Platform Sessions - Wiley Online Library

Epilepsia, 52(Suppl. 6): 4–22, 2011 doi: 10.1111/j.1528-1167.2011.03206.x

29TH IEC PROCEEDINGS

29th International Epilepsy Congress, Rome, 28 August–1 September 2011 Platform Sessions Monday, 29 August 2011 14:30–16:00 Hall 2 Platform Session 1 Pediatric epilepsy: Triggers, language and spasms

002 RELATION BETWEEN VACCINATION AND OCCURRENCE OF SEIZURES IN SCN1A MUTATION POSITIVE PATIENTS: THE FIRST ITALIAN MULTICENTRIC STUDY Petrelli C1, Passamonti C1, Baldassari C2, Verrotti A3, Capovilla G4, Viri M5, Coppola G6, Vignoli A7, Zamponi N1 1 Department of Pediatric Neurology, Ospedali Riuniti, Ancona, Italy, 2Department of Child Neurology and Psychiatry, Istituto Neurologico C. Mondino, Pavia, Italy, 3Department of Pediatrics, University of Chieti, Chieti, Italy, 4Department of Child Neuropsychiatry, Epilepsy Center, C. Poma Hospital, Mantova, Italy, 5Epilepsy Center, San Paolo Hospital, Milano, Italy, 6Clinic of Child Neuropsychiatry, Second University of Naples, Naples, Italy, 7Department of Child Neuropsychiatry and Neurophysiology, Epilepsy Center, Fatebenefratelli e Oftalmico Hospital, Milano, Italy

001 SEIZURE TRIGGERS IN CHILDREN WITH SCN1A-RELATED EPILEPSY Sanchez-Carpintero R1, Urestarrazu E1, Perea DA2, Aznarez N1, Narbona-Garcia J1 1 Clinica Universidad de Navarra, Pamplona, Spain, 2Hospital Donostia, San Sebastian, Spain Purpose: Seizures in SCN1A-related epilepsy (SCN1A-RE), are frequently precipitated by fever. Other stimuli have also been recognized to trigger seizures such as visual patterns, intermittent photic stimulation and constant light brightness. We looked at the frequency that sensory stimuli triggered seizures in children with SCN1A-RE. Because seizure precipitants are often recognized in children with frequent seizures, we used a control group of children with drug-resistant epilepsy other than SCN1A-RE.

Purpose: Relation between epileptic seizures and vaccinations in patients with Dravet syndrome (DS) is currently debated. The present work was aimed to delineate the effects of vaccination on seizures' onset and clinical outcome in patient with DS or GEFS+ phenotype. Method: Sixty-one patients (median age at inclusion: 9 years) with diagnosis of DS (52) or GEFS+ (9), all carrying SCN1A mutations, were included. Additional eleven patients with the same clinical diagnosis but no mutation were selected as controls. Information on vaccination type, temporal relationship between vaccination and first seizure, seizure type, developmental quotient (DQ), number of status epilepticus (SE) and vaccinations’ completion was obtained by review of clinical records and parental interviews. On the basis of the temporal relationship (in days) between vaccination and seizure's onset, patients were divided into two groups (Proximate: 2 days).

Method: A questionnaire on seizure triggers was filled-in by caregivers of 38 children with epilepsy. Twenty-four had SCN1A-RE and 14 had drug-resistant epilepsy of different origin. Type of triggering stimulus and frequency of seizure triggering were recorded in both groups. Results: Fever triggered seizures in 100% of children with SCN1ARE versus 53% in the control group. Temperature changes provoked by cold or hot baths or extreme ambient temperature triggered seizures in 91% of SCN1A-RE versus 28% in control patients. Intermittent light, visual patterns or light brightness triggered seizures in 46% and 28% of children with SCN1A-RE and controls respectively. Other stimuli (noises, music, touch or startle) triggered seizures in 8– 16% of patients in both groups. Curiously 25% of children with SCN1A-RE but none in the control group had seizures triggered by eating. In total, 54% of SCN1A patients have seizures triggered by any sensory stimuli other than temperature versus 36% in the control group. A child with Dravet syndrome developed myoclonic seizures when certain type of music was played. Ictal EEG showed a focal origin of the seizure.

Results: Twenty-five percent of SCN1A mutation positive patients enter the proximate group, compared to 18% of SCN1A negative patients (ns). No significant differences between proximate and distant group was observed in seizure type, number of SE, DQ at 2 years and clinical phenotype (DS or GEFS+). Age at seizure onset was significantly earlier in proximate group (4.6 months vs. 7 months). These patients were also more likely to discontinue vaccination Conclusion: Vaccination-related seizures are present in about 25% of DS and GEFS+ patients, regardless of SCN1A mutation. In this subset of patients preventive measures for subsequent vaccinations should be considered. However, a close relationship between seizure's onset and vaccination does not affect clinical and cognitive evolution.

Conclusion: Fever and other changes in temperature are very specific triggers of seizures in children with SCN1A-RE. Triggers related to other sensory stimuli are also reported by caregivers but the same is found, although less frequently, in children with severe epilepsy. A role of sensory cortex or thalamic hiperexcitability can be speculated for this sensitivity to sensory stimuli in children with SCN1A-RE. We could demonstrate in one case that the triggering factor provoked a true reflex seizure.

003 FUNCTIONAL CONNECTIVITY OF LANGUAGE ACTIVATION IN CHILDHOOD FOCAL EPILEPSY Sepeta L1, Zimmaro LA1,2, Duke ES1, Berl MM1, VanMeter J3, Vaidya CJ1, Yerys B1, Gaillard WD1,2

4

5 29th IEC Proceedings 1

Children's National, Washington, DC, U.S.A., 2NIH NINDS, Bethesda, MD, U.S.A., 3Georgetown University, Washington, DC, U.S.A.

Purpose: Language processing requires coordinated activity between spatially remote brain regions. Functional connectivity (fcMRI) can quantify this synchronous processing. Functional connectivity between language regions is different in adult patients with left lateralized epilepsy compared to controls. We examined functional connectivity of language networks in children with focal epilepsy. Method: We studied children with left hemisphere focal epilepsy and normal MRI (n = 40; mean age = 8.6 € 2.5 years; range 4–12 years) and healthy controls (n = 58; mean age = 8.8 years € 2.6; range 4– 12 years). We used a region of interest (ROI) based linear correlation coefficients fcMRI method to assess functional connectivity during an auditory description decision task. Three ROIs were selected based on previous study of language networks: Wernicke's area (WA), inferior frontal gyrus (IFG), and middle frontal gyrus (MFG). Time series data for each subject was extracted for the three left ROIs and their right homologues. Results: Overall functional connectivity between inter- and intrahemispheric pairs of language regions did not differ by group (p > 0.18). However, functional connectivity between two inter-hemispheric pairs of language regions was decreased in the patients compared to controls: Left WA-Left IFG (p < 0.01) and Left IFG-Left MFG (p < 0.001). There was no difference in overall connectivity between those with recent onset and chronic focal epilepsy (p > 0.86) or for each of the nine connections (p > 0.15). Conclusion: Left sided language network functional connectivity is decreased in the primary language processing regions during a language task in children with left lateralized focal epilepsy compared to controls; these differences are present at the onset of epilepsy.

