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Epilepsy Research (2012) 99, 335—345

jou rn al h om epa ge: www.elsev ier .com/ locate /ep i lepsyres

Occipital lobe epilepsy in children: Characterization,evaluation and surgical outcomes

George M. Ibrahim, Aria Fallah, Gregory W. Albert, Teresa Withers,Hiroshi Otsubo, Ayako Ochi, Tomoyuki Akiyama, Elizabeth J. Donner,Shelly Weiss, O. Carter Snead III, James M. Drake, James T. Rutka ∗

Divisions of Neurosurgery and Neurology, Hospital for Sick Children, Toronto, Ontario, Canada

Received 30 September 2011; received in revised form 26 November 2011; accepted 26 December 2011Available online 17 January 2012

KEYWORDSOccipital lobeepilepsy;Surgical resection;Intractable epilepsy;Children

SummaryIntroduction: Occipital lobe epilepsy (OLE) poses a diagnostic challenge to clinicians. Here,we present our experience in the surgical management of OLE in children using magnetoen-cephalography (MEG) in the pre-operative evaluation.Methods: Retrospective chart review was performed from 2000 to 2010 to identify patientswith OLE. Patients were analyzed in two categories: isolated OLE (11 patients) and extendedOLE (parietooccipital, temporooccipital, and temporoparietooccipital; 30 patients). Survivalanalysis and multivariate Cox proportional hazards regression were used to identify independentpredictors of seizure outcome.Results: Forty-one patients with a mean follow-up of 3.1 years were identified with an over-all 68% rate of satisfactory seizure outcome. Patients with extended OLE had younger ages atseizure onset and different seizure semiologies compared with those with isolated OLE. None ofthe latter underwent insertion of subdural grid electrodes for localization of the epileptogeniczone compared with 77% of the former (p < 0.001). On multivariate analysis, the strongest inde-pendent predictor of unsatisfactory outcome was MEG dipoles in the occipital lobe contralateralto resection.

Abbreviations: AED, anti-epileptic drug; CT, computed tomography; ECoG, electrocorticography; EEG, electroencephalography; EMU,epilepsy monitoring unit; FCD, focal cortical dysplasia; FDG, fluorodeoxyglucose; GFAP, glial fibrillary acidic protein; HE, hematoxylin—eosin;HE-LFB, hematoxylin—eosin—luxol-Fast-Blue; ILAE, International League Against Epilepsy; MCD, malformations of cortical development;MEG, magnetoencephalography; MRI, magnetic resonance imaging; MST, multiple subpial transactions; NS, not statistically significant; OLE,occipital lobe epilepsy; PET, positron emission tomography; PO, parietooccipital; SPECT, single-photon emission computed tomography; TO,temporooccipital; TPO, temporoparietooccipital; WHO, World Health Organization.

∗ Corresponding author at: The Hospital for Sick Children, Suite 1503, 555 University Ave., Toronto, ON, Canada M5G 1X8.Tel.: +1 416 813 8441; fax: +1 416 813 4975.

E-mail address: james.rutka@sickkids.ca (J.T. Rutka).

0920-1211/$ — see front matter © 2012 Elsevier B.V. All rights reserved.doi:10.1016/j.eplepsyres.2011.12.015

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336 G.M. Ibrahim et al.

Conclusion: Here, we find similar seizure outcomes for isolated and extended OLE foci despitethe use of less invasive strategies for the former. Furthermore, we describe the role of MEG inevaluation, surgical planning and prognostication of children with OLE.© 2012 Elsevier B.V. All rights reserved.

Introduction

Occipital lobe epilepsy (OLE) represents less than 10%of extratemporal epilepsies and as few as 2% of resec-tive epilepsy procedures (Bien et al., 2000; Kuzniecky,1998; Purpura et al., 1952; Rasmussen, 1975). OLE wasfirst described by Sir William Richard Gowers in 1879 as‘‘epileptoid attacks with visual auras’’ in a patient witha parietooccipital tumor(Gowers, 1879). Sir Gordon Holmessubsequently attributed visual auras to occipital lobe injuryin combat situations (Holmes, 1927; Salanova et al., 1992).Finally, Penfield and Erickson were able to reproduce theseauras in patients with OLE through cortical stimulation(Penfield and Erickson, 1941).

The relative depth of the occipital lobe and rapid seizurepropagation from occipital foci make diagnosis and treat-ment of OLE difficult (Babb et al., 1981; Kun Lee et al.,2005). White matter tracts connect the occipital lobe tothe frontal lobe, adjacent temporal and parietal lobes aswell as the midbrain tegmentum (Jones and Powell, 1970);therefore, seizure semiology and electrophysiological inves-tigations may be unreliable. Here, we report our experiencein the evaluation and surgical management of OLE at theHospital for Sick Children from 2000 to 2010. The cur-rent series is the first to report outcomes in an exclusivelypediatric population and with the routine use of magnetoen-cephalography (MEG) in the pre-surgical assessment.

