Morphological Characteristics of Brain Tumors Causing Seizures

Morphological Characteristics of Brain Tumors CausingSeizures

Jong Woo Lee MD PhD Patrick Y Wen MD Shelley Hurwitz PhD Peter Black MD PhDSantosh Kesari MD PhD Jan Drappatz MD PhD Alexandra J Golby MD PhD William MWells III PhD Simon K Warfield PhD Ron Kikinis PhD and Edward B Bromfield MDdaggerDepartments of Neurology (Drs Lee Wen Kesari Drappatz and Bromfield) Biostatistics (DrHurwitz) Neurosurgery (Drs Black and Golby) and Radiology (Drs Wells and Kikinis) Brighamand Womenrsquos Hospital and Department of Radiology Childrenrsquos Hospital of Boston (Dr Warfield)Harvard Medical School Boston Massachusetts and Moores Cancer Center Department ofNeurosciences University of California San Diego La Jolla (Dr Kesari)

AbstractObjectivemdashTo quantify size and localization differences between tumors presenting withseizures vs nonseizure neurological symptoms

DesignmdashRetrospective imaging survey We performed magnetic resonance imagingndashbasedmorphometric analysis and nonparametric mapping in patients with brain tumors

SettingmdashUniversity-affiliated teaching hospital

Patients or Other ParticipantsmdashOne hundred twenty-four patients with newly diagnosedsupratentorial glial tumors

Main Outcome MeasuresmdashVolumetric and mapping methods were used to evaluatedifferences in size and location of the tumors in patients who presented with seizures as comparedwith patients who presented with other symptoms

ResultsmdashIn high-grade gliomas tumors presenting with seizures were smaller than tumorspresenting with other neurological symptoms whereas in low-grade gliomas tumors presentingwith seizures were larger Tumor location maps revealed that in high-grade gliomas deep-seatedtumors in the pericallosal regions were more likely to present with nonseizure neurologicalsymptoms In low-grade gliomas tumors of the temporal lobe as well as the insular region weremore likely to present with seizures

ConclusionsmdashThe influence of size and location of the tumors on their propensity to causeseizures varies with the grade of the tumor In high-grade gliomas rapidly growing tumorsparticularly those situated in deeper structures present with nonndashseizure-related symptoms Inlow-grade gliomas lesions in the temporal lobe or the insula grow large without other symptoms

copy2010 American Medical Association All rights reservedCorrespondence Jong Woo Lee MD PhD Department of Neurology Brigham and Womenrsquos Hospital Boston MA 02115(jlee38partnersorg)Author Contributions Study concept and design Lee Warfield and Bromfield Acquisition of data Lee Wen Black KesariDrappatz Golby Wells Warfield Kikinis and Bromfield Analysis and interpretation of data Lee Wen Hurwitz Golby andBromfield Drafting of the manuscript Lee Golby and Bromfield Critical revision of the manuscript for important intellectualcontent Lee Wen Hurwitz Black Kesari Drappatz Golby Wells Warfield and Kikinis Statistical analysis Lee Hurwitz GolbyWells and Bromfield Obtained funding Lee Warfield and Bromfield Administrative technical and material support Lee WenBlack Drappatz Golby Warfield and Bromfield Study supervision Black Kesari Golby Wells Warfield Kikinis and BromfielddaggerDeceasedFinancial Disclosure None reported

NIH Public AccessAuthor ManuscriptArch Neurol Author manuscript available in PMC 2010 December 1

Published in final edited form asArch Neurol 2010 March 67(3) 336ndash342 doi101001archneurol20102

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-PA Author Manuscript

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and eventually cause seizures Quantitative image analysis allows for the mapping of regions ineach group that are more or less susceptible to seizures

Seizures are encountered in a majority of patients with primary brain tumors and are a majorcause of morbidity in these patients12 Thirty percent to 50 of patients experience aseizure by the time their tumors are diagnosed and an additional 6 to 45 of patients whodo not initially present with seizures eventually develop them3-5 Characteristics of braintumors and their mechanism in causing seizures in patients are incompletely understood46Low-grade well-differentiated gliomas16-9 cortically located tumors310-14 and location inthe temporalfrontal and motorsensory cortices6815-17 are more frequently associated withseizures

Although there is a high incidence of seizures in these patients treatment strategies remainpoorly defined Prophylactic anticonvulsant therapy shown to be ineffective in preventingseizures in patients with brain tumors in multiple large-scale studies1218-20 is notrecommended by the American Academy of Neurology5 None-theless prophylaxis remainsa wide-spread practice21 because of difficulty in determining which patients are at greatestrisk for seizures Determination of morphometric factors influencing seizures would help inidentifying patients at greatest risk for early targeted treatment and prevent potentiallytoxic unnecessary treatment in patients at minimal risk

Although studies examining brain tumors in relationship to epilepsy have localized tumorsto a particular lobe10 few studies have performed quantitative volumetric or spatial mappinganalysis of tumors in relation to their epileptogenic potential Regions within a particularlobe are likely to exhibit different epileptogenic potential to tumor invasion and tumorsfrequently affect multiple contiguous lobes6

Modern imaging techniques allow for analysis of lesions over a large group of subjectsthrough registration and mapping techniques In this study we used these techniques toexamine the size and location of primary supratentorial glial brain tumors and characterizedtheir propensity to cause seizures at presentation

METHODSThis retrospective study examined patients who underwent surgical evaluation of a braintumor at the Brigham and Womenrsquos Hospital between January 2005 and September 2007Inclusion criteria were age 18 years or older new diagnosis of brain tumor supratentoriallocation pathologically proven glial tumor and preoperative acquisition of high-qualityvolumetric magnetic resonance imaging (MRI) scan Tumors were designated ldquolow graderdquo(World Health Organization grade I or II) or ldquohigh graderdquo (World Health Organization gradeIII or IV)

A total of 81 patients presented with low-grade gliomas during the study period Of these 24patients were excluded from the analysis because of lack of access to preoperativevolumetric MRI scans (13 patients) unclear clinical history (2 patients) clinical orradiological suspicion of higher-grade lesion than suggested from pathological examination(3 patients) poorly defined lesion (1 patient) suspicion of neuroglial component (1 patient)and inconclusive pathological examination (6 patients)

All 57 patients with low-grade glioma who met the criteria were analyzed Because of theirvastly larger numbers 67 consecutive patients with high-grade gliomas who obtainedidentical MRI sequences between the dates March 24 2005 and May 20 2006 from 317eligible patients during the study period were selected Patient records were reviewed to

Lee et al Page 2

Arch Neurol Author manuscript available in PMC 2010 December 1

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determine the presenting symptom Approval for this study was obtained from the localhuman research institutional review board

IMAGE ACQUISITIONPatients with low-grade tumors underwent preoperative imaging with 1 of several MRIscanners from which T2 and volumetric T1 images were obtained 05-T MRI (SignaSP GEMedical Systems Milwaukee Wisconsin) 15-T General Electric Signa Excite scanner and3-T General Electric Signa scanner Patients with high-grade tumors underwent imagingwith a 15-T General Electric Signa scanner

IMAGE PROCESSINGTumors were manually segmented from the MRI by a blinded rater using standard imageprocessing software to create a lesion mask (3D Slicer wwwslicerorg and MNI Displaywww bicmnimcgillca) For low-grade tumors T2-weighted images were resampled andregistered into T1-weighted space the tumor margin was determined by the extent of T2signal abnormality2223 For high-grade gliomas tumor margin was delineated by the area ofcontrast enhancement on the volumetric T1-weighted image24

Magnetic resonance images were transformed into a standardized coordinate space based onthe Talairach atlas25 to account for differences in brain orientation and differences inintracranial volume Automatic registration using linear affine transformation wasperformed from the T1-weighted images26 Because distortions of the anatomy caused theregistration procedure to fail at times registration validity was checked by selecting 6 pointson both the template and the target brains (maximal anterior and posterior cortical extentalong the anterior-posterior commissure line upper and lower extent along the perpendicularline through the anterior commissure left and right extent along the third axis formed by the2 previous lines) if the root mean square was greater than 5 mm registration wasreperformed using the manually selected coordinates (MNI Registerwwwbicmnimcgillca) Tumor volumes were calculated after registration (MATLABMathWorks Natick Massachusetts)