004 THE ASSOCIATION BETWEEN FREQUENCY OF NOCTURNAL EPILEPSY AND LANGUAGE DISTURBANCE IN CHILDREN Overvliet GM1,2,3, Besseling R3, Vles J1,2, Hofman P3, Debeij-van Hall M1, Backes W3, Aldenkamp A1,2 1 Epilepsy Center Kempenhaeghe, Heeze, The Netherlands, 2 Maastricht University Medical Center, Maastricht, The Netherlands, 3Department of Mental Health and Neuroscience, University Maastricht, Maastricht, The Netherlands Purpose: In clinical practice, an association is commonly suggested between nocturnal epileptiform activity and language disorders in children. However, this is not studied systematically. The aim of the study was to explore the correlation between daily and nocturnal epileptiform discharges ratio, frequency of nocturnal epileptiform discharges, severity of nocturnal seizures in correlation with the severity of language impairment. Method: Three hundred twenty-six children referred to the epilepsy center Kempenhaeghe were included. All children had a 24 h electroencephalogram, a neuropsychological assessment and a reconfirmed diagnosis of epilepsy. We focussed on the balance between verbal and performance IQ scores of the Wechsler Intelligence scale for children. Results: A significant correlation between the severity of nocturnal seizures and lower verbal IQ scores compared with performance IQ scores was found (p < 0.05). There was a clinically relevant difference between performance IQ and verbal IQ between the groups of children with only nocturnal epileptiform EEG discharges and only epileptiform EEG discharges during wake (p = 0.033).

Conclusion: Children with nocturnal epileptiform EEG discharges have lower verbal than performance IQs when compared with children with only epileptiform EEG discharges during wake. Although a causal relationship is unclear, this indicates an association between the occurrence of nocturnal epileptiform EEG discharges and language disturbance.

005 LATERALIZING SIGNS IN INFANTILE SPASMS: DIFFERENCES IN VIDEO AND EEG ANALYSIS Dressler A1, Klaus M-T1, Muehlebner A1, Moerzinger M1, Pahs G1, Benninger F2, Feucht M1 1 Universittskinderklinik, Medizinische Universitt Wien, Wien, Austria, 2Department of Adolescence and Child Neuropsychiatry, Medical University of Vienna, Vienna, Austria Purpose: Seizure phenomenology is important for the identification of the epileptogenic zone. A variety of so-called clinical lateralizing signs have been reported almost exclusively in adults and older children (primarily in patients with temporal lobe epilepsy). Data on reliable lateralizing features in infants, especially those with infantile spasms are scarce as the repertoire of seizure manifestation in the first 3 years of life appears to be limited. However, focal clonic or tonic activity, version, nystagmus and postictal hemiparesis were found consistently contralateral to the hemisphere of seizure-onset in some studies (Hamer et al 1999; Loddenkemper et al 2004; Acharaya et al 1997; Fogarasi et al 2005– 2007). Our objectives were to identify reliable lateralizing signs in children with symptomatic infantile spasms. Method: Forty-two infants with localization-related infantile spasms who were referred to the Pediatric Epilepsy Monitoring Unit at the Medical University of Vienna between October 1997 and January 2009 were included. In an open-label, retrospective, double blind study all arifact-free seizures recorded during long-term monitoring were analyzed. Results: Specific clinical features included tonic phenomena seen primarily on the ipsilateral side and clonic phenomena seen mostly contralateral to the seizure-onset zone. Myoclonic phenomena were predominantly bilateral. Unilateral elementary automatisms and eyelid myoclonias were found significantly more often ipsilateral. EEG and video seemed to have a higher specificity with regard to lateralization than video alone: Ictal and interictal unilateral fast activity, as well as unilateral slow waves, were the most reliable EEG patterns. Conclusion: Candidacy for surgery in infantile spasms is usually evaluated on the basis of ictal and interictal long-term video-EEG and MRI. However, our results show that clinical phenomenology is helpful also in these patients in defining the epileptogenic zone.

006 RELATIONSHIP BETWEEN INITIAL EEG CHARACTERISTICS AND SEIZURE OUTCOMES IN THE CHILDREN OF INFANTILE SPASMS WITH NORMAL MRI FINDING Yeon GM, Kim YM, Nam SO, Lee Y-J Pusan National University Children's Hospital, Yangsan-si, Korea Purpose: To characterize the initial interictal electroencephalography (EEG) activities associated with seizure outcomes in children of infantile spasms (IS) with normal MRI finding and their worth in predicting the outcomes of seizure-free (SF) versus no seizure-free (NoSF).

Epilepsia, 52(Suppl. 6):4–22, 2011 doi: 10.1111/j.1528-1167.2011.03206.x

6 29th IEC Proceedings Method: We retrospectively reviewed the initial scalp EEGs of at least 30 min duration and medical records of 58 children who were diagnosed as IS without MRI lesion in our hospital and were followed for 4.2 € 2.1 years. We assessed the following clinical and EEG findings; seizures onset, development, underlying etiologies, initial interictal EEGs, and seizure evolution. These variables were compared between two groups of SF versus NoSF who had incompletely controlled or relapsed seizures. Results: Thirty (51.7%) children had SF outcomes and 28 (48.3%) had NoSF outcomes during long-term follow-up (4.1 € 2.3 vs. 4.2 € 2.0 years). Age at seizure onset was similar in SF and NoSF groups (5.0 € 3.0 vs. 6.4 € 3.2 months). Time lag between seizure onset and the start of medication was similar in SF and NoSF groups (1.7 € 1.6 vs. 1.4 € 0.8 months). Delayed development before spasms was similarly observed in two groups (33.3% vs. 53.6%). Preceding other seizures were more frequently seen in NoSF than SF group (25.0% vs. 6.7%, p = 0.054). Initial EEG findings significantly differed with posterior-dominant generalized epileptiform discharges (ED) (50.0% vs. 3.6%, p = 0.0001) and normal or borderline sleep spindle (SS) (60.0% vs. 28.6%, p = 0.016) being involved more often in SF group, and typical hypsarrhythmia (78.6% vs. 50.0%, p = 0.024), multiple independent spike foci (75.0% vs. 46.7%, p = 0.028), frontal-dominant generalized ED (17.9% vs. 0.0%, p = 0.008) or frontal-dominant focal ED (7.1% vs. 0.0%, p = 0.023), and no normal SS (71.4% vs. 40.0%, p = 0.016) involved more often in NoSF group. Conclusion: Initial interictal EEG findings may predict seizure outcomes in patients of IS without MRI lesion. Patients with SF outcomes showed the posterior-dominant generalized ED and normal or borderline SS, and NoSF group had more often typical hypsarrhythmia, frontaldominant generalized or focal ED and no normal SS.