Methods

Patient population

A retrospective chart review was performed to identifypatients undergoing surgical treatment for OLE at the Hos-pital for Sick Children from 2000 to 2010. All patientshad medically intractable epilepsy and resective epilepsysurgery involving at least the occipital lobe. Patients wereincluded if they fulfilled the following criteria: (1) seizuresemiology consistent with occipital onset (i.e. visual auras)(Ludwig and Marsan, 1975); (2) ictal or interictal EEGlocalization to the posterior quadrant; (3) radiographicabnormality in the occipital lobe(s); and/or (4) MEG dipolecluster involving the occipital cortex. Furthermore, all chil-dren had at least 1-year follow-up from the time of surgery.Patients with multilobar epileptogenic foci were included inthe analysis providing the occipital cortex was also involved.Forty-one patients met the criteria for inclusion in this study,which was approved by our institutional Research EthicsBoard (REB number: 1000021924).

To determine the localization of the epilepsy, elec-trophysiological data and MR imaging and operative andhistopathological reports were reviewed. Patients weredivided into two groups (isolated and extended OLE) basedon the site of resection (Binder et al., 2008). The latter

includes seizures localized to the parietooccipital (PO),temporooccipital (TO) and temporoparietooccipital (TPO)cortex.

Diagnostic studies

Video electroencephalography (EEG) monitoring was per-formed with electrodes placed according to the Interna-tional 10—20 system (BMSI System 4000 and 5000; Nicolet,Madison, WI; HARMONY, Natus, Oakville, ON, Canada).For the subset of patients who became seizure-free post-operatively, ictal and interictal EEGs were describe as(1) ‘‘localizing’’ if they localized to the posterior quad-rant; (2) ‘‘lateralizing’’ if they identified the hemispherewithin which the epileptogenic lobe is located; (3) ‘‘non-lateralizing’’ if the result is normal or both hemisphereswere involved; and (4) ‘‘falsely-localizing’’ if other lobeswithin the epileptogenic hemisphere were identified(KunLee et al., 2005). Intracranial EEG was performed in selectedpatients. The decision to proceed with invasive electro-corticography and the placement of subdural and depthelectrodes was based on concordance in the data of scalpvideo-EEG, MRI and MEG, as well as the need to map elo-quent cortex.

Interictal MEG was performed on nearly all patientsincluded in this review, as per institutional protocol. Thesestudies were performed using a whole head gradiometer(Omega system, 151 channels, VSM MedTech Ltd., PortCoquitlam, BC, Canada). For each patient, 15 two-minuteperiods of spontaneous MEG data were obtained, with asampling rate of 625 Hz. MEG data was cross referencedwith simultaneous EEG recording and a single moving dipoleanalysis was performed with a single-shell, whole head, indi-vidually created spherical model for a period of 50 ms beforeand after the peak of each spike, as previously described(Iida et al., 2005). MEG dipole sources were subsequentlymapped onto the MRI (T1-WI; 2 mm thickness, no skip) pixelsby using the MARK VOXEL program (VSM MedTech Ltd.,PortCoquitlam, BC, Canada). The number of dipoles within thepresumed epileptogenic and contralateral occipital lobe andpresumed epileptogenic and contralateral hemisphere wasrecorded. Dipoles within clusters centered in the occipitallobe, but extending into adjacent cortex were included asoccipital dipoles. Spike clusters were defined as 20 or morespike sources with adjacent sources located within 1 cm ofeach other (Iida et al., 2005).

The MRI technique utilized volumetric acquisition and3D reconstruction in multiplanar cuts of T1, T2, and fluid-attenuated inversion recovery (FLAIR) sequences with aSiemens 1.5 or 3-T/64-MHz MR system (Siemens MedicalSolutions USA, Inc., Malvern, PA). If a lesion suspiciousfor a tumor or vascular malformation was detected, T1-weighted sequences before and after gadolinium injectionwere acquired.

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Occipital lobe epilepsy in children: Characterization, evaluation and surgical outcomes 337

All studies were interpreted by experienced clinical neu-rophysiologists and/or neuroradiologists.

Surgery and surgical outcome

The goals of surgery were to resect the epileptogenic zone,while preserving eloquent cortex. The margins of the resec-tion were determined by imaging and electrophysiologicalstudies (including MEG and implanted subdural electrodes).In most cases, we co-registered imaging and MEG dipole dataas previously published (Iida et al., 2005). Surgical outcomewas evaluated using the Engel classification at the last clin-ical visit (Engel et al., 1987). Engel classes I and II werecategorized as a satisfactory seizure outcome, while Engelclasses III and IV were categorized as an unsatisfactory out-come.