STATISTICAL ANALYSESLogistic regression was used to estimate odds ratios and 95 confidence intervals forpatient characteristics SAS version 91 was used (SAS Institute Cary North Carolina) Toassess the localizing value of the tumors causing seizures a χ2 statistic map was calculatedAt each voxel the group of patients presenting with a tumor at that voxel was determinedFrom this group the number of patients who presented with seizures as compared with theexpected number (the product of the number of patients with a tumor at that voxel and theratio of the patients presenting with seizures in the study population) was used to calculatethe χ2 statistic In voxels where the number of patients with seizures exceeded the number ofpatients without seizures a higher value of χ2 is indicative of a stronger likelihood thatpatients with a tumor at that location would present with seizures than at other locations Acomplementary χ2 map was calculated to determine ldquoprotectiverdquo locations eg wherepresentation with seizures is less likely

To assess the significance of the χ2 statistic a nonparametric mapping method based onpermutation testing was used27 which requires making minimal assumptions regarding ourdata The χ2 was used as an omnibus statistic The χ2 map was masked to include onlyvoxels that exceeded the suprathreshold level of 2 These were grouped into discrete clustersusing a 6-connectivity model and a cluster mass was calculated28 Thereafter the labelingof each patient as ldquoseizurerdquo vs ldquono seizurerdquo was randomly reassigned with the constraint ofpreserving the original ratio of the number of patients with ldquoseizurerdquo and ldquono seizurerdquo From

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the relabeled group a χ2 map and clusters were again calculated and the largest cluster massrecorded This was repeated 5000 times to obtain a null hypothesis distribution of maximalcluster sizes2829 Clusters of the original image whose masses exceeded significance of Plt05 were used to calculate a P value map Analysis was performed using MATLAB version76 (R2008a)

RESULTSPATIENT POPULATION

One hundred twenty-four patients were included in this study Their main clinical andpathological characteristics are listed in Table 1 odds ratios regarding these characteristicsare listed in Table 2 Patients with presumed low-grade gliomas not included in the studywere compared with patients who were included Of the 24 patients 15 were male 14 hadleft-sided tumors 7 had temporal tumors and 15 had seizures their average age was 463years (range 18-83 years) The age of the excluded patients was higher than the includedgroup but the other characteristics did not differ significantly

Patients with low-grade tumors were more likely to present with seizures than patients withhigh-grade tumors Age was significantly protective overall (P=02) with a reduction inlikelihood of 23 per decade However subgroup analysis revealed that patients with high-grade tumors were significantly older than those with low-grade tumors

LOBE INVOLVEMENTPatients with tumors involving the temporal lobe were more than twice as likely to presentwith seizures This tendency was significant in low-grade tumors and there was a similar butslightly weaker tendency in patients with high-grade tumors Low-grade tumors in thetemporal lobe were more likely to present with seizures (16 of 20 patients) High-gradetumors in the temporal lobe were neither more nor less likely to present with seizures (14 of29 patients)

VOLUME AND SEIZURESThere was significant qualitative interaction between tumor volume and grade (P=004)Tumor volume was predictive of presenting with seizures in patients with low-grade tumors(P=01) with a 3 increase in likelihood per cubic centimeter (Figure 1) In high-gradetumors there was a slight tendency for tumor volume to be protective in relation to seizurepresentation (P=13)

LOCATION MODELINGThe aggregate of all the tumors generated from the sum of the binary tumor masks is shownfor high-grade (Figure 2A) and low-grade (Figure 2B) gliomas The χ2 maps of high-gradetumors were created indicating where seizures were more likely to occur and where otherneurological symptoms were more likely to occur Cluster analysis revealed 1 cluster thatreached statistical significance (Plt05) to indicate regions where patients were more likelyto present with nonseizure neurological symptoms (Figure 3) The cluster was located in thefrontal pericallosal region and was 704 cm3 in volume No clusters of significant size werefound indicating where seizures were more likely to occur including the temporal region

The χ2 maps of low-grade tumors indicating where seizures were more likely to occur andwhere other neurological symptoms were more likely to occur were created Significantclusters where patients were more likely to present with seizures were found in the righthemisphere (size 565 cm3) and in the left hemisphere (size 704 cm3) (Figure 4A) Clustersin both hemispheres involved the temporal lobe while the right hemisphere cluster included

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the insular region There were no statistically significant clusters to denote regions wherepatients were more likely to present with nonseizure neurological symptoms

Because of concern of uneven spatial distribution of the low-grade tumors between the 2hemispheres cluster analysis was repeated after inverting all right hemispheric tumorsacross the midline to simulate 58 left hemispheric tumors This revealed a single significantcluster of 1156 cm3 that included the insular as well as most of the temporal lobe (Figure4B)

SEIZURE SEMIOLOGYOf the 26 patients with high-grade tumors with seizures 11 patients had generalizedconvulsions 7 had simple partial seizures and 7 had complex partial seizures There wasinsufficient information to determine accurate seizure semiology in 1 patient Of the 35patients with low-grade tumors and seizure presentations 21 had generalized convulsions10 had simple partial seizures and 4 had complex partial seizures No significant differenceswere seen between the 2 groups (P=24)

COMMENTWe examined the effects of glioma size and location on propensity to generate seizures as anearly symptom using quantitative image analysis techniques

SEIZURES AND SIZE OF TUMORIn this study 34 of patients with high-grade tumors and 62 of those with low-gradetumors presented with seizures consistent with the previously reported values1-3830-36

High- and low-grade tumors differ in terms of their relationship between seizure sizelocation and the propensity to present with seizures High-grade tumors presenting withseizures are likely to be smaller than those presenting with other symptoms We postulatethat rapidly growing tumors cause symptoms related to mass effect such as headachecognitive deficits or focal weakness rather than seizures The reverse was found with low-grade tumors where large tumors were more likely to present with seizures than smalltumors We postulate that large tumor size is indicative of the long duration of silent growthallowing more time for seizures to develop

Small low-grade tumors are sometimes found on imaging studies acquired to evaluatenonspecific symptoms that may be unrelated as was the case in 7 patients Whether tumorswere completely incidental or whether they contributed to the presenting symptom isdifficult to determine

LOCATION OF THE TUMORPatients with high-grade tumors in the pericallosal region likely representing so-calledbutterfly gliomas were significantly less likely to present with seizures Such deeply seatedrapidly growing tumors are more likely to cause symptoms due to mass effect rather thanseizures

Patients who presented with high-grade tumors in the temporal lobes were not more likely topresent with seizures than other neurological symptoms However in comparison with therelatively low rates of seizures in deeply seated pericallosal tumors this result indicates arelative increase in the epileptogenicity in this region In contrast patients with low-gradetumors were more likely to present with seizures if their tumors were located in the temporallobe

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Patients with tumors in the insular cortex were also more likely to present with seizures Theinsular cortex is often a region of seizure spread in temporal lobe epilepsy Clinicallyseizures originating from the insular region are difficult to distinguish from those arisingfrom elsewhere in the temporal lobe37 and 10 of patients initially thought to have temporallobe epilepsy may in fact have seizures originating in the insular cortex38 though detailedinvestigation revealed distinct clinical differences3940 In a recent large retrospective reviewof 51 insular grade II gliomas 50 patients presented with seizures and 45 patients hadnormal neurological examination results41 High frequency of preoperative seizures hasbeen reported in other smaller series describing low-grade insular tumors342-45 Theseresults suggest that tumors located in the insular cortex are likely to be clinically silent untilthe patient experiences a seizure

ASYMMETRY OF LOW-GRADE TUMORSAlthough the number of patients with low-grade tumors in the left hemisphere was equal tothe number of right hemisphere tumors and the volumes of the tumors in both hemisphereswere comparable the aggregate tumor image (Figure 2B) revealed that the distribution ofthe tumors was not identical a large number of tumors were located in the right insularregion many of which presented with seizures We are unaware of any studies in theliterature that have systematically examined this asymmetry though similar asymmetrieshave been found in some studies4143

Although volumes of regions of significance were similar over both hemispheres regions ofhighest correlation with seizure presentation were located over the right hemisphere It ispossible that left hemisphere tumors are less likely to present with seizures perhaps becauseof increased presentation with other neurological findings as a result of greater eloquence ofthe dominant hemisphere

LIMITATIONSBecause of the retrospective nature of this study we were unable to control for a number offactors Magnetic resonance imaging scanning parameters were not homogeneous over theduration of this study This is a historical artifact representing the development of imagingtechnology at our institution We minimized the influence of this variability by selectingonly patients who had received volumetric T1-weighted scans to obtain the highest-resolution images available at the time