Monday, 29 August 2011 14:30–16:00 Hall 3 Platform Session 2 Death, injuries and epilepsy 007 POSTICTAL DECEREBRATE RIGIDITY: CLINICAL EVIDENCE OF THE INVOLVEMENT OF CEREBRAL ELECTRICAL SHUTDOWN COMBINED WITH RESPIRATORY DISTRESS AS A POSSIBLE MECHANISM OF SUDEP Cenusa M, Mothersill IW, Grunwald T, Krmer G Swiss Epilepsy Center, Zrich, Switzerland Purpose: To supply clinical evidence of the possible involvement of cerebral electrical shutdown combined with cerebral hypoxia/anoxia in the mechanism of SUDEP. Method: EEG-video intensive monitoring of a 17-year-old female patient with cryptogenic epilepsy. Results: During monitoring a secondary generalized seizure was recorded, seizure origin in the surface EEG being left frontal. Postictally typical flattening of the EEG was observed. Despite being put into a semi-prone position, severe respiratory distress with hypoventilation and apnoeic phases occurred during the immediate postictal phase, the EEG during this phase remaining flat. After approximately 1 min the patient presented with opisthotonic posturing typical for decerebrate rigidity. The opisthotonus and CES ended after respiration spontaneously normalized.


Conclusion: In cases SUDEP recorded in the EEG it has been postulated that a massive, prolonged postictal irreversible flattening of the EEG, so called cerebral electrical shutdown causes death due to centrally mediated cardiorespiratory failure. It has however been shown that a prolonged flattening of the EEG and associated cardiovascular dysfunction requires additional lowering of blood oxygen content e.g., due to respiratory dysfunction and that restored ventilation can prevent cardiovascular dysfunction. Although not resulting in SUDEP our case with severe postictal respiratory distress associated with clinical anoxic signs, decerebrate rigidity, and prolonged flattening of the EEG supplies further evidence to support the hypothesis that postictal hypoventilation can lead to failure of recovery of cortical function and subsequent cardiac failure. In such cases respiratory distress causes a ‘‘normal’’ postictal EEG flattening to become a life threatening event.

008 CAUSE-SPECIFIC MORTALITY AMONG PATIENTS WITH EPILEPSY: RESULTS OF A 40-YEAR COHORT STUDY Granbichler CA1,2, Oberaigner W3, Kuchukhidze G2, Unterberger I2, Ndayisaba J-P2, Bauer G2, Trinka E1,2 1 Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria, 2University Hospital for Neurology, Medical University of Innsbruck, Innsbruck, Austria, 3Institute for Clinical Epidemiology, TILAK, Innsbruck, Austria Objective: Death rates of epilepsy patients are two to three times higher than expected, but only few investigated the cause of the difference. Methods: Our outpatient epilepsy clinic prospectively enrolled all patients with confirmed epilepsy treated at between 1970 and 2009. Patients were followed until death or December 31, 2009. Standardized mortality ratios (SMRs) were calculated using reference rates from the same region. Results: After 63,366.75 person years of follow-up, 826 of 4752 patients had died, leading to an age-adjusted overall SMR of 1.7 (95% CI, 1.6–1.9). The highest SMRs were for patients during the first year following diagnosis (2.3 [95% CI 1.8–2.9]), those with more than four antiepileptic drugs used in history (2.3 [95% CI 1.6–3.2]), recurrent seizures (2.2 [95% CI 2.0–2.4]), generalized epilepsies (2.0 [95% CI 1.7–2.3]), and status epilepticus in their histories (2.0 [95% CI 1.5– 2.6]). The highest cause-specific SMRs were for epilepsy (68.3 [95% CI, 52.0–88.1]), brain tumors (14.6 [95% CI, 11.0–19.1]), congenital anomalies (6.5 [95% CI 2.1–15.2]), and suicide (4.0 [95% CI, 1.8– 7.5]). Conclusion: Epilepsy patients have a higher than expected risk of death throughout life and especially during the first year following diagnosis. Ongoing seizure activity and a high number of antiepileptic drugs results in particularly high risk. Generalized epilepsies and previous status epilepticus are strongly related to excess mortality.

009 CIRCADIAN SEIZURE PATTERNS IN SUDEP: PATIENTS WITH NOCTURNAL SEIZURES ARE AT HIGHEST RISK Lamberts RJ1, Laffan A2, Thijs RD1,3, Sander JW1,4, Langan Y2 1 Epilepsy Institute in the Netherlands Foundation, Heemstede, The Netherlands, 2St. James's Hospital, Dublin, Ireland, 3Leiden University Medical Center, Leiden, The Netherlands, 4UCL Institute of Neurology, London, United Kingdom

7 29th IEC Proceedings Purpose: Most people with epilepsy who die suddenly are found in or by the bed. We therefore analyzed (1) whether people with SUDEP are more likely to have nocturnal seizures. (2) whether seizure patterns (diurnal vs. nocturnal) differ between people who died of SUDEP and living epilepsy controls. Methods: We have used the cohort of a SUDEP case–control study that consisted of 154 autopsy-confirmed SUDEP cases and 616 living epilepsy controls. (Langan et al. Neurology 2005; 64: 1131–1133). Information on seizures patterns in the last 3 months was extracted from questionaires. Seizure patterns were classified as ‘‘exclusively diurnal’’ or ‘‘including nocturnal seizures.’’ We assumed death occurred in sleep for cases found in bed, or by the bed with additional seizure evidence. Cases found outside the bedroom were assumed to be awake at time of death. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. The variable ‘‘seizure patterns’’ was then added to the regression model used in the original analysis to establish if it was an independent predictor for SUDEP. Results: (1) People who died of sleep-related SUDEP were more likely to have a history of nocturnal seizures: OR 3.6. 95% CI 1.4– 9.4. (2) Compared to living epilepsy controls, people who died of SUDEP more frequently had a history of nocturnal seizures: OR 3.9. 95% CI 2.5–6.0. When correcting for other known SUDEP risk factors in the logistic regression model, ‘‘nocturnal seizures’’ remained significant. Conclusions: Nocturnal seizures seem an independent risk factor for SUDEP. These findings underscore the importance of preventive measures including night supervision.