Histological findings

Surgical specimen was fixed in 10% buffered forma-lin, embedded in paraffin and stained with hematoxylinand eosin (HE) and hematoxylin—eosin—luxol-fast-blue(HE-LFB). Immunohistochemical stains were used at thediscretion of the examining pathologist and includedglial fibrillary acidic protein (GFAP), synaptophysin, NeuN,Vimentin, MIB1 and alpha beta-crystallin. Malformations ofcortical development were graded according to the classi-fication outlined by International League Against Epilepsy(ILAE) and tumors were classified based on the World HealthOrganization (WHO) system (Blümcke et al., 2011; Louiset al., 2007).

Statistical analysis

Binary and dichotomized categorical variables were ana-lyzed using the two-tailed Fisher’s exact test. For continuousvariables, a two-tailed Student’s t-test was used to iden-tify differences between desired outcomes. For the survivalanalysis, our primary outcome was time to unfavourableseizure outcome following surgery, defined as the pointat which the patient becomes Engel Class II. Seizures inthe first postoperative week were ignored as they couldbe related to the procedure itself. We used time-to-eventanalysis in order to allow for (1) the inclusion of censoredpatients and therefore account for the variability in follow-up; and (2) the assessment of covariates with the primaryoutcome. Kaplan—Meier plots were created to demonstratethe primary outcome in both isolated and extended OLEgroups.

The relationship between biologically plausible covari-ates and time-to-unfavourable seizure outcomes wasalso analyzed using univariate regression. Covariateswith p < 0.20 were entered into a multivariate Coxproportional hazards regression to identify independentpredictors of seizure outcome. p-Values of less than0.05 from multivariate regression were accepted asstatistically significant. Hazard ratios with confidence inter-vals were derived from the Cox proportional hazardsmodel. All analysis was performed using SPSS statisticalsoftware.

Results

Patient demographics and clinical features

Of the 41 patients included in this study, 11(27%) hadisolated OLE, while 30(73%) had extended OLE, involv-ing at least one other lobe. Of the latter, 6(15%),11(27%) and 13(32%) had parietooccipital, temporooccipi-tal, and temporoparietooccipital localizations respectively.The demographic and clinical information for both groupsare presented in Table 1. Six patients (15%) had undergoneprior epilepsy surgery. This included temporal lobectomywith or without resection of the mesial temporal structures(3), tumor resections (2), and cortical resections (3). Noneof the patients had previous occipital lobe resections.

As summarized in Table 2, seizure semiology differedbased on the specific location of seizure onset. Patientswith temporooccipital seizure onset were significantly morelikely to exhibit non-visual auras, which include dizziness(3), nausea (2), auditory (1), gustatory (1), olfactory (1)and pain sensation (1). The most common seizure type wascomplex partial seizures (27 patients, 66%), followed by gen-eralized tonic clonic seizures (21 patients, 51%). Patientswith isolated OLE had significantly fewer complex partialseizures consisting of staring spells compared to those withextended OLE (p < 0.05) The prevalence of epileptic spasmswas too low to define meaningful differences betweenpatients with isolated occipital and extended OLE.

Diagnostic studies

Thirty-nine patients were admitted to the Epilepsy Moni-toring Unit (EMU) for prolonged video-EEG monitoring. Twopatients, one with an occipital AVM and the other with apilocytic astrocytoma did not undergo EMU admission. Onaverage, 10 ± 10 seizures were recorded per patient. Forpatients who went on to have a satisfactory seizure out-come (27 patients), ictal EEG was localizing in 19 patients(76%), lateralizing in 1 patients (4%) and non-lateralizing in3 patients (12%). In two of these patients (5%), bilateraloccipital ictal activity was detected and in the third patient(3%), seizures were not well-localized. In two patients (8%),the ictal EEG was falsely-localizing to the temporal andfrontal lobes respectively. There was no significant differ-ence between patients with isolated and extended OLE withregards to ictal EEG findings (Table 3).

Interictal EEG was localizing in 17 patients (71%) whowent on to have a satisfactory seizure outcome. Patientswith extended OLE were more likely to have localizing EEGscompared to those with isolated OLE (33% vs. 76 p = 0.08).Of the 6 patients (25%) with non-lateralizing interictal EEGs,3(8%) had bilateral occipital interictal activity.

Thirty-seven patients underwent magnetoencephalogra-phy (MEG). The average number of dipoles was 72 ± 53 with59 ± 53 dipoles in the presumed epileptogenic occipital lobeand 2 ± 4 dipoles in the contralateral occipital lobe. Whilepatients with extended OLE had more extraoccipital (ipsi-lateral and contralateral) dipoles than those with isolatedOLE, this did not reach statistical significance.

No patients with isolated OLE underwent insertion ofsubdural grids for seizure localization compared with 23

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Table 1 Demographic and clinical characteristics for patients with isolated occipital and extended occipital lobe epilepsy.