No regions of significantly increased risk for seizures were found for low-grade tumors inother areas where small tumors are believed to typically cause seizures (motorsensorycortices hippocampus) We also did not find that occipital tumors are unlikely to presentwith seizures These negative findings may be due to a low number of tumors at thoselocations in our study

It is likely that the tumor extends beyond the edge of the enhancing lesion in high-gradegliomas and that T2 signal changes in low-grade gliomas in some areas may represent anedematous process rather than tumor However these methods result in boundaries that areeasily identified and provide reasonable delineation of tumors

The registration procedure in patients with large lesions is challenging46 causing automatedregistration to fail when tumors substantially distort cortical structure We chose to correctthe registration errors manually which decreases interrater reproducibility as compared withautomated techniques such automated registration procedures are not yet well established

We used a clustering algorithm rather than a voxel-based statistic The cluster mass test isknown to have increased sensitivity and specificity compared with tests based on voxel

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intensity when the signal is spatially extended47-49 and as a result these tests are morepowerful than single-threshold approaches but result in reduced localizing power We chosea low primary threshold level (χ2=2) resulting in large clusters emphasizing the high spatialcorrelation between adjacent voxels in our population in doing so we were unable to detectintense focal signals The optimal selection of primary thresholds with permutation labelingremains to be resolved27

Despite these limitations volumetric imaging analysis is useful to localize regions that areparticularly susceptible to seizures as well as define regions that are relatively protectiveagainst seizures Future studies using similar techniques may be used to identify patientswho are at greater and lower risk for seizures prospectively and postoperatively allowingfor early selection of patients for targeted antiepileptic drug therapy

AcknowledgmentsFundingSupport This study was supported by funding from the National Epifellows Foundation (Dr Lee) grantU41 RR019703 from the National Center for Image-Guided Therapy and grants 5P01CA067165-11 andP41RR13218 from the National Institutes of Health

REFERENCES1 Hildebrand J Lecaille C Perennes J Delattre JY Epileptic seizures during follow-up of patients

treated for primary brain tumors Neurology 200565(2)212ndash215 [PubMed 16043788]2 Moots PL Maciunas RJ Eisert DR Parker RA Laporte K Abou-Khalil B The course of seizure

disorders in patients with malignant gliomas Arch Neurol 199552(7)717ndash724 [PubMed7619029]

3 Chang EF Potts MB Keles GE et al Seizure characteristics and control following resection in 332patients with low-grade gliomas J Neurosurg 2008108(2)227ndash235 [PubMed 18240916]

4 van Breemen MS Wilms EB Vecht CJ Epilepsy in patients with brain tumours epidemiologymechanisms and management Lancet Neurol 20076(5)421ndash430 [PubMed 17434097]

5 Glantz MJ Cole BF Forsyth PA et al Report of the Quality Standards Subcommittee of theAmerican Academy of Neurology Practice parameter anticonvulsant prophylaxis in patients withnewly diagnosed brain tumors Neurology 200054(10)1886ndash1893 [PubMed 10822423]

6 Liigant A Haldre S Oun A et al Seizure disorders in patients with brain tumors Eur Neurol200145(1)46ndash51 [PubMed 11150841]

7 Vertosick FT Jr Selker RG Arena VC Survival of patients with well-differentiated astrocytomadiagnosed in the era of computed tomography Neurosurgery 199128(4)496ndash501 [PubMed1851971]

8 Lynam LM Lyons MK Drazkowski JF et al Frequency of seizures in patients with newlydiagnosed brain tumors a retrospective review Clin Neurol Neurosurg 2007109(7)634ndash638[PubMed 17601658]

9 Lote K Stenwig AE Skullerud K Hirschberg H Prevalence and prognostic significance of epilepsyin patients with gliomas Eur J Cancer 199834(1)98ndash102 [PubMed 9624245]

10 Fried I Kim JH Spencer DD Limbic and neocortical gliomas associated with intractable seizuresa distinct clinicopathological group Neurosurgery 199434(5)815ndash823 [PubMed 8052378]

11 Bronen RA Fulbright RK Spencer DD Spencer SS Kim JH Lange RC MR characteristics ofneoplasms and vascular malformations associated with epilepsy Magn Reson Imaging199513(8)1153ndash1162 [PubMed 8750330]

12 Glantz MJ Cole BF Friedberg MH et al A randomized blinded placebocontrolled trial ofdivalproex sodium prophylaxis in adults with newly diagnosed brain tumors Neurology199646(4)985ndash991 [PubMed 8780077]

13 Penfield W Erickson TC Tarlov I Relation of intracranial tumors and symptomatic epilepsyArch Neurol Psychiatry 194044(2)300ndash315

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14 Smith DF Hutton JL Sandemann D et al The prognosis of primary intracerebral tumourspresenting with epilepsy the outcome of medical and surgical management J Neurol NeurosurgPsychiatry 199154(10)915ndash920 [PubMed 1744647]

15 Lund M Epilepsy in association with intracranial tumour Acta Psychiatr Neurol Scand Suppl1952811ndash149 [PubMed 14933179]

16 Zaatreh MM Spencer DD Thompson JL et al Frontal lobe tumoral epilepsy clinicalneurophysiologic features and predictors of surgical outcome Epilepsia 200243(7)727ndash733[PubMed 12102675]

17 Zaatreh MM Firlik KS Spencer DD Spencer SS Temporal lobe tumoral epilepsy characteristicsand predictors of surgical outcome Neurology 200361(5)636ndash641 [PubMed 12963754]

18 Forsyth PA Weaver S Fulton D et al Prophylactic anticonvulsants in patients with brain tumourCan J Neurol Sci 200330(2)106ndash112 [PubMed 12774949]

19 Franceschetti S Binelli S Casazza M et al Influence of surgery and antiepileptic drugs onseizures symptomatic of cerebral tumours Acta Neurochir (Wien) 1990103(1-2)47ndash51[PubMed 2360466]

20 North JB Penhall RK Hanieh A Frewin DB Taylor WB Phenytoin and postoperative epilepsy adouble-blind study J Neurosurg 198358(5)672ndash677 [PubMed 6339686]

21 Siomin V Angelov L Li L Vogelbaum MA Results of a survey of neurosurgical practice patternsregarding the prophylactic use of anti-epilepsy drugs in patients with brain tumors J Neurooncol200574(2)211ndash215 [PubMed 16193395]

22 Talos IF Zou KH Ohno-Machado L et al Supratentorial low-grade glioma resectabilitystatistical predictive analysis based on anatomic MR features and tumor characteristics Radiology2006239(2)506ndash513 [PubMed 16641355]

23 Nimsky C Fujita A Ganslandt O Von Keller B Fahlbusch R Volumetric assessment of gliomaremoval by intraoperative high-field magnetic resonance imaging Neurosurgery 200455(2)358ndash370 discussion 370-371 [PubMed 15271242]

24 Lacroix M Abi-Said D Fourney DR et al A multivariate analysis of 416 patients withglioblastoma multiforme prognosis extent of resection and survival J Neurosurg 200195(2)190ndash198 [PubMed 11780887]

25 Talairach J Tournoux P Co-planar Stereotaxic Atlas of the Human Brain 3-DimensionalProportional System An Approach to Cerebral Imaging Thieme Stuttgart German 1988

26 Collins DL Neelin P Peters TM Evans AC Automatic 3D intersubject registration of MRvolumetric data in standardized Talairach space J Comput Assist Tomogr 199418(2)192ndash205[PubMed 8126267]

27 Nichols TE Holmes AP Nonparametric permutation tests for functional neuroimaging a primerwith examples Hum Brain Mapp 200215(1)1ndash25 [PubMed 11747097]

28 Bullmore ET Suckling J Overmeyer S Rabe-Hesketh S Taylor E Brammer MJ Global voxeland cluster tests by theory and permutation for a difference between two groups of structural MRimages of the brain IEEE Trans Med Imaging 199918(1)32ndash42 [PubMed 10193695]

29 Manly BJF Randomization and Monte Carlo Methods in Biology Chapman and Hall LondonEngland 1991

30 Ulutin C Fayda M Aksu G et al Primary glioblastoma multiforme in younger patients a single-institution experience Tumori 200692(5)407ndash411 [PubMed 17168433]

31 Salmaggi A Silvani A Merli R et al Multicentre prospective collection of newly diagnosedglioblastoma patients update on the Lombardia experience Neurol Sci 200829(2)77ndash83[PubMed 18483704]

