweden, 5Neuropharmacology, Ever Neuro Pharma, Oberburgau, Austria, 6clinical Neurosciences, university Hospital University of Medicine & Pharmacy, cluj-Napoca, Romania

Objectives: Parkinson’s Diseases (PD) is altered nitric oxide synthase (NOS) metabolism. An increased production of neuronal NOS (nNOS) or inducible NOS (iNOS) occurs in the animal models of PD. Thus, downregulation of NOS may have some neuroprotective effects in PD. Since oxidative stress in PD is responsible for nitric oxide (NO) production and cellular injury, in this investi-gation influence of cerebrolysin, a potent neuroprotective agent with marked antioxidant activity was examined in a mouse PD model.Methods: The PD like symptoms were induced by 4 methamphetamine (METH, 10 mg/kg, i.p.) or 1-metyl-4-fenyl-1,2,3,6-tetrahydropyridin, (MPTP, 20 mg/kg, i.p.) injections daily within two h intervals for 5 days. This dose and time schedule on 8th day produces PD like symptoms in striatum (ST) and substantia niagra (SN). In groups cerebrolysin or saline was given (3 to 5 ml/kg, i.v.) in identical manner for 1 week. In these rats, immunohistochemical analyses were made to detect nNOS, iNOS, activation of microglia and astro-cytes together with neuronal injuries using Nissl staining.Results: Our results showed pronounced activation of microglia, astrocytes and neuronal damages together with overexpression of nNOS and iNOS in the ST and in SN in MPTP or METH treated mice. Cerebrolysin significantly attenuated neuronal damage, astrocytic and microglial activation and down-regulated the nNOS and iNOS in a dose dependent manner.Conclusions: These observations are the first to show that the NO has a potential role in PD pathology and chronic cerebrolysin induced marked neu-roprotection in mice indicating its neurotherapeutic role in PD.No conflict of interest.

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PROBIOTIC CONTAINING “BEETLE WITCH-DOCTOR” EFFECTIVELY SUPPRESSES MPTP-INDUCED DISORDERS IN MOUSE MODEL OF PARKINSONISMI. Zavalko1,*, N.A. Ushakova2, V.M. Kovalzon2, A.V. Revishchin3, G.V. Pavlova3

1Movement Disorders Center, Federal Medical Biophysical Center, Moscow, Russia, 2Innovaion Technologies, Severtsov Institute Ecology/Evolution, Moscow, Russia, 3Neurogenetics, Institute Gene Biology, Moscow, Russia

Objectives: There are number of reports that uncontrolled voluntary oral use of “beetle witch-doctor” Ulomoides dermestoides improves the state of Parkinson’s disease patients. We decided to check-up this folk remedy using MPTP mouse model of Parkinsonism.Methods: We prepared two experimental preparations: first was simple mixture of probiotic consortium in milk medium with powder of living beetles and solid vegetable sorbent; in second, mixture was specially biologically processed. Both preparations were added to mice food in amount of 0.4% of total weight. First group of C57Bl/6 mice (N = 8) received preparation 1 during 2 weeks, then injection of 40 mg/kg MPTP toxin. Then mice continued to consume same food for 2 weeks more. Finally, they were tested in Rota-Rod apparatus and sacrificed for brain histology. For second group procedures were same except they consumed preparation 2. Third group received no preparations.



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Results: Striking contrast in movement ability have been found between group 2 (16.7; 12.1–21.0 min on rotating rod), on one hand, and groups 1 (2.4; 2.1–6.2) and 3 (0.5; 0.3–12.0), on another. Also, group 2 only demonstrated weight gain. Histology revealed less TH-positive neurons in SN/pc zone in group 3 as compared to groups 1 and 2.Conclusions: So, preparation 2 demonstrated clear capacity to inhibit MPTP-induced effects in mouse model of Parkinsonism.Supported by: RFFI 13-04-00327a, State Contract 8150.No conflict of interest.

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ROTENONE INDUCED NEURODEGENERATION IN DIFFERENT REGIONS OF MICE BRAIN: GENDER WISE VARIATION IN STATUS OF ENDOGENOUS ESTROGEN AND GLIAL CELLSS. Mitra1,*, N. Chakrabarti2, A. Bhattacharyya1

1Zoology, University of Calcutta, Kolkata, India, 2Physiology, University of Calcutta, Kolkata, India

Objectives: Our present study aims to evaluate the variety of ROS genera-tion, nuclear and cytosolic receptor mediated estrogen signaling, glial cell conditions in between control brain regions (frontal cortex, hippocampus and substantia nigra) and during RT treated condition in both male and female mice and to evaluate possible cellular and molecular correlation.Methods: To address our objectives we have used biochemical methods, western blot, immunohistochemistry, FACS, immunoprecipitation etc.Results: Variations of glial cell status, dopaminergic and non dopaminergic neuronal status and receptor mediated estrogen signaling has been found in brain region wise as well as gender wise in control mice. RT treatment altered the cellular and molecular status of these CNS cell types and nuclear/cytosolic receptor mediated estrogen signaling with the consistent neuroinflammation (in-dicated by TNF-α) in different brain regions (pre mentioned) of both the genders.Conclusions: Our results indicate that changes in microglial and astroglial cellular status largely imposed the critical concentration of estrogen and its signaling via either ERα or/and ERβ and binding of estrogen to its nuclear or cytosolic receptors that might have promoted variable status of dopaminergic and non dopaminergic cell loss during RT treatment condition.No conflict of interest.

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GUT-BRAIN CROSS TALK IN MURINE MODELS FOR PARKINSON’S DISEASEP. Perez Pardo1,*, H. Douna1, T. Wijnands1, S. Lopes da Silva2, C.B. Forsyth3, H.B. Dodiya3, J. Garssen1, B. Olivier1, A. Keshavarzian3, A.D. Kraneveld1

1Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands, 2Medical Nutrition, Danone Research Center for Specialized Nutrition, Utrecht, Netherlands, 3Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, USA

Objectives: Gastrointestinal dysfunction, particularly slow intestinal transit and delayed gastric emptying, are common symptoms in patients suffer-ing from Parkinson’s disease (PD). These symptoms precede the onset of classical motor symptoms by many years, and their occurrence in otherwise healthy people is associated with an increased risk of developing the disease. Pesticide rotenone exposure in rodents is a frequently used model for studying PD. Since both intragastric and intrastriatal administration of the pesticide can produce PD like motor symptoms in mice, we used rotenone mice models to better understand the relationship between enteric nervous system (ENS) and central nervous system (CNS) in PD.Methods: C57BL/6J mice were given rotenone either orally (10 mg/kg daily by oral gavage for 28 days) or by a unilateral injection in the striatum (5.4 μg).Results: Our results show that oral and intrastriatal administration of rotenone induces motor deficits, delayed intestinal transit time and α-synuclein accu-mulation in the ENS in mice. Moreover, we observed inflammation in the gut in both animal models characterized by reduced colon length, an increased number of CD3 positive cells and neutrophil infiltration.Conclusions: Oral and CNS administration of rotenone caused: [1] similar PD like motor deficits; [2] α-synuclein pathology in ENS and [3] intestinal motor dysfunction and inflammation. Our results support our hypothesis that gut/brain cross-talk plays a central role in α-synuclein-induced PD pathology. Our mod-els may therefore, provide a means to investigate pathological and bidirectional brain-gut mechanism in PD and identify new (intestinal) therapeutic targets.

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BEHAVIORAL ALTERATIONS IN ROTENONE MODEL OF PARKINSON’S DISEASE AND ITS ATTENUATION BY SIDA CORDIFOLIAN. Khurana1,*, N. Sharma2, A. Gajbhiye1

1Department of Pharmaceutical Sciences, Dr. Harisingh Gour Central University, Sagar, India, 2Adesh Institute of Pharmacy, Adesh University, Bathinda, India

Objectives: The present study was designed to investigate the protective ef-fect of aqueous extract of Sida cordifolia (AESC), and its different fractions;

hexane (HFSC), chloroform (CFSC) and aqueous (AFSC), against rotenone induced behavioral alterations in a rat model of Parkinson’s disease (PD).Methods: Sprague Dawley male rats were divided into different groups for administration of varying doses (50, 100 and 250 mg/kg; p.o.) of different test treatments (AESC, HFSC, CFSC and AFSC), along with co–administra-tion of rotenone (2 mg/kg; s.c.), consecutively for a period of 35 days. The test treated groups were compared with vehicle (control), rotenone per se (negative control) and L-deprenyl (positive control; 10 mg/kg; i.p.) treated groups for PD-like behavior alterations, mid brain dopamine level and lipid peroxidation.Results: The rotenone treated rats showed PD-like behavior alterations, as evident by the significant (P < 0.05) increase in behavior scores, catalepsy and posture instability along with decrease in locomotor activity, muscle coordina-tion and rearing behavior, when compared with the control group. Significant (P < 0.05) decrease in dopamine content and increase in lipid peroxidation was observed in rotenone treated animals as compared to control group. These PD-like behavior alterations along with associated changes in dopa-mine content and lipid peroxidation were significantly (P < 0.05) attenuated by co-treatment with varying doses of AESC and AFSC. The maximum effect was observed in AFSC (100 mg/kg) treated group, which was comparable to the L-deprenyl treated positive control group.Conclusions: The present study suggested the scope of AFSC in developing therapeutic strategies for PD.No conflict of interest.

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STRIATAL MT2 MELATONIN RECEPTOR IS INVOLVED IN THE ANXIETY-LIKE BEHAVIORS INDUCED BY PARADOXICAL SLEEP DEPRIVATION IN AN INTRANIGRAL ROTENONE MODEL OF PARKINSON’S DISEASEA. Noseda1, L. Rodrigues1, A. Targa1, M. Fortes1, M. Lima1,*1Physiology, Federal University of Paraná, Curitiba, Brazil

Objectives: This study investigated the role of striatal MT2 melatonin recep-tors in the anxiety-like behaviors mediated by a paradoxical sleep deprivation anxiogenic paradigm in the intranigral rotenone model of Parkinson’s disease.Methods: Rats received bilateral intranigral rotenone or vehicle infusions (12 μg/1 μL of DMSO), through stereotaxic surgeries and also the placement of bilateral cannula within the striatum. At the 7th day after the surgery the animals underwent a 24 h of paradoxical sleep deprivation (PSP) followed by a single administration of 8-M-PDOT (5 μg/μl – MT2 agonist), 4-P-PDOT (10 μg/μl – MT2 antagonist) or vehicle (DMSO). Thirty minutes later we tested the groups in the elevated plus maze (EPM).Results: The PSP modulation inflicted an anxiogenic-like effect. However, the 8-M-PDOT treatment promoted an anxiolytic-like effect in the control groups that was sustained in the PSP period. Although, we detected an increased exploration of the closed arms for the 8-M-PDOT rotenone group (P < 0.05). Remarkably, the PSP generated an anxiolytic-like effect in the 8-M-PDOT rotenone group, which was also observed for the 4-P-PDOT-treated groups. Notwithstanding, we demonstrated that the administration of 4-P-PDOT in the sham control and rotenone control groups elicited an increased exploration of the closed arms (P < 0.05) and (P < 0.01), respectively.Conclusions: These results indicated that the striatal MT2 melatonin recep-tor is involved in the anxiety-like behaviors. Furthermore, the PSP modula-tion purportedly evidenced an anxiolytic-like effect mostly related on the nigral degeneration.No conflict of interest.

509

INTRANIGRAL ROTENONE ADMINISTRATION ASSOCIATED TO PARADO-XICAL SLEEP DEPRIVATION PROMOTED OLFACTORY DISCRIMINATION IMPAIRMENTM. Fortes1, L. Rodrigues1, A. Targa1, A. Noseda1, M. Lima1,*1Physiology, Federal University of Paraná, Curitiba, Brazil

Objectives: To evaluate the possible occurrence of locomotor and olfactory deficits induced by the intranigral rotenone administration associated to selec-tive paradoxical sleep deprivation (PSP).Methods: Rats received bilateral intranigral rotenone or vehicle infusions (12 μg/1 μL of DMSO), through stereotaxic surgeries, afterward, the PSP oc-curred from the 7th to the 9th day. At this point we performed the olfactory discrimination and the open-field tests. Such analysis was also made at the rebound period (11th day).Results: One-way ANOVA and subsequent Newman-Keuls post hoc test showed that the sham PSP group exhibited an increased locomotor activity compared to the rotenone PSP group (P < 0.01), sham control (P < 0.01) and ro-tenone control (P < 0.001). The comparison of PSP and rebound evidenced that the PSP-induced effect is accute, weakening after the rebound. Regarding the olfactory parameters, we observed that the sham control (P < 0.001), rotenone control (P < 0.001) and sham PSP (P < 0.01) groups demonstrated significant discrimination of the novel odor. However, the rotenone PSP group showed sig-



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nificant impairment of this function. We also observed that this effect was com-pensated after the rebound period, expressed by increased discrimination of the novel odor.Conclusions: The present data show increased locomotion induced by PSP, which may be due to the dopaminergic supersensitivity. In addition, the asso-ciation of nigral lesion induced by rotenone and PSP generated a remarkable olfactory discrimination deficit.No conflict of interest.

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ASSOCIATION BETWEEN DOPAMINERGIC OLFACTORY BULB LESION AND PARADOXICAL SLEEP DEPRIVATION IMPAIRS THE OLFACTORY DISCRIMINATION TASKL. Rodrigues1, A. Targa1, A. Noseda1, M. Fortes1, M. Lima1,*1Physiology, Federal University of Paraná, Curitiba, Brazil

Objectives: This study evaluated the olfactory discrimination behavior of rats that received a rotenone administration within the olfactory bulb and were ex-posed to paradoxical sleep deprivation (PSP) before the olfactory discrimina-tion task (ODT).Methods: Female Wistar rats (300 g) were submitted to stereotaxic surgery to allow rotenone (12 μg/μL) or vehicle (dimethylsulphoxide) administration in the olfactory bulb. The open-field test was performed in 1st, 7th, 14th, 15th and 16th days after surgery. At 13th day the animals were exposed to PSP for 24 h and subsequently subject to ODT. This test consists in two compartments, one containing a non-social odor (lemon) and another with water. Finally, we tested the animals in the 15th and 16th days (sleep rebound period).Results: The OF test indicated a motor impairment only in the first day after surgery. The sham PSP (P < 0.05) and the rotenone control (P < 0.05) groups exhibited decreased exploration times of the non-social odor at the 14th day of test. However, this effect was not detected for the rotenone PSP group. A simi-lar, pattern was also observed at the 15th day of rotenone, for the rotenone control (P < 0.01) group. Notwithstanding, the rotenone PSP group (P < 0.01) demonstrated significant aversion of the non-social odor at 16th day.Conclusions: Therefore, this study suggests the involvement of the dopamin-ergic neurons, within olfactory bulb, in the ODT, and demonstrated a synergistic association of the PSP, that was potentiated by the lesion in the olfactory bulb.No conflict of interest.

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ANTI-INFLAMMATORY EFFECTS OF CARBENOXOLONE, A HSP INDUCER IN THE ROTENONE MODEL OF PARKINSON’S DISEASEP. Thakur1,*, B. Nehru1

1Department of Biophysics, Panjab University Chandigarh, Chandigarh, India

Objectives: Aggregated α-synuclein, a hallmark of PD, is a potent activator of immune response, which in turn accentuates the oxidative stress. Exploiting HSP inducer such as carbenoxolone, which reduce protein aggregation; hold a promise in mitigating neuroinflammation and mitochondrial dysfunction.Methods: In a rotenone (2 mg/kg b.w. s.c.) based model of PD, carbenox-olone (20 mg/kg b.w. i.p.) was administered in conjunction to the male SD rats. After 5 weeks of respective drug treatmenst, mid-brains were removed and as-sessed for various markers of neuroinflammation and mitochondrial functions.Results: Following carbenoxolone treatment, a large decline in the number of ac-tivated astrocytes was observed which was increased enormously after rotenone treatment. It also limited the concomitant increase of proinflammatory cytokines TNF-α, IL-1β and IL-6 as compared to rotenone treated animals. Additionally, a decrease in levels of inflammatory mediators like COX-2 and NF-kB was also ob-served. Further, Carbenoxolone treatment was able to significantly improve the rotenone-mediated decline in the activity of complex-I, complex-II and complex-IV. It also improved the Mn-SOD activity as well as levels of mitochondrial GSH as compared to rotenone treated animals. These effects might be mediated by decline in protein aggregation, which is known contributor to neuroinflammation.Conclusions: Here we conclude that carbenoxolone holds a promise for neu-roprotection in PD as it has both anti-inflammatory and anti-oxidative effects in addition to HSP induction.No conflict of interest.

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EFFECT OF CYNODON DACTYLON ON ROTENONE INDUCED PARKIN-SON’S DISEASE RAT MODELN. Sharma1,*, N. Khurana2, A.C. Rana3, P. Bafna3

1Adesh Institute of Pharmacy, Adesh University, Bathinda, India, 2Department of Pharmaceutical Sciences, Dr. Harisingh Gour Central University, Sagar, India, 3Rayat Institute of Pharmacy, Rayat and Bahra Campus, Nawanshahr, India

Objectives: The present study was designed to evaluate the effect of aqueous extract of Cynodon dactylon (AECD) on behaviour alterations in rotenone model of Parkinson’s disease. Exposure of rats to the complex I inhibitor rotenone reproduces feature of Parkinson’s disease, including selec-tive nigrostriatal dopaminergic degeneration which leads to impaired motor functions.Methods: Rotenone (2 mg/kg) was administered to different groups of rats on daily basis by subcutaneous injection over a period of 28 days and these groups were then subjected to different behavioural evaluation tests (cata-lepsy, locomotor activity and muscle activity).Results: Rotenone administered rats showed significant motor dysfunctions as observed by increase in catalepsy along with decrease in locomotor and muscle activity as compared to control group. Rats co-treated with AECD (300 mg/kg i.p. for 28 days) showed significant attenuation of the motor dysfunctions, induced by rotenone toxicity as compared to rotenone per se group.Conclusions: The present study provides evidence that AECD co-treatment attenuates rotenone induced behaviour alterations in rats. These finding can be useful for the development of new neuroprotective strategies based on our rich natural resources.No conflict of interest.

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THE IMPROVEMENT OF MEMORY DEFICITS IN APPV7171 TRANSGENIC MICE BY GENIPOSIDE, GINSENOSIDE TREATMENTY. Tan1,*, K.Y. Yang2, F. Wang1, J. Li1, Y. Zhang1, N. Yao1, Q. Hua1

1Scientific Research Centre, Beijing University of Chinese Medicine, Beijing, China, 2Pharmacy, Dalian No. 4 People Hospital, Dalian, China

Objectives: To illustrate the preventive effect of TLJN on improving spatial memory and inhibitory avoidance learning deficits in APPV717I mice among different genders.Methods: We have examined the effect of TLJN in APPV717I transgenic (Tg) mice on open field, Morris water maze and step-down inhibitory avoid-ance task. There are two treatment strategies: one is preventive treatment in 3-month-old of Tg mice lasting for 3 months and the other is early treatment begun with 6-month-old Tg mice and lasting for 4 months.Results: In open field test, there was no disturbance of locomotor activity and anxiety of Tg mice in both gender. In Morris Water Maze, with pretreatment strategy, both genders were improved by TLJN treatment in spatial learning process, however, at the very first day of this test, male mice had obtained a significant better learning performance, and their retrieval processes were improved significantly; with early treatment strategy, male mice showed more prominent in retrieval processe by TLJN treatment. In Step-down test, learning process of inhibitory avoidance was improved after TLJN administration. In all, male Tg mice enjoyed better behaviors in high-dose, whereas the low-dose treatment was preferred to female Tg mice.Conclusions: This study suggests that the herbal medicine, TLJN, has the potential capability to postpone cognitive impairment in APPV717I Tg mice, but with dose-dependence among gender differences..Reference1. Available upon request.No conflict of interest.

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CLEARANCE OF SOLUBLE α-SYNUCLEIN PROTOFIBRILS IN THE CNS OF TRANSGENIC MICE FOLLOWING CHRONIC TREATMENT WITH A PROTOFIBRIL-SELECTIVE ANTIBODYE. Nordstrom1,*, J. Sigvardson1, V. Lindström2, T. Fagerqvist2, A. Lord1, S. Tucker1, M. Johannesson1, C. Möller1, P. Gellerfors1, J. Bergström2, L. Lannfelt2, M. Ingelsson2

1BioArctic Neuroscience, Stockholm, Sweden, 2Department of Public Health and Caring Sciences Molecular Geriatrics, Uppsala University, Uppsala, Sweden

Objectives: To generate α-synuclein protofibril selective monoclonal antibodies and to perform a proof-of-concept study with a protofibril-selective antibody in α-synuclein transgenic mice. Large soluble α-synuclein oligom-ers (protofibrils) have been shown to have pronounced neurotoxic properties. Such species are therefore attractive therapeutic targets in Parkinson’s dis-ease and dementia with Lewy bodies, where α-synuclein deposition is be-lieved to be a central pathogenic event.Methods: Monoclonal antibodies were generated by immunization of mice with 4-hydroxy-2-nonenal (HNE)-α-synuclein protofibrils. α-synuclein reactive hybridomas were selected and evaluated for protofibril selectivity and the gen-erated monoclonal antibody (mAb) 47 was used for immunotherapy in (Thy-1) h[A30P]aSYN mice1.Results: Mice treated with mAb47 displayed significantly lower lev-els of α-synuclein protofibrils in the CNS as compared to placebo treated



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mice. Immunohistochemical staining against fibrillar and phosphorylated α-synuclein revealed no difference between mAb47-treated and the placebo group.Conclusions: Treatment with mAb47 resulted in a significant reduction of α-synuclein protofibrils in CNS of transgenic mice. Staining for fibrillar forms and for phosphorylated α-synuclein revealed that these forms are not targeted by the antibody.Reference1. Kahle et al. (2000). Subcellular localization of wild type and Parkinson’s

disease-associated mutant α-synuclein in human and transgenic mouse brain. J. Neurosci 20: 6365–6375.


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INTERACTIVE EFFECTS OF LEAD (PB) AND ROTENONE ON MOTOR DYSFUNCTION, OXIDATIVE STRESS AND MITOCHONDRIAL DYSFUNCTIONS IN DROSOPHILA MELANOGASTER: RELEVANCE TO PARKINSON’S DISEASEL.K. Venkareddy1,*, G. Chandran1, M. Muralidhara1

1Biochemistry and Nutrition, CSIR-Central Food Technological Research Institute, Mysore, India

Objectives: While pesticide exposure is an etiological factor in the develop-ment of Parkinson’s disease (PD), chronic exposure to heavy metal/s is impli-cated in several movement disorders. However, few studies have addressed the interactive neurotoxicity between pesticides and metals and their possible role in the pathophysiology of PD. In a co-exposure paradigm, we examined the interactive effects of lead (Pb) and Rotenone (ROT, a complex I inhibitor) in Drosophila (adults/larvae).Methods: Adult Flies (Wild D. melanogaster) exposed (72 h) to lead acetate (Pb, 1- 20 mM) and ROT (100–250 μM) in the medium was monitored for de-velopment of motor phenotype and various biochemical markers. In another study, we assessed the oxidative dysfunctions among III instar larvae exposed to Pb (25–100 μM, 24 h) with ROT.Results: Flies exposed to Pb per se exhibited higher motor activity (measured as speed) only at lower concentrations (upto 2.5 mM) and mortality (25% at 20 mM). In the co-exposure paradigm, significant potentiation was evident in terms of elevated mortality, higher (2–3 fold) motor activity which was associ-ated with elevated oxidative stress, altered cholinergic function and dopamine levels. In contrast, larvae exposed to either of the neurotoxicant showed typi-cal locomotor phenotype (reduced crawling behavior). Co-exposure resulted in higher cytosolic oxidative stress, enhanced GSH levels and most interest-ingly normal complex I activity which was significantly inhibited with individual neurotoxicant.Conclusions: Significant interactive toxicity evident between Pb and ROT in the Drosophila system merits further investigation and may aid in delineating the possible role of such interactions in the pathophysiology of PD.Reference1. Girish Chandran and Muralidhara (2012) NeurotToxicology 33(3): 444–456No conflict of interest.

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EXTENSION OF LIFESPAN AND ATTENUATION OF CHRONIC ROTENONE–INDUCED NEUROTOXICITY IN DROSOPHILA MELANOGASTER BY EXTRACTS OF SELAGINELLA DELICATULA (A PTERIDOPHYTE): RELEVANCE TO PARKINSON’S DISEASEM. Muralidhara1,*, G. Chandran1

1Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore, India

Objectives: Recently we have demonstrated that extracts of Selaginella deli-catula (SD, a pteridophyte) possess significant neuromodulatory propensity against rotenone in Drosophila and mice models. We have tested the hypoth-esis that SD extracts (aqueous- SDAE; methanolic-SDME) could extend the mean longevity, age-related neurodegeneration in Drosophila. Further their propensity to offset neurotoxic implications in a chronic rotenone model was examined.Methods: Young flies (Wild D. melanogaster) were maintained on SDAE and SDME -enriched medium (0.05 and 0.01%) with or without Rotenone (ROT- 50 μM) throughout their lifetime. At regular intervals, locomotor phe-notype, oxidative stress, apoptosis and selected biochemical end points were determined.Results: SDAE at both levels significantly increased the survival time of normal wild type flies (by 15–20%). Interestingly, those flies exhibited bet-ter climbing efficiency compared to flies provided regular diet. Exposure

to ROT (50 μM) resulted in concentration /duration –dependent locomo-tor deficits measured at 1–2 wks and 100% mortality within 15–21 d. In contrast, flies receiving ROT with SD enriched -diet survived for longer duration (30–40 d more compared to ROT flies). Both SDME and SDAE sig-nificantly alleviated neurodegeneration as evident by lower oxidative stress levels, improved cholinergic function, dopamine levels and mitochondrial functions.Conclusions: Our findings for the first time provide evidence of neuroprotec-tive efficacy of Selaginella, a pteridophyte plant regarded as sanjeevani (the resurrection herb) in Hindu mythology. Further basic insights on the molecular mechanisms underlying the neuroprotection and longevity extension of SD extracts may aid in understanding its relevance as a therapeutic adjuvant in Parkinson’s disease.No conflict of interest.

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EVALUATION OF ANTI-PARKINSONS POTENTIAL OF PISUM SATIVUM SEEDS EXTRACTS IN DROSOPHILA MELANOGESTER AND DANIO RERIO (ZEBRA FISH) MODELD. Khatri1,*, S. Fazel1, M. Juvekar2, A. Juvekar1

1Department of Pharmaceutical Science & Technology, Institute of Chemical Technology, Mumbai, India, 2Department of Homeopathic Research, Shri Bhagwan Homeopathic College and Hospital, Aurangabad, India

Objectives: Objective of the present research work was to evaluate this plant for in vitro antioxidant activity and in vivo Parkinson’s disease activity in order to provide scientific basis for usage of this plant in therapy.Methods: The seeds of Pisum sativum were extracted for with water and hy-droalcohol to obtain aqueous extract (PSA) and hydroalcoholic extract (PSH). Theses extract were further used for its in-vitro antioxidant assay by using DPPH (1, 1-diphenyl-2-picrylhydrazyl) and Lipid Peroxidation by TBARS method. Efficacy evaluation of extracts at different dose level was done on rotenone induced Parkinsonism in Drosophila melanogaster evaluated by negative geotaxis assay and Danio rerio (Zebrafish) evaluated by observing locomotion.Results: Aqueous (PSA) and hydroalcoholic (PSH) extract at different dose level have shown significant (P < 0.01) activity against Parkinson induced in Drosophila melanogaster and Danio rerio (Zebrafish).Conclusions: Both the aqueous and hydroalcoholic extracts of Pisum sati-vum seeds have antiparkinson potential in rotenone induced Parkinsonism in Drosophila melanogaster and Danio rerio (Zebrafish).References1. Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV,

Greenamyre JT Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci (2000) 3:1301–1306.