010 EFFECT OF INTERICTAL EPILEPTIC ACTIVITIES ON HEART RATE VARIABILITY IN UNILATERAL TEMPORAL LOBE EPILEPSY Kinoshita M1, Demura Y1, Matsumoto R2, Ikeda A2 1 Utano National Hospital, Kyoto, Japan, 2Graduate School of Medicine, Kyoto University, Kyoto, Japan Purpose: To investigate whether interictal epileptic activities affect heart rate variability in patients with temporal lobe epilepsy of unilateral foci. Method: Data was obtained from eight adult patients with clinically defined unilateral temporal lobe epilepsy (mean age 39 years). Four patients had epileptic focus on the right side and four had on the left. All patients were right handed. Seizure frequency was monthly in two patients and yearly in six patients. Electroencephalography (EEG) and electrocardiography (ECG) were recorded digitally during sleep. Twenty events of interictal EEG epileptic activities (spikes, sharp waves, and rhythmic slow activities; 12 left-sided events and eight right-sided events), any of which was neither followed nor preceded by another one at least for 80 s, were selected. Heart rate variability indices of high frequency component (HF) associated with cardiac parasympathetic tone, low frequency component (LF), and their ratio (LF/HF) associated with cardiac sympathetic tone, were analyzed using ECG of 30 s each before and after events. Results: HF both before and after right-sided events was significantly lower than those of left-sided events. HF significantly increased after left-sided events. LF/HF after left-sided events was significantly lower than that of right-sided events (p < 0.05, Wilcoxon signed-rank test and Mann–Whitney test). Conclusion: Our data suggest that cardiac parasympathetic tone may be chronically suppressed in patients with epileptogenic foci in right temporal lobe, and that cardiac parasympathetic tone may increase after interictal epileptic activities in left temporal lobe, possibly in association with decreased sympathetic tone.

011 THE FREQUENCY AND ASSOCIATED RISK FACTORS OF SEIZURE-RELATED INJURY, NEAR-DROWNING AND VEHICULAR CRASHES IN A COMMUNITY SAMPLE OF PATIENTS WITH EPILEPSY D’Souza WJ1,2, Tan M1, Ficker D3, O’Brien T4, Cook M1 1 Department of Medicine, St Vincent's Hospital Melbourne, The University of Melbourne, Melbourne, Vic., Australia, 2Centre for MEGA Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Vic., Australia, 3 Department of Neurology, University of Cincinnati Academic Health Center, Cincinnati, OH, U.S.A., 4Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Vic., Australia Purpose: The epidemiology of injury, near drowning and vehicular crashes in patients with epilepsy (PWE) has mostly been researched in hospital samples, which are prone to selection bias. We investigated the frequency and risk factors of seizure-related injury, near drowning and vehicular crashes in a community-treated sample of PWE. Method: The Australian national prescription database was used to recruit patients with epilepsy onto the Tasmanian Epilepsy Register (TER). Baseline assessment included assessment of lifetime and 12 month frequency of injury, near-drowning and vehicular crashes by validated interviewer-administered questionnaire. Univariate analysis was performed to identify potential risk factors (p < 0.05) and stepwise logistic regression with likelihood ratio tests performed on variables identified in the univariate analysis (p < 0.05). Results: Of the 1180 initially enrolled on the TER, 1101 were subsequently available (43 withdrew, 36 died) with 997 (90.6%) completing interviewing. Eight hundred sixty-six were included in the injury and near-drowning analyses (excluding nonepileptic seizures and uncertain seizures). In addition, 679 were only included in the driving analyses (age >16 years, no physical or cognitive disability to driving). The estimated lifetime and 12 month frequency was: any injury 203 (20.4%), 63 (6.3%); bathing or swimming 74 (7.4%); 18 (1.8%), vehicular crash 75 (7.5%), 5 (0.5%). Head injuries (8.6%) and burns/scalds (6.0%) were the most common specific types. Multivariate analysis revealed: younger age of epilepsy onset, poor seizure-control (seizure in last 12 months, emergency department presentation in last 12 months) and a diagnosis of IGE were independent risk factors for seizure-related injury. Treatment with single antiepileptic drugs was protective. Conclusion: Consistent with previous studies, younger age of epilepsy onset, poor seizure control, and refractory disease are independent risk factors for seizure-related injury. In addition, a diagnosis of IGE was also found to be a risk factor. Poor seizure control and refractory disease were also independent risk factors for swimming/bathing related accidents. No independent risk factors for vehicular crashes were demonstrated.

012 REDUCED HEART RATE VARIABILITY IS ASSOCIATED WITH ICTAL HYPOXEMIA Bateman LM, Wong V, Pathak SR, Seyal M University of California, Davis, Sacramento, CA, U.S.A. Purpose: Respiratory and cardiac dysfunction have been proposed as contributors to SUDEP. Low HRV suggests abnormal autonomic regulation and has been associated with increased mortality. It is not clear whether cardiac and respiratory dysfunction associated with seizures are related or independent processes. Method: We reviewed EEG and EKG recordings of patients who underwent elective inpatient video-EEG telemetry monitoring for medically intractable partial epilepsy. We evaluated 96 temporal onset seizures with accompanying oxygen saturation data, chosen consecutively by degree Epilepsia, 52(Suppl. 6):4–22, 2011 doi: 10.1111/j.1528-1167.2011.03206.x

8 29th IEC Proceedings of oxygen desaturation. Normal to normal RR intervals (NN) were measured for a 1-min interval during each seizure, beginning at the point of oxygen saturation nadir. In seizures with no significant desaturation, measurements were obtained starting at the time of mean desaturation nadir across all other seizures (1:30 after seizure onset). Results: Thirty-two seizures had no oxygen desaturations 6 months. All patients reported ‡1 adverse event (AE), mostly grade 1/2 in severity and consistent with those previously reported, and none led to everolimus discontinuation. During the entire study, single cases of grade 3 drug-related AEs were reported at 36 months (neutropenia); no drug-related grade 4 events were reported. Conclusion: This study confirmed benefits and safety of long-term everolimus therapy for treatment of TSC patients with SEGA. In patients who received everolimus ‡3 years, effect on tumor burden was maintained, the drug was well-tolerated, and no new safety concerns emerged. Acknowledgment: Funding for this research supported by Novartis Pharmaceuticals, Inc.