32 Hwang SL Lin CL Lee KS et al Factors influencing seizures in adult patients with supratentorialastrocytic tumors Acta Neurochir (Wien) 2004146(6)589ndash594 discussion 594 [PubMed15168227]

33 Walker MD Alexander E Jr Hunt WE et al Evaluation of BCNU andor radiotherapy in thetreatment of anaplastic gliomas a cooperative clinical trial J Neurosurg 197849(3)333ndash343[PubMed 355604]

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34 Lebrun C Fontaine D Bourg V et al Treatment of newly diagnosed symptomatic pure low-gradeoligodendrogliomas with PCV chemotherapy Eur J Neurol 200714(4)391ndash398 [PubMed17388986]

35 Lebrun C Fontaine D Ramaioli A et al Nice Brain Tumor Study Group Long-term outcome ofoligodendrogliomas Neurology 200462(10)1783ndash1787 [PubMed 15159478]

36 Grabenbauer GG Roedel CM Paulus W et al Supratentorial low-grade glioma results andprognostic factors following postoperative radiotherapy Strahlenther Onkol 2000176(6)259ndash264[PubMed 10897252]

37 Penfield W Faulk ME Jr The insula further observations on its function Brain 195578(4)445ndash470 [PubMed 13293263]

38 Isnard J Guenot M Ostrowsky K Sindou M Mauguiere F The role of the insular cortex intemporal lobe epilepsy Ann Neurol 200048(4)614ndash623 [PubMed 11026445]

39 Isnard J Guenot M Sindou M Mauguiere F Clinical manifestations of insular lobe seizures astereo-electroencephalographic study Epilepsia 200445(9)1079ndash1090 [PubMed 15329073]

40 Rossetti AO Mortati KA Black PM Bromfield EB Simple partial seizures with hemisensoryphenomena and dysgeusia an insular pattern Epilepsia 200546(4)590ndash591 [PubMed15816958]

41 Duffau H A personal consecutive series of surgically treated 51 cases of insular WHO grade IIglioma advances and limitations J Neurosurg 2009110(4)696ndash708 [PubMed 19133753]

42 Moshel YA Marcus JD Parker EC Kelly PJ Resection of insular gliomas the importance oflenticulostriate artery position J Neurosurg 2008109(5)825ndash834 [PubMed 18976071]

43 Zentner J Meyer B Stangl A Schramm J Intrinsic tumors of the insula a prospective surgicalstudy of 30 patients J Neurosurg 199685(2)263ndash271 [PubMed 8755755]

44 Neuloh G Pechstein U Schramm J Motor tract monitoring during insular glioma surgery JNeurosurg 2007106(4)582ndash592 [PubMed 17432707]

45 Shankar A Rajshekhar V Radiological and clinical outcome following stereotactic biopsy andradiotherapy for low-grade insular astrocytomas Neurol India 200351(4)503ndash506 [PubMed14742933]

46 Crinion J Ashburner J Leff A Brett M Price C Friston K Spatial normalization of lesionedbrains performance evaluation and impact on fMRI analyses Neuroimage 200737(3)866ndash875[PubMed 17616402]

47 Friston KJ Holmes A Poline JB Price CJ Frith CD Detecting activations in PET and fMRIlevels of inference and power Neuroimage 19964(3 pt 1)223ndash235 [PubMed 9345513]

48 Hayasaka S Nichols TE Validating cluster size inference random field and permutation methodsNeuroimage 200320(4)2343ndash2356 [PubMed 14683734]

49 Poline JB Worsley KJ Evans AC Friston KJ Combining spatial extent and peak intensity to testfor activations in functional imaging Neuroimage 19975(2)83ndash96 [PubMed 9345540]

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Figure 1Tumor volume and grade

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Figure 2Summed statistic image At each voxel the number of patients presenting with tumors iscalculated A High-grade tumors B Low-grade tumors

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Figure 3High-grade tumors χ2 map A χ2 value was calculated at each voxel from the expectednumber and the observed number of tumors at that voxel Region of statistical significance(Plt05) where nonseizure neurological symptoms are more likely was calculated byclustering analysis

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Figure 4Low-grade tumors χ2 map A Region of significance where seizures are more likely BAnalysis repeated after inverting all right temporal tumors to the left hemisphere

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Table 1Patient Demographics

No of Patients

Seizure(n = 61)

No Seizure(n = 63)

High grade 26 41

Low grade 35 22

Histology

Glioblastoma 16 33

Astrocytoma 14 9

Oligodendroglioma 15 13

Oligoastrocytoma (mixed) 16 8

Age y median (range) 42 (18-88) 50 (18-88)

High grade 55 (26-88) 57 (21-88)

Low grade 38 (18-56) 38 (18-64)

Sex MF 3328 2835

High grade 1610 2318

Low grade 1718 517

Hemisphere LR 3229 3724

High grade 1511 2514 (2 midline)

Low grade 1718 1210

Temporal 31 18

Extratemporal 30 45

High grade temporal 15 14

High grade extratemporal 11 27

Low grade temporal 16 4

Low grade extratemporal 19 18

Location corticalnoncortical 512 4019

High grade 221 2118

Low grade 291 191

Hippocampal location 8 4

High grade 3 2

Low grade 5 2

Tumor volume cm3 median 347 397

High grade 30 467

Low grade 378 144

High-grade glioma left 237 467

High-grade glioma right 347 457

Low-grade glioma left 484 151

Low-grade glioma right 34 135


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Table 2Odds Ratios and 95 Confidence Intervals for Patient and Tumor Characteristics toPredict Presentation With Seizures

No ()

Variable No Seizure(n=63)a

Seizure(n=61)a

Odds Ratio (95Confidence

Interval)

PValue

Grade 01

Low 22 (35) 35 (57) 251 (122-519)

High 41 (65) 26 (43) 040 (019-082)

Age per decade y median (range)

Overall 50 (18-88) 42 (18-88) 077 (061-096) 02

Low grade 38 (18-64) 38 (18-56) 100 (060-166) 99

High grade 57 (21-88) 55 (26-88) 080 (059-110) 17

Tumor volume median (range) per 10 cm3a

Overall 41 (10-166) 35 (03-205) 105 (096-115) 31

Low grade 14 (10-87) 38 (03-205) 131 (106-160) 01

High grade 47 (26-167) 30 (20-143) 088 (074-104) 13

Male

Overall 28 (44) 33 (54) 147 (073-299) 28

Low grade 5 (23) 17 (49) 321 (097-1063) 06

High grade 23 (56) 16 (62) 125 (046-341) 66

Temporal

Overall 18 (29) 31 (51) 258 (123-543) 01

Low grade 4 (18) 16 (46) 379 (106-1351) 04

High grade 14 (34) 15 (58) 263 (096-723) 06

Hippocampal

Overall 4 (64) 8 (131) 223 (063-782) 21

Low grade 2 (91) 5 (143) 167 (029-944) 56

High grade 2 (49) 3 (115) 254 (040-1637) 32

Corticalb

Overall 40 (63) 51 (84) 293 (125-686) 01

Low grade 19 (86) 29 (83) 076 (017-343) 72

High grade 21 (51) 22 (85) 524 (153-1791) 01

Left hemisphere

Overall 37 (59) 32 (52) 078 (038-158) 48

Low grade 12 (55) 17 (49) 079 (027-229) 66

High grade 25 (61) 15 (58) 087 (032-237) 79

aInteraction with grade P=004

bInteraction with grade P=05


and eventually cause seizures Quantitative image analysis allows for the mapping of regions ineach group that are more or less susceptible to seizures

Seizures are encountered in a majority of patients with primary brain tumors and are a majorcause of morbidity in these patients12 Thirty percent to 50 of patients experience aseizure by the time their tumors are diagnosed and an additional 6 to 45 of patients whodo not initially present with seizures eventually develop them3-5 Characteristics of braintumors and their mechanism in causing seizures in patients are incompletely understood46Low-grade well-differentiated gliomas16-9 cortically located tumors310-14 and location inthe temporalfrontal and motorsensory cortices6815-17 are more frequently associated withseizures

Although there is a high incidence of seizures in these patients treatment strategies remainpoorly defined Prophylactic anticonvulsant therapy shown to be ineffective in preventingseizures in patients with brain tumors in multiple large-scale studies1218-20 is notrecommended by the American Academy of Neurology5 None-theless prophylaxis remainsa wide-spread practice21 because of difficulty in determining which patients are at greatestrisk for seizures Determination of morphometric factors influencing seizures would help inidentifying patients at greatest risk for early targeted treatment and prevent potentiallytoxic unnecessary treatment in patients at minimal risk