2. Bretaud S, Lee S, Su Guo Sensitivity of zebrafish to environmental toxins implicated in Parkinson’s disease Neurotoxicology and Teratology, (2004) 857–864.

3. Yu Shu, Jiang Meng, Xia Yeng Rotenone induces more serious learn-ing and memory impairment than α-synuclein A30P does in Drosophila J Shanghai Univ (Engl Ed), (2011), 15(3): 229–234.


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APIGENIN REDUCES THE OXIDATIVE STRESS IN THE BRAINS OF TRANSGENIC DROSOPHILA MODEL OF PARKINSON’S DISEASEY. Siddique1, T. Beg2,*, F. Naz1, S. Jyoti11Department of Zoology, Aligarh Muslim University, Aligarh, India, 2Biology Department, Jazan University, Jazan, Saudi Arabia

Objectives: In our earlier study apigenin was reported to delay the loss of climbing ability in the PD model flies expressing normal alpha synu-clein. In the present study we have studied the antioxidant potential of apigenin.Methods: The flies were cultured on standard Drosophila food at 25°C. Crosses were set up using six virgin females of UAS-Hsap/SNCA. F5B were mated to three males of GAL4elav. The progeny expressing the human α-synuclein (PD flies) were exposed to 0.1, 0.5, and 1.0 μl/ml of apigenin mixed in the diet for 24 days. Hsap/SNCA.F strains were taken as control. The lipid peroxidation and protein carbonyl content was measured as a marker of oxidative stress in the brains of flies.Results: A dose dependent significant decrease in the lipid peroxidation (Figure 1) and protein carbonyl content (Figure 2) was observed.Conclusions: Apigenin is potent in reducing the oxidative stress in the brains of PD model flies.



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PROTECTIVE EFFECT OF RUTIN, A POLYPHENOLIC FLAVONOID AGAINST NEUROLEPTIC-INDUCED OROFACIAL DYSKINESIA AND ASSOCIATED CHANGESM. Bishnoi1,*, S.K. Kulkarni1, K. Chopra1

1Pharmacology, Panjab University, Chandigarh, India

Objectives: Tardive dyskinesia (TD) has been considered a major clinical is-sue in the treatment of schizophrenia. The molecular mechanism underlying the pathophysiology of TD is not completely known. Several animal studies have demonstrated an enhancement of oxidative damage after chronic ad-ministration of neuroleptics. The present study investigated the effect of rutin in haloperidol-induced orofacial dyskinesia.Methods: We have used different behavioural (orofacial dyskinetic move-ments, stereotypic rearing, locomotor activity, percent retention), biochemi-cal [lipid peroxidation, reduced glutathione levels, antioxidant enzyme levels (SOD and catalase)] and neurochemical (neurotransmitter levels) parameters.Results: Chronic administration of haloperidol (1 mg/kg i.p. for 21 days) sig-nificantly increased vacuous chewing movements, tongue protrusions and facial jerking in rats, which were significantly inhibited by rutin. Chronic ad-ministration of haloperidol also resulted in dopamine receptor sensitivity as evident by a well-shaped response (initial decrease followed by increase) in locomotor activity and stereotypic rearing and also decreased percent reten-tion time on elevated plus maze paradigm. Pretreatment with rutin reversed these behavioural changes. Haloperidol also induced oxidative damage in all regions of brain which was prevented by rutin. Although turnover of dopamine

and nor-adrenaline decreased in both cortical and sub-cortical regions after chronic administration of haloperidol, it was significantly reversed by high-dose rutin treatment.Conclusions: The findings of the present study suggested the involvement of free radicals in the development of neuroleptic-induced orofacial dyskinesia, a putative model of TD, and rutin as a possible therapeutic option to treat this hyperkinetic movement disorder.No conflict of interest.

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EFFECT OF GINGEROL ON THE CLIMBING ABILITY OF PARKINSON DISEASE MODEL FLIEST. Beg1,*, Y.H. Siddique2, S. Jyoti2, F. Naz2, S.F. Mujtaba3

1Biology Department College of Science, Jazan University, Jazan, Saudi Arabia, 2Drosophila Transgenic Laboratory Department of Zoology, Aligarh Muslim University, Aligarh, India, 3Photobiology Division, CSIR-Indian Institute of Toxicology Research, Lucknow, India

Objectives: Gingerol has been reported to show antioxidant activity through scavenging of superoxide, hydroxyl radicals and by inhibiting lipid peroxida-tion. It is an alcohol of oleoresin and the aroma of ginger is due to its oil. The model flies of Parkinson’s Disease (PD) based on α-synuclein (αS) (wild form) expression in flies were used in the present study. A time dependent loss of dopaminergic neurons and the formation of intracellular aggregates of αS (Lewy bodies) have been reported in the PD model flies. In the pre-sent study, the effect of gingerol supplementation in diet was studied in PD model flies.Methods: The flies were cultured on standard Drosophila food at 25°C. Crosses were set up using six virgin females of UAS-Hsap/SNCA. F5B were mated to three males of GAL4elav. The progeny expressing the human α-synuclein (PD flies) were exposed to 50, 100, and 150 μM of gingerol mixed in the diet for 24 days. Hsap/SNCA.F strains were taken as control. The climb-ing assay was performed after 24 days of the exposure. The mean values of various fly groups were statistically compared using unpaired group of the student t-test.Results: The results showed a dose dependent significant delay in the loss of climbing ability (Figure 1).

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Conclusions: Gingerol is potent in delaying the loss of climbing ability in the PD model flies.No conflict of interest.

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EFFECT OF GENISTEIN ON THE CLIMBING ABILITY OF PARKINSON DISEASE MODEL FLIEST. Beg1,*, Y.H. Siddique2, S.F. Mujtaba3, S. Jyoti4, F. Naz4

1Biology Department College of Science, Jazan University, Jazan, Saudi Arabia, 2Department of Zoology, Aligarh Muslim University, Aligarh, India, 3Photobiology Division, CSIR-Indian Institute of Toxicology Research, Lucknow, India, 4Drosophila Transgenic Laboratory Department of Zoology, Aligarh Muslim University, Aligarh, India



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Objectives: Genistein is found in soybean seeds in the form of glycosides. Besides having anti-carcinogenic effect, it is the inhibitor of kinases and has antioxidant properties. There are various genetic models of Parkinson’s Disease (PD) based on α-synuclein (αS), primarily the transgenic over ex-pression of mutant or wild forms in mice or flies. A time dependent loss of dopaminergic neurons and the formation of intracellular aggregates of αS (Lewy bodies) have been reported in the PD model flies. In the present study, the effect of genistein supplementation in diet was studied in PD model flies.Methods: The flies were cultured on standard Drosophila food at 25°C. Crosses were set up using six virgin females of UAS-Hsap/SNCA. F5B were mated to three males of GAL4elav. The progeny expressing the hu-man α-synuclein (PD flies) were exposed to 50, 100, and 150 μM of genistein mixed in the diet for 24 days. Hsap/SNCA.F strains were taken as control. The climbing assay was performed after 24 days of the exposure. The mean values of various fly groups were statistically compared using unpaired group of the student t-test.Results: The results showed a dose dependent significant delay in the loss of climbing ability (Figure 1).

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Conclusions: Genistein is potent in delaying the loss of climbing abilityNo conflict of interest.

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PROTECTIVE EFFECT OF NORDIHYDROGUAIARETIC ACID IN TRANSGENIC DROSOPHILA MODEL OF PARKINSON’S DISEASEY.H. Siddique1, T. Beg2,*, F. Naz1, S. Jyoti11Drosophila Transgenic Laboratory Department of Zoology, Aligarh Muslim University, Aligarh, India, 2Biology Department College of Science, Jazan University, Jazan, Saudi Arabia

Objectives: Nordihydroguaiaretic acid (NDGA) is a potent anti-oxidant com-pound of Larrea tridentata and has been reported to reduce cell damage by free radicals. In our earlier study on fly model of Parkinson’s disesase (PD) it delayed the loss of climbing ability. It has also been reported to inhibit the accumulation of α-synuclein that plays a fundamental role in the etiology and pathogenesis of PD. In the present study the effect of NDGA was studied on lipid peroxidation and protein carbonyl content in the brains of transgenic Drosophila model of PD.Methods: The flies were cultured on standard Drosophila food at 25°C. Crosses were set up using six virgin females of UAS-Hsap/SNCA.F 5B were mated to three males of GAL4elav. The progeny expressing the human α-synuclein (PD flies) were exposed to 0.1, 0.5 and 1.0 μl/ml of NDGA mixed in the diet for 24 days. Hsap/SNCA.F strains were taken as control. The lipid peroxidation and protein carbonyl content was measured in the brains of con-trol, treated with NDGA, L-dopamine, untreated and control flies treated with NDGA flies.Results: A dose dependent significant decrease in the lipid peroxidation (Figure 1) and protein carbonyl content (Figure 2) was observed in the brains of PD flies.Conclusions: NDGA is potent in reducing the oxidative stress in the brains of PD model flies.No conflict of interest.

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Figure 2. Effect of NDGA on Protein Carbonyl content measured in the brain of transgenic Drosophila melanogaster after 24 days in various treated groups. [asignificant with respect to control p < 0.05; asignificant with respect to PD model flies p < 0.05].

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TARGETING PRO-INFLAMMATORY CYTOKINES BY GINSENG ATTENUATES QUINOLINIC ACID INDUCED HUNTINGTON’S DISEASE LIKE SYMPTOMS IN RATS: POSSIBLE NITRIC OXIDE MECHANISMJ. Mishra1,*, A. Kumar1

1Uinversity Institute of Pharmaceutical Sciences, Panjab University Chandigarh, Chandigarh, India

Objectives: The present study has been undertaken to investigate neuropro-tective mechanism of ginseng against QA induced neurotoxicity in rats.Methods: QA (200 nmol) was bilaterally administered into the striatum to induce HD-like alterations in rats. Ginseng (100 and 200 mg/kg), L-Arginine (50 mg/kg) and L-NAME (10 mg/kg) were administered for 21 days. Behavioral parameters like locomotor, rotarod, and elevated plus maze performances were assessed. Oxidative stress, mitochondrial dysfunction, pro-inflammatory cytokines were assessed on day 21 after behavioral assessments.Results: QA (200 nmol) administration caused significant alterations in body weight, motor and memory performance, oxidative status, mitochondrial com-plex enzyme (I, II, III and IV) activities, tumour necrosis factor-α and inter-leukin-6 levels in striatum as compared to the sham group. Unlike ginseng (100 mg/kg), 21 days treatment with ginseng (200 mg/kg) significantly attenu-ated these behavioral and biochemical alterations as compared to control group. Further, pre-treatment of L-Arginine (50 mg/kg) in combination with ginseng (100 mg/kg) significantly reversed the protective effect of ginseng, whereas L-NAME (10 mg/kg) pre-treatment in combination with ginseng (100 mg/kg) potentiated their protective effect which was significant as com-pared to their effects per se.



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Conclusions: The results suggest towards possible involvement of NO-cGMP pathway in the neuroprotective effect of ginseng.Reference1. Scattoni ML, Valanzano A, Pezzola A, March ZD, Fusco FR, Popoli P,

Calamandrei G: Adenosine A2A receptor blockade before striatal excito-toxic lesions prevents long term behavioural disturbances in the quinolinic rat model of Huntington’s disease. Behav. Brain Res., 2007, 176, 216–221.


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INHIBITION OF NITRODATIVE-INFLAMMATORY CASCADE IN EXPERIMENTAL PARADIGM OF QUINOLINIC ACID -INDUCED NEUROTOXICITY: NEUROPROTECTIVE PROFILE OF SESAMOL AND QUERCETINA. Kuhad1,*, S. Singla1, V. Arora1, K. Chopra1

1University Institute of Pharmaceutical Sciences, Panjab University Chandigarh, Chandigarh, India

Objectives: The study was designed to investigate the neuroprotective role of naturally occuring antioxidants like sesamol and quercetin in the experimental paradigm of Huntington’s disease.Methods: Rats were intrastriatally administered quinolinic acid and were treated with sesamol (4, 8 and 16 mg/kg, i.p) and quercetin (25, 50 and 100 mg/kg, i.p) for 14 days before and 14 days after quinolinic acid adminis-tration, with these natural antioxidants. Results demonstrated that intrastriatal injection of QA leads to increased escape latency, impaired locomotor activity, as well as significant increase in immobility time in forced swim test, This be-havioural deficit was integrated with the increased nitrodative stress markers along with the significant increase in the TNF-α levels in rat brain suggesting QA mediated oxidative and neuroinflammatory damage. More over intrastri-atal administration of QA resulted in significant decrease in the levels of dopa-mine, serotonin and norepinephrine in the rat forebrain.Results: Chronic treatment with sesamol and quercetin attenuated these be-havioral, biochemical and neurochemical alterations in the rat brain and these effects were attributed to their strong antioxidant and anti-inflammatory potential.Conclusions: Conclusively it is suggested that major features of QUIN-induced neurotoxicity are mediated by nitrodative stress induced neuroin-flammation and the neuroprotective role of sesamol and quercetin should be explored further as effective agents in the management of Huntington’s disease.Reference1. Cabrera J, Reiter RJ, Tan DX, Qi WB, Sainz RM, Mayo JC, et al. Melatonin

reduces oxidative neurotoxicity due to quinolinic acid: In vitro and in vivo findings. Neuropharmacology. 2000;39:507–14.


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EXTRACELLULAR DEPOSITS OF BETA-AMYLOID IN THE PDAPP TRANSGENIC MOUSE MODEL OF ALZHEIMERS DISEASEH. Omidi1,*, P. Pasbakhsh2, N. Omidi31Commerchial Mannagement, Azad University of Tehran/Olom Tahghyghat branch, Tehran, Iran, 2Anatomy, Tehran University of Medical Sciences/Medical School, Tehran, Iran, 3Heart and Vascular Diseases, Ghazvin University of Medical Sciences/Velayat Hospital, Ghazvin, Iran

Objectives: Alzheimers disease (AD) is a uniquely human disorder. Although the pathogenesis of AD is not fully understood, growing evidence indicates that the deposition of beta-amyloid(Aß) and the local reactions of various cell types to this protein play major roles in the development of the diseaseMethods: In the present study transgenic mice expressing mutant amyloid precursor protein (APP) has been used. These mice exhibit selective neuronal death in the brain region that are most affected in AD, suggesting that amyloid plaque formation is directly involved in AD neurons loss. Brains from 12 trans-genic animals and 12 age-matched non transgenic littermate controls (1 and 2 years old) were examined histopathologicallyResults: One year old transgenic animals (n = 6) exhibit deposits of human Aß in the hippocampus, corpus callosum and cerebral cortex. By 2 years of age, a great number of diffuse and mature plaques were present in the cortex and hippocampus, and subcortical regions like thalamus and striatum. Another major finding was reduction of cholinergic cells in the medial septum, striatum and diagonal band of BrocaConclusions: The present data are consistent with the hypothesis that the neuropathology begins in the cerebral cortex and hippocampus before spreading in a retrograde fashion to subcortical regionsReference1. Ron LH. Diagnosing AD: A systematic review of economic evaluations

03-06- 2013No conflict of interest.

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EXISTENCE OF IETM IN ALZEIMER’S DISEASE AND ITS EFFECT ON THE SEVERITY OF ADB. Han1,*, X. San1, Q. Sun1, D. Han2, F. Wang2, F. Wu2

1Institute of Vertigo Disease, General Hospital of CAPF, Beijing, China, 2Department of Pathophysiology, Shanxi Medical University, Taiyuan, China

Objectives: Alzheimer’s disease (AD) brains are characterized by accumu-lation of amyloid β protein (Aβ) and neuroinflammation. Deposition of Aβ is the main component of the plaques, and the neurofibrillary tangles, cell loss, vascular damage, and dementia follow as a direct result of this deposition.Methods: In this study, the AD model was established in rat by intraperitoneal injection of D-galactose (D-gal) and aluminum (Al) consecutively, the affiliating effect of intestinal endotoxemia (IETM) on learning and memory ability and its possible corelationship with AD we analyzed as well.Results: The results showed that the animal with AD had longer latency and more error times in Morris water maze test compared with the normal. At the same time, the levels of LPS, TNF-α, PD, APP and PS1 mRNA expression in AD rats were increased.Conclusions: These data suggested that the rat model of Alzheimer’s disease is accompanied IETM and that may plays an important role in the development of AD.Reference1. Culpan D, MacGowan SH, Ford JM, et al. Tumour necrosis factor alpha

gene polymorphisms and Alzheimer’s disease [J]. Neurosci Lett,2003, 350 (1) : 61–65.

Document not received

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PTEROCARPUS MARSUPIUM AND EUGENIA JAMBOLANA REVERSES STREPTOZOTOCIN INDUCED ALZHEIMER’S DISEASE PATHOLOGY BY ENHANCING GLUCAGON-LIKE PEPTIDE-1 IN BRAINJ. Kosaraju1,*, S. Chinni2, R. Khatwal3, A.N.I.L. Dubala3, S. M.N2, D. Basavan1

1Pharmacognosy, JSS College of Pharmacy, Ooty, India, 2Pharmacology, JSS College of Pharmacy, Ooty, India, 3Pharmaceutical Biotechnology, JSS College of Pharmacy, Ooty, India

Objectives: A growing body of evidence shows that pharmacological agents used for the treatment of T2D have become valuable candidates as disease modifying agents in the treatment of Alzheimer’s disease (AD). Thus present study investigates the neuroprotective roles of PM and EJ in streptozotocin (STZ) induced AD.Methods: Male Wistar rats were administered with STZ intracerebrally to in-duce AD like pathology. PM heartwood extract and EJ fruit extract were ad-ministered at a dose range of 200 and 400 mg/kg each respectively following 3 months after intracerebral STZ injection. Behavioral parameters including radial arm maze and hole-board tasks were evaluated during the course of treatment. After 30 days treatment with the extracts animals were sacrificed and brains were extracted for the evaluation of biochemical parameters includ-ing amyloid beta 42 (Aβ42), tau hyperphosphorylation (p-tau), glucagon-like peptide-1 (GLP-1) and inflammatory markers.Results: Extracts show dose- and time-dependent attenuation of AD pathol-ogy by decreasing Aβ42, p-tau and neuro-inflammation with an increase in GLP-1 levels in the hippocampus and cortex at the end of 30 days treatment.Conclusions: Our finding suggests that PM and EJ are the potential cogni-tive enhances and possess neuroprotective activity against STZ induced AD.References1. D’Amico, M., Di Filippo, C., Marfella, R., Abbatecola, A.M., Ferraraccio, F.,

Rossi, F., Paolisso, G., 2010. Long-term inhibition of dipeptidyl peptidase-4 in Alzheimer’s prone mice. Exp. Gerontol. 45, 202–207.

2. McClean, P.L., Parthsarathy, V., Faivre, E., Holscher, C., 2011. The diabe-tes drug Liraglutide prevents degenerative processes in a mouse model of Alzheimer’s disease. J. Neurosci. 31, 6587–6594.


528

NEUROPROTECTION BY A NOVEL M1 MUSCARINIC ACETYLCHOLINE RECEPTOR SELECTIVE ALLOSTERIC POTENTIATOR BQCA LOADED LIPID DRUG CONJUGATE NANOPARTICLESR.B. Khatwal1,*, J. Kosaraju2, A. Dubala1, S.V. Chinni3, M. Narayanappa1, A. Azam4, M.N. Satish Kumar3, S. Malay Kumar1

1Pharmaceutical Biotechnology, JSS College of Pharmacy, Ooty, India, 2Pharmacognosy, JSS College of Pharmacy, Ooty, India, 3Pharmacology, JSS College of Pharmacy, Ooty, India, 4Pharmaceutical Chemistry, JSS College of Pharmacy, Ooty, India

Objectives: Drugs deliver through nano-drug delivery could enhance neuro-protection by rapid accumulation of drugs in the brain and a slow metabolism



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of the compound. The objective of the work was to develop lipid–drug con-jugate nanoparticles (LDC-NPs) for A Novel Selective Allosteric Potentiator of the M1 Muscarinic Acetylcholine Receptor BQCA like Benzyl Quinolone Carboxilic Acid (BQCA) to enhance neuroprotection by rapid accumulation within the target area through across BBB followed by slow release and/or reduced metabolism of BQCA in the Brain over a period of days or weeks after injection.Methods: The LDC-NPs of BQCA evaluated for brain targeting efficacy after intraperitoneal injection in rats as BQCA was administered alone, bound to LDC-NPs and bound to polysorbate-80 coated LDC-NPs and also evaluated influence of developed LDC-NPs of BQCA on learning and memory capaci-ties, Morris Water Maze Test was performed in streptozotocin-induced rat model.Results: Administration of BQCA solution in streptozotocin-induced animals did not result in any noticeable improvement in learning and memory ca-pacities, whereas administration of polysorbate-80 coated LDC-NPs NPs of BQCA in streptozotocin-induced animals significantly decreased escape latency.Conclusions: In conclusion, this study indicates that developed LDC-NPs could be a feasible carrier for a novel Allosteric Potentiator BQCA to deliver rapid and higher extent of transport into the brain and anticipated that the de-veloped formulation may improve neuroprotection caused by streptozotocin-induced in rats.Reference1. Ma L, et al., Proc Natl Acad Sci U S A 106:15950 –15955.No conflict of interest.

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ROLE OF GRAPE SEED EXTRACT IN LIPOPOLYSACCHARIDE INDUCED ALZHEIMER’S DISEASE MODEL: POSSIBLE IMPLICATION ON AMYLOID BETA FORMATIONN. Al Shehaby1,*, O. Heikal1, N. Hamdi2, N. El Sayed1

1Pharmacology and Toxicology, Faculty of Pharmacy & Biotechnology German University in Cairo, Cairo, Egypt, 2Pathology, Faculty of Pharmacy & Biotechnology German University in Cairo, Cairo, Egypt

Objectives: A hallmark of Alzheimer’s disease (AD) pathogenesis is the ag-gregation of toxic amyloid beta (Aβ) oligomers inside and outside brain neu-rons. AD is also notable for the presence of an inflammatory response that is often associated with the Aβ deposits. Grape Seed Extract (GSE) have been studied over the years for its possible effect on AD. This research is conducted to study the possible effect of GSE as early and late treatment on a systemic Lipopolysaccharide (LPS)-induced AD mouse model in reference to the selec-tive cyclooxygenase-2 (COX-2) inhibitor, Celecoxib.Methods: Locomotor activity, spatial and non-spatial memory were evalu-ated using open-field, Y-maze, and new object recognition tests respectively. Aβ1–42 deposition in the brain was evaluated using immunohistochemistry. The content of Aβ oligomers and expression of COX-2 enzyme in the brain were both evaluated using Western Blot analysis.Results: Single Intraperitoneal (i.p.) injection of LPS (0.80 mg/kg) resulted in locomotor deficit as well as spatial and non-spatial memory impairment. This was accompanied by marked Aβ1–42 deposition and a significant increase in Aβ oligomers and COX-2 enzyme levels. Celecoxib (30 mg/kg i.p.) and GSE (50 mg/kg i.p.) as an early or late treatment to LPS-treated mice resulted in improvements in behavioral tests as well as Aβ1–42 depostion, Aβ oligomers content and COX-2 enzyme levels.Conclusions: This study suggests that GSE can be highly beneficial in the treatment of AD at its early as well as its late stage.Reference1. Sakono, Masafumi, and Tamotsu Zako. “Amyloid oligomers : formation

and toxicity of ab oligomers.” FEBS 277 (2010): 1348–1358.No conflict of interest.

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NEUROPROTECTIVE EFFECTS OF 17-BETA-ESTRADIOL: A THERAPEUTIC POTENTIAL DRUG FOR ALZHEIMER’S DISEASEP. Kumar1,*, K. Prakash2, R.K. Kale1, N.Z. Baquer1

1School of Life Sciences, Jawaharlal Nehru University, New Delhi, India, 2School of Biological Sciences, Central University of Bihar, Patna, India

Objectives: Alzheimer’s disease (AD) is the most common form of dementia in the elderly. The aim of the present study was to determine the effect of neu-ropeptide, neurokinin B (NKB) and amyloid beta fragment Aβ (25–35) on 17β estradiol (E2) treated aging female rat brain of 3 months (young), 12 months (adult) and 24 months (old) age groups.Methods: The aged rats (12 and 24 months old) (n = 8 for each group) were given subcutaneous injection of 17b-estradiol (0.1 μg/g body weight) daily for 1 month. After 30 days of hormone treatment, experimental animals of all the groups were sacrificed and brains were isolated for further study.

Results: The results obtained in the present work revealed that increased activities of antioxidant enzymes, membrane bound ATPases and de-crease in level of calcium levels, monoamine oxidase activity and lipid peroxidation in presence of NKB and combined NKB and Aβ in vivo estra-diol (E2) treated ageing rat brain. NKB treatment reversed the beneficial in preventing some of the age related changes in the brain. An in vitro incubation of E2 treated synaptosomes with Aβ showed toxic effects on all the parameters, while NKB showed stimulating effects and the combined NKB and Aβ showed a partial effects as compared to Aβ (25–35) and NKB alone.Conclusions: Present study elucidates an antioxidant, neuromodulatory and neuroprotective role of tachykinin peptide NKB against the beta amyloid in-duced toxicity in E2 treated female rats. NKB treatment reversed the beneficial in preventing some of the age related changes in the brain.No conflict of interest.

531

STUDY OF LOCOMOTOR AND COGNITIVE DISORDERS IN THE OVARIECTOMIZED FEMALE WISTAR RATSJ. Sellame1,*, A. Mesfioui1, B. Benazzouz1, A. Ouichou1, A. El Hessni11Biology, Laboratory of Genetics Neuro-endocrinology and Biotechnology IBN Tofail University Faculty of Sciences, Kenitra, Morocco

Objectives: Menopause is accompanied by a cognitive and neurodegenera-tive dysfunction. These disorders are mainly due to the collapse of the level of estrogen causing a chronic inflammation in the brain associated with a sev-eral unbalance in neurotransmission. This study has for objective to study the impact of the deficit in estrogens on the levels of anxiety on ovariectomized female Wistar rat.Methods: Female rats (172 to 226 g), aged 6 months, were used during this study. The animals were randomly divided into two groups: a control group „C” and an ovariectomized group „OVX”. Three months later, the levels of anxiety were evaluated by valid behavioral tests, Open Field test (OFT) and elevated plus maze (EPM).Results: The parameter values are collected and statically analyzed show partiality that: * In the OFT, the number of central squares visited as well as the time spent in the central squares by the OVX rats are significantly lower than the recorded values among the control. * In the test EPM test, the time spent in the open arms by the OVX rats is substantially lower than that recorded by the control rats.Conclusions: These preliminary results suggest that the ovariectomy is as-sociated with an increase in the level of anxiety, which would be due to a decrease in the secretion of ovarian hormones, particularly estrogen.