024 PRENATAL EXPOSURE TO ANTIEPILEPTIC DRUGS: COGNITIVE FUNCTIONING AT 6 YEARS OF AGE Bromley RL1, Shallcross R2, Gummery A3, Mawer G4, ClaytonSmith J4, Briggs M4, Cheyne C5, Garca-FiÇana M5, Baker G2, Liverpool and Manchester Neurodevelopment Group 1 University of Manchester, Manchester, United Kingdom, 2 University of Liverpool, Liverpool, United Kingdom, 3The Walton Centre for Neurology and Neurosurgery, Liverpool, United Kingdom, 4Manchester Biomedical Research Centre, Manchester, United Kingdom, 5Department of Biostatistics University of Liverpool, Liverpool, United Kingdom Purpose: To investigate the potential effects posed by antiepileptic drugs (AEDs) on the cognitive functioning of the child exposed in utero. Method: Women with epilepsy (WWE) and control women without epilepsy were recruited prospectively from antenatal clinics. Blinded Epilepsia, 52(Suppl. 6):4–22, 2011 doi: 10.1111/j.1528-1167.2011.03206.x

12 29th IEC Proceedings assessments were completed at 6 years of age. Multivariate analyses were conducted to control for the influence of confounding variables on specific areas of cognitive development and functioning. Results: Prenatal exposure to sodium valproate (VPA, n = 51) was associated with a significant decrease in scores for general cognitive ability (p < 0.001), language comprehension (p < 0.001), expressive language (p < 0.001), memory (p < 0.001), auditory attention (p < 0.001) and rate of learning (p < 0.001). Increased incidence of educational needs (p < 0.001) and speech therapy (p < 0.001) were also found for the children exposed to VPA. The risk of cognitive difficulties was larger than that of major congenital malformations for those exposed to VPA prenatally. Prenatal exposure to carbamazepine (n = 50) or lamotrigine (n = 30) was not associated with poorer cognitive outcomes at 6 years of age in the multivariate model. Conclusion: Preconceptual counselling for WWE who are currently prescribed or who are considering VPA must include information surrounding the cognitive outcomes in the future child. Children with a history of prenatal exposure to VPA should be monitored closely during early childhood to allow for early intervention. Further prospective research is required to investigate the possible presence of milder cognitive impairments following prenatal exposure to other AEDs.

Tuesday, 30 August 2011 14:00–15:30 Hall 3 Platform Session 5 Global outreach 025 THE PREVALENCE OF EPILEPSY, TREATMENT GAP AND EDUCATION LEVELS OF PEOPLE LIVING WITH EPILEPSY IN MALAWI Amos A1, Wapling L2 1 Federation of Disability Organisations in Malawi, Blantyre, Malawi, 2DFID, London, United Kingdom Purpose: The objectives were to determine prevalence of epilepsy, treatment gap, education levels gender and age distribution of people with epilepsy. Method: (1) Convenience sampling, (2) random sampling. Population of 10,230 from seven districts whose population represents 38% of the whole country. Data collection: Household surveys, Study of epilepsy patient's records, observation of health facilities, interviews. Data Analysis and Reporting: Qualitative and quantitative. Results: Prevalence: Prevalence rate is 28 per 1000 people. Distribution by Gender and Age: Men are 55% with the rest being women. The most affected age groups are 6–18 with 48%, followed by the 19–40 with 24% and then 0–5 with 17%. Treatment Gap: The treatment gap is 32% due to social perspectives, poor healthcare and pharmacotherapy systems. Education Levels: Sixty-nine percent of the people with epilepsy have never been to school, with average year of education been 4 years for females and eight for males. Conclusion: Communities and professionals lack awareness on epilepsy and with strong cultural beliefs surrounding the condition many remain undiagnosed and diagnosed are not compliant. Gearing up campaign for epilepsy is necessary. Development of a national association and national plan will help the prioritization and inclusion of epilepsy in the essential health package. The national plan should cover all spheres of epilepsy Epilepsia, 52(Suppl. 6):4–22, 2011 doi: 10.1111/j.1528-1167.2011.03206.x

such as health, disability, education, women, children and youth. Strengthening the epilepsy capacity of service providers in health and education. More research to be done on epilepsy mainly on women and children. Collaboration with international institution working on epilepsy.

026 AN ANTHROPOLOGICAL STUDY ON EPILEPSY AMONG GUARAN COMMUNITIES IN BOLIVIA Bruno E1, Bartoloni A2, Sofia V1, Rafael F3, Magnelli D2, Ortiz E4, Padilla S4, Quattrocchi G1, Bartalesi F2, Segundo H5, Zappia M1, Preux PM3, Nicoletti A1 1 Department of Neurosciences, University of Catania, Catania, Italy, 2Infectious and Tropical Diseases Unit University of Florence, Florence, Italy, 3Institute of Neuroepidemiology and Tropical Neurology (EA 3174), Limoges, France, 4Centre of Antropological Researches of the Teko Guaran, Camiri, Bolivia, 5Servicio Departamental de Salud, Santa Cruz, Camiri, Bolivia Purpose: This study was performed to analyse sociocultural beliefs about epilepsy among Guaran communities in Bolivia. Method: The fieldwork was carried out through focus group discussions (FGD) and semistructured interviews conduced in the local language. People with epilepsy (PWE), their family members and general population of the communities were interviewed about the meaning, beliefs, feelings and practices toward epilepsy. An interview directed to the local health care personnel was also realized. Results: Epilepsy is called ‘‘mano-mano,’’ a term that means being in a constant passage between life and death. The disease was mainly attributed to the nonobservance of a fasting period and to others eating habits. Natural remedies were the most recommended treatments. The restrictions highlighted concerned especially performance activities and establishing relationships. Half of respondents reported that the use of antiepileptic drugs (AEDs) could be effective for controlling epilepsy but more than a quarter do not trust ‘‘white doctors.’’ Conversely local nurses seem to be well accepted by the communities. Conclusion: The conception of epilepsy as an embodied disease with natural causes appears to differ from that documented in others traditional societies. PWE do not represent a threat for the community that seems to have an attitude aimed at their protection. Moreover people from these communities appear to be in favour of a combination of biomedical and traditional care systems in which the local health care personnel might assume a very important role