Isolated occipital Extended occipital Total p-value

Number of patients 11(27) 30(73) 41 —Male gender 6(55) 17(57) 23(56) 1.00Family history 2(18) 4(13) 6(15) 0.65Age (years)

At onset 7.7 ± 5.5 (range 0—16) 3.6 ± 4.4 (range 0—14) 4.7 ± 5.0 0.02At surgery 11.2 ± 5.6 (range 2—18) 10.2 ± 6.2 (range 1—18) 10.5 ± 5.9 0.67

Mean duration (years) 3.5 ± 4.4 (range 0—10) 6.8 ± 5.2 (range 1—16) 5.9 ± 5.2 0.07Pre-operative self-reported seizure frequency/day 3 ± 4 (range 0—8) 9 ± 19 (range 0—100) 7 ± 16 0.43Number of distinct seizure types 2 ± 1 (range 1—4) 3 ± 2 (range 1—7) 3 ± 1 0.056Number of medications attempted 4 ± 4 (range 1—13) 5 ± 3 (range 2—10) 5 ± 3 0.25Previous epilepsy surgery 0 6(20) 6(15) 0.17Epilepsy risk factors

Hemorrhage 1(9) 1(3) 2(5) 0.46Infarct/HIE 0 3(10) 3(7) 0.55Infection 1(9) 0 1(2) 0.26Known syndromea 0 6(20) 6(15) 0.17

Pre-operative examNormal 10(91) 13(43) 23(56) 0.77Visual field deficits 0 6(20) 6(14) 0.17Non-visual deficitsb 1(9) 11(37) 12(29) 0.13

Developmental delay 4(36) 22(76) 26(63) 0.06

Values in parentheses denote percentage unless stated otherwise. Error measurements represent standard deviation; numbers in paren-theses denote percentages unless stated otherwise; HIE — hypoxic ischemic injury.

a Includes tuberous sclerosis (4) and Sturge—Weber syndrome (2).b Includes hemiparesis, spasticity, hyperreflexia, hypotonia, hemi-neglect.

patients (77%) of those with extended OLE (p < 0.0001).Of the former, 5 patients (45%) underwent lesionectomy,whi| (55%) underwent a lesionectomy with a MEG clusterec-tomy.

Representative imaging and electrophysiological infor-mation is shown in Fig. 1 to demonstrate the incorporation ofmultiple modalities in resective surgical strategies for OLEthrough co-registration of perioperative neuronavigation.

Table 2 Seizure types in patients with isolated and extended occipital seizure foci.

Isolated occipital Extended occipitala (N = 30) Total

PO TO TPO

N 11 6 11 13 41Auras

Visual 4(36) 2(33) 3(27) 2(15) 11(27)Non-visualb 1(9) 1(20) 5(45)* 2(15) 9(22)

Seizures typeSPS 3(27) 2(33) 3(27) 3(23) 11(27)CPS 6(55) 6(100) 8(72) 7(54) 27(66)GTC 5(45) 3(50) 4(36) 9(69) 21(51)SPS + GTC 1(9) 0 0 0 1(2)CPS + GTC 2(18) 0 2(18) 0 4(10)Atonic 0 0 1(9) 2(15) 3(7)ES 1(9) 1(17) 3(27) 1(8) 6(14)

Values in parentheses denote percentages. PO — parietooccipital; TO — temporooccipital; TPO — temporoparietooccipital; SPS — simplepartial seizures; CPS — complex partial seizures; GTC — generalizing tonic clonic seizures; ES — epileptic spasms; numbers in parenthesesdenote percentages.

a Localization based on location of surgical resection; two patients also underwent limited frontal resections were grouped in the TOand TPO categories.

b Non-visual auras include dizziness (3), nausea (2), auditory (1), gustatory (1), olfactory (1) and pain sensation (1).* Denotes statistical significance, p < 0.05 by Fisher’s Exact test.

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Occipital lobe epilepsy in children: Characterization, evaluation and surgical outcomes 339

Table 3 Localization of epileptogenic zone in OLE.