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PROTECTIVE POTENTIAL OF METFORMIN ON MEMBRANE LINKED FUNCTIONS IN DIABETIC AGING FEMALE RATS.P. Kumar1,*, R.K. Kale1, K. Prakash2, N.Z. Baquer1

1School of Life Sciences, Jawaharlal Nehru University, New Delhi, India, 2School of Biological Sciences, Central University of Bihar, Patna, India

Objectives: The objective of this study was to investigate protective potential of metformin on membrane linked functions and glucose transporter in dia-betic aging female rats.Methods: Young (3 months) adult (12 months) and aged (24 months) rats will be diabetic by using alloxan monohydrate. After metformin was given i.p dose 200 mg/Kg for 1 month to both control and diabetic aging rats. A detailed study was carried on membrane linked enzymes, membrane fluidity, lipofuscin, an-tioxidant enzymes, glucose transporter, bcl-2 and DNA degradation to identify the antidiabetic and antiaging role of metformin using biochemical, molecular and histiochemical study.Results: Present study shows that there was a similar pattern of increased lipid peroxidation, neurolipofuscin, DNA degradation and monoamine oxi-dase activity and a decrease in membrane fluidity, Na+ K+ ATPse, Ca2+ ATPase, sueroxidase dismutase and glutathione S-transferases activities, glucose transporter-4 (GLUT4) in both aging and diabetes. Metformin was found to be an effective treatment in stabilizing and normalizing the mem-brane functions; therefore this therapy can be considered an alternative to be explored further as a means of diabetic and aged related disorders con-trol. Metformin treatment also helped to reverse the age related changes studied, to normal levels, elucidating an anti-aging, antidiabetic and neuro-protective action.Conclusions: The cumulative deficits in learning and membrane functions in aged diabetic rats indicate that the effects of diabetes and ageing on the brain could interact. The results of this study will be useful for pharmacological modification of the aging process and applying new strategies for control of age related disorders including metabolic syndrome.No conflict of interest.



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Section 2: Basic Science

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DEVELOPMENT OF DOPAMINE BIOSENSOR BASED ON TYROSINASE USING NAFION MODIFIED GLASSY CARBON ELECTRODES. Rahman1,*, Y. Kim1, S. Park1, J. Park1, D. Park1

1Interdisciplinary Program of Bioenergy and Biomaterial Engineering, Chonnam National University, Gwangju, Korea

Objectives: A loss of dopamine concentration levels has been found related with various diseases, such as Parkinson’s and schizophrenia. A dopamine sensor based on tyrosinase was developed using Nafion modified glassy car-bon electrode.Methods: The electrochemical behavior of the sensor for dopamine in various pH of the buffer was investigated by cyclic voltammetry.Results: The analytical characteristic of sensor, including lower detection limit, pH, diffusion coefficient, and storage stability, are described. Application for dopamine sensor in the presence of ascorbic acid was also investigated. The electrochemical potential difference between dopamine and ascorbic acid was measured individually and simultaneously.Conclusions: These results and interference studies showed that the modi-fied electrode possesses the good potential sensitivity and selectivity for determination of dopamine.No conflict of interest.

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DISSECTION OF DOPAMINOTOXIN CYTOPATHIC EFFECTS ON DOPA-MINERGIC PRIMARY CULTURED NEURONSN. Callizot1,*, P. Poindron1

1R&D, Neuro-Sys, Gardanne, France

Objectives: Parkinson’s disease (PD) is the second most common neurode-generative disease, associated with substantia nigra dopaminergic neurons degeneration. There are obvious evidences that mitochondrial dysregulation plays a central role. The urgent need for new efficient therapies is crucial; thus robust models dissecting the physiopathological aspects of the disease are needed. This is the main aim of our work.Methods: Rotenone, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, its active metabolite 1-methyl-4-phenylpyridinium (MPP+), and 6-hydroxydopamine (6-OHDA) are neurotoxic compounds targeting the respiratory chain of the mitochondria. The exposure of these toxins induces similar response to PD (in vivo/in vitro) including cell death, reactive oxygen species... Primary cell cultures from rat embryos were used (ventral portions of the mesencephalic flexure). Cells were seeded into 96 well-plates and kept for 6 days (day of intoxication).Results: We showed that the 3 toxins involved a specific timing and path-way (apoptosis versus necrosis). Rotenone induced cell death involv-ing caspase-3 activation, apoptosis and glycolysis changes. By contrast, MPP+ seemed involved some necrosis events as well as a depletion of ATP reserve capacity. 6-OHDA seemed inducing apoptosis pathway and a large oxidative stress. Altogether, these results showed that dopaminergic neu-rotoxins induced cell death through distinct mechanisms (necrosis versus apoptosis).Conclusions: We showed that despite the fact of all the 3 toxins were able to block the respiratory chain complexes; they have well distinct pathways lead-ing to dopaminergic neuron death. A deep knowledge of the cytopathologic effects of each toxin is absolutely fundamental in the process of drug discov-ery of neuroprotective compounds in PD indication.No conflict of interest.

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STATINS INDUCE NEURITE OUTGROWTH AND INCREASE THE EXPRESSION OF DOPAMINERGIC SYSTEM-RELATED SYNAPTIC VESICLE PROTEINS IN SH-SY5Y NEUROBLASTOMA CELLSM. Schmitt1,*, B. Dehay1, E. Bezard1, F.J. Garcia-Ladona2

1Institut des Maladies Neurodégénératives UMR 5293, University of Bordeaux, Bordeaux, France, 2Neurosciences Therapeutic Area, New Medicines UCB Pharma S.A., Braine l’Alleud, Belgium

Objectives: Statins show protective effects against neurodegenerative mech-anisms. Several studies have reported a decreased risk of development of Parkinson’s disease (PD) by the therapeutic use of statins. The biological basis for above findings remains to be fully understood. Present study aimed the identification of statin-mediated effects in the neuronal differentiation of SHSY5Y cells and on the expression of synaptic proteins associated with the dopaminergic system.

Methods: Cells were treated with compounds for 24 h and 48 h. Neurite out-growth (NOG) and modulation of synaptic markers were determined using high content imaging.Results: SHSY5Y cells showed neurite extension over spontaneous growth after statin-treatment. Lovastatin and simvastatin significantly induced NOG over vehicle (maximal total growth/cell of 37.5% and 41%, respectively). The reference NOG-inducer, Y-27632, triggered NOG of 141.6% of total growth/cell. Higher levels of synaptic vesicle transporters (VMAT2, SV2C) and UCHL-1 protein were observed after 48 h of lovastatin treatment (maximal fluorescence signal increased by 36%, 31.3% and 33.1%, respectively). In contrast, Y-27632 did not significantly increase expression levels of these proteins.Conclusions: Our data demonstrate that statins induce neuronal differentia-tion as well as elevated levels of synaptic vesicle proteins of the dopaminergic system (SV2C, VMAT2) and of UCHL-1, a synaptic protein that is an impor-tant target of the PD neurodegenerative mechanisms. These findings suggest a potential mechanism of action of statins on the dopaminergic system and support previously proposed therapeutic potential of statins in PD and associ-ated disorders.

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HYPERPHOSPHORYLATION OF CREB IN HUMAN DOPAMINERGIC NEURONS: A KINETIC STUDY OF CELLULAR DISTRIBUTION OF TOTAL CREB AND PCREB FOLLOWING OXIDATIVE STRESSB. Ahmed1,*, O. Hasnain1, R. Stafford2, A. Gujar1, K. Patel1, M. Howard1, V. Moradiya1

1Department of Life Sciences, University of Bedfordshire, Luton, United Kingdom, 2School of Applied Sciences, Bournemouth University, Fern Barrow Poole, United Kingdom

Objectives: The neurotoxin, 6-Hydroxydopamine (6-OHDA) has been shown to mimic the neuropathological characteristics of Parkinson’s disease by inducing oxidative stress in dopaminergic neurons (DCN). Oxidative stress influences modulates the function of several enzymes and transcription fac-tors including CREB. We aimed to determine the changes in amount of tCREB and its phosphorylated form (pCREB) in DCN in normal and stressed condi-tions. We also asked whether the changes found in tCREB and pCREB levels affect activities of tCREB and pCREB. Furthermore, we determined the ratio of pCREB and tCREB in cytosol, mitochondria and nucleus to find if oxidative stress alters nucleo-cytoplasmic and mito-cytoplasmic transport in DCN at dif-ferent time intervals.Methods: We measured the activities and levels of tCREB and pCREB in cytosolic, mitochondrial and nuclear compartments in control and stressed DCN, differentiated from ReNVM cell line following oxidative stress.Results: Our results indicate that CREB phosphorylation occurs in all stud-ied locations and shows significant disruption of phosphorylation process by 6-OHDA treatment. It demonstrates tridirectional trafficking of tCREB and pCREB between cytosol, mitochondria and nucleus.Conclusions: The study shows the presence of specific signaling molecules in all studied compartments, where tCREB and pCREB levels and activities are either upregulated or downregulated to balance each other for their roles.No conflict of interest.

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THE IMPORTANCE OF CHEMICAL SPECIATION IN MANGANESE (MN)-INDUCED NEUROMUSCULAR AND NEUROCOGNITIVE DISORDERS IN ZEBRAFISH LARVAE AND ITS IMPORTANCE FOR MN-INDUCED DEMENTIAR. Hernandez1,*, E.C. Babinski1, M.I. Nishita1

1Exact Sciences and Earth, Institute for Environmental Chemical and Pharmaceutical Sciences, Diadema, Brazil

Objectives: Manganese (Mn) is essential for living organisms, playing an important role in nervous system function but chronic exposure for this metal can lead to neurotoxicity by unclear mechanisms. Thus, we proposed to study the role of chemical speciation in Mn neurotoxicity.Methods: Mn species preparation and zebrafish exposure were performed according to Hernández (2009). Neurobehavioral activity were evaluated in the ZEBRALAB system (ViewPoint – FR), according to Rihel et al. (2010) and Ahmad and Richardson (2013). Toxicogenomic performed using the “Affymetrix GeneChip® Zebrafish Genome Array”. Statistical analyses were performed using both GraphPad Prism version 5.00 for Windows, GraphPad Software, La Jolla California USA Transcriptome Analysis Console (Affymetrix).Results: We verified that the zebrafish larvae exposure to manganese during 72 h (48–120 hour for fertilization – hpf) or 120 h (2–122 hpf) showed signifi-cant decreasing of locomotors activity and alteration of the color preference patter, specially when exposed to citrate of Mn(II) (Mn(II)Cit) instead of man-ganese chloride. These events can be associated with the genes bcat2, cenpj, dpp4, eif2s1, ell2, erbb2ip, mmp2, myl6, sgce, slc14a2 and tcea3 because

8.Day 3 Wednesday, Section 2 Basic Science.indd 1448.Day 3 Wednesday, Section 2 Basic Science.indd 144 10/28/13 5:51 PM10/28/13 5:51 PM


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which were significantly unregulated by Mn(II)Cit. These genes are associated with dementia (Parkinsonism, AlS and Alzheimer’s) and protein metabolism pathway too.Conclusions: Our results suggest that Mn-induced neurotoxicity and neu-robehavioral disruption is chemical speciation depending and potentially asso-ciated with protein metabolism impairment.References1. Hernández, R.B. (2009). http://www.teses.usp.br/teses/disponiveis/46/46134/

tde-27042010–085048/2. Nagel & Der vollst¨andige. UBA – Texteband 58/98. Umweltbundesamt,

Berlin (1998).3. Rihel, J. et al. 2010. Science 327, 348.4. Ahmad, F and Richardson, M.K. 2013. Behavioural Processes 92 (2013)

88– 98.No conflict of interest.

538

ROS-MEDIATED DYSREGULATION OF DNMT1 AND DNMT3A AND ASSOCIATED CHANGES OF SNCA METHYLATION IN A MPP+-INDUCED CELLULAR MODEL OF PARKINSON’S DISEASEX. Cheng1, H. You2, B.L. Hu1, J.H. Zhu2, X. Zhang1,*1Department of Neurology and Geriatrics the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, China, 2Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, China

Objectives: Parkinson’s disease (PD) is a multi-factorial disease and its pathogenesis involves both genetic and non-genetic factors. Recently increas-ing attention has been packed on aberrant epigenetic regulation in neurode-generative disorders. In this study we aimed to examine the changes in DNA methylation-related enzymes and their roles in regulating the expression of SNCA gene encoding for α-synuclein.Methods: The SH-SY5Y cells treated with 1-methyl-4-phenylpyridinium (MPP+) was adopted as a cellular PD model. DNA methyltransferases includ-ing DNMT1, DNMT3a and DNMT3b, and MBD2 (a methyl-CpG binding domain protein) were examined by Western blot.Results: We found DNMT1 and DNMT3a were decreased in a dose- and time-dependent manner upon MPP+ treatment in SH-SY5Y cells, while DNMT3b and MBD2 displayed little change. Bisulfite sequencing analysis showed the CpG methylation level in SNCA intron 1 was attenuated and the mRNA expres-sion of SNCA was accordingly increased as detected by real-time Q-PCR. As oxidative stress is well-known involved in the pathogenesis of PD, we fur-ther analyzed the role of reactive oxygen species (ROS) in regulating DNA methylation. The results showed that N-acetylcysteine, a ROS scavenger, blocked the MPP+-induced decrease in DNMT1 and DNMT3a and prevented the decrease of DNA methylation in SNCA intron 1 as well as the increase in SNCA mRNA expression.Conclusions: In conclusion, our data suggest a ROS-mediated dysregulation of DNMT1 and DNMT3a in MPP+-induced cellular PD model, which leads to aberrant methylation in SNCA gene and subsequent change in its expression.No conflict of interest.

539

α-SYNUCLEIN IS PRESENT AS A MONOMER IN THE BIOLOGICAL FLUIDSH. Tatebe1,*, T. Tokuda2, R. Ishi1, K. Taguchi3, T. Kasai1, Y. Watanabe3, I. Mizuta1, T. Masaki3, M. Nakagawa4, T. Mizuno1

1Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan, 2Molecular Pathobiology of Brain Diseases, Kyoto Prefectural University of Medicine, Kyoto, Japan, 3Basic Geriatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan, 4North Medical Center, Kyoto Prefectural University of Medicine, Kyoto, Japan

Objectives: Recent studies have suggested that α-synuclein (α-syn) (molecular weight: 14 kDa) exists predominantly as a tetramer (~58 kDa) in solution [1]. However, a subsequent report has shown that brain- and RBC-derived α-syn protein is present as a natively unfolded monomer [2]. Therefore, the native structure of α-syn remains controversial.Methods: To determine the higher molecular structure of the α-syn pro-tein in biological fluids, we analyzed cerebrospinal fluid (CSF) or red blood cells (RBCs) fractionated using size-exclusion chromatography (SEC) with a Superose-12 (molecular weight range: 1–300 kDa) column, as well as Western blotting (WB) and ELISA. We also expressed the A140C α-syn variant, which forms α-syn dimers, and wild-type α-syn in Escherichia coli (recombinant α-syn proteins), which were then analyzed after fractionation with SEC. Recombinant α-syn proteins were subsequently compared with native α-syn in biological fluids.Results: When α-syn was evaluated with non-denaturing gels or SEC col-umns, α-syn monomers migrated as 50- to 60-kDa proteins; however, in dena-turing gels, they migrated as 15-kDa proteins (Figure 1).

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2520

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The disulfide-linked dimer (A140C) and oligomer migrated slower than either the unfolded recombinant α-syn or the native α-syn in SEC. Native endog-enous α-syn from biological fluid co-migrated with recombinant unfolded α-syn WT monomers: 50~60 kDa in SEC, 15 kDa in WB (Figure 2).

12200KDa 66KDa 29KDa 12.4KDa

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(KDa)11 12

2 3 4 5 6 7 8 9 10 11 12

Conclusions: α-Syn exists predominantly as a disordered monomer in CSF and RBCs.References1. Bartels T et al., Nature 477, 107–110 (2011).2. Fauvet B et al., J. Biol. Chem. 287, 15345–15364 (2012).No conflict of interest.

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PHOSPHORYLATED α-SYNUCLEIN IN PARKINSONIAN DISORDERSY. Wang1,*1Neurosurgery, Huazhong University of Science and Technology, Wuhan, China

Objectives: We investigated whether PS-129 is present in human CSF, and if so, whether it is possible to use it, alone or in combination with total SNCA, as PD severity or parkinsonian differential diagnostic biomarkers.



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Methods: The identification of PS-129 in human CSF was accomplished using mass spectrometry (MS). To translate MS based technology to a more robust practical assay to monitor CSF PS-129, a Luminex assay was estab-lished. After establishing a sensitive and specific assay, CSF PS-129, along with total α-synuclein, was determined in ~600 samples of patients with PD as well as healthy and diseased controls.Results: The results revealed that CSF PS-129 levels correlated with PD severity and, when combined with total α-synuclein, provided high sensi-tivity and specificity for differential diagnosis among clinical overlapping parkinsonisms.Conclusions: Ser129 phosphorylation of SNCA might be one of the critical processes leading to different forms of parkinsonism; and therefore, defining the mechanism leading to the phosphorylation will likely shed light on the pathogenesis of MSA and PSP.References1. Mollenhauer, B., et al. α-Synuclein and tau concentrations in cerebrospi-

nal fluid of patients presenting with parkinsonism: a cohort study. Lancet Neurol 10, 230–240 (2011).

2. Hong, Z., et al. DJ-1 and α-synuclein in human cerebrospinal fluid as bio-markers of Parkinson’s disease. Brain 133, 713–726 (2009).

3. Chen, L. & Feany, M.B. α-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease. Nat Neurosci 8, 657–663 (2005).


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DOPAMINE CYTOTOXICITY IN SHSY5Y CELLS: INVOLVEMENT OF NF-KB AND α-SYNUCLEIN: IMPLICATIONS TO PARKINSON’S DISEASEO. Sen Nag1,*, A. Sahoo1, A. Ganguly1, P. Banerjee1, V.K. Khemka1, S. Chakrabarti11Department of Biochemistry, Institute of Post Graduate Medical Education and Research, Kolkata, India

Objectives: The cytotoxicity of dopamine (DA) in cultured catecholamin-ergic cell lines like SHSY5Y or PC12 is considered as an useful model to study dopaminergic neuronal death in sporadic Parkinson’s Disease (PD). In our study, we have attempted to develop a model of DA cytotoxicity by exposing SHSY5Y cells to a physiologically relevant low concentration of DA.Methods: SHSY5Y cells have been exposed to 10 μM of DA for 96 h with or without other additions and mitochondrial dysfunction, protein aggrega-tion and cell death with apoptotic activation assessed in control and treated cells. In another set of experiments, the same parameters of DA cytotoxicity have been assessed in cells after siRNA mediated silencing of α-synuclein gene.Results: DA (10 μM) causes a moderate (about 30%) degree of cell death with features of apoptosis and evidence of mitochondrial dysfunctions and α-synuclein accumulation. All of these effects are significantly abolished by co-treatment with the oxygen radical scavenger, N-acetyl cysteine (NAC, 2.5 mM) and the NF-κB inhibitor, sn50 (20 μM). Further, preliminary results from α-synuclein gene silencing experiments indicate the involvement of α-synuclein in DA cytotoxicity.Conclusions: The cytotoxicity of DA in a physiologically relevant concentra-tion is mediated by ROS and involves the redox sensitive transcription factor NF-κB.No conflict of interest.

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THE RELATIVE IMPORTANCE OF NUCLEATION AND GROWTH PRO-CESSES IN α-SYNUCLEIN AGGREGATIONA. Buell1,*, C. Galvagnion1, M. Vendruscolo1, T. Knowles1, C. Dobson1

1Chemistry, University of Cambridge, Cambridge, United Kingdom

Objectives: Recently, the molecular mechanism of aggregation of the Aβ(1–42) peptide into amyloid fibrils, implicated in Alzheimer’s disease has been elucidated through a combination of kinetic experiments and theoretical modeling (Cohen et al., PNAS 2013). Such insight is currently lacking for the aggregation of α-synuclein, a hallmark of Parkinson’s disease. Our objective is to achieve a similar level of understanding for this protein.Methods: We use a combination of accurate kinetic measurements in the pres-ence of varying concentrations of pre-formed seed fibrils of α-synuclein in order to elucidate the relative importance of fibril growth and proliferation through sec-ondary processes, such as fibril fragmentation, to the overall conversion process from soluble to aggregated protein. By means of theoretical kinetic analysis we extract the individual molecular rate constants or upper bounds thereof.Results: We find that while amyloid fibrils of α-synuclein in the presence of physiological concentrations of soluble protein grow with similar rates than

those formed by the Aβ(1–42) peptides, the rates of homogeneous primary and secondary nucleation, processes that produce new amyloid fibrils, are at least 6 orders of magnitude slower in the case of α-synuclein.Conclusions: Our results provide novel insight into the relative importance of the molecular processes that are responsible for the transformation of soluble protein into amyloid fibrils. In particular, we show that the balance of nuclea-tion and growth processes can be very different for proteins linked to different neurodegenerative diseases that have the common hallmark of amyloid fibrils.Reference1. SIA Cohen et al., PNAS 2013, 110, 9758–9763.No conflict of interest.

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PROLYL OLIGOPEPTIDASE INHIBITION INCREASES THE FORMATION OF AUTOPHAGOSOMES AND ENHANCES THE CLEARANCE OF α-SYNUCLEINM. Savolainen1,*, C. Richie2, B. Harvey2, K.A. Maguire-Zeiss3, T.T. Myöhänen1

1Department of Pharmacology and Toxicology, University of Helsinki, Helsinki, Finland, 2Optogenetics and Transgenic Technology Core, National Institute of Drug Abuse, Baltimore MD, USA, 3Department of Neuroscience, Georgetown University Medical Center, Washington DC, USA

Objectives: α-synuclein (aSyn) aggregation has been connected with pathol-ogy of Parkinson’s disease. We have earlier shown that inhibition of prolyl oligopeptidase (PREP) reduces aSyn aggregation and enhances clearance of aSyn aggregates. Role of PREP inhibition on autophagy, an important factor of clearance of aSyn aggregates, was further studied.Methods: In cells, we studied effects of PREP overexpression on autophagy and effects of PREP inhibition on impaired autophagy (autophagy inhibitors, 3-methyladenine (inhibits autophagosome formation) or bafilomycin A1 (inhib-its the interaction of autophagosome and autolysosome)), in the presence or absence of a PREP inhibitor, KYP-2047. Cells were also transfected with aSyn, and incubated with KYP-2047. Changes in autophagy markers, p62 (accumulation marker) and LC3BII (autophagosome marker), were monitored by Western blot. In vivo, KYP-2047 was administered to aSyn transgenic mice, levels of aSyn, p62 and LC3BII were studied.Results: In vitro, PREP overexpression significantly decreased LC3BII levels, indicating reduced autophagosome formation. PREP inhibition overcame the effect of 3-methyladenine on autophagosome formation, restoring the p62 and LC3BII levels to control level. Bafilomycin A1 significantly increased LC3BII levels, and with KYP-2047, the increase was even higher. aSyn overexpres-sion increased significantly p62 levels, while LC3BII remained unchanged. Incubation with KYP-2047 reduced p62 levels to normal, and increased LC3BII levels. In vivo, administration of KYP-2047 significantly reduced aSyn immunoreactivity and increased LC3BII levels in mice.Conclusions: Results suggest that PREP negatively regulates autophago-some formation, and PREP inhibition reverts this effect. Furthermore, PREP inhibition enhances the clearance of excess aSyn in transgenic mouse, proposing PREP inhibition as a potential therapy for Parkinson’s disease.No conflict of interest.

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MUTATIONS AT THE FIRST AND SECOND KTKEGV REPEATS OF α-SYNUCLEIN AFFECT BINDING TO MEMBRANE PHOSPHOLIPIDS AND LINK SOLUBLE OLIGOMERS WITH ENDOCYTOSISR. Sharon1,*, Y. Zarbiv1, D. Simhi-Haham1, E. Israeli11Biochemistry and Molecular Biology, Hadassah–Hebrew University, Jerusalem, Israel

Objectives: While α-Synuclein (α-Syn) is mainly detected as a cytosolic pro-tein, a portion of it is recovered bound to membranes. It is suggested that binding to membrane phospholipids controls α-Syn structure, physiology and pathogenesis. Yet, it is currently unclear whether normal α-Syn activity causes its toxicity. We aimed at investigating the role of membrane phospholipid bind-ing on aspects related to the physiology and pathogenesis of α-Syn.Methods: We focused on the positively-charged lysine residues at the KTKEGV repeat motif in mediating α-Syn associations with negative phospholipids. Specifically, two lysine (K) residues were replaced with two glutamic acid (E) residues at either the first or second motifs. The effect of these mutations on membrane binding was compared to wild-type α-Syn and to the Parkinson’s disease-causing mutations, A53T and A30P. A novel method, phospholipid-ELISA was developed to quantify α-Syn associations with phospholipids.Results: We found that the K to E substitutions affected binding to phospho-lipids to the same degree as the A53T and A30P mutations. However, unlike the Parkinson’s disease mutation, the steady state of soluble oligomers for K to E substitutions was dramatically lower. In accord, we found significantly larger intracellular inclusions in cells expressing the K to E mutations, sug-gesting a preference for aggregation. Importantly, an association was found between levels of soluble oligomers and FM1–43 endocytosis.



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Conclusions: Our results suggest a role for lysine residues at the N-terminal repeat domain in the stabilization of soluble α-Syn oligomers and suggest that the physiology of α-Syn is associated with its pathogenesis.No conflict of interest.

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APPARENT PROTEIN SOLUBILITY PRODUCING MASKED AMYLOID AGGREGATION KINETICSR. Crespo Rodríguez1,*, F. Rocha1, A.M. Damas2, P.M. Martins3

1Chemical Engineer, FEUP University of Porto, Porto, Portugal, 2Molecular Biology, ICBAS University of Porto, Porto, Portugal, 3Chemical Engineer/ Molecular Biology, FEUP/ ICBAS University of Porto, Porto, Portugal

Objectives: A simple and theoretically consistent Crystallization-Like Model (CLM) was recently presented by our group (Crespo et al. 2012). This model is able to describe classic types of amyloid fibrillization kinetics, from sigmoidal to hyperbolic, based on the interplay of the nucleation and growth steps. The CLM is used to quantify impact of apparent solubility on the analysis of amy-loid inhibition kinetics. Our goal is to be able to recognize false positives much earlier during the drug discovery process.Methods: Lysozyme aggregation kinetics were measured ‘in vitro’ and were interpreted in the light of the CLM.Results: Our preliminary results indicate the existence of an apparent solubil-ity associated to higher end-point concentrations as the initial protein concen-tration increases. The apparent solubility tends to decrease towards the true thermodynamic value as the fraction of fibrils in solution decreases.Conclusions: This effect is apparently determined by interface phenom-ena similar to those recently reported for α-synuclein [Pronchik et al. (2010) Journal of the American Chemical Society, 132 (28) 9797–803].Reference1. R Crespo, F Rocha, AM Damas and PM Martins (2012). A generic

Crystallization-Like Model that describes the kinetics of amyloid fibril for-mation. Journal of Biological Chemistry, 287(36), 30585–30594.


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MECHANISM OF AMYLOID FORMATION OF α-SYNUCLEIN IN THE PRESENCE OF LIPID VESICLESC. Galvagnion1,*, A.K. Buell1, T.C.T. Michaels1, M. Vendruscolo1, T.P.J. Knowles1, C.M. Dobson1

1Department of Chemistry, University of Cambridge, Cambridge, United Kingdom

Objectives: Substantial evidence links α-synuclein (α-syn) to Parkinson’s dis-ease (PD). When isolated in solution, the protein is intrinsically disordered, but in the presence of lipid surfaces α-syn can adopt a predominantly α-helical structure that is believed to mediate its normal functions, notably synaptic plasticity. Our study aims at elucidating the detailed mechanism of amyloid formation of α-syn in the presence of lipid vesicles as well as determining the molecular rates of the corresponding individual processes.Methods: We use circular dichroism to monitor the structural changes of α-syn upon binding to lipid vesicles as well as a combination of ThT fluores-cence assays and kinetic analysis to characterize the details of the mecha-nism of amyloid formation.Results: In the presence of lipid bilayers, the formation of amyloid fibrils by α-syn is dominated by primary nucleation followed by growth of fibrils. The number of nucleation events as well as the total number of fibrils formed depends on the number of protein molecules initially bound to the lipid vesi-cles. The nucleation rate constant was determined using global kinetic analy-ses of aggregation time courses.Conclusions: For the first time, we were able to quantitatively determine the mechanism of amyloid fibril formation of α-syn in the presence of lipid bilay-ers. Such insight is crucial for the development of new effective therapeutic strategies.Reference1. Ruipérez V, Darios F, Davletov B., α-synuclein, lipids and Parkinson’s dis-

ease, 2010, Prog Lipid Res.No conflict of interest.