Although studies examining brain tumors in relationship to epilepsy have localized tumorsto a particular lobe10 few studies have performed quantitative volumetric or spatial mappinganalysis of tumors in relation to their epileptogenic potential Regions within a particularlobe are likely to exhibit different epileptogenic potential to tumor invasion and tumorsfrequently affect multiple contiguous lobes6

Modern imaging techniques allow for analysis of lesions over a large group of subjectsthrough registration and mapping techniques In this study we used these techniques toexamine the size and location of primary supratentorial glial brain tumors and characterizedtheir propensity to cause seizures at presentation

METHODSThis retrospective study examined patients who underwent surgical evaluation of a braintumor at the Brigham and Womenrsquos Hospital between January 2005 and September 2007Inclusion criteria were age 18 years or older new diagnosis of brain tumor supratentoriallocation pathologically proven glial tumor and preoperative acquisition of high-qualityvolumetric magnetic resonance imaging (MRI) scan Tumors were designated ldquolow graderdquo(World Health Organization grade I or II) or ldquohigh graderdquo (World Health Organization gradeIII or IV)

A total of 81 patients presented with low-grade gliomas during the study period Of these 24patients were excluded from the analysis because of lack of access to preoperativevolumetric MRI scans (13 patients) unclear clinical history (2 patients) clinical orradiological suspicion of higher-grade lesion than suggested from pathological examination(3 patients) poorly defined lesion (1 patient) suspicion of neuroglial component (1 patient)and inconclusive pathological examination (6 patients)

All 57 patients with low-grade glioma who met the criteria were analyzed Because of theirvastly larger numbers 67 consecutive patients with high-grade gliomas who obtainedidentical MRI sequences between the dates March 24 2005 and May 20 2006 from 317eligible patients during the study period were selected Patient records were reviewed to

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No of Patients

Seizure(n = 61)

No Seizure(n = 63)

High grade 26 41

Low grade 35 22

Histology

Glioblastoma 16 33

Astrocytoma 14 9




High grade 55 (26-88) 57 (21-88)

Low grade 38 (18-56) 38 (18-64)

Sex MF 3328 2835


Low grade 1718 517



Low grade 1718 1210

Temporal 31 18

Extratemporal 30 45






High grade 221 2118

Low grade 291 191


High grade 3 2

Low grade 5 2


High grade 30 467

Low grade 378 144






NIH


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Lee et al Page 15


No ()


Seizure(n=61)a


Interval)

PValue

Grade 01

Low 22 (35) 35 (57) 251 (122-519)

High 41 (65) 26 (43) 040 (019-082)


Overall 50 (18-88) 42 (18-88) 077 (061-096) 02

Low grade 38 (18-64) 38 (18-56) 100 (060-166) 99

High grade 57 (21-88) 55 (26-88) 080 (059-110) 17


Overall 41 (10-166) 35 (03-205) 105 (096-115) 31

Low grade 14 (10-87) 38 (03-205) 131 (106-160) 01

High grade 47 (26-167) 30 (20-143) 088 (074-104) 13

Male

Overall 28 (44) 33 (54) 147 (073-299) 28

Low grade 5 (23) 17 (49) 321 (097-1063) 06

High grade 23 (56) 16 (62) 125 (046-341) 66

Temporal

Overall 18 (29) 31 (51) 258 (123-543) 01

Low grade 4 (18) 16 (46) 379 (106-1351) 04

High grade 14 (34) 15 (58) 263 (096-723) 06

Hippocampal

Overall 4 (64) 8 (131) 223 (063-782) 21

Low grade 2 (91) 5 (143) 167 (029-944) 56

High grade 2 (49) 3 (115) 254 (040-1637) 32

Corticalb

Overall 40 (63) 51 (84) 293 (125-686) 01

Low grade 19 (86) 29 (83) 076 (017-343) 72

High grade 21 (51) 22 (85) 524 (153-1791) 01

Left hemisphere

Overall 37 (59) 32 (52) 078 (038-158) 48

Low grade 12 (55) 17 (49) 079 (027-229) 66

High grade 25 (61) 15 (58) 087 (032-237) 79










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No of Patients

Seizure(n = 61)

No Seizure(n = 63)

High grade 26 41

Low grade 35 22

Histology

Glioblastoma 16 33

Astrocytoma 14 9




High grade 55 (26-88) 57 (21-88)

Low grade 38 (18-56) 38 (18-64)

Sex MF 3328 2835


Low grade 1718 517



Low grade 1718 1210

Temporal 31 18

Extratemporal 30 45






High grade 221 2118

Low grade 291 191


High grade 3 2

Low grade 5 2


High grade 30 467

Low grade 378 144






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Lee et al Page 15


No ()


Seizure(n=61)a


Interval)

PValue

Grade 01

Low 22 (35) 35 (57) 251 (122-519)

High 41 (65) 26 (43) 040 (019-082)


Overall 50 (18-88) 42 (18-88) 077 (061-096) 02

Low grade 38 (18-64) 38 (18-56) 100 (060-166) 99

High grade 57 (21-88) 55 (26-88) 080 (059-110) 17


Overall 41 (10-166) 35 (03-205) 105 (096-115) 31

Low grade 14 (10-87) 38 (03-205) 131 (106-160) 01

High grade 47 (26-167) 30 (20-143) 088 (074-104) 13

Male

Overall 28 (44) 33 (54) 147 (073-299) 28

Low grade 5 (23) 17 (49) 321 (097-1063) 06

High grade 23 (56) 16 (62) 125 (046-341) 66

Temporal

Overall 18 (29) 31 (51) 258 (123-543) 01

Low grade 4 (18) 16 (46) 379 (106-1351) 04

High grade 14 (34) 15 (58) 263 (096-723) 06

Hippocampal

Overall 4 (64) 8 (131) 223 (063-782) 21

Low grade 2 (91) 5 (143) 167 (029-944) 56

High grade 2 (49) 3 (115) 254 (040-1637) 32

Corticalb

Overall 40 (63) 51 (84) 293 (125-686) 01

Low grade 19 (86) 29 (83) 076 (017-343) 72

High grade 21 (51) 22 (85) 524 (153-1791) 01

Left hemisphere

Overall 37 (59) 32 (52) 078 (038-158) 48

Low grade 12 (55) 17 (49) 079 (027-229) 66

High grade 25 (61) 15 (58) 087 (032-237) 79












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No of Patients

Seizure(n = 61)

No Seizure(n = 63)

High grade 26 41

Low grade 35 22

Histology

Glioblastoma 16 33

Astrocytoma 14 9




High grade 55 (26-88) 57 (21-88)

Low grade 38 (18-56) 38 (18-64)

Sex MF 3328 2835


Low grade 1718 517



Low grade 1718 1210

Temporal 31 18

Extratemporal 30 45






High grade 221 2118

Low grade 291 191


High grade 3 2

Low grade 5 2


High grade 30 467

Low grade 378 144






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Lee et al Page 15


No ()


Seizure(n=61)a


Interval)

PValue

Grade 01

Low 22 (35) 35 (57) 251 (122-519)

High 41 (65) 26 (43) 040 (019-082)


Overall 50 (18-88) 42 (18-88) 077 (061-096) 02

Low grade 38 (18-64) 38 (18-56) 100 (060-166) 99

High grade 57 (21-88) 55 (26-88) 080 (059-110) 17


Overall 41 (10-166) 35 (03-205) 105 (096-115) 31

Low grade 14 (10-87) 38 (03-205) 131 (106-160) 01

High grade 47 (26-167) 30 (20-143) 088 (074-104) 13

Male

Overall 28 (44) 33 (54) 147 (073-299) 28

Low grade 5 (23) 17 (49) 321 (097-1063) 06

High grade 23 (56) 16 (62) 125 (046-341) 66

Temporal

Overall 18 (29) 31 (51) 258 (123-543) 01

Low grade 4 (18) 16 (46) 379 (106-1351) 04

High grade 14 (34) 15 (58) 263 (096-723) 06

Hippocampal

Overall 4 (64) 8 (131) 223 (063-782) 21

Low grade 2 (91) 5 (143) 167 (029-944) 56

High grade 2 (49) 3 (115) 254 (040-1637) 32

Corticalb

Overall 40 (63) 51 (84) 293 (125-686) 01

Low grade 19 (86) 29 (83) 076 (017-343) 72

High grade 21 (51) 22 (85) 524 (153-1791) 01

Left hemisphere

Overall 37 (59) 32 (52) 078 (038-158) 48

Low grade 12 (55) 17 (49) 079 (027-229) 66

High grade 25 (61) 15 (58) 087 (032-237) 79













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No of Patients

Seizure(n = 61)