027 EPILEPSY AWARENESS AMONG STUDENTS: AN OBSERVATION IN METROPOLITAN CITY OF DELHI, INDIA Bala K, Khurana S, Sharma V, Singh R Institute of Human Behavior and Allied Sciences (IHBAS), Delhi, India Purpose: To assess the knowledge and attitude towards epilepsy among students and to find out the need for health education training in schools of metropolitan city, Delhi, India Method: Knowledge and attitude assessment of students was done before and after health care awareness program using a semistructured questionnaire comprising 20 questions. Students from 10 schools of Delhi (five govt. and five govt. aided) were assessed. Results: A total of 2259 students (12–19 years of age) were assessed. The level of awareness was categorized into four groups—poor

13 29th IEC Proceedings knowledge group (PKG), fair knowledge group (FKG), good knowledge group (GKG) and very good knowledge group (VGKG). Before conducting awareness programs, 49% were in GKG, 39.3% in FKG, whereas, very few students were in PKG and VGKG ie. Fifteen percent and 0.5% respectively. The post–awareness assessment showed statistically significant improvement among student's knowledge and attitude ie 84% students in GKG with a 35% increase from preawareness levels, whereas, only 10.4% were in FKG group. A significant decrease in number of students in PKG group, from 15.0% to 0.4%and a significant increase in VGKG group was observed, ie., from 0.5% to 4.8%.

1

Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, 2Bong-Seng Memorial Hospital, Pusan, Korea, 3 CHA University, Bundang, Korea, 4University of Ulsan, Ulsan, Korea, 5SoonChunHyang University, Cheonan, Korea, 6Hanil Hospital, Seoul, Korea, 7University of Ulsan, Gangneung, Korea, 8Hallym University, Chuncheon, Korea, 9Yonsei University College of Medicine, Seoul, Korea, 10Gyeongsang National University, Pusan, Korea

Conclusion: Although, overall levels of awareness amongst students ranged from fair to good, health care awareness program resulted in a significant shift of response towards good knowledge group. Regular awareness programs may, thus, be beneficial in knowledge upgradation of students leading to wider social acceptance of Epilepsy.

Purpose: The stigmatizing nature of epilepsy and its associated psychological distress have a significant impact on the quality of life in individuals with epilepsy. However, the factors generating feelings of stigma are not fully known. So, we investigated which factors predict the development of the perceived stigma for 1 year after the diagnosis in people with newly diagnosed epilepsy.

028 THE RISK FACTORS FOR EPILEPSY TREATMENT GAP AND NONADHERENCE TO ANTIEPILEPTIC DRUGS IN KILIFI, KENYA Mbuba CK1, Ngugi AK1, Muchohi SN1, Edwards T2, Odermatt P3, Carter JA4, Newton CR1 1 KEMRI-Wellcome Trust Research Program, Kilifi, Kenya, 2 London School of Hygiene and Tropical Medicine, London, United Kingdom, 3Swiss Tropical and Public Health Institute, Basel, Switzerland, 4University College London, London, United Kingdom

Method: People with newly diagnosed epilepsy were recruited from 10 university hospitals in Korea. Data were collected initially at the time of diagnosis and 1 year later. Clinical information about seizures was obtained by neurologists, and other information was collected from selfcompleted questionnaires. Baseline questionnaires included stigma scale, Rosenberg Self-esteem Scale, Eysenck Personality Questionnaire (short form), Stress Coping Style Checklist, and Hospital Anxiety Depression Scale. Follow-up questionnaires included stigma scale, disclosure management items, Social Support Scale, questionnaire for episodes of discrimination, and QOLIE-31.

Purpose: Many people with epilepsy (PWE) in resource poor countries do not receive appropriate treatment for their condition, a phenomenon known as the treatment gap (TG). We estimated the TG in Kilifi and investigated the risk factors for the TG and nonadherence to antiepileptic drugs (AEDs). Method: A cross-sectional survey was conducted among PWE by trained field staff. The TG was determined using detectable blood levels of AEDs. Putative factors influencing treatment seeking and adherence that were investigated were explored using logistic regression models. Variables with a p-value £ 0.05 in multivariate analysis were considered significant. Results: A total of 673 PWE were interviewed, of whom 499 (74.1%) reported seeking treatment from a health facility but only 385 (77.2%) were on AEDs. Out of the 385, 341 (88.6%) gave blood but only 169 (49.6%) had detectable levels of AEDs. The TG was 74.9% (95% CI; 71.4–78.1). In multivariate analysis, the significant predictors for treatment seeking were duration of epilepsy aOR = 9.00 (95% CI; 2.87–18.97); religion 1.94 (1.25–5.80); distance to health facilities 0.19 (0.07–0.51); paying for AEDs 3.56 (1.84–6.88); injury during a seizure 2.56 (1.37–4.78) and beliefs about causes of epilepsy 3.36 (1.41–8.01). Factors influencing adherence were duration of medication aOR = 6.50 (95% CI; 1.58– 9.63); seizure frequency 3.87 (2.79–6.42); injury during a seizure 2.55 (1.35–5.74) and number of AEDs prescribed 2.51 (1.45–4.35). Conclusion: The TG and nonadherence to AEDs were associated with modifiable factors that could be addressed through the development of appropriate interventions.

029 FACTORS INFLUENCING THE DEVELOPMENT OF THE PERCEIVED STIGMA IN PEOPLE WITH NEWLY DIAGNOSED EPILEPSY: THE 1 YEAR PROSPECTIVE STUDY Lee S-A1, No S-K2, Kim O-J3, Kwon J-H4, Park H-K5, Ryu JY6, Jo K-D7, Lee S-M8, Kim W-J9, Kwon O-Y10

Results: The 153 people with newly diagnosed epilepsy were included in this study. Among them, 27 (17.6%) felt stigmatized by their condition 1 year after the diagnosis of epilepsy and in 7 (4.3%) of these the stigma was severe. Patients with feeling of stigma had significantly lower quality of life than those without stigma. Logistic regression analysis identified two independent factors predicting the development of the perceived stigma: introverted personality (p = 0.002) and experiences of actual discrimination from society (p = 0.007). Other variables including lower level of social support, lower economic status, and higher level of anxiety/depression tended to be associated with the development of the perceived stigma, but they did not reach statistical significance (p < 0.05). Seizure-related variables such as seizure frequency and types were not related to generate the perceived stigma. Conclusion: Introverted personality and episodes of actual discrimination may be important to generating the perceived stigma in people with newly diagnosed epilepsy. These findings may provide a basis for further studies to prevent the development of the stigma in people with epilepsy.