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WILDE TYPE AND MUTATED α-SYNUCLEIN OVEREXPRESSION DIFFERENTIALLY INDUCE CELLULAR MODIFICATIONS AND TOXICITYD. Marmolino1,*, L. Staelens2, A. Michel1, F. Hustadt1, R. Rose3, D. Scheller1

1CNS-Parkinson, UCB Pharma, Braine l’alleud, Belgium, 2Development Regulatory Bioanalaysis, UCB Pharma, Braine l’alleud, Belgium, 3PASG, UCB Pharma, Slough, United Kingdom

Objectives: Identifying the configuration of α-synuclein (a-syn) in normal and pathological conditions and investigating the influence of the overexpression of its mutated forms on cell toxicity and viability by monitoring gene expres-sion pathways.Methods: Cells overexpressing human full length a-syn and point muta-tions A30P, A46K, A53T, S129, S129D were generated. rtPCR was used for gene expression. Size exclusion chromatography, mass spectrometry and western blots were used for protein analysis. ELISA was used to detect oligomers.Results: Mutated a-syn differently impaired cell proliferation and viability compared to wt, with the A53T mutation being the most toxic one. Additional challenges using H2O2 and L-Dopa showed highest toxicity in the A53T and E46K mutated cells. The toxicity showed a mutation-specific profile whereas iron administration was equally toxic over the different cell lines. Conformation analysis showed that a-syn and its mutations occurred mainly as monomers in vitro, with a slight presence of dimers and tetramers.Conclusions: In vitro, α-synuclein occurred as monomer and the mutations did not affect that overall appearance. A53T and E46K point appeared more toxic in vitro than the other mutations causing a significant reduction of cell proliferation and viability in a long term expression. Toxins and oxidative stress differently affected the cell lines expressing the mutated forms of α-synuclein suggesting a different mechanism of toxicity.References1. α-synuclein occurs physiologically as a helically folded tetramer that

resists aggregation. Bartels T, et al. Nature. 2011.2. α-Synuclein in central nervous system and from erythrocytes, mammalian

cells, and Escherichia coli exists predominantly as disordered monomer. Fauvet B, et al. J Biol Chem. 2012.


548

MODULATING AMPK ACTIVITY AS A NOVEL NEUROPROTECTIVE STRATEGY IN NEURONS ACCUMULATING HUMAN α-SYNUCLEINW. Bobela1,*, P. Aebischer1, B. Schneider1

1Sciences de la vie – Brain Mind Institute, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

Objectives: As brain aging is a major risk factor for Parkinson’s disease (PD), metabolic perturbations associated with aging may play an important role in neuronal degeneration. We assess how the activity of the AMPK com-plex determines neuronal survival when α-synuclein accumulates in neuronal cells. The activity of the AMPK α2 subunit (AMPKα2) is modulated in a genetic model of PD based on α-synuclein overexpression.Methods: Rats were unilaterally injected into Substantia nigra (SN) with AAV vectors, encoding the following variants of AMPK α2: the wild-type (WT) subunit, a dominant-negative variant (K45R), and constitutively active AMPKα2 (CA). All animals were co-injected with the virus encoding α-synuclein to induce neuronal degeneration.Results: Tyrosine hydroxylase staining of both striatum and SN indicated a significant protection of both dopaminergic fibers and cell bodies against α-synuclein induced neurodegeneration in animals over-expressing WT and K45R forms of AMPKα2, with a stronger effect in the latter. All groups over-expressing human α-synuclein showed a gradual decline in spontaneous motor activity (cylinder test), with a non-significant trend towards improve-ment in the groups expressing WT and K45R AMPKα2. In neuronal cultures, we found that WT AMPKα2 reduces basal oxygen consumption and the pro-duction of reactive oxygen species, as well as increases ATP content.Conclusions: Surprisingly, both WT and K45R AMPKs are protective against α-synuclein-induced toxicity, albeit with modest effect on motor behavior. In vitro experiments indicate beneficial effects of WT AMPKα2 on metabolic profile and decreased oxidative stress, suggesting a possible mechanism for neuroprotection.No conflict of interest.

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IMMUNOHISTCHEMICAL STUDY OF α-SYNUCLEIN AND TAU PATHOLOGY IN THE GABAERGIC NEURONS IN BRAINS OF PATIENTS WITH DEMENTIA WITH LEWY BODIESS. Iritani1,*, M. Miyata2, H. Sekiguchi1, C. Habuchi1, Y. Torii1, K. Umeda1, H. Fujishiro1, M. Yoshida3, N. Ozaki11Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan, 2Department of Psychiatry, Okehazama Hospital Fujita Mental Care Center, Nagoya, Japan, 3Medical Science of Ageing, Aichi Medical University, Nagakute, Japan

Objectives: Dementia with Lewy bodies (DLB) was diagnosed by observed the Lewy pathology in the cerebral cortex neuropathologically. Beside, the common form of DLB was also observed the tau pathology. But it was



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unknown precisely what kind of neuron was suffered from Lewy pathology or tau pathology. We try to declare what kind of neuron would be suffered by the Lewy or tau pathology.Methods: Four brains of DLB diagnosed neuropathologically were used. Using the technique of the double stain immunohistochemistry for anti-phos-phorylated α-synuclein or AT-8 (tau protein phosphorylated) and GABAergic neuron makers (Calbindin D28K (CaBp) or parvalbumin), we have observed the co-existence of these proteins.Results: CaBp positive and parvalbumin positive neuron does not coexist the α-synuclein and tau protein phosphorylated. That is to say, GABAergic neu-rons does not contain α-synuclein and tau protein phosphorylated in the limbic area and cerebral cortex. Also CaBp and parvalbumin positive fiber does not co-exist α-synuclein and tau protein phosphorylated neurite. As the results, GABAergic neuronal system was hardly suffered the α-synuclein pathology and tau pathology.Conclusions: It was reported that Calcium binding protein has been resist for neurodegenerative changes. The neuron with this protein would tend to be maintained, but Calcium binding protein might be distinguished in exchanging to the neurodegenerative protein such as α-synuclein and tau protein phos-phorylated in the progress of neurodegenerative course at end stage. Anyway, GABAergic neurons would have resistant character for the neurodegeneration.Reference1. Iritani S et al. Neuropathology 21:162–7:2001.No conflict of interest.

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EXPLORATION OF CURCUMIN ANALOGUES AS INHIBITORS OF α- SYNUCLEIN AGGREGATION FOR TREATMENT OF PARKINSON’S DISEASE (PD) –A PRELIMINARY REPORTN. Ahsan1,*, S. Mishra1, S. Gupta1, A. Surolia2

1Molecular Science Laboratory, National Institute of Immunology, New Delhi, India, 2Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India

Objectives: To carry out an in vitro screening of curcumin analogues for their efficacy and potency as α-synuclein aggregation inhibitors.Methods: Curcumin isoxazole and pyrazole were screened through Thioflavin T assay for their inhibitory potency. As the pyrazole was found to be more potent than its isoxazole counterpart and even curcumin, sixteen more deriva-tives were designed, synthesized and screened. Potent compounds were selected and explored in detail through turbidimetric and congo red binding studies.Results: Thioflavin T binding was less in the aggregation set up with curcumin pyrazole as compared to curcumin alone as opposed to curcumin isoxazole. This prompted us to synthesize more pyrazole derivatives. Among all the derivatives synthesized; two analogues were found to give a positive result in Thioflavin T assay. Congo red binding results confirmed the same. An increase in turbidity @ 360nm was found for one of the analogues.Conclusions: Decreased Thioflavin T and congo red binding whereas an increase in turbidity suggests that these analogues inhibit fibrillization but not oligomerization. Biophysical and imaging studies are highly warranted to understand the mechanics of inhibition in detail.No conflict of interest.

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EPIGENETIC REGULATION OF PARKINSON’S DISEASEG.H. Park1, D. Wang2, K. Xia2, Q. Pan2, Z. Zhang2,*1Graduate School of Biomedical Sciences, Sanford–Burnham Medical Research Institute, San Diego, USA, 2State Key Laboratory of Medical Genetics, Central South University, Changsha, China

Objectives: Parkinson disease (PD) is the most common age-dependent neurodegenerative movement disorder. Solid evidences indicate both environmental and genetic factors play important roles in PD pathogen-esis. Nevertheless, interaction between environment and genetics in PD etiology remains unclear. Our objective is to determine the epige-netic mechanisms of PD that are potentially affected by environmental factors.Methods: DNA methylation is determined by bisulfite sequencing. Histone acetylation is analyzed by regular biochemical assays.Results: In this study, we first determined DNA methylation changes in PD brain tissues. Results reveal that abnormal DNA methylation in brain tissues of PD patients affects genes enriched in neurogenesis, particu-larly, wnt pathways. Consistently, cells treated with MPP+ showed signifi-cantly reduced expression of genes in wnt pathway. Next, we analyzed that effects of PD related neurotoxins in histone acetylation. Results show that expression and acetylation of multiple histones in cultured cells and mid-brain dopaminergic (DA) neurons of mouse are increased with treatments

of PD related neurotoxins. In agreement with these findings, the protein levels and acetylation of histones are remarkably higher in midbrain DA neurons of PD patients comparing to those of the matched control individu-als. Further analysis suggest that multiple histone deacetylases (HDACs) are concurrently decreased in MPTP-treated cells and mouse brains, as well as midbrain tissues of human PD patients. Inhibition of histone acetyl-transferase (HAT) protects while inhibition of HDAC1 and HDAC2 potenti-ates neuronal death.Conclusions: The results suggest that both abnormal DNA methylation and HDAC regulated aberrant histone acetylation likely plays important roles in PD pathogenesis.No conflict of interest.

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IMPACT OF PARKINSON’S DISEASE RELATED LRRK2 PROTEIN KINASE ACTIVITY AT THE PRE-SYNAPTIC SITEM.D. Cirnaru1,*, E. Belluzzi2, I. Russo2, A. Marte3, F. Pischedda1, F. Onofri3, G. Piccoli11Neuroscience, CNR – Neuroscience Institute, Milano, Italy, 2Department of Biology, University of Padova, Padova, Italy, 3DIMES, University of Genova, Genova, Italy

Objectives: Mutations in Leucine-rich repeat kinase 2 (LRRK2) are the single most common cause of inherited Parkinson’s disease (PD), but little is known about the physiological role of LRRK2. We believe that kinase activity is tightly implicated in LRRK2 function at the pre-synaptic bouton, influencing synaptic vesicles (SV) dynamics, DA release/turnover and, ultimately, the nigrostriatal pathway function. Thus, we aim to study how LRRK2 kinase activity impacts on synaptic function.Methods: To gain an insight on the role of LRRK2 kinase activity on the syn-aptic function, we studied presynaptic performances in presence/absence of LRRK2 kinase inhibitor IN-1 by the means of electrophysiological and imaging assays. Next we analyzed LRRK2 interactions at the synaptic site combining immunoprecipitation and co-sedimentation approaches. Finally we evaluated LRRK2 kinase activity towards selected presynaptic interactors.Results: Our results indicate that LRRK2 kinase activity modulates presyn-aptic release, LRRK2 binding to SV and influences SNARE complex stability. Furthermore we found that LRRK2 robustly phosphorylates NSF and synapsin 1. NSF permits the disassembly of presynaptic SNARE complex thus allowing the next cycle of SV fusion while Synapsin 1 tethers SV to actin cytoskeleton via direct binding.Conclusions: Both NSF and synapsin 1 functions are tightly modulated by phosphorylation: thus LRRK2 kinase activity might regulate their action at the presynaptic site. Therefore, we hypothesize that LRRK2 is a pivotal regula-tor of SV cycle and that presynaptic SV release represents a pathological target in PD.No conflict of interest.

553

LRRK2 BINDS TO NEURONAL VESICLES THROUGH PROTEIN INTERACTIONS MEDIATED BY ITS C-TERMINAL WD40 DOMAING. Piccoli1,*, M.D. Cirnaru1, F. Onofri2, A. Kastenmüller3, F. Pischedda1, A. Marte2, A. Vogt4, F. Giesert5, N. Pan6, C. Kiel7, C. Sala1, F. Antonucci8, M. Zhang6, M. Matteoli8, M. Ueffing4, C.J. Gloeckner5

1Neuroscience, CNR – Neuroscience Institute, Milano, Italy, 2DIMES, University of Genova, Genova, Italy, 3Chemistry, Technical University of Munich, Munich, Germany, 4Medical Proteomic Center, Eberhard Karls University, Tübingen, Germany, 5Institute of Developmental Genetic, Helmholtz Zentrum München, Munich, Germany, 6Division of Life Science Centre of Systems Biology and Human Health, Institute for Advanced Study and School of Science, Hong-Kong, China, 7Centre de Regulació Genòmica, CRG-EMBL, Barcelona, Spain, 8Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, University of Milan, Milano, Italy

Objectives: Mutations in Lucien-rich repeat kinase 2 gene (LRRK2) are associated with familial and sporadic Parkinson’s disease (PD). A sequence variant (G2385R) within the WD40 domain has been implicated as a risk factor for PD, but its physiological and pathological function has not been systematically addressed yet. In this study we analyzed functional and molecular features of the WD40 domain and we addressed the implication of the G2385R variant.Methods: To investigate the protein-protein interactions conferred to LRRK2 by its WD40 C-terminal domain we performed GST pull downs coupled with Western-blot and LC-MS/MS analysis. To experimentally address the struc-tural properties of the LRRK2 C-terminus and the impact of G2385R muta-tion, we analyzed by Transmission Electron Microscopy GST-fusion proteins



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encompassing LRRK2 WD40 wild type as well as G2385R. Finally, we evalu-ated the role of LRRK2 WD40 domain in neuronal functions combining bio-chemical and imaging assays.Results: Our results suggest that LRRK2 WD40 domain serves as a hub for protein interactions setting LRRK2 as part of a protein network involved in synaptic vesicle trafficking. Furthermore we showed that the G2385R mutation influences WD40 domain features in terms of folding and binding properties.Conclusions: By establishing LRRK2 as a presynaptic scaffold protein, these data strongly support the idea that different protein-binding/scaffolding capa-bilities might underlie LRRK2-associated forms of PD.No conflict of interest.

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LRRK2 INTERACTS WITH SYNAPTIC VESICLES IN THE NERVE TERMINALA. Marte1,*, E. Belluzzi2, F. Pischedda3, M.D. Cirnaru3, I. Russo2, G. Piccoli3, E. Greggio2, F. Onofri11Department of Experimental Medicine, University of Genova, Genova, Italy, 2Department of Biology, University of Padova, Padova, Italy, 3Institute of Neuroscience, CNR, Milano, Italy

Objectives: Recent studies have enlightened that synaptic dysfunction is a key factor in Parkinson’s disease (PD) and an early stage marker in pre-symptomatic patients. Mutations in the Leucine-rich repeat kinase 2 (LRRK2) gene are linked to late-onset autosomal dominant PD. LRRK2 function and its role in PD are not clear, but there are evidences that the most common disease segregating mutation, G2019S, is linked to an increase in LRRK2 kinase activity. In view of these findings, the aim of our study was to charac-terize the subcellular distribution of LRRK2 and its interaction with synaptic vesicles (SV), and to understand how LRRK2 pathogenic mutation influences its interactions.Methods: LRKK2 interaction with SV was evaluated by co-sedimentation approach using endogenous LRRK2, in presence/absence of its inhibitor or exogenous Flag-LRRK2 (WT and G2019S); LRRK2 and synapsin I interaction was investigated by co-immunoprecipitation assays from SV.Results: We have demonstrated that LRRK2 is present in the nerve terminal and interacts with SV and that this interaction is modulated by LRRK2 kinase activity. Moreover we found that the G2019S protein shows reduced binding compared to WT. Finally LRRK2 interacts with different proteins in the nerve terminal including synapsin I and these interactions are modulated by LRRK2 activity.Conclusions: Since LRRK2 interacts with SV in a kinase activity dependent manner, we propose that the hyperactive G2019S mutation can affect the SV dynamics in the nerve terminal.No conflict of interest.

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THE GROUP II P21-ACTIVATED KINASES AS THERAPAUTIC TARGETS IN LRRK2-RELATED PARKINSON’S DISEASEE. Greggio1,*, L. Civiero1, I. Russo1, U. Rodella1, E. Belluzzi1, A. Beilina2, D.M. Cirnaru3, V. Baekelandt4, L. Bubacco1, G. Piccoli3, M.R. Cookson2, J.M. Taymans4

1Department of Biology, University of Padua, Padova, Italy, 2Laboratory of Neurogenetics, National Institute on Aging (NIH), Bethesda, USA, 3Institute of Neuroscience, Research National Council, Milano, Italy, 4Laboratory for Neurobiology and Gene Therapy, KU Leuven, Leuven, Belgium

Objectives: LRRK2 is an attractive therapeutic target in Parkinson’s disease (PD) as the most common pathological mutation G2019S increases LRRK2 kinase activity in vitro and LRRK2 kinase activity is required for the neurotox-icity exerted by mutant proteins. To date, a number of selective and potent LRRK2 inhibitors have been developed but it remains unclear whether acute inhibition of LRRK2 activity protects against neuronal death. Interestingly, pharmacological inhibition of LRRK2 abolishes serine 910 and 935 phospho-rylation. This is similar to observations in cells overexpressing mutant LRRK2 and in brains from knock-in R1441C mice1.Methods: To gain insights into LRRK2 function, we performed a protoar-ray screen for LRRK2 specific binding partners and identified p21-activated kinase 6 (PAK6) as a novel interactor.Results: PAKs are serine-threonine kinases implicated in different morphoge-netic processes through remodeling of actin cytoskeleton and, in the context of the nervous system, are key factors for the development and maintenance of synapses. Using a combination of in vitro and in vivo assays we collected evidence that formation of a LRRK2-PAK6 complex impacts actin cytoskeleton dynamics and neurite outgrowth. Furthermore, we demonstrated that kinase activity of group II PAKs (which includes PAK6) negatively regulates LRRK2 phosphorylation.

Conclusions: Our findings suggest that inhibition of this class of kinases has the potential to specifically target pathological LRRK2 function, thus providing a new avenue for PD therapeutics.Reference1. Nichols RJ et al., Biochem J, 2009, 424(1):47–60.No conflict of interest.

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INTRANIGRAL ROTENONE ADMINISTRATION ASSOCIATED TO PARADOX-ICAL SLEEP DEPRIVATION PROMOTED OLFACTORY DISCRIMINATION IMPAIRMENTM. Fortes1, L. Rodrigues1, A. Targa1, A. Noseda1, M. Lima1,*1Physiology, Federal University of Paraná, Curitiba, Brazil

Objectives: To evaluate the possible occurrence of locomotor and olfactory deficits induced by the intranigral rotenone administration associated to selec-tive paradoxical sleep deprivation (PSP).Methods: Rats received bilateral intranigral rotenone or vehicle infusions (12μg/1μL of DMSO), through stereotaxic surgeries, afterward, the PSP occurred from the 7th to the 9th day. At this point we performed the olfactory discrimination and the open-field tests. Such analysis was also made at the rebound period (11th day).Results: One-way ANOVA and subsequent Newman–Keuls post hoc test showed that the sham PSP group exhibited an increased locomotor activity com-pared to the rotenone PSP group (P < 0.01), sham control (P < 0.01) and rote-none control (P < 0,001). The comparison of PSP and rebound evidenced that the PSP-induced effect is acute, weakening after the rebound. Regarding the olfac-tory parameters, we observed that the sham control (P < 0.001), rotenone control (P < 0.001) and sham PSP (P < 0.01) groups demonstrated significant discrimi-nation of the novel odor. However, the rotenone PSP group showed significant impairment of this function. We also observed that this effect was compensated after the rebound period, expressed by increased discrimination of the novel odor.Conclusions: The present data show increased locomotion induced by PSP, which may be due to the dopaminergic supersensitivity. In addition, the asso-ciation of nigral lesion induced by rotenone and PSP generated a remarkable olfactory discrimination deficit.No conflict of interest.

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THE CHEMICAL FREE ENERGY PRODUCTION IS THE MAIN FUNCTION OF THE SUBSTANTIA NIGRA IN THE MIDBRAINA. Solis-Herrera1,*, M. Arias-Esparza1

1R&D&I, Human Photosynthesis Study Center, Aguascalientes, Mexico

Objectives: The presence of melanin in the substantia nigra in the midbrain, is usually considered to be an adduct of dopamine metabolism. Discovery of the intrinsic property of melanin to dissociate and re-form the water molecule explains the insistence of nature in place melanin in the midbrain. Melanin transforms this photon energy into free chemical energy through the dissocia-tion of the water molecule, as the plant is carried out. Our “photosynthesis” is more efficient than the leaves of the plants, as chlorophyll uses only the ends of the visible light (red and purple) to irreversibly dissociate the water molecule, expelling oxygen into the atmosphere. Melanin, however not only is able to use the entire electromagnetic spectrum, from radio waves to gamma rays, but also to dissociate and re-form the water molecule, which is a unique example in nature, as that would free chemical energy occurs, which is indis-pensable for the functioning of the human eukaryotic cell.Methods: In an airtight container, with an aqueous solution of 10% mela-nin, two metal electrodes, to record electrical changes in the solution, for every two molecules of water that melanin reform, is generates four high-energy electrons, which translates into a voltage detectable by a voltmeter.Results: All cells produce voltage ranging from 40 mV to 1.5 V. From certain voltage lights can be lit LEDs.Conclusions: Melanin is able to produces free chemical energy.Reference1. Solis Herrera, A. Energy production, the main role of melanin in the mes-

encephalon. J. Applied Med Sciences Vol 2, No 2, 2013 11–20.No conflict of interest.

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THE ROLE OF NEUROMELANIN IN THE CNS IS THE PRODUCTION OF ENERGY, THROUGH THE DISSOCIATION OF THE WATER MOLECULEA. Solis-Herrera1,*, M.C. Arias-Esparza1

1R&D&I, Human Photosynthesis Study Center, Aguascalientes, Mexico

Objectives: Neuromelanin possess the intrinsic property to split and re-form the water molecule, an astonishing finding termed as human photosynthe-sis by analogy with plants, whose life starts also with the dissociation of the



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water molecule. The transformation of the photonic energy (from light) into free chemical energy is the form in which nature initiate the life, thereby the dissociation of the water molecule is fundamental step in the biology of the eukaryotic cell. This basic reaction was known only in plants, however, during a study about the Age-Related Macular Degeneration initiated in 1990, gradu-ally we could understood this previously unknown extraordinary capacity of neuro-melanin.The capacity to split and re-form the water molecule begin to lose at 26-year-old, approx. 10% each decade and after 50 s goes into free fall, besides that cold turning-down the process like in plants also happen. When the energy released by melanin is not sufficient to impel the myriad of chemical reac-tions that mold the life, characteristically a generalized failure ensued and some CNS will develop. Our main aim in this work is to demonstrate that the enhancement of the human photosynthesis is conceptual revolution of biblical proportions.Methods: Medical enhancement of human photosynthesis in AD patients. (2006–2013), 600 patients.Results: The improvement is very encouraging.Conclusions: The sacred role of glucose as source of energy of CNS now is broken into small pieces, If glucose were a source of energy, then diabetic patients should be able to fly.Reference1. Solis-Herrera Biomedical Research 2010.No conflict of interest.

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ANALYSIS OF NEUROMELANIN GRANULES AND SYNAPTOSOMES FROM HUMAN SUBSTANTIA NIGRA PARS COMPACTAS. Plum1,*, S. Helling1, C. Theiss2, R.E.P. Leite3, C. May4, M. Jacob-Filho5, M. Eisenacher4, K. Kuhlmann4, H.E. Meyer4, P. Riederer6, L.T. Grinberg3, M. Gerlach7, K. Marcus1

1Functional Proteomics, Ruhr Universität Bochum, Bochum, Germany, 2Department of Cytology, Ruhr Universität Bochum, Bochum, Germany, 3Brazilian Aging Brain Study Group – LIM22, University of São Paulo Medical School, São Paulo, Brazil, 4Medical Proteomics/Bioanalytics, Ruhr Universität Bochum, Bochum, Germany, 5Geriatrics discipline, University of São Paulo Medical School, São Paulo, Brazil, 6Clinical Neurochemistry Clinic and Policlinic of Psychiatry Psychosomatics and Psychotherapy, Bavarian Julius-Maximilians-Universität, Würzburg, Germany, 7Laboratory of Clinical Neurobiology Department of Child and Adolescent Psychiatry Psychosomatics and Psychotherapy, Bavarian Julius-Maximilians-Universität, Würzburg, Germany

Objectives: During the progress of Parkinson’s disease (PD) neuromela-nin containing dopaminergic neurons of the substantia nigra pars compacta (Snpc) degenerate and synaptic processes are impaired. Using proteomic techniques we aim to further characterize neuromelanin as well as synap-tosomal structures of human Snpc using high-end proteomic and mass spectrometric technologies in order to better understand underlying patho-mechanisms leading to PD.Methods: Neuromelanin granules and synaptosomes are enriched as described [1,2] and subsequently used for proteomic/mass spectrometric analysis.Results: A first differential study was performed comparing neuromela-nin granules from healthy control and PD individuals. This revealed several proteins to be regulated differently in healthy controls in compar-ison to PD individuals e.g., structural proteins involved in axonal growth.Conclusions: First studies lead to the identification of interesting candidate proteins which may have striking effects on PD progression.References1. Tribl, F., Gerlach, M., Marcus, K., Asan, E., et al., “Subcellular proteom-

ics” of neuromelanin granules isolated from the human brain. Molecular & Cellular Proteomics 2005, 4, 945–957.

2. Plum, S., Helling, S., Theiss, C., Leite, R.E.P., et al., Combined enrichment of neuromelanin granules and synaptosomes from human substantia nigra pars compacta tissue for proteomic analysis. Journal of Proteomics (in press).


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AUTOPHAGIC DYSFUNCTION AND IMPAIRED PROTEASOMAL ACTIVITY IN VULNERABLE BRAIN REGIONS DURING THE PROGRESSION OF PD PATHOLOGYA. Dijkstra1,*, A. Ingrassia1, L. Pardo1, A.J.M. Rozemuller2, P. Heutink3, W.D.J. van de Berg1

1Anatomy and Neurosciences, VU University Medical Center, Amsterdam, Netherlands, 2Pathology, VU University Medical Center, Amsterdam, Netherlands, 3Neurodegenerative Diseases, German Center for Neurodegenerative diseases, Tubingen, Germany

Objectives: Abnormal α-synuclein aggregation is a pathological hallmark of Parkinson’s disease (PD). The α-synuclein pathology spreads from the brainstem to the neocortex in six stages which may correlate with the clini-cal features of the prodromal and motor phases of the disease. In this study, we aim to elucidate the molecular mechanisms underlying the presence of α-synuclein aggregation and progression of PD pathology as defined by Braak α-synuclein stages 0–6.Methods: Subjects with incidental Lewy body disease (iLBD) may represent the premotor stage of PD. We profiled the transcriptome of post-mortem olfactory bulb, medulla oblongata, locus coeruleus and substantia nigra of 17 iLBD, 24 PD donors and 19 controls with Braak α-synuclein stages ranging from 0 to 6 using microarray technology (Affymetrix). Nominal differentially expressed genes were grouped into functional pathways using IPA software (p-value <0.05).Results: Deregulation of mitochondrial dysfunction and protein ubiquitination pathway was observed upon presence of α-synuclein aggregation. Common altered pathways in the different brain regions in iLBD donors compared to controls are related to autophagy, endocytosis and immune response, and include B cell development and Clathrin-mediated endocytosis. In PD com-pared to controls, altered pathways were related to axonal signaling and immune response, and include IL-2 signaling and protein kinase A signaling.Conclusions: Molecular mechanisms related to ubiquitin proteasome sys-tem and cellular stress seem to be involved in the presence of α-synuclein aggregates in the brainstem and OB. In addition, autophagic dysfunction was observed in the early stages of PD pathology and may hold the key to the disease progression in PDNo conflict of interest.