No Seizure(n = 63)

High grade 26 41

Low grade 35 22

Histology

Glioblastoma 16 33

Astrocytoma 14 9




High grade 55 (26-88) 57 (21-88)

Low grade 38 (18-56) 38 (18-64)

Sex MF 3328 2835


Low grade 1718 517



Low grade 1718 1210

Temporal 31 18

Extratemporal 30 45






High grade 221 2118

Low grade 291 191


High grade 3 2

Low grade 5 2


High grade 30 467

Low grade 378 144






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No ()


Seizure(n=61)a


Interval)

PValue

Grade 01

Low 22 (35) 35 (57) 251 (122-519)

High 41 (65) 26 (43) 040 (019-082)


Overall 50 (18-88) 42 (18-88) 077 (061-096) 02

Low grade 38 (18-64) 38 (18-56) 100 (060-166) 99

High grade 57 (21-88) 55 (26-88) 080 (059-110) 17


Overall 41 (10-166) 35 (03-205) 105 (096-115) 31

Low grade 14 (10-87) 38 (03-205) 131 (106-160) 01

High grade 47 (26-167) 30 (20-143) 088 (074-104) 13

Male

Overall 28 (44) 33 (54) 147 (073-299) 28

Low grade 5 (23) 17 (49) 321 (097-1063) 06

High grade 23 (56) 16 (62) 125 (046-341) 66

Temporal

Overall 18 (29) 31 (51) 258 (123-543) 01

Low grade 4 (18) 16 (46) 379 (106-1351) 04

High grade 14 (34) 15 (58) 263 (096-723) 06

Hippocampal

Overall 4 (64) 8 (131) 223 (063-782) 21

Low grade 2 (91) 5 (143) 167 (029-944) 56

High grade 2 (49) 3 (115) 254 (040-1637) 32

Corticalb

Overall 40 (63) 51 (84) 293 (125-686) 01

Low grade 19 (86) 29 (83) 076 (017-343) 72

High grade 21 (51) 22 (85) 524 (153-1791) 01

Left hemisphere

Overall 37 (59) 32 (52) 078 (038-158) 48

Low grade 12 (55) 17 (49) 079 (027-229) 66

High grade 25 (61) 15 (58) 087 (032-237) 79












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No of Patients

Seizure(n = 61)

No Seizure(n = 63)

High grade 26 41

Low grade 35 22

Histology

Glioblastoma 16 33

Astrocytoma 14 9




High grade 55 (26-88) 57 (21-88)

Low grade 38 (18-56) 38 (18-64)

Sex MF 3328 2835


Low grade 1718 517



Low grade 1718 1210

Temporal 31 18

Extratemporal 30 45






High grade 221 2118

Low grade 291 191


High grade 3 2

Low grade 5 2


High grade 30 467

Low grade 378 144






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No ()


Seizure(n=61)a


Interval)

PValue

Grade 01

Low 22 (35) 35 (57) 251 (122-519)

High 41 (65) 26 (43) 040 (019-082)


Overall 50 (18-88) 42 (18-88) 077 (061-096) 02

Low grade 38 (18-64) 38 (18-56) 100 (060-166) 99

High grade 57 (21-88) 55 (26-88) 080 (059-110) 17


Overall 41 (10-166) 35 (03-205) 105 (096-115) 31

Low grade 14 (10-87) 38 (03-205) 131 (106-160) 01

High grade 47 (26-167) 30 (20-143) 088 (074-104) 13

Male

Overall 28 (44) 33 (54) 147 (073-299) 28

Low grade 5 (23) 17 (49) 321 (097-1063) 06

High grade 23 (56) 16 (62) 125 (046-341) 66

Temporal

Overall 18 (29) 31 (51) 258 (123-543) 01

Low grade 4 (18) 16 (46) 379 (106-1351) 04

High grade 14 (34) 15 (58) 263 (096-723) 06

Hippocampal

Overall 4 (64) 8 (131) 223 (063-782) 21

Low grade 2 (91) 5 (143) 167 (029-944) 56

High grade 2 (49) 3 (115) 254 (040-1637) 32

Corticalb

Overall 40 (63) 51 (84) 293 (125-686) 01

Low grade 19 (86) 29 (83) 076 (017-343) 72

High grade 21 (51) 22 (85) 524 (153-1791) 01

Left hemisphere

Overall 37 (59) 32 (52) 078 (038-158) 48

Low grade 12 (55) 17 (49) 079 (027-229) 66

High grade 25 (61) 15 (58) 087 (032-237) 79





















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No of Patients

Seizure(n = 61)

No Seizure(n = 63)

High grade 26 41

Low grade 35 22

Histology

Glioblastoma 16 33

Astrocytoma 14 9




High grade 55 (26-88) 57 (21-88)

Low grade 38 (18-56) 38 (18-64)

Sex MF 3328 2835


Low grade 1718 517



Low grade 1718 1210

Temporal 31 18

Extratemporal 30 45






High grade 221 2118

Low grade 291 191


High grade 3 2

Low grade 5 2


High grade 30 467

Low grade 378 144






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No ()


Seizure(n=61)a


Interval)

PValue

Grade 01

Low 22 (35) 35 (57) 251 (122-519)

High 41 (65) 26 (43) 040 (019-082)


Overall 50 (18-88) 42 (18-88) 077 (061-096) 02

Low grade 38 (18-64) 38 (18-56) 100 (060-166) 99

High grade 57 (21-88) 55 (26-88) 080 (059-110) 17


Overall 41 (10-166) 35 (03-205) 105 (096-115) 31

Low grade 14 (10-87) 38 (03-205) 131 (106-160) 01

High grade 47 (26-167) 30 (20-143) 088 (074-104) 13

Male

Overall 28 (44) 33 (54) 147 (073-299) 28

Low grade 5 (23) 17 (49) 321 (097-1063) 06

High grade 23 (56) 16 (62) 125 (046-341) 66

Temporal

Overall 18 (29) 31 (51) 258 (123-543) 01

Low grade 4 (18) 16 (46) 379 (106-1351) 04

High grade 14 (34) 15 (58) 263 (096-723) 06

Hippocampal

Overall 4 (64) 8 (131) 223 (063-782) 21

Low grade 2 (91) 5 (143) 167 (029-944) 56

High grade 2 (49) 3 (115) 254 (040-1637) 32

Corticalb

Overall 40 (63) 51 (84) 293 (125-686) 01

Low grade 19 (86) 29 (83) 076 (017-343) 72

High grade 21 (51) 22 (85) 524 (153-1791) 01

Left hemisphere

Overall 37 (59) 32 (52) 078 (038-158) 48

Low grade 12 (55) 17 (49) 079 (027-229) 66

High grade 25 (61) 15 (58) 087 (032-237) 79
























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No of Patients

Seizure(n = 61)

No Seizure(n = 63)

High grade 26 41

Low grade 35 22

Histology

Glioblastoma 16 33

Astrocytoma 14 9




High grade 55 (26-88) 57 (21-88)

Low grade 38 (18-56) 38 (18-64)

Sex MF 3328 2835


Low grade 1718 517



Low grade 1718 1210

Temporal 31 18

Extratemporal 30 45






High grade 221 2118

Low grade 291 191


High grade 3 2

Low grade 5 2


High grade 30 467

Low grade 378 144






NIH


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Lee et al Page 15


No ()


Seizure(n=61)a


Interval)

PValue

Grade 01

Low 22 (35) 35 (57) 251 (122-519)

High 41 (65) 26 (43) 040 (019-082)