030 WOMEN WITH EPILEPSY: HOW KNOWLEDGEABLE ARE THEY ABOUT ISSUES RELATED TO PREGNANCY IN EPILEPSY? Jette N1,2,3, Metcalfe A1,2,3, Roberts J1,2, Abdulla F1, Hanson A1, Federico P1,2, Wiebe S1,2,3 1 Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada, 2University of Calgary, Hotchkiss Brain Institute, Calgary, AB, Canada, 3Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada Purpose: In 2009, new guidelines were established by the American Academy of Neurology regarding pregnancy in women with epilepsy (WWE). It is unclear what the level of awareness for these guidelines is amongst patients. Our objective was to assess the current level of knowledge regarding women's issues related to pregnancy in WWE.


14 29th IEC Proceedings Method: A 10-item questionnaire was developed to assess patients’ knowledge of current guidelines related to epilepsy and pregnancy. Consecutive women with epilepsy were screened for eligibility from the epilepsy clinics at a large tertiary care centre in Canada. Women were eligible to participate if they were female, between the ages of 18–50, did not suffer from moderate-severe developmental delay and had active epilepsy for at least 6 months. Pearson's correlation and t-tests were used to assess the association between the knowledge of women's issues in epilepsy and participant demographics. Results: One hundred WWE (median age 29 years; median epilepsy duration 12 years) completed the survey for a response rate of 87% and a median correct score of 40%. Of those surveyed, 47% had previously been pregnant. Significant knowledge gaps were identified. For example, only 18% of respondents knew that WWE are not more likely to have complications (e.g., Cesarean section, early delivery etc) during pregnancy compared to women without epilepsy. Only 10% of respondents knew that WWE are more likely to have a small for gestational age baby. More than a third of respondents did not know that pregnancy could ‘‘change the way your body processes (e.g., breaks down) antiseizure medications.’’ A significant positive correlation was found between total score and years of education (p < 0.001). No significant associations were found between total score and epilepsy duration (p = 0.37), prior pregnancy (p = 0.22), or polytherapy (p = 0.31). Conclusion: Women's knowledge about issues related to pregnancy and their epilepsy was poor. More knowledge translation efforts are required to increase knowledge of issues related to pregnancy for women with epilepsy.

Tuesday, 30 August 2011 14:00–15:30 Hall 4 Platform Session 6 Neurodiagnostics 031 INTEGRATIVE ANALYSIS OF PET, ECOG AND DTI DATA IN ORDER TO ASSESS THE SPATIAL RELATIONSHIP BETWEEN MULTIMODALITY DATA SETS IN CHILDREN WITH EPILEPSY Muzik O, Pai D, Juhasz C, Hua J Wayne State University, Detroit, MI, U.S.A. Purpose: The purpose of this study was to assess the spatial relationship between F18-deoxyglucose (FDG) PET abnormalities, onset/ spiking electrodes as defined based on intracranial electrocorticography (ECoG) and major fiber tracts (based on diffusion tensor imaging – DTI) in children with nonlesional epilepsy. The integration of complementing modalities takes advantage of qualitatively different information inherent in a variety of neuroimaging datasets and is likely to improve our understanding of mechanisms involved in seizure propagation. Method: We developed a cohesive computational framework that allows quantitative assessment of the spatial relationship between multimodality neuroimaging data obtained during presurgical evaluation of children with epilepsy. Our approach is based on the parcellation of the cortical surface in native space using landmarkconstrained conformal mapping, yielding finite cortical elements that are homotopic across subjects and that allow standardized representation in 2D space. We applied this framework to five young children who underwent presurgical evaluation and compared the


obtained functional/connectivity patterns against 12 age-matched normal children. Results: Only few PET abnormalities were determined within the EEG confirmed seizure onset area, however, PET abnormalities were frequently observed adjacent to this area in the temporal and parietal lobes, most likely the result of functional disconnection of this area from ictal involvement. For connectivity analysis (using probabilistic fiber tracking), cortical areas representing PET abnormalities in the parieto-temporal lobe showed unilaterally lower connectivity to the frontal lobe. Conclusion: Our approach indicates that functional PET abnormalities are frequently located in the borderzone to EEG-defined seizure onset regions. Moreover, in addition to decreased fractional anisotropy (FA), the cortical distribution pattern of fibers originating in the seizure onset zone or from the functional abnormality region differs from a normative pattern.

032 SIMPLE VISUAL ASSESSMENT OF INTRACEREBRALLY RECORDED HIGH FREQUENCY OSCILLATIONS VERSUS THEIR AUTOMATED DETECTION Brazdil M1,2, Pail M1,2, Halamek J3, Daniel P1, Kuba R1,2, Tyrlikova I1, Chrastina J1, Jurak P3 1 Brno Epilepsy Center, Masaryk University, Brno, Czech Republic, 2Behavioral and Social Neuroscience Research Group, Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic, 3Institute of Scientific Instruments, Academy of Sciences of the Czech Republic, Brno, Czech Republic Purpose: Interictal high-frequency oscillations (HFO) have been recently identified in recordings from depth macroelectrodes in epileptic patients. They are generally split into two categories according to their frequency: ripples (R) ranging between 80 and 200 Hz and fast ripples (FR) in the range of 200–500 Hz. While ripples are considered to be a signature of both normal and pathologic brain processes, fast ripples are believed to reflect the neuronal substrates of epileptogenesis and epileptogenicity. The optimal algorithm for HFO study in macroEEG recordings is obviously still under progress. Method: In the present study we analyzed SEEG recordings in twenty patients with medically intractable partial seizures (10 TLE/10 ETLE). Independently using simple visual assessment (analogous to standard ‘‘clinical’’ evaluation of SEEG traces) and automated detection of HFO based on ‘‘line length’’ we identified depth electrode contacts with maximum occurrence of R and FR. Seizure onset zone was determined by independent visual identification in standard SEEG recordings and the congruence with results of visual versus automated HFO detection was compared. Results: Automated detection of ripples correctly identified SOZ in 14 out of 20 patients, simple visual assessment of SEEG records in fitting frequency range correctly pointed to SOZ in 13 patients. Specificity of both approaches was lower for FR detection. Automated analysis of FR made the right choice of SOZ in 10 and visual analysis in nine subjects. Importantly discrepancy between both approaches was surprisingly frequent: in ripples range this was present in five subjects and in FR bandpass in seven subjects. Conclusion: Simple visual assessments of SEEG traces (filtered in frequency ranges 80–200 Hz and 200–450 Hz) and standard automated detection of HFO seem to contribute comparably to identification of seizure onset zone in patients with focal epilepsies. The study was supported by MMT CˇR Research Program no. ˇ R P103/11/0933. MSM0021622404 and by the grant GAC