Isolated occipital Extended occipital Total p-Value

Ictal EEGN (satisfactory outcome only) 4 21 25 —Localizing 3(75) 16(76) 19(76) 1.00Lateralizing 0 1(5) 1(4) 1.00Non-lateralizing 0 3(14) 3(12) 1.00Falsely localizing 1(25)a 1(5)b 2(8) 0.30

Interictal EEGN (satisfactory outcome only) 4 21 24 —Localizing 1(25) 16(76) 17(71) 0.08Lateralizing 1(25) 2(10) 3(12) 0.42Non-lateralizing 2(50) 3(14) 5(21) 0.17Falsely localizing 0 0 0 —

MEGN 9 28 37 —Total number of dipoles 75 ± 66 (Range 0—197) 71 ± 49 (Range 8-186) 72 ± 53 0.87Ipsilateral occipital dipoles 67 ± 66 56 ± 49 59 ± 53 0.62Ipsilateral extraoccipital dipoles 3 ± 5 10 ± 13 8 ± 12 0.11Contralateral occipital dipoles 3 ± 5 1 ± 4 2 ± 4 0.16Contralateral extraoccipital dipoles 1 ± 2 4 ± 6 3 ± 5 0.18

MRILocalizing lesion 11(100) 24(80) 35(85) 0.17

Surgical strategySubdural grid insertion 0c 23(77) 23(56) < 0.0001

Error measurements denote standard deviation; values in parentheses denote percentages unless stated otherwise; EEG — electroen-cephalography; MRI — magnetic resonance imaging; MEG — magnetoencephalography.

a Temporal onset.b Frontal onset.c Patients underwent lesion resection and/or image-guided MEG clusterectomy.

Surgical outcome

Nineteen patients (46%) underwent an occipital corticec-tomy while 17(41%) underwent an occipital lobectomy. Ofthe remaining patients, 5 (12%) underwent tumor resec-tion and one patient (2%) had an occipital AVM resected.Additionally, 15 patients (37%) underwent a temporal lobec-tomy, of whom 13 (32%) underwent resection of themesial temporal structures. Three patients (7%) underwentmultiple subpial transections (MST) of the posterior tem-poral lobe. The histopathological findings are presented inTable 4.

The mean follow-up time was 3.1 ± 2.6 years with onepatient (2%) lost to follow-up. Overall, 27 patients (68%)had a satisfactory outcome defined as Engel class I or II.Of the patients with seizure foci exclusively in the occipitallobe, 6 patients (60%) had satisfactory outcomes, comparedwith 21 patients (70%) with extended OLE (p = NS). Of thepatients with satisfactory outcomes, 21 patients (78%) werecompletely seizure-free since surgery (Engel IA), 2 patients(7%) continued to have auras (Engel 1B), 2 patients (7%) hadseizures with AED withdrawal only (Engel 1D) and 1 patient(4%) had non-epileptic seizures. One patient (4%) continuedto have rare nocturnal seizures (Engel IID).

The remaining 13 patients (32%) had unsatisfactory out-come (Engel class III and IV). Of these, 7 patients (54%) hada worthwhile improvement, while 6 patients (46%) had no

appreciable change in seizure frequency. No patients hadworsening of their seizures post-operatively. Four patients(10%) with unchanged seizure frequency went on to haveadditional procedures (1 additional resection, 1 insertionof a vagus nerve stimulator and 2 peri-insular hemisphero-tomies). Survival analysis (Fig. 2) revealed an estimatedmean time to poor seizure outcome of 4.47 (95% CI:2.65—6.29) and 6.85 years for the isolated and extendedOLE groups respectively.

On univariate analysis (Table 5), younger age of seizureonset (p = 0.08), younger age at surgery (p = 0.04), greaternumber of seizure types (p = 0.16), higher pre-operativeseizure frequency (p = 0.01), presence of neurodevelop-mental delay (p = 0.12), normal MRI (p = 0.07) and greaternumber of spikes in the occipital lobe contralateral to resec-tion (p = 0.02) met the selection criteria for inclusion inthe multivariate analysis. In the Cox proportional hazardsmultivariate regression model (Table 6), the only significantindependent predictor of unfavourable seizure outcome wasthe presence of greater number of MEG dipoles in thecontralateral occipital lobe (HR 1.33; 95% CI: 1.04—1.71;p = 0.03). Each contralateral occipital spike increased thechance of seizure recurrence by approximately 33%. Inter-estingly, patients who had subdural grids inserted did nothave higher rates of satisfactory outcome compared topatients who underwent lesionectomy and/or MEG clus-terectomy on univariate analysis (70% vs. 65%; p = 0.75).

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Table 4 Histopathological diagnoses in 41 patients with OLE.

Isolated occipital Extended occipital Total p-Value

Number of patients 11 30 41 —Gliosis 1(9) 6(20)a 7(17) 0.65Infarct 1(9) 1(3) 2(5) 0.47

MCD

FCD 3(27) 9(45) 12(29) 0.73Grey matter heterotopia 1(9) 1(3) 2(5)Pachygyria 1(9) 0 1(2)Sturge—Weber 0 2(7) 2(5)Tuberous sclerosis 0 4(13) 4(10)

Tumors

Pilocytic astrocytic 2(18) 0 2(5) 0.36DNET 1(9) 2(7) 3(7)Ganglioglioma 0 1(3) 1(2)Infiltrative mixed glioneuronal tumor 0 1(3) 1(2)

Porencephalic cyst 0 1(3) 1(2) 1.00AVM 1(9) 0 1(2) 0.27Glial cytoplasmic inclusions 0 1(3) 1(2) 1.00No pathological diagnosis 0 1(3) 1(2) 1.00

Values in parentheses denote percentages; MCD — malformations of cortical development; FCD — focal cortical dysplasia; DNET —dysembroplastic neuroectodermal tumor; AVM — arteriovenous malformation.

a One patient also had mesial temporal sclerosis.