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ISOLATED APRAXIA OF LID OPENING CAUSED BY ROPINIROLE WITHDRAWALH. Kim1,*, H.J. Kang2, S.H. Han1

1Department of Neurology, Konkuk University Medical Center, Seoul, Korea, 2Department of Neurology, Senam Hospital, Seoul, Korea

Objectives: Apraxia of lid opening (ALO) is defined as a nonparalytic motor abnormality characterized by difficulty in initiating the act of eyelid elevation. However, the pathogenesis of ALO is not well understood.Methods: We report on one patient who suffered from disabling ALO after dopamine agonist withdrawal.Results: An 80-year-old woman with a history of Parkinson’s disease and dementia was referred for evaluation of decreased mentality. She was diag-nosed with hypoglycemia and regained alertness following glycemic control. Although she was on 4 mg of ropinirole per day for Parkinson’s disease, par-kinsonian feature was not found. Thus, we withdraw ropinirole. On the third day after withdrawal of ropinirole, we noticed that she had difficulty in lifting her eyelids despites frontalis muscle contraction. There was no evidence of pto-sis. Abnormal contraction of orbicularis oculi muscles or parkinsonian features was not seen. Diffusion-weighted magnetic resonance imaging was negative. Based on previous literatures reporting levodopa responsive ALO, we put her on levodopa/benserazide 100/25 mg three times a day, which dramatically improved inability to open her eyelids on that day. And the remission was sus-tained when she restarted ropinirole instead of taking levodopa/benserazide.Conclusions: The reversible eyelid opening difficulty in our patients was con-sistent with ALO. Our case suggests the importance of considering changes in dopaminergic medications when dealing with ALO and possible role of dopa-minergic pathways in the pathogenesis of ALO.Reference1. Dewey RB Jr, Maraganore DM. Isolated eyelid-opening apraxia: report of

a new levodopa-responsive syndrome. Neurology. 1994; 44(9):1752–4.No conflict of interest.

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INTERACTION BETWEEN NECROPTOSIS AND APOPTOSIS; CLAR -IFYING THE POTENT NEUROPROTECTIVE EFFECTS OF CHITOOLI-GOSACHARIDE ON BOTH PATHWAYS AS A MITIGATORY SUBJECTP. Sadeghi1,*, F. Khodagholi11Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Objectives: Determination between necroptosis and apoptosis could be a great criteria that needs to be clarified by researches focusing on molecu-lar pathways of both signaling. For this, we administrated H2O2 as a stress inducer and Necrostatin-1 by targeting Rip kinases for the inhibition of necrop-tosis. Evaluating factors take part in both pathways could reveal important indications of the cell death occurrence. Furthermore, administration of Chitooligosaccharide (COS) as a neuroprotective issue could be suggested for therapeutic aims.Methods: PC12 cells were incubated with/without a variety of concentrations of Necrostatin-1 prior to exposure to H2O2(150 μM). Also, some groups were



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pretreated with different concentrations of Chitooligosaccharide for its capa-bility to combat oxidative stress condition. The levels of Rip kinases family including Rip-1, Rip-2, Rip-3 and also Caspase-8 were evaluated at men-tioned concentrations in different cell groups using western blot technique. Also, specific staining and MTT test was conducted.Results: Applying Necrostatin-1 in PC12 cells inhibited Rip kinases family members and necroptosis as a result. H2O2-insulted cell groups were detected having apoptotic factors at increased levels including Caspase-3 and the ratio of Bax/Bcl-2. Interaction of apoptosis and necroptosis was observed in the cells with administration of both Nec-1 and H2O2. Finally, administration of Chitooligosaccharide (100 μM) could protect the neurons against oxidative stress condition.Conclusions: The comparison of different cell groups indicated the propor-tional relations between apoptotic and necroptotic pathways. It is worth to be noted that Chitooligosaccharide could modulate death pathways, thus could be applied for pharmacological researches as therapeutic agent.References1. doi: 10.1083/jcb.200608022.2. doi: 10.1038/onc.2008.311.No conflict of interest.

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MULTIPLE FACTORS FROM BRADYKININ-CHALLENGED ASTROCYTES CONTRIBUTE TO THE NEURONAL APOPTOSIS: INVOLVEMENT OF ASTROGLIAL ROS, MMP-9, AND HO-1/CO SYSTEMC. Yang1,*, P.L. Chi11Pharmacology, Chang Gung University, Taoyuan, Taiwan

Objectives: Bradykinin (BK) has been shown to induce the expression of inflammatory mediators, including reactive oxygen species (ROS) and matrix metalloproteinases (MMPs) in brain astrocytes. These mediators may con-tribute to neuronal dysfunction/death in various neurological disorders. The effects of inflammatory mediators released from BK-challenged astrocytes on neuronal cells are investigated.Methods: Conditioned media (BK-CM) were prepared from RBA-1 incubated with BK. BK-CM was applied to human SK-N-SH cells to evaluate the cell viability and apoptosis by CCK-8 kit and Hoechst 33342 staining. ROS gener-ation, MMP-9 expression, and HO-1 expression were determined by lucigenin, gelatin zymography, and Western blot.Results: We found that multiple factors were released from brain astrocytes (RBA-1) exposed to BK in the conditioned culture media (BK-CM), including ROS, MMP-9, and heme oxygenase-1 (HO-1)/carbon monoxide (CO), lead-ing to neuronal cell (SK-N-SH) death. Exposure of SK-N-SH cells to BK-CM or H2O2 reduced cell viability and induced cell apoptosis which were attenu-ated by N-acetyl cysteine, immunoprecipitation of BK-CM with anti-MMP-9 antibody (MMP-9-IP-CM), or MMP2/9 inhibitor, indicating the involvement of ROS and MMP-9 in these responses. The involvement of HO-1/CO in BK-CM-induced cellular responses was revealed by overexpression of HO-1 in SK-N-SH infected with Adv-HO-1 and incubation with a CO donor CO-RM2, which was reversed by hemoglobin. BK-CM-induced cell apoptosis was due to the activation of caspase-3 and cleavage of PARP.Conclusions: BK-induced several neurotoxic factors, including ROS, MMP-9, and CO released from astrocytes, may induce neuronal death through a caspase-3-dependent apoptotic pathway.Document not received.

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T LYMPHOCYTES CONTROL MICROGLIAL ACTIVATION THROUGH CD40 IN NEURODEGENERATIVE DISEASEST. Okuno1,*, S. Tada1, Y. Nakatsuji1, H. Mochizuki11Neurology, Osaka University, Suita Osaka, Japan

Objectives: T lymphocytes and microglial activation have been suggested to affect neurodegenerative processes in Parkinson’s disease (PD) and amyo-trophic lateral sclerosis (ALS). CD40 ligand (CD40L) expressed on T-cells interacts with microglial CD40, playing critical roles in the microglial activa-tion. In this study, we aimed to analyze the role of T-cell-microglia interaction through CD40 in PD and ALS.Methods: To investigate the role of lymphocytes, ALS mouse model defi-cient for lymphocytes (mSOD1/RAG2−/−) were produced by crossing trans-genic mice overexpressing the familial ALS-associated G93A SOD1 mutation (mSOD1mice) with RAG2−/−mice. We analyzed clinical phenotype of both groups. The expression of CD40 in the lesions of PD and ALS was analyzed immunohistochemically. To elucidate the role of CD40 in vitro, we stimulated primary cultures of mouse mixed glial cell, nigra and spinal cord with agonistic anti-CD40 antibody and analyzed neuronal cell death along with the expres-sion of inducible nitric oxide synthase (iNOS).Results: Significant delay of clinical onset in mSOD1/RAG2−/− was observed compared to control mice (mSOD1/RAG2+/+), suggesting a deleterious effects of lymphocytes. However, the difference in symptoms disappeared at

the later stage. The expression of CD40 was increased in reactive glia in the lesions of ALS and PD. The expression of iNOS was up-regulated in primary glial cultures by CD40 stimulation. CD40 stimulation in primary mix spinal cord or nigral cultures caused motor or dopaminergic neuron loss that was pro-tected by iNOS inhibitor.Conclusions: Our data suggest that T lymphocytes deteriorate neurodegen-erative processes in PD and ALS via CD40.Reference1. Tada et al. J. Neuroinflammation. 2011, 23; 8(1):19.No conflict of interest.

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PAROXETINE AMELIORATES LIPOPOLYSACCHARIDE-INDUCED MI-CROGLIA ACTIVATION VIA DIFFERENTIAL REGULATION OF MAPK SIGNALINGR.P. Liu1, M. Zou1, J.Y. Wang1, J.J. Zhu1, J.M. Lai1, L.L. Zhou1, S.F. Chen1, X. Zhang1, J.H. Zhu2,*1Department of Neurology and Geriatrics the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, China, 2Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, China

Objectives: Paroxetine, a selective serotonin reuptake inhibitor for counter-acting depression, has been recently suggested a role in prevention of dopa-minergic neuronal degeneration in substantia nigra, a hallmark of Parkinson’s disease (PD). The pathogenesis of this type of neurological disorders often involves the activation of microglia and associated inflammatory processes. Thus in this study we aimed to understand the role of paroxetine in microglia activation and to elucidate the underlying mechanism(s).Methods: BV2 microglial cells were pretreated with paroxetine and stimu-lated with lipopolysaccharide (LPS). Cells were assessed for the responses of pro-inflammatory mediator and cytokines, and the related signaling pathways were evaluated and analyzed.Results: Paroxetine significantly inhibited LPS-induced production of nitric oxide (NO) and pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β). Further analysis showed inducible nitric oxide synthase (iNOS) and mRNA expression of TNF-α and IL-1β were attenuated by paroxetine pretreatment. Analyses in signaling pathways demonstrated that paroxetine led to suppression of LPS-induced JNK1/2 activation and baseline ERK1/2 activity, but had little effect on the activa-tion of p38 and p65/NF-κB. Interference with specific inhibitors revealed that paroxetine-mediated suppression of NO production was via JNK1/2 pathway while the cytokine suppression was via both JNK1/2 and ERK1/2 pathways. Furthermore, conditioned media culture showed that paroxetine suppressed the microglia-mediated neurotoxicity.Conclusions: Paroxetine inhibits LPS-stimulated microglia activa-tion through collective regulation of JNK1/2 and ERK1/2 signaling. Our results indicate that besides targeting for depression paroxetine may be neuroprotective in relieving pathological progression of PD via anti-neuroinflammation.No conflict of interest.

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ACTIVATION OF GLYCOGEN SYNTHASE KINASE-3 MEDIATES THE OLFACTORY DEFICIT-INDUCED HIPPOCAMPAL IMPAIRMENTSL.Q. Zhu1,*, D. Liu1, J.Z. Wang1

1Pathophysiology, Tongji Medical College, Wuhan, China

Objectives: The populations with olfactory dysfunction show an increased chance for hippocampus-dependent episodic memory deficit. Although it is known that the olfactory nerve fibers project anatomically to the hippocampus through entorhinal cortex layer II, the molecular mechanisms linking olfactory deficit to the hippocampus is not understood.Methods: Morris water maze, step-down passive avoidance and step-through avoidance test to evaluate the memory retention, electrophysiological record-ing for LTP measurement, Golgi staining and electronic microscopy were applied to evaluate the dendritic spine and synapse. Western blot and immu-nohistochemistry were used to measure protein levels.Results: Using bilateral olfactory bulbectomy (OBX) as a model, we found that OBX induced memory deficits with activation of several memory-related protein kinases in the hippocampal extracts, including glycogen synthase kinase-3b (GSK-3b), protein kinase A (PKA), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), phosphatidylinositol-3-kinase (PI3K), and protein kinase B (PKB). The OBX rats also show suppression of long term potentiation (LTP); reduction of synapsin I, synaptophysin, NR2A/B and PSD95; thinner presynaptic active zoon and postsynaptic density with enlarged synaptic space; decreased spine numbers and mushroom-type spines; and tau hyperphosphorylation. Selective inhibition of GSK-3b by vena caudalis injection of SB216763 ameliorated the OBX-induced memory deficits with recovery of the synaptic components and tau phosphorylation.



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Conclusions: Our data indicate that GSK-3 activation mediates the olfac-tory deficits to the hippocampus and targeting GSK-3 blocks the pathological connection.No conflict of interest.

567

INCREASED NEUROGENESIS IN THE RAT HIPPOCAMPUS AND DEN-TATE GYRUS AFTER SPREADING DEPRESSIONM. Lotfinia1,*1Neuroscience, Shefa Neuroscience Research Center, Tehran, Iran

Objectives: Spreading depression (SD) known by transient loss of spon-taneous and evoked neuronal activity and changes in ionic, metabolic and hemodynamic characteristics of the brain. Neuronal damage followed by SD, supposed to have a dramatic impression on SD-derived pathologic con-ditions. We aimed to determine whether SD is able to stimulate persistent neurogenesis.Methods: Wistar rats (60–80 g) randomly chosen and 3M KCl injected for induction of SD. Four weeks after the first injection, all rats were decapitated and the brains removed. The density of mitotic cells, divided cells, and new neurons in the pyramidal cell layer of hippocampal CA1 and CA3 and granular cell layer of dentate gyrus was assessed. We also detect the DNA during the S phase using Bromodeoxyuridine (BrdU).Results: A remarkable increase occurred in the number of BrdU-labeled cells in hippocampal region, detected by immunohistochemistry method. The den-sity of mitotic cells, divided cells, and new neurons in hippocampal CA1 and CA3 and granular cell layer of dentate gyrus also increased.Conclusions: We conclude that SD potentiates to trigger persistent neuro-genesis in rat hippocampus.No conflict of interest.

568

DUAL EFFECTS OF 3,4-METHYLENEDIOXYMETHAMPHETAMINE (EC-STASY) ON SURVIVAL AND APOPTOSIS OF PRIMARY HIPPOCAMPAL NEURONSG. HassanZadeh1,*, P. Pasbakhsh1, A. Azami21Anatomy, Tehran University of Medical Sciences/Medical School, Tehran, Iran, 2Anatomy, Kashan University of Medical Sciences/Medical School, Kashan, Iran

Objectives: 3,4-methylenedioxymethamphetamine (MDMA, also known as “ecstasy”) has been shown to exhibit neurotoxic effects on the hippocampus. However, exposure to sublethal insults of MDMA has been reported to result in neuroprotection. To investigate the effects of MDMA on hippocampal neu-ronal viability, caspase-3 activity, and mRNA expression of the N-methyl-D-aspartate (NMDA) receptor 2B (NR2B) subunit.Methods: Hippocampal neuronal viability was detected by MTT assay. Varying concentrations of MDMA (100–5000 μmol/L) were used to determine lethal concentration 50 (LC50), which was around 1500 μmol/L. Five concentrations of MDMA below 1500 μmol/L (100, 200, 400, 800, and 1050 μmol/L) were used for the remaining experiments. After 24 h of MDMA treatment, NR2B mRNA expression was detected by RT-PCR, and caspase-3 relative activity was deter-mined by colorimetric assay. MAIN OUTCOME MEASURES: Hippocampal neuronal viability, caspase-3 activity, and NR2B mRNA expression.Results: A high dose of ecstasy caused profound mitochondrial dysfunction, around 40%: MDMA-induced neurotoxicity in hippocampal neuronal cultures was dose-dependent. In high concentrations (1000–5000 μmol/L) of MDMA, neuronal viability was decreased. However, with a 500 μmol/L dose of MDMA, neuronal viability was significantly increased (P < 0.01). Low concentrations of MDMA (200 and 400 μmol/L) significantly decreased caspase-3 activity (P < 0.01), whereas high concentrations of MDMA significantly increased cas-

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pase-3 activity (P < 0.01). NR2B subunit mRNA expression was not signifi-cantly altered after 100–1050 μmol/L MDMA exposureConclusions: MDMA exhibits dual effects on hippocampal neuronal viabil-ity and caspase-3 activity. These effects are independent from NR2B subunit expression levels.Reference1. Gholamreza Hassanzadeh Cell J. 2011 Spring; 13(1): 25–30.No conflict of interest.

569

DYSREGULATION OF NEUROTROPHINS MEDIATED SIGNALING MILLEU IN THE HIPPOCAMPUS FROM SUICIDE: AN ANALYSIS IN HUMAN POSTMORTEM BRAINR. Banerjee1,*, A.K. Ghosh2, B. Ghosh3, A.C. Mondal41Physiology, RPM College Uttarpara, Uttarpara, India, 2Instrumentation Science, Jadavpur University, Kolkata, India, 3Pharmacology, Calcutta Medical College and Hospital, Kolkata, India, 4Physiology, RPM College Uttarpara, Uttarpara, India

Objectives: Despite the devastating effect of suicide on numerous lives, there is still a dearth of knowledge concerning its neurochemical aspects. Several clinical and epidemiological studies have identified stress as an important risk factor in suicide. There is increasing evidence that brain-derived neurotrophic factor (BDNF) and Nerve growth factor (NGF) are involved in the pathophysiology and treatment of depression through binding and activating their receptors. To analyzed and statistically evaluate the expression profiles of neurotrophins along with their respective receptors and few of their downstream signaling molecules in the hippocampus of sui-cide victims.Methods: These studies were performed in hippocampus obtained from 21 suicide subjects and 19 non-psychiatric healthy controls. The neurotrophin levels were measured through Sandwich ELISA, the expression levels of neu-rotrophin receptors and their down stream signaling molecules were deter-mined by Western Blot. Finally mRNA levels of BDNF, TrkB and NGF, TrkA were determined by RT PCR.Results: An unique parallel decrease of the protein levels of BDNF, NGF and their cognate receptors in post-mortem suicide victims clearly corre-lated with the significant reduction of their mRNA levels at the hippocam-pal regions compared to the normal individuals. A marked alteration in the expression profiles of down stream signaling molecules like PLCγ, PKCδ, ERK 1,2, Akt and CREB of suicide victims compared to non-psychiatric controls.Conclusions: Significant reduction of BDNF, NGF and their cognate recep-tors along with the dysregulation in BDNF/TrkB and NGF/TrkA signaling cas-cades in post-mortem brains might be of relevance to its pathophysiology of depression.No conflict of interest.

570

GROWTH FACTORS ARE ALTERED IN NEUROGENIC REGIONS OF THE PARKINSON’S DISEASE BRAINS. Virachit1,*, E. Werry2, E. Galli3, E. Rappou3, P. Pulkkila3, M. Saarma3, G. Halliday1, C.S. Weickert1, K.L. Double4

1Neuroscience Research Australia, Sydney, Australia, 2Faculty of Health Sciences, University of Sydney, Sydney, Australia, 3Institute of Biotechnology, University of Helsinki, Helsinki, Finland, 4Sydney Medical School, University of Sydney, Sydney, Australia

Objectives: Proliferating cells in the hippocampus and subventricular zone (SVZ) are decreased in the Parkinson’s disease (PD) brain [1].Methods: As growth factors are proposed to play a role in the regulation of neurogenesis and cell survival, we employed enzyme-linked immunoassays (ELISA) to quantify levels of growth and neurotrophic factors in fresh frozen hip-pocampal and SVZ tissue from 9 control and 10 age-matched PD human brains.Results: Hippocampal levels of basic fibroblast growth factor (FGF2) were significantly increased by 29%, whilst levels of glial cell line-derived neuro-trophic factor (GDNF) were significantly decreased by 19% in the PD brain. In the SVZ, levels of epidermal growth factor (30%) and GDNF (29%) were significantly decreased in PD, whilst levels of FGF2 were increased by 22% in PD.Conclusions: Decreased levels of the potent neuronal survival factor GDNF may underlie observed decreases in neurogenesis in these neurogenic regions in PD and increases in the potent mitogen FGF2 may be attempts to compensate for these changes.Reference1. Hoglinger et al., Nature Neuroscience 2004, 7(7): 726–735.No conflict of interest.

571

SELECTIVE NURR1 ACTIVATION BY IRX4204 PREVENTS SYNUCLEIN-MEDIATED DOPAMINERGIC NEURODEGENERATION: THERAPEUTIC IMPLICATIONSG. Pasinetti1,*1Neurology, Mount Sinai School of Medicine, New York, USA

Objectives: Parkinson’s disease (PD) is a disease of aging which currently affects approximately 1–2% of the world’s population over age 65. The num-ber of individuals with PD is expected to double by 2030, affecting up to 9.3 million. The molecular mechanisms underlying the disease are unknown, but are likely to involve interactions among genetic and environmental factors. There is increasing evidence that activation of the nuclear receptor Retinoid X Receptor (RXR) may protect against PD by providing trophic support for dopa-minergic (DA) neurons. The protective benefit of RXR on DA neuron survival is thought to be mediated by signal transductions involving the heterodimeric RXR-Nurr1 nuclear receptor. This study is designed to test IRX4204, a second generation RXR with higher potency and specificity in Nurr1-mediated neuro-protection, against PD-like pathology.Methods: Plasma pharmacokinetics and brain bioavailability were performed. Receptor binding activities were evaluated. Preclinical efficacy was performed in 6-hydroxydopamine lesion model of PD in rats. Paw placement and apo-morphine-induced rotation were performed to evaluate motor function and neuropathology in the brain was examined.Results: We found that oral administration of IRX4204 resulted in brain accu-mulation of IRX4204 at nanomolar concentrations and causally activated Nurr1 downstream genes in substantia nigra. Moreover, IRX4204 treatment attenuated PD-like motor impairment and neuropathology in a rat model of PD.Conclusions: Our study, for the first time, provided experimental evidence that specific RXR agonists can be further developed for the prevention and/or treatment of PD through mechanisms associated with Nurr1 transactivation mediated neuroprotection.No conflict of interest.

572

EVALUATION OF POTENTIAL MECHANISMS OF CELLULAR TOXICITY BY NITROCATECHOL COMT INHIBITORS: OPICAPONE, ENTACAPONE AND TOLCAPONEM.J. Bonifácio1,*, F. Sousa1, A.I. Loureiro1, L.C. Wright1, P. Soares-da-Silva1

1LIF, BIAL – Portela & Co, S. Mamede do Coronado, Portugal

Objectives: Drug-induced liver toxicity has been one of the most frequent reasons for restriction or withdrawal of an approved medicinal product from the market. This study evaluated the potential hepatotoxicity risk of opicapone, a third generation novel nitrocatechol catechol-O-methyl transferase inhibitor, as compared to tolcapone and entacapone.Methods: The following cytotoxicity indicators were evaluated: ATP depletion (cell viability), caspase 3/7 activation (apoptosis), loss of the mitochondrial membrane potential (mitochondrial dysfunction), glutathione depletion (reactive metabolite formation) and reactive metabolite formation in liver microsomes.Results: Opicapone was found not to affect the viability of human pri-mary hepatocytes, whereas tolcapone reduced human hepatocyte viability and altered cellular morphology. Opicapone was also the least potent com-pound in decreasing both the mitochondrial membrane potential (MMP) and the ATP content in human primary hepatocytes with IC50 values in MMP and ATP content of, respectively, 74.8 μg/ml and 40.5 μg/ml, whereas for tolcapone the values obtained were, respectively, 7.9 μg/ml and 6.8 μg/ml. In HepaRG cells opicapone and entacapone (up to 200 μM) did not affect cell viability, caspase activation or glutathione depletion, whereas tolcapone (200 μM) significantly compromised cell viability and depleted glutathione. Regarding mitochondrial dysfunction, MMP IC50 values for opicapone and tolcapone were of 500 μM and 120 μM, respectively. No GSH-adducts of opicapone were detected in liver microsomes, whereas GSH-adducts from tolcapone and entacapone metabolites were found.Conclusions: Opicapone appears to be devoid of toxicity effects in human hepatocytes and in HepaRG cells under the conditions tested.No conflict of interest.

573

GLUCURONIDATION OF OPICAPONE, A NITROCATECHOL-TYPE COMT INHIBITOR, BY RECOMBINANT UGTS AND HUMAN MICROSOMESA.I. Loureiro1,*, C. Fernades-Lopes1, L.C. Wright1, P. Soares-da-Silva1

1Department of Research and Development, BIAL – Portela & Co, S. Mameded do Coronado, Portugal

Objectives: Opicapone (BIA 9-1067; 2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide), is a novel



155

catechol-O-methyltransferase (COMT) inhibitor, currently in phase III clinical trials. Non-clinical studies revealed that opicapone’s major metabolic pathway involves conjugation to opicapone 3-O-glucuronide (BIA 9-1106) and opicapone 3-O-sulfate (BIA 9-1103). In this study, in vitro assays were used to characterize the opicapone glucuronidation pathway in human liver and intestine.Methods: Kinetic analysis of opicapone glucuronidation was performed in pooled microsomal fractions of human liver (HLM) and intestine (HIM) and recombinant glucotransferases UGTs 1A1, 1A3, 1A6, 1A7, 1A10, 2B7 1A8, 1A9, 1A4, 2B4, 2B15 and 2B17 with subsequent quantification of opicapone 3-O-glucuronide by LC-MS/MS.Results: The apparent kinetic parameters derived from kinetic curves fitted to the Michaelis–Menten equation for HLM and Houston and Kenworthy for HIM. Only UGTs 1A7, 1A8, 1A9 and 1A10 produced significant amounts of BIA 9-1106 (0.43–1.2 nmol/mg prot/min). UGT 1A1, 1A3, 2B7, 2B15, 1A6 and 2B17 produced small amounts of BIA 9-1106. No metabolite formation was detected over an incubation period of 60 min for UGT1A4 and 2B4.Conclusions: The present results indicate that glucuronidation of opicapone is catalyzed by several UGTs in human liver and intestine. UGTs 1A1, 1A3, 1A7, 1A8, 1A9, 1A10 and 2B7 may play an important role in opicapone glucuronidation.No conflict of interest.