Overall 50 (18-88) 42 (18-88) 077 (061-096) 02

Low grade 38 (18-64) 38 (18-56) 100 (060-166) 99

High grade 57 (21-88) 55 (26-88) 080 (059-110) 17


Overall 41 (10-166) 35 (03-205) 105 (096-115) 31

Low grade 14 (10-87) 38 (03-205) 131 (106-160) 01

High grade 47 (26-167) 30 (20-143) 088 (074-104) 13

Male

Overall 28 (44) 33 (54) 147 (073-299) 28

Low grade 5 (23) 17 (49) 321 (097-1063) 06

High grade 23 (56) 16 (62) 125 (046-341) 66

Temporal

Overall 18 (29) 31 (51) 258 (123-543) 01

Low grade 4 (18) 16 (46) 379 (106-1351) 04

High grade 14 (34) 15 (58) 263 (096-723) 06

Hippocampal

Overall 4 (64) 8 (131) 223 (063-782) 21

Low grade 2 (91) 5 (143) 167 (029-944) 56

High grade 2 (49) 3 (115) 254 (040-1637) 32

Corticalb

Overall 40 (63) 51 (84) 293 (125-686) 01

Low grade 19 (86) 29 (83) 076 (017-343) 72

High grade 21 (51) 22 (85) 524 (153-1791) 01

Left hemisphere

Overall 37 (59) 32 (52) 078 (038-158) 48

Low grade 12 (55) 17 (49) 079 (027-229) 66

High grade 25 (61) 15 (58) 087 (032-237) 79




















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No of Patients

Seizure(n = 61)

No Seizure(n = 63)

High grade 26 41

Low grade 35 22

Histology

Glioblastoma 16 33

Astrocytoma 14 9




High grade 55 (26-88) 57 (21-88)

Low grade 38 (18-56) 38 (18-64)

Sex MF 3328 2835


Low grade 1718 517



Low grade 1718 1210

Temporal 31 18

Extratemporal 30 45






High grade 221 2118

Low grade 291 191


High grade 3 2

Low grade 5 2


High grade 30 467

Low grade 378 144






NIH


NIH


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Lee et al Page 15


No ()


Seizure(n=61)a


Interval)

PValue

Grade 01

Low 22 (35) 35 (57) 251 (122-519)

High 41 (65) 26 (43) 040 (019-082)


Overall 50 (18-88) 42 (18-88) 077 (061-096) 02

Low grade 38 (18-64) 38 (18-56) 100 (060-166) 99

High grade 57 (21-88) 55 (26-88) 080 (059-110) 17


Overall 41 (10-166) 35 (03-205) 105 (096-115) 31

Low grade 14 (10-87) 38 (03-205) 131 (106-160) 01

High grade 47 (26-167) 30 (20-143) 088 (074-104) 13

Male

Overall 28 (44) 33 (54) 147 (073-299) 28

Low grade 5 (23) 17 (49) 321 (097-1063) 06

High grade 23 (56) 16 (62) 125 (046-341) 66

Temporal

Overall 18 (29) 31 (51) 258 (123-543) 01

Low grade 4 (18) 16 (46) 379 (106-1351) 04

High grade 14 (34) 15 (58) 263 (096-723) 06

Hippocampal

Overall 4 (64) 8 (131) 223 (063-782) 21

Low grade 2 (91) 5 (143) 167 (029-944) 56

High grade 2 (49) 3 (115) 254 (040-1637) 32

Corticalb

Overall 40 (63) 51 (84) 293 (125-686) 01

Low grade 19 (86) 29 (83) 076 (017-343) 72

High grade 21 (51) 22 (85) 524 (153-1791) 01

Left hemisphere

Overall 37 (59) 32 (52) 078 (038-158) 48

Low grade 12 (55) 17 (49) 079 (027-229) 66

High grade 25 (61) 15 (58) 087 (032-237) 79





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No of Patients

Seizure(n = 61)

No Seizure(n = 63)

High grade 26 41

Low grade 35 22

Histology

Glioblastoma 16 33

Astrocytoma 14 9




High grade 55 (26-88) 57 (21-88)

Low grade 38 (18-56) 38 (18-64)

Sex MF 3328 2835


Low grade 1718 517



Low grade 1718 1210

Temporal 31 18

Extratemporal 30 45






High grade 221 2118

Low grade 291 191


High grade 3 2

Low grade 5 2


High grade 30 467

Low grade 378 144






NIH


NIH


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No ()


Seizure(n=61)a


Interval)

PValue

Grade 01

Low 22 (35) 35 (57) 251 (122-519)

High 41 (65) 26 (43) 040 (019-082)


Overall 50 (18-88) 42 (18-88) 077 (061-096) 02

Low grade 38 (18-64) 38 (18-56) 100 (060-166) 99

High grade 57 (21-88) 55 (26-88) 080 (059-110) 17


Overall 41 (10-166) 35 (03-205) 105 (096-115) 31

Low grade 14 (10-87) 38 (03-205) 131 (106-160) 01

High grade 47 (26-167) 30 (20-143) 088 (074-104) 13

Male

Overall 28 (44) 33 (54) 147 (073-299) 28

Low grade 5 (23) 17 (49) 321 (097-1063) 06

High grade 23 (56) 16 (62) 125 (046-341) 66

Temporal

Overall 18 (29) 31 (51) 258 (123-543) 01

Low grade 4 (18) 16 (46) 379 (106-1351) 04

High grade 14 (34) 15 (58) 263 (096-723) 06

Hippocampal

Overall 4 (64) 8 (131) 223 (063-782) 21

Low grade 2 (91) 5 (143) 167 (029-944) 56

High grade 2 (49) 3 (115) 254 (040-1637) 32

Corticalb

Overall 40 (63) 51 (84) 293 (125-686) 01

Low grade 19 (86) 29 (83) 076 (017-343) 72

High grade 21 (51) 22 (85) 524 (153-1791) 01

Left hemisphere

Overall 37 (59) 32 (52) 078 (038-158) 48

Low grade 12 (55) 17 (49) 079 (027-229) 66

High grade 25 (61) 15 (58) 087 (032-237) 79





Lee et al


NIH


NIH


NIH



Lee et al Page 12


NIH


NIH


NIH



Lee et al Page 13


NIH


NIH


NIH


NIH


NIH


NIH


Lee et al Page 14


No of Patients

Seizure(n = 61)

No Seizure(n = 63)

High grade 26 41

Low grade 35 22

Histology

Glioblastoma 16 33

Astrocytoma 14 9




High grade 55 (26-88) 57 (21-88)

Low grade 38 (18-56) 38 (18-64)

Sex MF 3328 2835


Low grade 1718 517



Low grade 1718 1210

Temporal 31 18

Extratemporal 30 45






High grade 221 2118

Low grade 291 191


High grade 3 2

Low grade 5 2


High grade 30 467

Low grade 378 144






NIH


NIH


NIH


Lee et al Page 15


No ()


Seizure(n=61)a


Interval)

PValue

Grade 01

Low 22 (35) 35 (57) 251 (122-519)

High 41 (65) 26 (43) 040 (019-082)


Overall 50 (18-88) 42 (18-88) 077 (061-096) 02

Low grade 38 (18-64) 38 (18-56) 100 (060-166) 99

High grade 57 (21-88) 55 (26-88) 080 (059-110) 17


Overall 41 (10-166) 35 (03-205) 105 (096-115) 31

Low grade 14 (10-87) 38 (03-205) 131 (106-160) 01

High grade 47 (26-167) 30 (20-143) 088 (074-104) 13

Male

Overall 28 (44) 33 (54) 147 (073-299) 28

Low grade 5 (23) 17 (49) 321 (097-1063) 06

High grade 23 (56) 16 (62) 125 (046-341) 66

Temporal

Overall 18 (29) 31 (51) 258 (123-543) 01

Low grade 4 (18) 16 (46) 379 (106-1351) 04

High grade 14 (34) 15 (58) 263 (096-723) 06

Hippocampal

Overall 4 (64) 8 (131) 223 (063-782) 21

Low grade 2 (91) 5 (143) 167 (029-944) 56

High grade 2 (49) 3 (115) 254 (040-1637) 32

Corticalb

Overall 40 (63) 51 (84) 293 (125-686) 01

Low grade 19 (86) 29 (83) 076 (017-343) 72

High grade 21 (51) 22 (85) 524 (153-1791) 01

Left hemisphere

Overall 37 (59) 32 (52) 078 (038-158) 48

Low grade 12 (55) 17 (49) 079 (027-229) 66

High grade 25 (61) 15 (58) 087 (032-237) 79





Lee et al


NIH


NIH


NIH



Lee et al Page 13


NIH


NIH


NIH


NIH


NIH


NIH


Lee et al Page 14


No of Patients

Seizure(n = 61)

No Seizure(n = 63)

High grade 26 41

Low grade 35 22

Histology

Glioblastoma 16 33

Astrocytoma 14 9




High grade 55 (26-88) 57 (21-88)

Low grade 38 (18-56) 38 (18-64)

Sex MF 3328 2835


Low grade 1718 517



Low grade 1718 1210

Temporal 31 18

Extratemporal 30 45






High grade 221 2118

Low grade 291 191


High grade 3 2

Low grade 5 2


High grade 30 467

Low grade 378 144






NIH


NIH


NIH


Lee et al Page 15


No ()