Table 5 Factors correlating with unsatisfactory outcome on univariate analysis.

Hazard ratio 95% confidence interval p-Value

AgeAt onset 0.81 0.64—1.03 0.08*

At surgery 0.87 0.76—0.99 0.04*

Gender 1.08 0.31—3.85 0.90Known syndrome 1.93 0.24—15.27 0.53Generalized seizures 0.49 0.13—1.91 0.31Seizure frequency 1.00 1.00—1.00 0.01*

Number of seizure types 1.60 0.83—1.13 0.67Neurological deficit 2.12 0.62—7.37 0.23Developmental delay 5.28 0.67—41.71 0.12*

Extended (vs. isolated) occipital 1.33 0.28—6.27 0.72EEG

(localizing, lateralizing ornonlateralizing)

— — 0.22

Localizable MRI lesion 0.24 0.05—1.14 0.07*

MEGIpsilateral occipital dipoles 1.00 0.99—1.02 0.60Ipsilateral extraoccipital dipoles 0.98 0.92—1.05 0.58Contralateral occipital dipoles 1.16 1.03—1.30 0.02*

Contralateral extraoccipital dipoles 0.97 0.83—1.13 0.67Surgery

Grid placement 1.23 0.35—4.36 0.75Residual ECoG spikes 0.43 0.05—3.47 0.42Post-operative ECoG normal/abnormal 14/4 7/2 1.00

Pathology(gliosis, dysplasia, tuber, tumor orvascular malformation)

— — 0.78

ECoG — electrocorticography; EEG — electroencephalography; MEG — magnetoencephalography.* Meets selection criteria (p < 0.20) for inclusion in multivariate regression model.

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Occipital lobe epilepsy in children: Characterization, evaluation and surgical outcomes 341

Figure 1 A 6-year old girl with medically intractable epileptic spasms underwent evaluation and a subsequent resective procedurefor focal extended occipital lobe epilepsy. (A) Coronal FLAIR MRI sequence showed a subtle temporooccipital focal cortical dysplasia;(B) a MEG dipole cluster was localized to the area of MRI abnormality; (C) intraoperative neuronavigation was planned by co-registration of subdural grid electrodes (pink circles) and MEG dipole clusters (green dots represent location of individual MEGdipoles). Solid yellow line indicates planned resection margins; and (D) resection of electrocorticographic epileptogenic zone andMEG dipole cluster.

Complications

The average intraoperative blood loss was 330.4 ± 223.0cc. Two patients (5%) had post-operative wound heal-ing problems with one of these developing an epiduralabscess, requiring drainage. One patient (2%) developed a

pseudomeningocele, which resolved with conservative man-agement. Nine patients (23%) developed an expected densehomonymous hemianopsia with an additional 6 (15%) hav-ing a quadrantanopia. Five patients (13%) with extendedOLE developed a transient hemiparesis, which improved onfollow-up.

Table 6 Factors correlating with unsatisfactory outcome on multivariate analysis.

Hazard ratio 95% Confidence Interval p-Value

AgeAt onset 1.42 0.78—2.60 0.25At surgery 0.83 0.60—1.13 0.23

Seizure frequency 0.99 0.99—1.00 0.59Number of seizure types 1.07 0.61—1.13 0.23Developmental delay 6939913 0—1.63 × 10278 0.96Localizable MRI lesion 4.46 0.11—185.52 0.43Contralateral occipital MEG dipoles 1.33 1.04—1.71 0.03

MRI — magnetic resonance imaging; MEG – magnetoencepahlography.

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Figure 2 Kaplan—Meier plot showing time-to-unfavourableseizure outcome for isolated and extended OLE. The esti-mated mean time to unfavourable outcome was 4.47(95%CI: 2.65—6.29) and 6.85(95%CI:5.04—8.66) for isolated andextended OLE respectively.

Discussion

The localization of OLE is difficult due to the deep locationof the occipital lobe relative to scalp EEG and the potentialfor rapid propagation of seizures through functional whitematter tracts (Babb et al., 1981; Kun Lee et al., 2005.This has led some authors to speculate that some formsof non-localizable epilepsy may have their onset within theoccipital lobes (Jobst et al., 2010). In OLE, the most commonfindings on scalp EEG are spikes and sharp waves in tempo-ral and temporooccipital regions (Williamson et al., 1992).Frequency of spikes in the occipital region is reported tobe as low as 17% interictally and 30% ictally (Aykut-Bingolet al., 1998) and false localization/lateralization of occipitalseizures may occur in up to 28% of scalp EEGs(Foldvary et al.,2001). Furthermore, occipital slowing may not be a localiz-ing sign, but rather a marker of diffuse underlying pathologyassociated with a poor overall prognosis(Aykut-Bingol et al.,1998).