574

SULFATION OF OPICAPONE, A NITROCATECHOL-TYPE COMT INHIB-ITOR, BY HUMAN RECOMBINANT SULTS AND HUMAN S9 FRACTIONA.I. Loureiro1,*, C. Fernandes-Lopes1, L.C. Wright1, P. Soares-da-Silva1

1Department of Research and Development, BIAL – Portela & Co, S. Mamede do Coronado, Portugal

Objectives: Opicapone (BIA 9-1067; 2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide), is a novel catechol-O-methyltransferase (COMT) inhibitor, currently in phase III clinical trials. Non-clinical studies revealed that opicapone major metabolic pathway involves conjugation to opicapone 3-O-glucuronide (BIA 9-1106) and opi-capone 3-O-sulfate (BIA 9-1103). In this study, in vitro assays were used to characterize the sulfation of opicapone’s in human liver and intestine S9 frac-tions and human recombinant SULTs.Methods: Kinetic analysis of opicapone sulfation was performed in human liver and intestine pooled S9 fraction and human recombinant SULT 1A1*1, 1A1*2, 1A2, 1A3, 2A1, 1E1 and 1B1 with subsequent quantification of opi-capone sulfate by LC-MSMS.Results: The apparent kinetic parameters for sulfation of opicapone derived from human intestinal and liver S9 fraction curves were fitted to the allos-teric sigmoidal and Michaelis–Menten equations, respectively. Only SULT 1A1 isoform (SULT1A1*1 and 1A1*2) produced significant amounts of opicapone sulfate (1.17 ± 0.13 and 1.91 ± 0.13 pmol.mg prot−1 min−1, respectively), whereas SULT 1A2, 1A3, 2A1 and 1E1 produced small amounts of opicapone sulfate (from 0.03 to 0.22 pmol.mg prot−1 min−1). No metabolite formation was detected with SULT 1B1 over an incubation period of 60 min. Quercetin and 2,6-dichloro-4-nitrophenol completely inhibited sulfation with IC50s of 1.79 μM and 0.38 μM in human liver S9 fraction, and IC50s of 1.48 μM and 0.18 μM in human intestinal S9 fraction.Conclusions: Opicapone is mainly metabolized by SULT1A1 isoform which is generally recognized as the major xenobiotic-metabolizing SULT.No conflict of interest.

575

MELATONIN ATTENUATES SCOPOLAMINE-INDUCED MEMORY/SYNAPTIC DISORDER BY RESCUING EPACS/MIR-124/EGR1 PATHWAYX. Wang1,*1Department Pathophysiology, Tongji Medical College, Wuhan, China

Objectives: Alzheimer’s disease (AD) is a most prevalent dementia in aged people. The level of melatonin in the serum of AD patient is decreased and supplement of melatonin is able to reverse the AD pathological and memorial deficits in many animal experiments and clinical trials. However, the underly-ing mechanisms that melatonin rescues the AD-like memory/synaptic disorder is remain unknown.Methods: Morris water maze, step-down inhibitory avoidance task, in vivo LTP recording, Golgi staining, real-time PCR and western blot were used.Results: Intraperitoneal injection of melatonin (1 mg/kg/day) to rats for 14 days effectively reverses the memory and synaptic impairment in scopola-mine induced amnesia, a well-recognized dementia animal model. By using realtime PCR and western blot, we further identified that melatonin rescues the EPAC/miR-124/Egr1 signal pathway, which is important in the learning and memory as we reported recently.

Conclusions: Our studies provide a novel underlying epigenetic mechanism of melatonin to attenuate the synaptic disorder and could be benefit for the drug discovery in neurodegenerative diseases.Reference1. Zhu, L.Q., S.H. Wang, Z.Q. Ling, D.L. Wang, J.Z. Wang (2004). Effect

of inhibiting melatonin biosynthesis on spatial memory retention and tau phosphorylation in rat. J Pineal Res 37, 71–7.


576

HUMAN DENTAL PULP STEM CELLS EXHIBIT HIGHER PLASTICITY TOWARDS FUNCTIONAL DOPAMINERGIC CELL-TYPE THAN HUMAN WHARTON’S JELLY AND BONE-MARROW DERIVED MESENCHYMAL STROMAL CELLSI. Datta1,*, D. Majumdar1, M. Kanafi1, S. Mishra1, L. Mohanty1, R. Bhonde1

1Neuro-Regeneration Research Group, School of Regenerative Medicine Manipal University, Bangalore, India

Objectives: Success of cell-transplantation for Parkinson’s disease depends on selecting appropriate tissue-source of stem cells for specialized dopamin-ergic (DA) neurons. While MSCs isolated from different tissue-sources share common mesenchymal and immune-modulatory properties, the difference in their plasticity to functional dopaminergic-neurons is ill-defined. The focus of this study was to compare the plasticity of dental pulp stem cells (DPSCs), Wharton’s-jelly (WJ)-MSCs and bone-marrow (BM)-MSCs to functional DA cell-type in presence of midbrain cues.Methods: Stem cells from the three origins were exposed to midbrain cues sonic hedgehog (SHH) and fibroblast growth factor 8 (FGF8) along with FGF2. Characterization of control and induced cells was conducted by real-time RT-PCR, immunocytochemistry, flow-cytometry, fluorimetry and dopamine-ELISA.Results: Upon induction, stem cells from all the three tissue-type showed upregulation of dopaminergic neuron-specific transcription-factors Nurr1 and Engrailed1. Flow-cytometry analysis showed enhanced expression of mature neuronal marker Map2ab and dopaminergic-neuronal mark-ers [tyrosine hydroxylase (TH), Nurr1 and PitX3], with nearly 77% of induced DPSCs positive for TH in comparison to 65% positive expression by induced WJ-MSCs and BM-MSCs. Functional studies indicated that induced cells secreted dopamine constitutively and upon stimulation with potassium chloride (KCl) and adenosine triphosphate (ATP). Interestingly, only induced DPSCs showed intracellular Ca2+ influx in the presence of KCl, unlike induced WJ-MSCs and BM-MSCs. ATP-stimulated Ca2+ influx was observed in control and induced cells, but only the induced cells secreted dopamine.Conclusions: Our data demonstrates for the first time that DPSCs exhibit a higher plasticity towards functional dopaminergic-cells in comparison to WJ-MSCs and BM-MSCs in presence of midbrain cues.No conflict of interest.

577

DEVELOPMENT OF HUMAN IPSC-DERIVED MIDBRAIN DOPAMINERGIC NEURONS FOR DISEASE MODELINGS. DeLaura1,*, L. Chase2, C. McMahon3, N. Meyer4, D. Hussey5, V. Ott6, B. Swanson7, W. Wang8

1Product Manager, Cellular Dynamics International, Madison, USA, 2Group Leader, Cellular Dynamics International, Madison, USA, 3Senior Scientist, Cellular Dynamics International, Madison, USA, 4Scientist, Cellular Dynamics International, Madison, USA, 5Senior Account Manager-UK, Cellular Dynamics International, Madison, USA, 6Director of Marketing, Cellular Dynamics International, Madison, USA, 7Senior Director R&D Cell Biology, Cellular Dynamics International, Madison, USA, 8Senior Director R&D Process Sciences, Cellular Dynamics International, Madison, USA

Objectives: To evaluate human mid-brain dopaminergic neurons derived from induced pluripotent stem cells (iPSCs) for Parkinson’s disease (PD) research and to demonstrate the production of high quality cryopreserved differentiated neurons for disease panels.Methods: Highly pure floor plate-derived dopaminergic neurons were dif-ferentiated from human iPSCs and cryopreserved. The phenotype was measured using flow cytometry and immunostaining for the presence of the microtubule-associated protein 2 (MAP2), the floor plate marker, FOXA2, and tyrosine hydroxylase (TH). Additionally, electrophysiological characteristics were measured using single-cell patch clamp to detect action potentials as well as functional ion channels. Finally, human transgene-free, feeder-free iPSCs from a variety of somatic sources and donors were created and dif-ferentiated into neurons.Results: We developed a highly consistent and scalable protocol to differen-tiate and cryopreserve purified human iPSC-derived midbrain dopaminergic



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neurons. Phenotypically, these cells are >90% pure as measured by MAP2. The midbrain identity was confirmed by FOXA2 (>60%) and TH (>65%) labe-ling 3 days post-thaw. By day 14, the TH purity increased to >90%. Functionally, these cells reveal typical electrophysiological characteristics. Finally, a panel of iPSC-derived neurons from 15 different donors was produced with neuron purities of >90%.Conclusions: These data illustrate the successful generation highly pure iPSC-derived human midbrain dopaminergic neurons that are fully functional, cryopreserved and available in industrial-scale quantities. Additionally, the consistent production of iPSCs and neurons from a variety of donors will be an important tool for advancing PD research and drug discovery.No conflict of interest.

578

NEURONAL DISEASE MODELING ENABLED BY LARGE-SCALE MANUFACTURE OF HUMAN IPS CELL-DERIVED NEURONS AND ASTROCYTESD. Hussey1,*, C. Carlson2, S. DeLaura3, R. Llanas4, A. Thompson5, V. Ott6

1Senior Account Manager – UK, Cellular Dynamics International, Madison, USA, 2Application Development Manager, Cellular Dynamics International, Madison, USA, 3Product Manager, Cellular Dynamics International, Madison, USA, 4Technical Application Scientist II, Cellular Dynamics International, Madison, USA, 5Application Support Manager, Cellular Dynamics International, Madison, USA, 6Director of Marketing, Cellular Dynamics International, Madison, USA

Objectives: With the increasing number of people suffering from neurode-generative disorders, a better understanding of these debilitating disorders is an increasingly urgent healthcare need. Here we evaluate the utility of human induced pluripotent stem (iPS) cell-derived neurons and astrocytes as biologi-cally relevant human cellular model systems to model diseases and create a robust in vitro co-culture platform.Methods: Human iPS cell-derived neurons and astrocytes were devel-oped and manufactured at industrial-scale quantities. To model Alzheimer’s Disease, these neurons were exposed to beta amyloid peptide (Aß1–42) and the peptide toxicity and small-molecules mediated neuroprotective effects were monitored through multiple endpoint assays, including cell viability, and neurite outgrowth. Additionally, for infectious studies of botulinum neurotoxin (BoNT), the intact system for BoNT intoxication in these neurons was verified by Western blot. After exposure to BoNT/A1, the neurons SNAP-25 cleavage was monitored. Lastly, the astrocytes were plated with different densities of neurons to form healthy co-culture environments.Results: Large-scale quantities of human iPS cell-derived were reproducibly manufactured and cryopreserved. These neurons showed dose-dependent toxicity responses to Aß1–42 and were successful in identifying several neu-roprotective small-molecules in an Aß1–42 toxicity screen. Additionally, the neurons proved to be a more sensitive model for BoNT exposure than rat spinal cord neurons.Conclusions: Together, these data illustrate how iPS cell-derived neurons and astrocytes can be used as model systems to study neurological diseases, and more broadly how robust, reproducible ‘disease in a dish’ research will speed drug discovery.References1. Xu (2013).2. Whitemarsh (2012).No conflict of interest.

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INDUCED PLURIPOTENT STEM CELLS FROM ALS PATIENTSM. Deng1,*, X. Liu2, S. Gao3

1Medical Research Center, Peking University Third Hospital, Beijing, China2Department of Neurology, Peking University Third Hospital, Beijing, China 3Stem Cell, National Institute of Biological Sciences, Beijing, China

Objectives: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegen-erative disease which is lack of effective treatment. Induced pluripotent stem (iPS) cells are the perfect source for cell replacement therapy. We establish ALS-patient specific iPS cell lines to lay the foundation for future treatment.Methods: We introduce four transcription factors including Oct4, Sox2, Klf4, c-Myc into three familial ALS patient’s dermal fibroblasts carrying FUS P525L, SOD1 C11Y and SOD1 V14M mutations through retrovirus.Results: These ALS-iPS cells display the morphology of tightly packed and flat colonies. Immunocytochemistry showed that these iPS cells express human ES cell surface antigens such as OCT4, SOX2, SSEA-4, TRA-1-81, and Nanog. Realtime PCR analysis suggested ALS-iPS cells express human ES cell marker genes including OCT3/4, SOX2, NANOG, GDF3, FGF4, REX1, ESG1, DPPA2, DPPA4 and hTERT. Bisulfite genomic sequencing analyses showed that the CpG in the promoter regions of OCT4, NANOG, REX1 were

highly unmethylated. They have normal karyotypes of 46. They can form EBs by floating cultivation and differentiated into kinds of cell types. Furthermore, they have the ability to form teratomas when injected into immunodeficient mice and differentiate into three germ layers in vivo.Conclusions: We successfully established three familial ALS patient’s spe-cific iPS cell lines which is similar to human ES cells and are the first team to generate ALS-iPS cell lines of FUS gene mutation.Reference1. Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells

from adult human fibroblasts by defined factors. Cell, 2007, 131(5): 861–872.No conflict of interest.

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OVEREXPRESSION OF MICRORNA 219 IN HUMAN ENDOMETRIAL STEM CELLS REDUCE EXPRESSION OF NEURAL MARKERS AND INDUCE EXPRESSION OF MYELIN BASIC PROTEIN-MESSENGER RNA (MBP-MRNA)S. Ebrahimi Barough1, J. Ai11Tissue Engineering, School of Advanced Technologies in Medicine, Tehran, Iran

Objectives: Human Endometrial-derived stem cells (EnSCs) are the abundant and easy available adult stem cells with low immunological incompatibility, which could be considered for cell replacement therapy in future. miRNAs have a criti-cal role in oligodendrocyte development including cell proliferation, differentia-tion and myelin formation. MiR-219 is necessary to promote oligodendrocyte differentiation by repressing negative regulators of oligodendrocyte differen-tiation. Oligodendrocytes are myelinating cells in the central nervous system (CNS) that form the myelin sheath of axons to support rapid nerve conduction.Methods: The EnSCs after induction with FGF2, EGF, PDGF-AA, they were infected by miR-219-GFP-expressing lentiviruses. 4 days after infection, cells were collected and analyzed for expression MAP2 and NF-L as neural markers, PDGFRa, CNP and MBP as oligodendrocyte markers by Quantitative RT-PCR.Results: The result showed in the infected cells, expression of PDGFRa, MAP2 and NF-L compared with non infected and control cells significantly decreased and expression other oligodendrocyte markers such as CNP and MBP in the level of mRNA increased in compared with control and non infected cells.Conclusions: In conclusion, the EnSCs could be programmed into pre-oligo-dendrocyte cells by overexpression of miR-219, and may convince to consider these cells as safe source for cell replacement therapy of neurodegenerative diseases.References1. J.C. Dugas, L. Notterpek, MicroRNAs in oligodendrocyte and Schwann

cell differentiation, Developmental Neuroscience 33 (2011) 14–20.2. X. Zhao, X. He, X. Han, Y. Yu, F. Ye, Y. Chen, T. Hoang, X. Xu, Q. Mi,

MicroRNA-Mediated Control of Oligodendrocyte Differentiation, neuron. 65 (2010) 612–626.


581

17β-ESTRADIOL ENHANCES THE EFFICACY OF ADIPOSE-DERIVED MESENCHYMAL STEM CELLS ON REMYELINATION IN MOUSE MODEL OF MULTIPLE SCLEROSISP. Pasbakhsh1,*, I. Ragerdi Kashani1, A. Hedayatpour1

1Anatomy, Tehran University of Medical Sciences/Medical School, Tehran, Iran

Objectives: Previous studies have demonstrated the potential of monother-apy with either mesenchymal stem cells (MSCs) or estrogen in autoimmune and cuprizone models of multiple sclerosis (MS). The aim of this study was to examine the effects of co-administration of 17β-estradiol (E2) and adipose-derived mesenchymal stem cells (ADSCs) on remyelination of corpus callo-sum axons in a cuprizone model of MS.Methods: Forty eight male C57BL/6 mice were fed cuprizone (0.2%) for 6 weeks. At day 0 after cuprizone removal, animals were randomly divided into four groups. The E2 monotherapy, ADSCs monotherapy, E2/ADSCs com-bined therapy and vehicle control. Some mice of the same age were fed with their normal diet to serve as healthy control group. E2 pellets, designed to release 5.0 mg E2 over 10 days, were implanted subcutaneously. 106 PKH26 labeled ADSCs were transplanted into lateral tail. The extent of demyelina-tion, remyelination, and cell type’s composition of host brain were examined at 10 days post-transplantation in the body of the corpus callosum.Results: Transplanted cells migrated to the corpus callosum injury. Histological examination revealed efficacy of intravenous ADSCs transplantation in remy-elination of mouse cuprizone model of MS can be significantly enhanced by E2 administration. Flow cytometry showed that the mean percentages of expression of Iba-1, Olig2 and O4 were significantly increased in E2/ADSCs combined therapy in comparison with ADSCs monotherapy.



157

Conclusions: In conclusion, the findings of this study revealed that E2 admin-istration enhanced efficacy of intravenous ADSCs transplantation in remyeli-nation of corpus callosum axons in mouse cuprizone model of MS.Reference1. Connick P, Kolappan M,, Lancet Neurol 2012; 11(2):150–6.No conflict of interest.

582

PROMOTION OF REMYELINATION BY ADIPOSE MESENCHYMAL STEM CELL TRANSPLANTATION IN A CUPRIZONE MODEL OF MULTIPLE SCLEROSISA. Hedayatpour1,*, I. Ragerdi Kashani1, P. Pasbakhsh1

1Anatomy, Tehran University of Medical Sciences/Medical School, Tehran, Iran

Objectives: Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS). Stem cell transplantation is a new therapeutic approach for demyelinating diseases such as MS which may promote remyelination. In this study, we evaluate the remyelinating potential of adipose mesenchymal stem cells (ADSCs) and their effect on neural cell composition in the corpus callosum in an experimental model of MS.Methods: This experimental study used adult male C57BL/6 mice. Cultured ADSCs were confirmed to be CD73+, CD90+, CD31-, CD45-, and labeled by PKH26. Animals were fed with 0.2% w/w cuprizone added to ground breeder chow ad libitum for 6 weeks. At day 0 after cuprizone removal, mice were ran-domly divided into two groups: the ADSCs-transplanted group and the control vehicle group. Homing of ADSCs in demyelinated lesions was examined by fluorescent microscope. At 10 days after transplantation, the mice were eutha-nized and their cells analyzed by luxol fast blue staining (LFB), transmission electron microscope and flow cytometry. Results were analyzed by one-way analysis of variance (ANOVA).Results: According to fluorescent cell labeling, transplanted ADSCs appeared to survive and exhibited homing specificity. LFB staining and transmission electron microscope evaluation revealed enhanced remyelination in the trans-planted group compared to the control vehicle group. Flow cytometry analysis showed an increase in Olig2 and O4 cells and a decrease in GFAP and Iba-1 cells in the transplanted group.Conclusions: Our results indicate that ADSCs may provide a feasible, practi-cal way for remyelination in diseases such as MSReference1. Hasan KM.. J Neurol Sci. 2012; 313 (2): 99–109.No conflict of interest.

583

QUANTUM MECHANICS IMPROVES THE ALZHEIMER’S CATHEPSIN B INTERACTIONS WITH INHIBITORS HAVING WATER MOLECULES IN THE BINDING VICINITYN. Chitranshi1,*, D.R. Seth1, D.R. Tripathi21Bioinformatics Centre, Biotech Park, Lucknow, India, 2Pharmacy, Rameshwaram Institute of Technology and Management, Lucknow, India

Objectives: Water plays an important role in the binding vicinity for modeling new molecule.Methods: AutoDockTools software (1), widely used as interface for preparing input files, utilizes the either Gasteiger or Kollman partial charge calculation

method for both protein and ligand charge calculations. In common practice so far, the quantum chemical partial charges were applied to the ligands for docking calculations. The newly developed Mozyme function of MOPAC2009 (2) allows fast partial charge calculation of proteins by quantum mechanical semi-empirical methods.Results: Our results demonstrate that (i) the energetic of the key water molecule are more favorable for the binding site in the Cathepsin B protein (ii) Water bridging and triangle formation were seen between the key amino acid residue and the ligand (iii) The internal energy is significant factor for the binding modes of various ligands.Conclusions: Our findings indicate that the inclusion of water molecules in ligand-protein docking results in significant increases in docking accuracy when the use of quantum chemical partial charge assignment on both ligand and proteins for predicting the docking simulations.References1 Ali, H.I., Fujita, T., Akaho, E., Nagamatsu, T. (2010) A comparative study

of AutoDock and PMF scoring performances, and SAR of 2-substituted pyrazolotriazolopyrimidines and 4-substituted pyrazolopyrimidines as po-tent xanthine oxidase inhibitors, J Comput Aided Mol Des 24:57–75.

2. Damm W, Frontera A, Tirado-Rives J, Jorgensen W.L. (1997) OPLS all-atom force field for carbohydrates. Journal of Computational Chemistry 18(16):1955–1970.


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NEURONUTRIENT EFFECT OF WITHANIA SOMENIFERA ON BRAIN AGINGM. Sharma1,*, P. Srivastav1

1Department of Zoology, University of Rajasthan, M.S.J. College, Jaipur, India

Objectives: Aging is a generalized involution of the living body. Brain is the most vulnerable component because of neurons. According to Ayurveda cognitive function depleting by fourth decades of life and after eighth dec-ade the decision making intellect become inevitable. Withania Somenifera is known as Medhya Rasyan ie such rasyana retard brain aging and help in regeneration of neural tissues besides producing antistress, adaptogenic and memory enhancing effect. Objective of our study was evaluate effect of witha-nia somenifera leaves on brain aging of mice followed by stress.Methods: Experimental animal is mus musculus weighing 25–30 g of 4–5-month-old. Alcoholic extract of leaf used. Animal were divided into 6 groups and two dose of drug i.e., 200 mg and 500 mg/kg body weight were used followed by stress. ANOVA was used followed by post hoc Tukey test.Results: Brain was used for biochemical and histopathological study. Animal exposed to stress showed significant decrease in SOD, GSH and total protein. This was accompanied by simultaneous increase in TBARS level. Treatment with WS had no significant but moderate effect on antioxidant enzyme (SOD and CAT). But no effect of plant extract was seen on protein content.Conclusions: Present study provides evidences that oral administration of alcoholic extract of WS leaves have shown antiaging effect in stress.References1. Bhattacharya SK and Muruganandam AV (2003) Adaptogenic activity of

Withania somenifera: an experimental study using a rat model of chronic stress. Pharmacol. Biochem. Behav. 75, 547–555.

2. Dhuley JN (1998) Effect of ashwagandha on lipid peroxidation in stress-induced animals. J Ethnopharmacol. 60, 173–178.




159

Index of authors

AAarsland, D, 183Abbasi, L, 391Abbassian, A, 340Abdul Murad, NA, 165Abella, J, 38AbouAl-Shar, HA, 213Adachi, T, 140Addor, MC, 244Adib Saberi, F, 302Adrenelli, E, 339Adwani, SG, 137Aebischer, P, 221, 548Agid, Y, 360Aguirregomozcorta, M, 328Agúndez, JAG, 242Ahlskog, JE, 19, 373Ahmad, S, 473Ahmed, B, 536Ahn, JY, 204, 284Ahn, T, 450Ahood, A, 493, 494, 495, 496Ahsan, N, 550Ahtoniemi, T, 193Ai, J, 580Aji, BM, 393Akbarian, S, 216Akbostanci, MC, 395Akiashvili, N, 394Akiyma, H, 62Al Shehaby, N, 529Al Tassan, N, 213Albani, G, 71Alegre-Ayala, J, 89Aleric, Z, 98Alexandre, BS, 476Alexandru, R, 49, 409, 418Alexeev, M, 123Ali, SJ, 453Alifirova, V, 79Alimonti, D, 301, 354, 363Al-Jomaa, L, 213Alkhairallah, T, 213Allen, C, 33Allocca, R, 45Allocca, S, 273Almeida, L, 351, 417Alonso Canovas, A, 166Alonso-Navarro, H, 242Alramadhani, R, 280Alstrup, AKO, 437Altschüler, J, 477Alusi, SH, 393Álvarez, R, 328Álvarez-Avellón, T, 178Alves da Costa, C, 220Amboni, M, 45, 225Amirjanyan, H, 377, 379Amososva, NA, 32, 294Amouri, R, 53Anand, KS, 125, 371Andrade, GM, 475Andrenelli, E, 338Aneiros, A, 38Angelini, M, 75Angusti, T, 194Annesi, G, 212Antonini, A, 61, 183, 236, 295, 317Antonucci, F, 553Anwar, H, 342Aoki, M, 438Aquilano, M, 3Arablinskiy, A, 155Arckens, L, 133Argyropoulou, MI, 176Arias-Esparza, MC, 557, 558Ariga, H, 222Armentero, MT, 479

Arnet, I, 313Arora, V, 524Arpit, M, 415Arun, M, 230, 235, 249Arveschoug, A, 202Aryal, B, 433Asaadi, S, 340Asadi, MINA, 369Aschermann, Z, 330Ashonov, U, 256Ashrafi, F, 340Askhanov, G, 256Asselta, S, 212Assogna, F, 177Astrakas, L, 176Asuni, AA, 310Attems, J, 77, 156Au, WL, 180, 182Avagyan, G, 377, 379, 392Avakyan, G, 40Avetisyan, A, 377, 379, 392, 410Avila, P, 414Aviles-Olmos, I, 358, 359Ayala, A, 27Aygun, D, 352Ayturk, Z, 395Azam, A, 528Azami, A, 568Azmin, S, 165

BBa, F, 44Ba, M, 22, 401Baatar, B, 29Babinski, EC, 537Bäck, S, 430Baekelandt, V, 555Bafna, P, 512Bagepally, BS, 185, HT1-4Baggio, HC, 128, 142Baidina, T, 122Baiguera, C, 439Baik, J, 167Bajaj, N, 195, 196Baker, M, 168Balaam, M, 265Balachandar, V, 235, 249Balafkan, N, 229Balaguer, E, 328Balamuralikrishnan, B, 235, 249Balás, I, 408Balash, BY, 315Balaz, M, 353Ballard, C, 337Balma, M, 194Banerjee, P, 541Banerjee, R, 569Bansal, D, 20Bansal, P, 416Baquer, NZ, 530, 532Baracchi, F, 459Baradaran, N, 28Barban, F, 297Barbella, G, 273Barbosa, ER, 225, 283, 299, 414Barbosa, IG, 130Barbov, I, 144Bardinet, E, 360Bargallo, N, 128, 142Barkhof, F, 186Baro, F, 287Barone, P, 45, 225Bartesaghi, L, 242Bartl, J, HT2-1Basavan, D, 527Bass, A, 22, 401Bassetti, C, 459

Bassi, S, 61, 255Battaglia, G, 214Bauer, R, 344Bauer, V, 98, 289Baumann, CR, 52, 69, 343, 400Bayard, S, 143Bedetti, C, 145, 314Beg, T, 518, 520, 521, 522Behari, M, 101, 248Beilina, A, 555Belal, S, 57, 112, 126Bello Rodríguez, O, 277Bellucci, A, 439Belluzzi, E, 552, 554, 555Belotcerkovskaya, E, 226Ben Ali, N, 57, 112, 126Ben Djebara, M, 381Ben mahmoud, A, 407Ben Sassi, S, 53Benabid, AL, 364Benazzouz, B, 531Benesh, J, 318Benninger, D, 41Benrhouma, H, 370, 403, 407Bentivoglio, AR, 303Benz, N, 368Berendse, HW, 5, 124, 134, 148, 186, 198, 199Berg, J, 477Bergström, J, 514Bernabei, R, 303Bertotti, G, 323Bestwick, JP, 110Bezard, E, 276, 481, 535Bhalsing, KS, 185Bhargava, M, 312Bhargava, S, 311, 312Bhargava, V, 311Bhattacharya, KB, 66Bhattacharyya, AK, 66, 505Bhonde, R, 576Biermann, M, 229Bindoff, LA, 229Bishnoi, M, 519Bisi, G, 194Bisson, JF, 486Biundo, R, 183, 236, 295Blandini, F, 214, 479Blankenburg, H, 237Bleuse, SB, 209Bloem, BR, 189Bluhme, H, 202Bobela, W, 548Boczarska-Jedynak, M, 88Bode, M, 202Bodis-Wollner, I, HT1-6Boehm, C, 434Boetzel, K, 365Boeve, B, 19, 153Bogdanov, EI, 17Bogdanov, R, 91Bohlega, S, 213Bohlhalter, S, 105, 286Boissy, P, 266Boke, O, 352Bonato, S, 231Bondon-Guitton, E, 413Bongioanni, P, 3Bonifácio, MJ, 451, 572Bonifati, V, 210, 212, 225Bonito Oliva, A, 463Bonuccelli, U, 203Booij, J, 199Boon, AJW, 210Bordet, R, HT3-4Borellini, L, 231Borg, N, 300Borghammer, P, 202Borgohain, R, 87, 241