Seizure(n=61)a


Interval)

PValue

Grade 01

Low 22 (35) 35 (57) 251 (122-519)

High 41 (65) 26 (43) 040 (019-082)


Overall 50 (18-88) 42 (18-88) 077 (061-096) 02

Low grade 38 (18-64) 38 (18-56) 100 (060-166) 99

High grade 57 (21-88) 55 (26-88) 080 (059-110) 17


Overall 41 (10-166) 35 (03-205) 105 (096-115) 31

Low grade 14 (10-87) 38 (03-205) 131 (106-160) 01

High grade 47 (26-167) 30 (20-143) 088 (074-104) 13

Male

Overall 28 (44) 33 (54) 147 (073-299) 28

Low grade 5 (23) 17 (49) 321 (097-1063) 06

High grade 23 (56) 16 (62) 125 (046-341) 66

Temporal

Overall 18 (29) 31 (51) 258 (123-543) 01

Low grade 4 (18) 16 (46) 379 (106-1351) 04

High grade 14 (34) 15 (58) 263 (096-723) 06

Hippocampal

Overall 4 (64) 8 (131) 223 (063-782) 21

Low grade 2 (91) 5 (143) 167 (029-944) 56

High grade 2 (49) 3 (115) 254 (040-1637) 32

Corticalb

Overall 40 (63) 51 (84) 293 (125-686) 01

Low grade 19 (86) 29 (83) 076 (017-343) 72

High grade 21 (51) 22 (85) 524 (153-1791) 01

Left hemisphere

Overall 37 (59) 32 (52) 078 (038-158) 48

Low grade 12 (55) 17 (49) 079 (027-229) 66

High grade 25 (61) 15 (58) 087 (032-237) 79





Lee et al


NIH


NIH


NIH


NIH


NIH


NIH


Lee et al Page 14


No of Patients

Seizure(n = 61)

No Seizure(n = 63)

High grade 26 41

Low grade 35 22

Histology

Glioblastoma 16 33

Astrocytoma 14 9




High grade 55 (26-88) 57 (21-88)

Low grade 38 (18-56) 38 (18-64)

Sex MF 3328 2835


Low grade 1718 517



Low grade 1718 1210

Temporal 31 18

Extratemporal 30 45






High grade 221 2118

Low grade 291 191


High grade 3 2

Low grade 5 2


High grade 30 467

Low grade 378 144






NIH


NIH


NIH


Lee et al Page 15


No ()


Seizure(n=61)a


Interval)

PValue

Grade 01

Low 22 (35) 35 (57) 251 (122-519)

High 41 (65) 26 (43) 040 (019-082)


Overall 50 (18-88) 42 (18-88) 077 (061-096) 02

Low grade 38 (18-64) 38 (18-56) 100 (060-166) 99

High grade 57 (21-88) 55 (26-88) 080 (059-110) 17


Overall 41 (10-166) 35 (03-205) 105 (096-115) 31

Low grade 14 (10-87) 38 (03-205) 131 (106-160) 01

High grade 47 (26-167) 30 (20-143) 088 (074-104) 13

Male

Overall 28 (44) 33 (54) 147 (073-299) 28

Low grade 5 (23) 17 (49) 321 (097-1063) 06

High grade 23 (56) 16 (62) 125 (046-341) 66

Temporal

Overall 18 (29) 31 (51) 258 (123-543) 01

Low grade 4 (18) 16 (46) 379 (106-1351) 04

High grade 14 (34) 15 (58) 263 (096-723) 06

Hippocampal

Overall 4 (64) 8 (131) 223 (063-782) 21

Low grade 2 (91) 5 (143) 167 (029-944) 56

High grade 2 (49) 3 (115) 254 (040-1637) 32

Corticalb

Overall 40 (63) 51 (84) 293 (125-686) 01

Low grade 19 (86) 29 (83) 076 (017-343) 72

High grade 21 (51) 22 (85) 524 (153-1791) 01

Left hemisphere

Overall 37 (59) 32 (52) 078 (038-158) 48

Low grade 12 (55) 17 (49) 079 (027-229) 66

High grade 25 (61) 15 (58) 087 (032-237) 79




NIH


NIH


NIH


Lee et al


No of Patients

Seizure(n = 61)

No Seizure(n = 63)

High grade 26 41

Low grade 35 22

Histology

Glioblastoma 16 33

Astrocytoma 14 9




High grade 55 (26-88) 57 (21-88)

Low grade 38 (18-56) 38 (18-64)

Sex MF 3328 2835


Low grade 1718 517



Low grade 1718 1210

Temporal 31 18

Extratemporal 30 45






High grade 221 2118

Low grade 291 191


High grade 3 2

Low grade 5 2


High grade 30 467

Low grade 378 144






NIH


NIH


NIH


Lee et al Page 15


No ()


Seizure(n=61)a


Interval)

PValue

Grade 01

Low 22 (35) 35 (57) 251 (122-519)

High 41 (65) 26 (43) 040 (019-082)


Overall 50 (18-88) 42 (18-88) 077 (061-096) 02

Low grade 38 (18-64) 38 (18-56) 100 (060-166) 99

High grade 57 (21-88) 55 (26-88) 080 (059-110) 17


Overall 41 (10-166) 35 (03-205) 105 (096-115) 31

Low grade 14 (10-87) 38 (03-205) 131 (106-160) 01

High grade 47 (26-167) 30 (20-143) 088 (074-104) 13

Male

Overall 28 (44) 33 (54) 147 (073-299) 28

Low grade 5 (23) 17 (49) 321 (097-1063) 06

High grade 23 (56) 16 (62) 125 (046-341) 66

Temporal

Overall 18 (29) 31 (51) 258 (123-543) 01

Low grade 4 (18) 16 (46) 379 (106-1351) 04

High grade 14 (34) 15 (58) 263 (096-723) 06

Hippocampal

Overall 4 (64) 8 (131) 223 (063-782) 21

Low grade 2 (91) 5 (143) 167 (029-944) 56

High grade 2 (49) 3 (115) 254 (040-1637) 32

Corticalb

Overall 40 (63) 51 (84) 293 (125-686) 01

Low grade 19 (86) 29 (83) 076 (017-343) 72

High grade 21 (51) 22 (85) 524 (153-1791) 01

Left hemisphere

Overall 37 (59) 32 (52) 078 (038-158) 48

Low grade 12 (55) 17 (49) 079 (027-229) 66

High grade 25 (61) 15 (58) 087 (032-237) 79




NIH


NIH


NIH


Lee et al


No ()


Seizure(n=61)a


Interval)

PValue

Grade 01

Low 22 (35) 35 (57) 251 (122-519)

High 41 (65) 26 (43) 040 (019-082)


Overall 50 (18-88) 42 (18-88) 077 (061-096) 02

Low grade 38 (18-64) 38 (18-56) 100 (060-166) 99

High grade 57 (21-88) 55 (26-88) 080 (059-110) 17


Overall 41 (10-166) 35 (03-205) 105 (096-115) 31

Low grade 14 (10-87) 38 (03-205) 131 (106-160) 01

High grade 47 (26-167) 30 (20-143) 088 (074-104) 13

Male

Overall 28 (44) 33 (54) 147 (073-299) 28

Low grade 5 (23) 17 (49) 321 (097-1063) 06

High grade 23 (56) 16 (62) 125 (046-341) 66

Temporal

Overall 18 (29) 31 (51) 258 (123-543) 01

Low grade 4 (18) 16 (46) 379 (106-1351) 04

High grade 14 (34) 15 (58) 263 (096-723) 06

Hippocampal

Overall 4 (64) 8 (131) 223 (063-782) 21

Low grade 2 (91) 5 (143) 167 (029-944) 56

High grade 2 (49) 3 (115) 254 (040-1637) 32

Corticalb

Overall 40 (63) 51 (84) 293 (125-686) 01

Low grade 19 (86) 29 (83) 076 (017-343) 72

High grade 21 (51) 22 (85) 524 (153-1791) 01

Left hemisphere

Overall 37 (59) 32 (52) 078 (038-158) 48

Low grade 12 (55) 17 (49) 079 (027-229) 66

High grade 25 (61) 15 (58) 087 (032-237) 79




Morphological Characteristics of Brain Tumors Causing Seizures

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Transcript of Morphological Characteristics of Brain Tumors Causing Seizures