While several studies have been previously publisheddescribing surgical outcomes in OLE (Fig. 3) (Aykut-Bingolet al., 1998; Barba et al., 2005; Bautista et al., 1999;Bidzinski et al., 1992; Binder et al., 2008; Blume et al.,1991; Boesebeck et al., 2002; Caicoya et al., 2007; Dalmagroet al., 2005; Jobst et al., 2010; Kun Lee et al., 2005;Kuzniecky et al., 1997; Olivier and Boling, 2000; Salanovaet al., 1992; Sturm et al., 2000; Tandon et al., 2009; Urbachet al., 2007; Williamson et al., 1992; Yun et al., 2006;Zentner et al., 1996), our study is the first to report theroutine use of MEG in the pre-surgical evaluation of this con-dition and to perform a multivariate regression to identifyindependent predictors of surgical success in OLE. The hightemporal resolution (millisecond-range) of MEG renders it anattractive tool in the clinician’s armamentarium to addressthe challenges in localization of OLE (Iwasaki et al., 2002;Tovar-Spinoza et al., 2008). With a mean follow-up of 3.1years, we report an overall 68% satisfactory seizure outcome

Figure 3 Trends in surgical outcomes for occipital lobeepilepsy over time with red point showing current study andnumbers in parentheses denoting number of subjects in study.There has been a steady trend towards more consistent surgicaloutcomes over time. (For interpretation of references to colorin this figure legend, the reader is referred to the web versionof this article.)

in this series, which is comparable to existing literature. Inour series, we also find that while there was no significantdifference in underlying epileptogenic pathology betweenthe patients with isolated and extended OLE, the former didnot undergo insertion of subdural grid electrodes. Rather,a strategy of MEG clusterectomy and/or lesionectomy wasemployed with no difference in seizure outcome betweenthose who did or did not have subdural grid insertion. MEGmay therefore play a role in guiding less invasive surgicalstrategies in selected patients with OLE. This is an impor-tant finding as previous studies have suggested that subduralelectroencephalography is necessary in order to delineateseizure foci in the occipital lobes (Blume et al., 2005; Jobstet al., 2010).

We have previously reported that interictal MEG clusters(≥20 spikes in 1-cm area) correlate with electrocortico-graphic data (Iida et al., 2005). In two patients examinedin this study, (pathologies: FCD and chronic infarct), MEGfindings were discordant with scalp EEG. The MEG dipolecluster co-localized with the MRI lesion and in the for-mer and was posterior to the lesion in the latter. Bothunderwent lesionectomy and MEG clusterectomy withoutsubdural grid electrode implantation and both achieved sat-isfactory outcomes. MEG may therefore be of some utilityin the localization of OLE in the context of non-localizingor falsely-localizing scalp EEG. This has been previouslyobserved in other extratemporal epilepsies (Fischer et al.,2005; Gonzalez-Martinez et al., 2007).

In OLE, seizure patterns may vary considerably due tovariable spread patterns as opposed to temporal and frontallobe epilepsies, where seizures are more stereotyped.Spread below the Sylvian fissure to the temporal lobe mayproduce partial seizures with automatisms, while spreadto the lateral frontal cortex produces focal sensory andmotor seizures and medial spread to the supplementarymotor region produces asymmetrical tonic seizures (Babbet al., 1981; Ludwig and Marsan, 1975; Salanova et al.,1992; Sveinbjornsdottir and Duncan, 1993; Williamsonand Spencer, 1986). Furthermore, multiple seizure spreadpatterns can be present in a single patient (Kun Lee et al.,

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Occipital lobe epilepsy in children: Characterization, evaluation and surgical outcomes 343

2005). In this study, we show that patients with extendedOLE have higher number of distinct seizure types thanthose with isolated OLE (p = 0.056). We also demonstratethat those with temporooccipital and isolated occipitallocalizations have significantly more non-visual auras andfewer complex partial seizures consisting of staring spellsrespectively.