9.20th World Congress on Parkinson’s Disease and Related Disorders_Index.indd 1599.20th World Congress on Parkinson’s Disease and Related Disorders_Index.indd 159 10/28/13 8:00 PM10/28/13 8:00 PM


160

Borisova, E, 226Borovkova, N, 226Borrue, C, 162Borton, DA, 276Bosnyák, E, 330, 408Bötzel, K, 434Boubia, B, 481Bouchhima, I, 380Bougea, A, 11, 21, 290Bour, LJ, 356Bouras, C, 159Bousleiman, H, 121, 368Bouzidi, N, 380Boveri, N, 323Bower, J, 19Brand, G, 78Breedveld, GJ, 212, 225Bresolin, N, 231Bril, E, 355Brito, GA, 469, 475Brodacki, B, 501Broderick, D, 168Brucki, SM, 149Brugger, F, 344Bruna Rabassa, O, 136Bruneau, MA, 145, 314Bryan, K, 300Bubacco, L, 555Buell, AK, 542, 546Burkhard, PR, 159, 228, 239Burkhardt, K, 239Bustan, M, 398Butcher, C, 80Butkovic Soldo, S, 135

CCabantchik, ZI, HT3-4Caldara, M, 301Callizot, N, 534Caltagirone, C, 297Calzetti, S, 75Camicioli, R, 44, 181Campo, M, 295Candelario, J, 358Canesi, M, 272Cano-De-La-Cuerda, R, 89Cao, B, 218, 232, 234Cao, CJ, 50, 68, 72, 73, 76, 158, 169, 170, 171, 428Cao, M, 2Capaldo, G, 273, 321Capato, TTC, 283, 414Capecci, M, 338, 339Caramelli, P, 382Cardoso Vale, T, 382Cardoso, F, 382Cardozo, A, 328Carey, G, 300Carignan, B, 346, 361, 397Carlan, B, 49Carlesimo, G, 297Carlson, C, 578Carroll, C, 61Carrozza, MC, 3Casali, M, 278Castellani, R, 74, 489, 503Castellano, G, 194Castillo Moreno, L, 92Castleton, B, 300Cavalheiro, E, 469Cavallo, F, 3Cavanna, A, 151Ceravolo, MG, 338, 339Ceravolo, R, 203Cerqueira, G, 469Cerri, S, 479Chabenne, A, 435Chahidi, A, 384Chakrabarti, N, 505Chakrabarti, S, 541Chakravartty, R, 83Chalimoniuk, M, 497, 498, 501Chan, P, 8

Chandavanshi, L, 447Chandler, R, 180Chandra, SR, 137Chandran, G, 515, 516Chang, M, 308Chang, WH, 43, 341Chao, CJ, 117, 267Chartier-Harlin, MCCH, 209Chase, L, 577Chastan, N, 360Chatamra, K, 318Chaudhuri, KR, 83, 255Checler, F, 220Chehrehnegar, N, 391Chen, BJ, 251Chen, J, 219, 492Chen, K, 218, 232, 234Chen, SD, 462Chen, SF, 565Chen, X, 218, 232Chen, Y, 218, 232, 234Chen, ZJ, 50, 68, 76, 117, 158, 169, 170, 171, 428Cheng, F, 245Cheng, X, 538Chi, PL, 563Chiasserini, D, 5Chi-Burris, K, 337Chien, HF, 225Chin, J, 291Chinchaladze, L, 394Ching, SH, 499Chinni, SV, 527, 528Chiperi, R, 49, 398, 409, 418Chiquet-Ehrismann, R, 242Chirita, R, 16, 118Chirita, V, 16, 118Chitranshi, N, 583Cho, C, 500Cho, JW, 43, 187, 188, 291, 341Choi, SI, 406Choi, YY, 204Chondrogiorgi, M, 163, 176Chopra, K, 519, 524Chorely, C, 300Chouinard, S, 145Choung, O, 190Chow, AW, 429Chraa, M, 384Chrapusta, SJ, 497, 498, 501Chrast, R, 242Christo, PP, 130Chua, S, 173Chuang, J, 499Chunduri, MKV, 87Chung, S, 190Chupina, LP, 32, 294Cicolin, A, 164Cifu, D, 280CImas, I, 327Ciobica, A, 468, 471Cipresso, P, 71Cirnaru, DM, 555Cirnaru, MD, 552, 553, 554Cissé, O, 22, 401Civiero, L, 555Clarimón, J, 242Clifton-Bligh, R, 129Coch, C, 425Cohen, J, 449Cohen, R, 288Collado Vazquez, S, 92Comi, C, 323Comi, GP, 231Comotti, D, 301Compta, Y, 128, 142Constantinides, VC, 11, 290Contarino, MF, 356Cookson, MR, 555Coon, E, 373Coppola, C, 321Corcoran, B, 83Cordeiro, JG, 478Cordeiro, KK, 478

Corell, A, 366Coria, F, 242Cornu, P, 360Correia Guedes, L, 212Correia, A, 469Correia, J, 224Corti, S, 231Cossu, G, 212Costa, A, 297Costa, G, 490Costa, LAR, 86Costa, R, 325Coste, J, 348Côte, M, 239Courtine, G, 276Cova, I, 255Cras, P, 208, 233, HT2-5Cravo, AM, 58Crespo Rodríguez, R, 545Cresswell, S, 200Cronin-Golomb, A, 131Crosiers, D, 208, 233Cruts, M, 233Cubo, E, 257, 309Cuesta, JP, 257, 309Cui, G, 219Cukic, M, 42Cummings, J, 337Curry, SE, 111, 113Czech, D, 224Czernecki, V, 360

DD’Angelo, V, 458D’Hooge, R, 133Daikokuya, H, 172Damak, M, 380Damas, AM, 545Dan, X, 8Daneault, JF, 346, 361, 397Danielsen, EH, 202Dario, P, 3Das, S, 109Datieva, V, 51Dato, C, 273, 321Datta, I, 576Dawson, J, 39de Baat, C, 96de Bie, RM, 356de Boni, L, 216De Chazeron, I, 114de Deus, T, 38De Deyn, PP, 208, 233de Kock, CPJ, 454De La Casa- Fages, B, 402de la Fuente-fernández, R, 38De Leon, L, 129de Lima-Pardini, AC, 288De Luca, MA, 439De Pandis, MF, 278Dean, J, 305Debilly, B, 164Deeb, J, 399Defebvre, LD, 209, HT3-4Degroot, C, 145, 314Dehay, B, 535Deijen, JB, 148Dekopov, A, 355Del Gamba, C, 203del Val, J, 162DeLaura, S, 577, 578Delgado, T, 328Deli, G, 408Della Vida, G, 319Demchuk, N, 122Deng, M, 247, 579Deng, XH, 440Derkinderen, P, 103Derks, K, 214Derost, P, 164, 348Deshmukh, R, 416Destée, AD, 103, 209



161

Deswal, S, 243Devedjian, JC, HT3-4Devos, D, HT3-4Dhall, R, 337Dharmani, M, 480Dharwatkar, SN, 230Dhuriya, Y, 448Di Battista, ME, 177Di Biagio, L, 338Di Biase, E, 231Di Fonzo, A, 231Di Mauro, S, 236DI Pietro, C, 236Di Vossoli, A, 303Diaconu, N, 123Diagne, N, 22, 401Dias, A, 299Dick, J, 95Dickson, D, 153Díez-Tejedor, E, 404Dijkstra, A, 560Dimitrov, N, 83Dinelle, K, 200Ding, H, 219Ding, X, 219Diop, AG, 22, 401Diop, MS, 22, 401Ditty, B, 351Djelilovic, J, 424Djuric-Jovicic, M, 104Döbrössy, MD, 478Dobson, CM, 542, 546Dobson, R, 110Dóczi, T, 330, 408Dodiya, HB, 506Domingues, FS, 237Dondaine, T, 349Dong, H, 219Donoyama, N, 268, 269Dormont, D, 360Dorothy, KM, 110Dou, Y, 436, 484Double, KL, 570Doudet, DJ, 437, HT3-1Douna, H, 506Draganski, B, 175, 181Dragasevic, N, 378Dressler, D, 302Drotar, P, 90Du, Y, 169, 171Dubala, ANIL, 527, 528Dubow, J, 318Dufek, M, 12Dujardin, K, 114Dukart, J, 181Duman, T, 54Dumitru, MM, 16, 118Dummett, S, 39Duong, BT, 250Duplan, E, 220Dure, LS, 417Durif, F, 114, 164Dutkiewicz, J, 106, 108Duval, C, 266, 346, 361, 397

EEaton, S, 318Ebadi, M, 435Eberling, JL, 201Ebrahimi Barough, S, 580Ehrensperger, M, 368Eisenacher, M, 559Eisner, W, 364Ekins, E, 61El Hessni, A, 531El Sayed, N, 529Elia, B, 194Enea, A, 179, 184Engelborghs, S, 208, 233Engels, G, 59Ennok, M, 138, 150Epprecht, L, 52

Ergul, E, 227Erro, R, 45, 225Esartia, K, 394Espay, A, 36Esposito, D, 3Esposito, F, 228, 244Esposito, T, 273Essa, MM, 493, 494, 495, 496Estivill, X, 242Expósito, I, 38Ezquerra, M, 212Ezra, EA, 315

FFabene, PF, 439Facchini, S, 295Facheris, MF, 237Factor, S, 240Fagerqvist, T, 514Falcao, A, 324Falup-Pecurariu, C, 49, 56, 93, 398, 409, 418Falup-Pecurariu, O, 49, 409Fang, M, 225Fantini, M, 164Farrer, MJ, 228Fassbender, K, 147Fattapposta, F, 177Faundez-Zanuy, M, 90Fayed, Z, 342Fazel, S, 517Fedorenko, OA, 460Fedorova, N, 65, 355Fedorova, T, 411Feng, X, 482Ferman, T, 153Fernandes-Lopes, C, 573, 574Fernandez Carballal, C, 402Fernández Lago, H, 277Fernandez, H, 318Fernández-Del-Olmo, M, 277Ferrazoli, EG, 474Ferreira, JJ, 212, 325Ferrero, P, 194Fiasconaro, E, 203Figura, M, 421Filippi, P, 194Fiorenzato, L, 295Fischer, R, 102Fisher, W, 351Fisone, G, 463Fleury, V, 364Floresco, S, 200Florikyan, V, 274Foco, L, 237Fogang, Y, 24, 385Foguem, C, 78Foltynie, T, 358, 359Foncke, EMJ, 186Forjaz, CLM, 86Forjaz, MJ, 27, 257, 309Forsyth, CB, 506Fortes, M, 430, 431, 508, 509, 510, 556Fossati, C, 278Frades Payo, B, 257, 309Fraix, V, 364Franco, G, 231Fratalia, L, 393Fratta, M, 321Frau, L, 490Frazzitta, G, 323Friedman, A, 10, 106, 108, 192Frosini, D, 203Frossard, L, 397Fu, W, 466Fuchs, E, 455Fuhr, P, 121, 368Fujii, S, 362Fujikake, N, 438Fujioka, S, 111, 113, 168, 372Fujishiro, H, 154, 549Fujita, K, 154Fukushima, T, 120

Furlanetti, L, 478Fuse, M, 457

GGabova, A, 127Gabriels, S, 214Gabrielyan, I, 377, 379, 392, 410Gabrillargues, J, 348Gafurov, B, 256Gage, H, 300Gagliardi, M, 212Gajbhiye, A, 507Galanda, M, 366Galati, S, 456, 458, 459Galazka-Friedman, J, 192Galizzi, M, 301Gallagher, L, 61, 255Galley, S, 28Galli, E, 570Galli, M, 278Galvagnion, C, 542, 546Gamaleya, A, 355Gambaryan, PY, 470Gan, JING, 37Gandjean, D, 349Ganguli, P, 240Ganguly, A, 541Gantois, I, 133Gao, S, 205, 579Gao, Y, 492Garbizu, J, 402García Ruiz, P, 162Garcia, J, 478Garcia-Diaz, AI, 128Garcia-Ladona, FJ, 535García-Martin, E, 242Garcia-Ruiz, P, 166Garea Rodríguez, E, 455Gargouri, A, 381Garssen, J, 506Gasiorowska, A, 487, 488Gasser, UE, 313Gassert, R, 400Gassner, H, 271Gavrilovic, A, 116Gaye, NM, 22, 401Gee, M, 174, 181Gellerfors, P, 514Gentile, G, 295Gerlach, M, 559, HT2-2Gerrits, NJHM, 134, 198Gevorgyan, E, 410Ghezzi, C, 479Ghielen, I, 124Ghika, J, 228Ghilardi, MF, 323Ghosh, AK, 66, 569Ghosh, B, 569Ghosh, I, 66Ghosh, P, 66Ghosh, S, 34Gianni, P, 272Giannini, G, 237Giblin, L, 129Giese, A, 434Giesert, F, 553Gijselinck, I, 233Giladi, GN, 315Giladi, N, 189Gironell, A, 242Gladwin, MT, 502Gloeckner, CJ, 553Gnaanmirthan Pillai, J, 4Godinho, CM, 58Godinho, FL, 58, 157, 350Goldoni, M, 75Goldwurm, S, 212Golyk, V, 23Gonçalves, E, 414Gondulenko, N, 23Gonzalez, M, 200Goras, M, 487, 488



162

Gossen, M, 477Götze, O, 52Gouider, R, 381Gouider-Khouja, N, 407Graafland, J, 210, 212, 225Grachev, ID, 195, 196Graff-Radford, NR, 153Grainger, L, 300Grandas, F, 316, 402Grassini, P, 278Gray, W, 279Greco, R, 479Greggio, E, 554, 555Gregoric Kramberger, M, 146, 365Griesinger, C, 434Grimaldi, S, 194Grinberg, LT, 559Groenewegen, HJ, 134Grofik, M, 366Grossardt, B, 19Grosset, DG, 195Grunblatt, E, HT2-1Grundmann-Hauser, K, 245Gschwandtner, U, 121, 368Gu, Z, 8Gubanova, E, 65Gudala, K, 20Guerdoux, E, 143Guermazi, F, 380Gujar, A, 536Guntel, M, 54Guo, X, 218, 232, 234Guo, Y, 492Gupta, AK, 185Gupta, R, 426Gupta, S, 550Gurevich, GT, 315Gurevich, T, 189Guseva, AA, 470Guthrie, BL, 351Guyon, N, HT3-2

HHa, Y, 167Habuchi, C, 154, 549Hachicha, HEND, 380Haddad, MS, 414Haegele-Link, S, 344Haegelen, C, 349Haldar, N, 109, 109Hall, C, 318Halliday, GM, 251, 375, 570Hamada, M, 140Hambadzumyan, H, 392Hamdi, N, 529Hamdy, S, 95Hamza, F, 380Han, B, 526Han, D, 526Han, H, 466Han, SH, 331, 412, 561Han, YM, 406Hanganu, A, 145, 314Han-You, Xu, 263Hariz, M, 358, 359Harley, V, 224Harris, MM, 322Harrison, K, 449Harutyunyan, K, 377, 379, 392, 410Harvey, B, 543Hasegawa, K, 139Hasegawa, T, 438Hasegawa, Y, 191Hashish, A, 151Hasnain, O, 536HassanZadeh, G, 568Hatz, F, 121Haugarvoll, K, 229Hauser, RA, 195, 196Hauser, S, 69

Hayakawa, T, 120He, H, 37Heckman, MG, 113Hedayatpour, A, 581, 582Heffernan, N, 200Heikal, O, 529Helling, S, 559Helmich, RC, 189Helms, G, 175, 455Hendler, T, 189Hentati, F, 53Hepp, D, 186Herceg, M, 330Hernandez, R, 537Herranz Barcenas, A, 166Herrmann, FR, 159Herzberg, U, 193Herzel, S, 315Heutink, P, 560Hicks, AA, 237Hidaka, T, 120Hilel, HA, 315Hill-Burns, E, 240Hillebrand, A, 148Hirata, K, 457Hirsch, E, HT2-4, HT3-2Hirsch, MA, 304Hizem, Y, 381Hluckova, A, 353Ho, SL, 173Hoeijmakers, JH, 214Holmes, KM, 293Hong, JY, 97Hooker, DR, 26Hopes, LH, 209Hor, H, 242Horak, FB, 288Horiuchi, E, 139Houeto, JL, 114Houvenaghel, JF, 349Howard, M, 536Hritcu, L, 468, 471Hu, BL, 538Hu, H, 390Hu, J, 212Hu, Y, 50, 68, 76, 117, 158, 169, 170,

171, 428Hua, Q, 513Huang, H, 351Huang, R, 218, 234Huang, X, Huang, XY, 50, 72, 73, 117, 267, 428Huhtala, T, 193Humieniuk, M, 88Humm, AM, 244Hussey, D, 577, 578Hustadt, F, 547Hwang, SH, 386

IIannitti, T, 236Ibot, I, 162Idrisoglu, HA, 227Iguchi, H, 367Iguchi-Ariga, SMM, 222Ilyechova, EY, 14Imamovic, D, 424Imbach, LL, 400Ingelsson, M, 514Ingrassia, A, 560Ipatov, A, 23Iritani, S, 154, 549Isaacson, S, 332, 337Ishi, R, 539Israeli, E, 544Iudicello, M, 194Ivanova, E, 334, 472Iwaki, H, 258Iyer, SS, 304Izhboldina, O, 79

JJabeen, A, 87, 241Jackson, J, 36Jacob-Filho, M, 559Jacobi, H, 425Jahanshahi, M, 358Jakobsen, S, 437Jakovljevic, D, 81, 279Jamal, A, 473James, LE, 310Jancic, E, 98Janelidze, M, 394Jang, DH, 406Jang, W, 85, 383Janik, P, 419, 421Janitz, M, 251Jankovic, V, 193Jansa, J, 146Jansen, P, 271Janssens, J, 105, 286Janszky, J, 330, 408Janzen, A, 271Jarosz, J, 83Jaskólski, A, 281Jaskowiak, A, 421Jasra, H, 449Jávor-Duray, BN, 454Jayalakshmi, S, 345Jayaraman, M, 17, 211Jayesh, M, 446Jecmenica-Lukic, M, 378Jellinger, KA, 77Jenkinson, C, 39Jeong, Y, 190Jepperson, TN, 223Jessy, J, 446Jha, M, HT1-4Jia, J, 267Jian, L, 390Jiao, Y, 436, 484Jimenez, CR, 5Jiménez-Jiménez, FJ, 242Jitender, S, 185Jog, M, 266Johannesson, M, 514Johnson, A, 306Jordanova, A, 48, 107Joseph, U, 92Ju, X, 247Junque, C, 128, 142Juvekar, A, 517Juvekar, M, 517Jyoti, S, 518, 520, 521, 522

KKaavya, N, 180Kacem, I, 381Kack, M, 78Kadastik-Eerme, L, 31, 238Kaelin-Lang, A, 357Kägi, G, 344Kakamu, T, 120Kakoti, M, 253Kalampokini, S, 147Kale, RK, 530, 532Kamai, T, 457Kamensky, AA, 470Kanafi, M, 576Kanda, H, 120Kandadai, RM, 87, 241Kandiah, N, 180, 182Kanegusuku, H, 86Kang, HJ, 331, 412, 561Kang, SJ, 204, 284Kania, D, 497Kannikannan, MA, 87, 241Kantarci, K, 153Kanthasamy, V, 480Kantorova, E, 366Kapaki, E, 11, 21, 290



163

Kapianidze, S, 394Kapitsa, I, 334, 472Karabanov, A, 127Karachi, C, 360Karádi, K, 330Karagoz Sakalli, N, 160Karapetyan, A, 377, 379, 392, 410Kararizou, E, 11, 290Karpenko, MN, 13, 14Karpova, OV, 294Karthick Kumar, A, 249Kasai, T, 539Kasheverov, I, 485Kashihara, K, 336Kastenmüller, A, 553Katare, D, 473Kathyia, A, 493, 494, 495, 496Katunina, E, 40Kaut, O, 216, 425Kavanagh, T, 251Kawahara, Y, 251Kay, DG, 445Kaye, J, 300Kechaou, M, 57, 112, 126Kefalopoulou, Z, 358Kehr, J, 463Kellet, M, 95Kelly, L, 39Kennelly, KD, 111, 113Kenzelmann Broz, D, 242Kerckhofs, E, HT2-5Kerezoudi, E, 376Keshav, JK, HT1-4Keshavarao, S, 4Keshavarzian, A, 506Késmárki, I, 330Kessel, B, 61Khachatryan, L, 377, 379Khalil, D, 213Khalimova, K, 18Khan, M, 473Khanna, VK, 447, 448, 452Khatri, D, 517Khatwal, RB, 527, 528Khemka, VK, 541Kherif, F, 175Khodagholi, F, 562Khogali, AZZA, 435Khong, PL, 173Khubetova, I, 1Khurana, N, 507, 512Kiel, C, 553Kikuchi, A, 438Kim, HR, 55, 284, 331, 412, 561Kim, HT, 204Kim, JM, 55, 188, 291Kim, JS, 188Kim, JY, 204Kim, MW, 190, 406Kim, S, 341Kim, TJ, 55Kim, TW, 43Kim, WS, 251, 375Kim, YH, 43, 341, 533Kisiel-Sajewicz, K, 281Kissani, N, 384Klaa, H, 370, 403Klein, G, 201Kleist, P, 329Klimenko, VM, 14Klingelhoefer, L, 255Klockgether, T, 425Kloda, M, 106Kluza, J, HT3-4Knaani, KJ, 315Knowles, TPJ, 542, 546Knudsen, K, 202Kobayashi, M, 367Kobayashi, Y, 139Kocabiçak, E, 352Kocian, R, 343

Koks, S, 238Kokshenev, I, 334, 472Kolacheva, A, 485Komoly, S, 330, 408Kondracka, J, 423Kondrasheva, IG, 470Kone, Z, 24, 385Konitsiotis, S, 163, 176Konno, M, 438Korczyn, AD, HT1-1Korolev, M, 127Kosaraju, J, 527, 528Kosta, P, 176Kostic, V, 104, 378Kosutzka, Z, 358Kotenko, KV, 32, 294Kotov, S, 91Kott, A, 254Koulikov, MA, 115Kovács, N, 330, 408Kovacsova, Z, 374Kovalzon, VM, 504Kövari, E, 159, 239Kozina, E, 436Koziorowski, D, 10, 106, 108, 192Krack, P, 114, 364Kraneveld, AD, 506Kraoua, I, 370, 403Krastev, G, 374Krieglstein, K, 455Krivonos, OV, 32, 294Krommyda, M, 399Kruer, MC, 223Krüger, R, 318Krygier, M, 423Kryukova, E, 485Kuanova, L, 335Kuark, RG, 149, 157, 350Kubicki, K, 88Kuhad, A, 524Kuhlmann, K, 559Kulinski, R, 192Kulisevsky, J, 242Kulkarni, SK, 519Kulkuntrakorn, K, 47, 119Kulua, T, 65Kumagai, T, 120Kumar J, K, 137Kumar Pal, Pramod, 259Kumar, A, 523Kumar, N, 396Kumar, P, 530, 532Kumon, A, 139Kupsch, A, 196Kurca, E, 366Kurtis, M, 162Kurtz, A, 477Kurvits, L, 238Kutala, VK, 241Kuwabara, S, 457Kuznetsova, G, 127Kwiek, S, 88Kwon, H, 188

LLacombe, O, 481Lafontaine, AL, 145, 314Lai, JM, 565Lakhdar, I, 53Lal, S, 129Laloux, C, HT3-4Landau, AM, 437Lane, D, 195Lang, Y, 276Langager, D, 223Langfort, J, 497, 498, 501Lannfelt, L, 514Lapertot, B, 486Larner, AJ, 393Lauzé, M, 361, 397

Lavigne-Pelletier, C, 266, 346, 397Lazarova, S, 144Leahy, S, 449Leal, LK, 476Lebas, JF, 364Lee, CS, HT3-1Lee, DK, 187, 450Lee, H, 204, 284, 412Lee, JE, 55, 97, 224Lee, JH, 386Lee, JM, 187, HT3-1Lee, PH, 97Lee, SM, HT3-1Lee, Y, 190Lees, AJ, 110, 325Lefter, R, 471Legarda, I, 328Legendre, JPL, 209Lei, D, 440Leite, REP, 559Lemaire, JJ, 348Lemine, SOM, 22, 401Lena, C, HT3-2Léonard, G, 270Leonardo, M, 102Leonov, A, 434Leuenberger, K, 400Levandis, G, 479Levin, J, 434Levin, O, 51, 155Lewis, A, 306Li, C, 169, 170, 171Li, DTH, 173Li, JM, 440, 513Li, N, 427Lian, TH, 170Licker, V, 239Lilleng, PK, 229Lim, E, 429Lima, M, 430, 431, 442, 508, 509, 510, 556Limongi, J, 299Limousin, P, 358, 359Lindström, V, 514Ling, KH, 165Linnamagi, U, 150Linsalata, G, 203Liou, A, 492Litvinova, A, 91Liu, A, 28Liu, D, 566Liu, RP, 565Liu, W, 219Liu, X, 579Liu, ZG, 37, 50, 72, 73, 117, 267, 428, 462Lizan Tudela, L, 257, 309Ljubisavljevic, M, 42Llanas, R, 578Llaneza, M, 38Lobjanidze, N, 394Lobrinus, JA, 239Lobzin, S, 411Lokaj, J, 12Lolekha, P, 47, 119Longo, K, 45Lopatin, D, 449Lopes da Silva, S, 506Lopes, N, 324, 325Lopez Valdes, E, 162Lopez, L, 162López-Muñiz, A, 178, 197Lopiano, L, 164Lord, A, 514Lorenzo, JR, 327Lorenzo-Betancor, O, 242Lorio, S, 175Lotfinia, A, 461Lotfinia, M, 464, 567Loureiro, AI, 572, 573, 574Loureiro, APC, 289Low, PA, 373Lu, L, 37



164

Lu, Q, 467Lukacova, N, 497, 498Luo, Y, 120Lus, G, 321Lutti, A, 175Ly, H, 250Lyashenko, EA, 67Lyros, E, 147

MMN, S, 527Ma, J, 8Ma, S, 482Maat – Kievit, JA, 210Macedo, L, 164Machado-Filho, JA, 469Macias Macias, Y, 89, 92, 162Macías, M, 38Madeo, M, 223Madjidova, Y, 387Maeda, T, 141, 326, 336Maestri, R, 323Magnin, M, 58Magrashi, A, 213Maguire-Zeiss, KA, 543Mahdavi, R, 369Mahillo Fernandez, I, 166Maier, O, 400Maisuradze, T, 394Majerczak, J, 281Majumdar, D, 576Mak, E, 182Mak, HKF, 173Maki, F, 62Makotrova, T, 155Maksimovich, I, 389Malakouti, S, 369Malay Kumar, S, 528Malfroid, K, 286Malla, S, 20Mallet, L, 360Malykhin, A, 9Malykhina, N, 9Mamontov, SM, 460Mandel, S, HT3-5Mangione, AS, 479Manjunath, S, 132Manvelyan, H, 377, 379, 392, 410Marchesi, E, 75Marchetti, P, HT3-4Marcus, K, 559Marecek, R, 183Marek, K, 195, 196Maremmani, C, 3Marinescu, R, 162Marinho, NE, 58, 149, 157, 350Mario, A, 347Marmolino, D, 547Marques, AR, 164Marte, A, 552, 553, 554Martí, MJ, 128, 142, 212, 242Martin Llorente, C, 92Martin, A, 61Martin, E, 343, 344Martin, WRW, 44, 174, 181Martínez Castrillo, JC, 162, 166Martinez-Martin, P, 27, 61, 255, 257, 309Martínez-Rivera, M, 178, 197Martino, D, 61Martins, PM, 545Marusiak, J, 281Masaki, T, 539Masarova, L, 90Maslyuk, OA, 32, 294Masmoudi, H, 380Mastroberardino, PG, 214, 502Mata, M, 162, 166Matmurodov, R, 18Matsukawa, N, 362Matteoli, M, 553Mauro, A, 71Maxmudova, D, 296

May, C, 559Mazurkiewicz, M, 487, 488McConvey, V, 260Mckenzie, J, 200McKeown, MJ, 28, 200McMahon, C, 577McNaney, R, 265, 285Meco, G, 3, 177, 319Meglic, B, 365Mehrabian, S, 48, 107Mehrkens, JH, 365Meier, N, 360Mejia-Constain, B, 145, 314Mekyska, J, 90Melek, I, 54Melis, M, 212Meller, J, 455Mello, MT, 86Melnikova, M, 411Melo, A, 94Melone, M, 273, 321Melzi, V, 231Ménard, JG, 270Mencel, J, 281Menendez-Gonzalez, M, 178, 197Menig, A, 275Mercuri, NB, 463Merikle, E, 33, 36Mesfioui, A, 531Meyer, A, 121Meyer, HE, 559Meyer, K, 105Meyer, N, 577Mhiri, C, 380Miangolarra Page, JC, 92Michaels, TCT, 546Michel, A, 547Michel, PP, HT2-4Michou, E, 95Mielke, MM, 153Mihaljevic, I, 271Mihova, K, 48, 107Milanese, C, 214, 502Milanowski, L, 419Milesi, V, 349Miletic, H, 229Miller, C, 292Miller, N, 285Millevolte, M, 338Mills, JD, 251Mills, R, 337Milyukhina, I, IV, 13, 14, 226Mimura, M, 362Mina, S, 125Ming, HW, 28Minnerop, M, 425Mircea, R, 398, 409, 418Mirrelman, A, 189Misbahuddin, A, 399Misevic, S, 135Mishra, J, 523Mishra, N, 465Mishra, S, 550, 576Misra, D, 101, 253Mitev, V, 48, 107Mitra, S, 505Miura, E, 438Miyata, M, 154, 362, 549Mizuno, T, 539Mizuta, I, 539Moarcas, M, 49, 56, 93, 398, 409, 418Moccia, M, 45Mochizuki, H, 564Moeller, CJ, 456, 459Moeller, JC, 458Moessler, H, 74, 503Mohammed, F, 248Mohanadevi, S, 235, 249Mohanty, L, 576Mohd Fadly, F, 432Mohd Nawi, A, 165Mokaya, J, 26Moldovanu, I, 123

Moller, A, 437Möller, C, 514Mollik, MAH, 443Monchi, O, 145, 314Monda, M, 273Mondal, AC, 569Montastruc, JL, 320, 413Monteiro, L, 94Montero, H, 298Moon, C, 435Morabito, B, 303Moradiya, V, 536Moraes, OJ, 58, 350Morato, IB, 130Moreau, C, HT3-4Morelli, M, 439, 490Moreno, E, 195Mori, Y, 120Morley, D, 39Moroni, F, 272Morsing, A, 202Morucci, M, 319Motoula, DH, 24, 385Mounach, J, 70Mrabet, S, 57, 112, 126Mujtaba, SF, 520, 521Mukherjee, S, 215Mulder, AB, 454Mulholland, N, 83Muller, C, 486Mulliez, A, 348Munasipova, S, 420Murakami, S, 367Muralidhara, M, 515, 516Muraoka, R, 141Muresanu, D, 74, 489, 503Murgia, D, 212Murray, M, 153MustaqAhamed, S, 249Mutez, EM, 209Muthukumaran, K, 449Myöhänen, TT, 543

NNadella, K, 241Naffah-Mazzacoratti, MG, 469, 475Nagai, M, 258Nagai, Y, 438Nagata, K, 326Nagatsu, T, 252Nagy, F, 330Nahdi, H, 53Nakagawa, M, 539Nakashima, K, 140, 152Nakashita, S, 140, 152Nakatsuji, Y, 564Nampoothiri, M, 446Nansubuga, R, 25Napalkov, D, 91Narang, V, 101, 253Narayanan, S, 99, 100, 132Narayanappa, M, 528Nasri, A, 370, 381Navarro, S, 360Naz, F, 518, 520, 521, 522Ndiaye, MM, 22, 401Negre-Pages, P, 103Negrotti, A, 75Nehru, B, 511Nepoklonov, A, 472Nerobkova, L, 334Neves, AT, 157, 350Neves, KR, 469, 475Ng, A, 180Ngo, DN, 246, 250Ngo, TN, 250Nguyen, A, 28Nguyen, H, 246Nguyen, MH, 250Nguyen, PAH, 246Nguyen, PM, 246, 250Nguyen, TL, 246



165

Niculescu, G, 179, 184Niecko, T, 33, 36Niewiadomska, G, 487, 488Niewiadomski, W, 487, 488Nigmatullina, R, 127Nik Ruziyanei, NJ, 165Nikitina, M, 79Nikkhah, G, 478Nikolic, V, 116Nishikawa, N, 258Nishimura, H, 172Nishita, MI, 537Nisticò, R, 463Nitesh, K, 446Nitschke, S, 344Nobre, ME, 469Nobrega, A, 94Nodel, M, 115Nomoto, M, 258Noor, S, 480Norazit, A, 480Nordbeck, AH, 199Nordstrom, E, 514Norlelawati, A, 432Norlinah, MI, 165Norton, D, 131Noseda, A, 430, 431, 508, 509, 510, 556Noyce, AJ, 110Nunes, T, 324, 325Nurmi, A, 193Nwatchok, JC, 78Nyffeler, T, 286

OO’Brien, K, 444O’Brien, PL, 322O’Callaghan, A, 81, 82, 84, 279O’Gormann, R, 343O’Shea, T, 33Obaid, M, 44Obata, T, 491Obukhov, K, 127Obukhov, Y, 127Ocepek, L, 365Ochudlo, S, 405Odin, P, 61Oechsner, M, 275Oertel, M, 357Ogaki, K, 372Ohkoshi, N, 268, 269Ojo, C, 435Oka, Y, 362Okita, K, 362Okuno, T, 564Okuyucu, E, 54Olde Dubbelink, KTE, 148, 186Olgiati, S, 212, 225Oliveira, C, 325Oliveira, H, 102Oliveira, MO, 149Olivier, B, 506Olivier, P, 265, 285Olmedilla Gonzalez, N, 166Omidi, H, 525Omidi, N, 525Omrani, M, 340Onar, MK, 352Onofri, F, 552, 553, 554Onu, M, 179, 184Oostra, BA, 212, 225Orefice, G, 45Orni, C, 339Ortega-Cubero, S, 242Ortega-Pérez, I, HT3-2Oshima, R, 438Ospanov, A, 333Ossowski, S, 242Ostergaard, K, 202Otermín, P, 328Otsuka, T, 367Ott, T, 245Ott, V, 577, 578

Ou, R, 218Ouahmane, Y, 70Ouhabi, H, 70Ouichou, A, 531Ouyang, L, 212Ozaki, N, 154, 549Ozel, MD, 227Ozen Barut, B, 64Ozerden, M, 160

PPMarien, HT2-5Pace, M, 459Padilla-Lopez, S, 223Padmakumar, C, 306Padmakumar, G, 306Padurariu, M, 468, 471Pagano, G, 46Pagonabarraga, J, 328Pakarulrazy, NF, 165Pál, E, 330Pal, PK, 30, 137, 161, 185, HT1-4Pal, S, 61Palasz, E, 487, 488Pan Montojo, F, HT1-5Pan, F, 219Pan, N, 553Pan, Q, 551Pandey, S, 449Panigrahi, M, 345Panina, E, 411Pant, AB, 447, 448Papegaaij, S, 288Pappata, S, 225Paraskevas, G, 11, 21, 290Pardo, L, 560Parisi, J, 153Parizel, PM, HT2-5Park, D, 533Park, GH, 551Park, H, 55Park, J, 43, 533Park, S, 533Parra, J, 316Parry, M, 61Parthasarathi, G, 20Partington, L, 292Parvaresh-Rizi, M, 369Pasbakhsh, P, 525, 568, 581, 582Pasinetti, G, 571Pasioti, A, 376Pastor, P, 242Patel, K, 536Patkin, E, 226Patnaik, R, 74, 489, 503Pato, A, 327Pattij, T, 199Pavese, N, 202Paviour, D, 61Pavlic, G, 123Pavlova, GV, 504Pavlova, R, 48, 107Payami, H, 240Payan Gomez, C, 214Payzieva, S, 296Paz Ruiz, S, 309Peçanha, T, 86Pedroli, E, 71Pellecchia, MT, 45Pellerito, RE, 194Pellitteri, M, 439Peppe, A, 297Pereira, B, 114, 164, 348Perez Lloret, S, 103, 320, 413Perez Pardo, P, 506Perini, M, 323Perkusich, A, 102Péron, J, 349Petersen, R, 153Petrov, I, 144Petrova, M, 48, 107Pezzoli, G, 212, 323

Pham, TV, 5Philippens, I, 483Piccoli, G, 552, 553, 554, 555Pichler, I, 237Picillo, M, 45, 225Pickenbrock, H, 302Pickut, BA, 208, 233, HT2-5Pidoux, B, 360Piemonte, MEP, 283, 414Piepponen, TP, 430Piersma, SR, 5Pignatelli, M, 463Pilleri, M, 236, 295Pimentel, MEP, 86Pinho, P, 94Pinna, A, 439, 490Piñol, G, 328Pinto, NB, 476Pinto, R, 324Pirtosek, Z, 146Pischedda, F, 552, 553, 554Piu, C, 2Pizzi, M, 439Planken, A, 238Plotkin, M, 196Plum, S, 559Plumitallo, A, 490Podio, V, 194Poewe, W, 317, 364Poindron, P, 534Polanski, A, 88Pollak, P, 364Pollo, C, 357Pollock, CE, 7Poloni, M, 301, 354, 363Pomponi, M, 303Pooters, T, 133Popovic, M, 104Poryazova, R, 69Posada, I, 162Potrzebowska, I, 106Poulimenou, E, 376Poupardin, O, 481Pourcher, E, HT1-3Prakash, K, 530, 532Pramstaller, PP, 237Prasad, M, 109Pratibha, S, 259Preda, D, 317Predtechenskaya, E, 6Priano, L, 71Prior, JO, 228Prix, C, 434Prochnicki, A, 425Proença, M, 442Prosperetti, C, 456Provinciali, L, 339Przeklasa, L, 88Przybyszewski, A, 88Puchkova, LV, 14Puente, V, 328Pulkkila, P, 455, 570Purrello, M, 236Pusphender, K, 416Pussinen, R, 193Puussaar, T, 138

QQu, M, 466Quadri, M, 210, 212, 225Quarantelli, M, 225Quattrone, A, 212Queiroz, ACC, 86Qutubuddin, A, 280

RRabey, J, HT3-5Rademakers, R, 168, 207Radicati, FG, 278Radovanovic, S, 104, 378Ragerdi Kashani, I, 581, 582



166

Ragusa, M, 236Rahimi, F, 266Rahman, S, 533Raijmakers, P, 198, 199Raikhelson, K, 411Raimova, M, 18Rajini, P, 453Rajnar, R, 365Ramakrishna, T, 243Ramesh, A, 211Ramirez Boix, P, 257Ramiro Gonzalez, M, 92Rana, AC, 512Ranghetti, A, 272Rao, A, 99, 100Rao, CM, 243, 446Rappou, E, 570Rascol, O, 103, 320, 413Ratmanova, P, 91Rawal, PV, 351Ray-Chaudhuri, K, 61Rebai, I, 407Reddy, M, 100Reddy, YCJ, 161Reichmann, H, HT1-5Reimann, E, 238Reis, HJ, 130Reis, T, 280Rektor, I, 12, 353Rektorova, I, 12, 90, 183Ren, X, 37Renko, JM, 430Revishchin, AV, 504Rey, MV, 320, 413Riboldazzi, G, 323Ricchi, V, 212Ricciardi, D, 303Ricciardi, L, 303Richie, C, 543Riedel, L, 216Riederer, P, 559, HT1-2Rieu, I, 114Riva, G, 71Rizos, A, 61, 255Rizzetti, MC, 301Rizzuti, M, 231Roceanu, A, 184Roch, M, 477Rocha, F, 545Rocha, J, 324, 325Rocha, MS, 58, 149, 157, 350Rocha, NP, 130Rodella, U, 555Rodrigues, L, 430, 431, 508, 509, 510, 556Rodriguez Blazquez, C, 257, 309Rodriguez Cruz, PM, 402Rodriguez Sanz, A, 404Rodriguez-Blazquez, C, 27Rodriguez-Constenla, I, 327Roggen, D, 265Rogozina, A, 226Rojo, A, 162Rojo, JM, 27Romana, S, 194Romanenko, V, 60Romanenko, Y, 60Ronchi, D, 231Rood, JPMA, 210Rose, R, 547Rosenthal, M, 31Ross, OA, 207, 372Rossi, G, 3Rossignol, A, 143Rothwell, JOHN, 95Rouissi, A, 370, 403Rousseau, E, HT2-4Rovini, E, 3Rozemuller, AJM, 560Rubino, A, 177, 319Ruef, A, 175Ruikar, D, 345Ruiz Huete, C, 162Rusconi, M, 272

Russ, A, 224Russo, I, 552, 554, 555Rutten, S, 124Ryazanov, S, 434

SSaarma, M, 430, 455, 570Sadasivan, S, 444Saddi, V, 212Sadeghi, P, 562Sadikot, AF, 346, 361Saha, RN, 441Sahakyan, A, 377, 379, 392Sahoo, A, 541Sail, K, 33, 36Saini, J, HT1-4Saito, M, 141Sakakibara, R, 457Sala, C, 553Sala-Llonch, R, 142Sale, P, 278Salleron, JS, 209Salova, E, 355Salvadè, A, 458, 459Sampaio, M, 94San, X, 526Sanchez Alonso, P, 166Sanchez, JC, 239Sandhir, R, 388Sandhu, J, 449Sanjak, M, 304Sankar, K, 230, 235, 249Sankhwar, ML, 452Santos, D, 316Santos-García, D, 38Sanz, P, 328Saracino, D, 273, 321Saruwatari, M, 139Sasaki, N, 62Sasikala, K, 230, 235, 249Sasina, L, 226Sastre-Bataller, I, 358, 359Satish Kumar, MN, 528Satoh, Y, 326Satte, A, 70Sauerbier, A, 61, 83, 255Sauleau, P, 349Savica, R, 19, 153Savolainen, M, 543Sawada, M, 252Saxena, A, 432Sayadi, S, 391Sazci, A, 227Scalzo, PL, 130Scatozza, R, 177, 319Schaal, B, 78Scheller, D, 547Schelosky, LD, 103Scherder, EJA, 59Schindler, C, 121Schinwelski, M, 423Schlumbohm, C, 455Schmand, BA, 148Schmid, R, HT2-1Schmidt, F, 434Schmitt, I, 216Schmitt, M, 535Schneider, B, 221, 548Schoonheim, MM, 186Schreglmann, S, 52, 343, 400Schultz-Cherry, S, 444Schüpbach, M, 357, 360Schuurman, PR, 356Schwarz, N, 368Schwarzlmüller, T, 229Schwerk, A, 477Schwienbacher, C, 237Schwindt, TT, 474Schwirtz, A, 271Science, Computing, 285Scott, DJ, 201Seck, LB, 22, 401

Segura, B, 128, 142Seibyl, J, 195, 196Sekiguchi, H, 154, 549Selai, C, 151Sellame, J, 531Sellami, L, 381Selvaraju, S, 493, 494, 495, 496Sen Nag, O, 541Sens, S, 361, 397Sepe, S, 214, 502Serafin, A, 237Serafini, F, 297Seredenin, S, 334Serra, G, 360Serrano, C, 328Sertpolat, AY, 54Seth, DR, 583Severin, ES, 470Seydanova, A, 333Shaafi, S, 15Shabalov, V, 355Shahidi, G, 369Shang, H, 218, 232, 234Sharma, A, 74, 489, 503Sharma, D, 215, 465Sharma, H, 74, 489, 503Sharma, J, 80, HT2-6Sharma, M, 584Sharma, N, 507, 512Sharma, PL, 416Sharma, S, 435Sharon, R, 544Shaw, CA, 445Shelukhina, I, 485Sherwin, P, 195Shibata-Yamaguchi, C, 457Shih, CT, 499Shimizu, Y, 362Shin, CM, 55Shin, H, 187, 291Shinoda, T, 141Shiraishi, M, 62Shukla, RK, 447, 448Sica, G, 398Siclari, F, 228Siddique, YH, 518, 520, 521, 522Sigvardson, J, 514Sikorska, M, 449Silina, N, 411Silva Jr, ND, 86Silva, L, 102Silva, M, 7Silva-Batista, C, 86Silverdale, M, 61Simhi-Haham, D, 544Simonetto, M, 217Singer, W, 373Singh, D, 243Singh, I, 248Singla, S, 524Sitek, EJ, 423Sitoh, YY, 182Sivan, A, 30, 161Sivan, Anilkumar, 259Sjoquist, P, 489Skanjeti, A, 194Skelina, S, 48, 107Skvortsov, AN, 14Slawek, J, 423Sleegers, K, 233Slevin, JT, 318Slubowska, E, 108Smekal, Z, 90Smelser, LB, 351Smeyne, R, 444, 484Smeyne, RJ, 436Smiljkovic, P, 116Smiljkovic, T, 116Smirnova, O, 411Smit, AB, 483Smit, JH, 124Smith, B, 288Smith, G, 153



167

Smith, J, 449Smith, L, 129Smolentseva, IG, 32, 294Soares-da-Silva, P, 324, 325, 451, 572,

573, 574Sohn, Y, 97Soleiman zadeh Ardebili, R, 340Solic, K, 135Solis-Herrera, A, 557, 558Sommerauer, M, 69, 400Song, J, 120Song, W, 218, 232, 234Sonmez, E, 227Sood, A, 388Sordoni, E, 338Sordyl, R, 88Sorensen, JC, 437Sosorburam, T, 29Sossi, V, 200Sounga Bandzouzi, P, 24, 385Sousa, F, 572Sousa, MS, 130Souza-Machado, A, 94SOW, AD, 22, 401Soysal, A, 160Spano, PF, 439Specht, K, 229Spielberger, S, 364Spigolon, G, 463Spillantini, MG, 439Srinivasan, AV, 211Srisailapathy, CRS, 211Srivastav, P, 584Srivastava, AK, 248Srivastava, P, 448, 452Sruti, S, 502Staelens, L, 547Stafford, R, 536Stam, CJ, 148Staniland, J, 292Stanzione, P, 459Stawarz, M, 88Stefani, A, 456, 458Steiner, B, 477Steinschneider, R, 481Stephan, MA, 41Stepien, A, 501Stewart, CA, 322Stewart, DJ, 322Stieglitz, L, 357Stocchi, F, 278Stoessl, AJ, 200Stoffers, D, 148Strongosky, AJ, 111, 113, 207, 372Suarez, MD, 373Subasic, N, 424Subhani, A, 307Subhani, F, 307Subirana-Mirete, J, 136Suchkova, I, 226Sugeno, N, 438Suh, M, 291Suhy, J, 201Suljic, E, 424Sun, F, 466Sun, L, 8, 50, 72, 73, 117, 267, 428Sun, Q, 526Sundal, C, 168Sunwoo, MK, 97Suoh, S, 268, 269Surath, M, 345Suresh kumar, S, 230, 235, 249Surini Demiri, M, 239Surolia, A, 550Sürücü, O, 343Sushkova, O, 127, 127Suzuki, M, 438Svetel, M, 116, 378Swanson, B, 577Swartz, J, 254Sweeney, P, 193Szejko, N, 419Szlufik, S, 10, 106, 108

TTaba, P, 31, 138, 150, 238Tachibana, H, 172Tacik, P, 111, 113Tada, S, 564Tagliati, M, 46Taguchi, K, 539Tajiri, Y, 140, 152Takano, D, 326Takeda, A, 438Talanov, SA, 460Tallandier, M, 481Tamarit, L, 349Tambasco, N, 3Tamme, E, 150Tan, EL, 165Tan, LCS, 180, 182Tan, S, 28Tan, X, 120Tan, Y, 513Tanaka, K, 152Tarantino, P, 212Targa, A, 430, 431, 508, 509, 510, 556Tarkovskaya, L, 411Tasçilar, NF, 64Tatebe, H, 539Tateno, H, 457Tattersall, D, 482Taub, E, 368Tavares, F, 197Tawil, B, 213Taymans, JM, 555Teixeira, AL, 130Teixeira, LA, 288Terrier, P, 282Terzian, PR, 350Tesei, S, 212Tesi, A, 319Thakur, P, 511Thaler, A, 189Theiss, C, 559Theuns, J, 208, 233Thomas, AJ, 156Thompson, A, 578Thomson, A, 292Tikhomirova, M, 13Ting, S, 300Tison, F, 103Titova, N, 40Todorova, A, 61Tokuda, T, 539Tokunaga, T, 172Tolboom, SK, 483Tolosa, E, 128, 142, 212Tomasiuk, R, 10Tomic, S, 135Tomskiy, A, 355Tondiy, O, 274Toni, I, 189Torgan, T, 122Torii, Y, 154, 549Torrão, L, 451Torsney, KM, 110Torti, M, 278Touaiti, H, 407Touati, N, 403Touré, K, 22, 24, 385, 401Towne, A, 280Tran, GT, 229Traykov, L, 48, 107Traynor, S, 207Tremblay, L, 270Trend, P, 300Trenell, M, 81, 279Tres, ES, 149Trevisiol, E, 194Trezzi, I, 231Tripathi, DR, 583Triviño, JM, 27Trost, M, 146, 365Tsetlin, V, 485Tsuboi, R, 362, 367Tsuji, M, 120

Tsujii, T, 258Tsujikawa, K, 191Tsuneya, I, 111Tuazon, J, 61Tubashova, IA, 470Tucker, S, 514Tuominen, RK, 430Turbina, L, 91Turck, N, 239Turki, EMNA, 380Turki, I, 370, 403, 407Turla, M, 323Turton, J, 80Turuspekova, S, 333Twisk, JWR, 148Tzarouchi, LC, 176Tzoulis, C, 229

UUccellini, D, 323Uchiyama, T, 457Ueffing, M, 553Ugrinowitsch, C, 86Ugrumov, M, 127, 485Ulla, M, 164Ulrich, H, 474Umeda, K, 154, 549Umemura, A, 362Undela, K, 20University, Newcastle, 285, 285Unti, E, 203Upadhyaya, KC, 215Upon Tyne, Newcastle, 285, 285Ushakova, NA, 504Usmanova, D, 387

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168

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WWada, I, 362, 367Wada, K, 140Wada-Isoe, K, 152Wade, D, 300Waldvogel, D, 52Walitza, S, HT2-1Walker, HC, 351Walker, L, 77, 156Walker, R, 81, 82, 84, 279, 285Wan, YING, 37Wang, D, 551Wang, F, 50, 68, 76, 117, 158, 169, 170, 171, 267,

428, 513, 526Wang, JY, 28, 212, 225, 565Wang, JZ, 566Wang, K, 247Wang, P, 120Wang, W, 577Wang, X, 72, 73, 206, 267, 575Wang, Y, 83, 540Wang, Z, 492Wardas, J, 490Watanabe, Y, 539Waucquier, NW, 209Waugh, J, 429Wauters, E, 233Wei, L, 247Wei, Q, 232, 234Wei, Y, 37Weickert, CS, 570Weintraub, D, HT2-3Weis, L, 183, 236, 295Weiskopf, N, 175Welter, ML, 360

Werner, B, 343, 344Werry, E, 570Werth, E, 69Wesolowska-Waliszewska, J, 501White, R, 279Wider, C, 228, 244Wieler, M, 44, 174Wijnands, T, 506Williams, H, 337Williams, P, 300Winkler, C, 478Winter, C, 477Wissemann, W, 240Withanage, A, 306Wojciechowski, K, 88Wolf, E, 364Wolfgang, W, 240Wright, LC, 451, 572, 573, 574Wszolek, Z, 168Wszolek, ZK, 111, 113, 207, 228, 372Wu, B, 225Wu, F, 526Wu, J, 37Wüllner, U, 216, 425

XXia, K, 551Xifaras, M, 376Xu, 263, 264Xu, F, 225Xu, N, 212

YYadav, RS, 30, 137, 161, 185, 448,

452, HT1-4Yadav, Ravi, 259Yakhno, NN, 115Yakimovskii, A, 226Yalon, YL, 315Yamakawa, M, 152Yamamoto, M, 141, 336Yamamoto, T, 457Yamanishi, T, 457Yamasaki, S, 140Yamazaki, T, 326Yang, C, 563Yang, HW, 188Yang, J, 218Yang, KY, 513Yang, X, 212, 466Yao, N, 173, 513Yarrow, A, 223Yasui, K, 191Ybot Gorrín, I, 404Ye, MIN, 219Yegin, A, 317Yelnik, J, 360, 364Yeo, LL, 429Yildiz, O, 352Yokoi, S, 191Yokoyama, T, 139Yonga, P, 35Yoo, K, 190Yoon, HJ, HT3-1Yoon, J, 85, 383Yoshida, K, 336Yoshida, M, 154, 549Yoshitake, T, 463You, H, 538

You, S, 190Youn, JY, 188, 291, 341Yu, SY, 50, 68, 72, 73, 76, 117, 158, 169, 170, 171,

267, 428Yun, HJ, HT3-1Yun, SC, HT3-1

ZZabberoni, S, 297Zabetian, C, 240Zacharia, A, 358, 359Zadikoff, C, 33Zagury, S, 329Zainal, H, 180Zakaria, H, 165Zaljalova, Z, 127Zalyalova, ZA, 17, 420Zandi, S, 391Zanigni, S, 237Zanin, M, 444Zanon, A, 237Zappia, M, 236Zarbiv, Y, 544Zarowitz, B, 33Zaslawski, C, 129Zavalko, I, 504Zavalna, O, 274Zeidan, N, 197Zeligowska, E, 281Zeng, X, 466Zerhouni, A, 70Zhang, A, 180Zhang, BR, 205, 467Zhang, M, 482, 553Zhang, P, 265Zhang, W, 50, 68, 72, 73, 76, 117, 158, 169, 170,

171, 267, 428Zhang, X, 267, 538, 565Zhang, Y, 513Zhang, Z, 551Zhao, B, 218, 232, 234Zhao, P, 205Zhao, Y, 462Zheldybaeva, Z, 333Zheng, L, 221Zheng, T, 467Zheng, XY, 427Zhou, H, 182Zhou, LL, 565Zhou, M, 37Zhou, Y, 482Zhu, JH, 538, 565Zhu, JJ, 565Zhu, LQ, 266, 566Zhukova, I, 79Zhukova, N, 79Zibetti, M, 164, 194Zikou, A, 176Zimmerli, L, 52Zimmermann, R, 121, 368Zoladz, J, 281Zonta, F, 217Zotta, M, 194Zou, M, 565Zrinzo, L, 358, 359Zubaidah, A, 480Zuo, LJ, 50, 68, 72, 73, 76, 117, 158, 169, 170, 171,

267, 428Zuo, X, 247Zupancic Kriznar, N, 365


Effect of genistein on the climbing ability of Parkinson disease model flies

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