Despite its shortcomings, scalp EEG remains the mostuseful diagnostic tool in the localization of epileptogenicfoci, particularly in patients with non-lesional neocorticalepilepsy (Hong et al., 2002). We show that patients withextended OLE showed a trend towards higher rates of local-izing interictal EEG compared with isolated OLE (p = 0.08).This may be due to of the deep anatomy of the occipital loberelative to the scalp electrodes, which hinders detection ofepileptic spikes confined exclusively therein. Other meth-ods of OLE localization, such as ictal SPECT may be falselylocalizing in up to 70% of patients with OLE (Jobst et al.,2010). In one study, ictal SPECT localized the lesion in only25% of patients who went on to be seizure-free and 57%of patients who continued to have seizures(Kun Lee et al.,2005). Likewise, while PET scans may be useful in localizingOLE, they too may lead to false localization and lateraliza-tion (Henry et al., 1991, Hong et al., 2002). In our study,too few patients underwent PET and ictal SPECT studies todescribe meaningful results.

In the literature, there has been a trend towards moreconsistent surgical outcomes for OLE over time (Fig. 3).Several factors have correlated with satisfactory seizureoutcomes in OLE. These include lateralizing seizure semi-ology, fewer seizures, shorter duration of epilepsy, normalexamination, decreased or absence of spiking followingresection on electrocorticography, normal post-operativeEEG, concordance of diagnostic modalities, resection offocal lesions, tumors (as opposed to developmental anoma-lies) and the completeness of resection (Aykut-Bingol et al.,1998; Barba et al., 2005; Boesebeck et al., 2002; Dalmagroet al., 2005; Kun Lee et al., 2005; Salanova et al., 1992). Weare aware of only one study that performed a multivariateregression analysis to identify predictors of seizure outcomefollowing neocortical resection (Yun et al., 2006). Indepen-dent predictors of seizure-freedom on multivariate analysisincluded focal lesion on MRI, correct localization by PET andlocalizing ictal EEG.

In the current series, older age at time of surgery, lesspre-operative seizure frequency, and fewer MEG dipoles inthe contralateral occipital lobe were significantly associatedwith a higher rate of satisfactory outcome on univariateanalysis. The finding that older age at time of surgery isassociated with better outcomes may be attributed to dif-ferent epileptogenic pathologies in respective age groups.When the patients were dichotomized by their median age(11 years), younger patients (≤11 years) were found to havea significantly higher incidence of FCDs compared to those 12years or older (50% vs. 15%; p = 0.04). Although the presenceof FCD or MCD was not predictive of unsatisfactory outcomein this series, it has been previously shown to correlate withworse outcomes in OLE (Aykut-Bingol et al., 1998). Addi-tionally, older patients may have had more relatively benignepilepsies that did not require early surgery.

The only significant independent predictor of unsatis-factory outcome on multivariate analysis was the presence

of more MEG dipoles in the occipital lobe contralateral toresection was associated with an unsatisfactory seizure out-come. This is not surprising as several studies show thatfailure to resect MEG dipoles correlates with post-operativeseizure recurrence(Colon et al., 2009; Knowlton et al., 2009;RamachandranNair et al., 2007). Furthermore, in one studyassessing clinical ictal patterns, bilateral occipital epilepto-genic foci was associated with a significantly higher rate ofgeneralized seizures compared to isolated occipital, tem-porooccipital or more extensive foci (Ludwig and Marsan,1975). The finding that extraoccipital MEG dipoles in thenon-epileptogenic hemisphere did not correlate with seizureoutcome may be due to the analysis of too few patients todetect a significant association or the bias introduced in theselection of surgical patients, who may be less likely to havecontralateral epileptogenic activity.

Limitations of the current series include the retro-spective analysis, single-institution experience and biasesintroduced in patient selection and chart review. In additionto the inclusion of MEG in pre-surgical evaluation, strengthsof this series include the review of an exclusively pediatricpatient population with OLE. Mean or median ages at timeof operation in published series range from 17 to 39 years,whereas the mean age of our patients is 10.5 years due to thefact that we have an exclusively pediatric practice. Becausewe routinely use MEG as per institutional protocol to evalu-able children prior to epilepsy surgery, we are unable toprovide recommendations as to when it may be adequateto proceed with surgery without MEG data. We do howeverprovide evidence that this modality may be beneficial in theclinicians’ armamentarium to address challenges associatedwith the localization of OLE.

Conclusion

In this series of 41 patients with OLE, after a mean follow-up of 3.1 years, 68% achieved a satisfactory seizure outcome(Engel I and II). We identify differences in populations withisolated and extended OLE, with the latter presenting witha greater number of distinct seizures types at earlier ages.No patients with isolated OLE underwent subdural grid elec-trode implantation. Seizure outcome was not associatedwith surgical strategy or seizure location, and the onlysignificant independent predictor of good outcome on mul-tivariate analysis was the presence of fewer MEG dipoles inthe occipital lobe contralateral to resection. We thereforedescribe the utility of MEG in seizure localization, surgicalplanning and its potential use in prognostication of outcomesin patients with OLE. Additional studies are required to con-firm these findings in this small, retrospective series.

Source of support (if applicable)

There are no sources of support for this manuscript. It hasnot been published or presented in any form.

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