15 29th IEC Proceedings 033 WHAT IS THE IDEAL TIME TO PERFORM POSTOPERATIVE ELECTROENCEPHALOGRAM FOLLOWING ANTERIOR TEMPORAL LOBECTOMY? Rathore C, Radhakrishnan K Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India Purpose: To evaluate the differential value of postoperative electroencephalogram (EEG) performed at various time points for predicting seizure outcome in patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Methods: We studied 262 consecutive patients with MTLE-HS who had undergone serial EEGs at 7 days, 3 months, and at 1, 2 and 3 years after anterior temporal lobectomy (ATL). All patient had pathologically/ MRI verified HS. Presence of definite interictal epileptiform discharges (IED) was considered as abnormal. We defined favorable outcome as freedom from seizures/auras during the entire follow-up period (outcome 1) and during terminal 1-year follow-up (outcome 2). Results: During mean follow-up period of 7.6 (range 5–12) years, 129 (49.2%) patients had favorable outcome 1 and 218 (83.2%) had favorable outcome 2. Approximately 18% of EEGs were abnormal at each timepoint, except at 07 days when 25% of EEGs were abnormal. As compared to normal EEG, presence of IED at 3 months [p < 0.01; Odds ratio (OR), 2.1 (1.2–4.0)]; 1 year [p < 0.002; OR, 3.0 (1.5–6.1)]; 2 year [p < 0.01; OR, 2.6 (1.3–5.4)]; and 3 year [p < 0.0001; OR, 3.7 (1.8–7.7)] was significantly associated with unfavorable outcome 1 and 2. However, presence of IED at 07 day EEG did not predict the seizure outcome [p = 0.3; OR, 0.7 (0.4–1.3)]. Conclusions: Post-ATL EEGs done at 3 months or after strongly predicts seizure outcome. As an EEG done in early postoperative period is more likely to be abnormal and not predictive of seizure outcome, it is desirable to perform EEGs around 3rd postoperative month.

034 PRE- AND POSTOPERATIVE INTERICTAL EEG DISCHARGES AS PREDICTORS OF SEIZURE CONTROL AFTER SURGERY IN MESIAL TEMPORAL LOBE EPILEPSY ASSOCIATED WITH HIPPOCAMPAL SCLEROSIS Barbosa PH, Morita ME, Lizcano A, Yasuda CL, Cendes F UNICAMP, Campinas, Brazil Purpose: To evaluate the relationship of postoperative seizure control and presence of interictal epileptiform spikes (IES) on pre- and postoperative EEGs.

not associated with presence of uni or bilateral IES on preoperative or postoperative EEGs. However, the presence of unilateral HS on MRI was associated with better seizure control than bilateral HS (p = 0.0002). In addition, the presence of bilateral HS on MRI was associated with more frequent bilateral IES on preoperative EEGs (p = 0.0001). Conclusion: Unilateral or bilateral IES on pre- or postoperative EEGs are not good predictors of postoperative outcome. MRI evidence of unilateral HS was associated with good postoperative seizure control as demonstrated in previous studies. Although the presence of bilateral HS on MRI associated with bilateral IES, many patients with unilateral HS had bilateral IES on preoperative EEGs, explaining why interictal EEG is not a good isolated predictor of postoperative outcome.

035 HIGH DENSITY SIMULTANEOUS EEG-fMRI IN FOCAL EPILEPSY: ESI-fMRI FOR IMPROVED CHARACTERISATION OF INTERICTAL EVENTS Vogrin SJ1, Lau S2, D’Souza W1, Kuhlmann L2, Haueisen J3, Cook MJ1 1 Centre for Clinical Neurosciences, St. Vincents Hospital Melbourne, Fitzroy, Australia, 2Neuroengineering Group, Department of Electical and Electronic Engineering, University of Melbourne, Parkville, Vic., Australia, 3Institute of Biomedical Engineering and Informatics, Illmenau Technical University, Illmenau, Germany Purpose: To utilize electrical source imaging (ESI) techniques in assesing both high density EEG and high density simultaneous EEG-fMRI for improved characterisation of interictal events in a multimodal context. Method: A series of 10 patients with focal epilepsy Participants' high density EEG were recorded using 128-channel cap, in an electrically shielded room and during simultaneous EEG-fMRI acquired on a 1.5T Avanto Magnetom (Siemens, Erlangen, Germany) at St. Vincents Hospital Melbourne (Ethics approval HREC-A034/08). MR-gradient and Ballistocardiogram artifact were removed using commerically available algorithms in Scan 4.5 and CURRY 6.0 software (Neuroscan Compumedics, Charlotte, NC, USA & Hamburg, Germany). Interictal discharges confirmed to be concordant with EEG-only recordings were then used for establishing interictal event regressor in fMRI analysis to determine intracranial regions with correlated haemodynamic changes. Results: Averaged artifact-corrected interictal data from simultaneous EEG-fMRI was interrogated using source reconstruction techniques to assess nature of differences related to residual MR-induced noise. The reconstructed sources of scalp recordings demonstrate quantitatively and qualitatively the effectiveness of artifact removal techniques as they apply to individual recordings using interictal discharges characterized and localized from outside of scanner recordings for each subject.

Method: Patients with refractory MTLE and MRI signs of HS, without other associated MRI abnormalities, submitted to surgery. Surgery was based on comprehensive evaluation that included clinical, noninvasive EEG, MRI and neuropsychological evaluation. Patients had at least five routine EEGs prior to surgery. We included 80 patients who also had postoperative EEGs performed at least 6 months after surgery. We used Fisher's exact test to compare presence or absence of IES on pre and postoperative EEGs and MRI signs of HS to overall seizure control (seizurefree vs. not seizure-free).

Conclusion: This novel approach of refining interictal discharge selection from high density EEG enables improved characterization of epileptogenic features from artifact related discharges, providing superadditive localizing information in a noninvasive and multimodal context. Concordant simultaneous ESI and fMRI localization of interictal and ictal events shows promise in improving noninvasive presurgical evaluation of epilepsy.

Results: Mean follow-up period was 51 months (range 7–144, median 46 months). Files from 275 digital preoperative EEGs were available for review. Based on lateralization of preoperative IES, 45 patients were grouped as unilateral; and 35 as bilateral (33 of these underwent telemetry and early seizure activity was ipsilateral to the side of HS on MRI). Sixty-five patients underwent amygdalohippocampectomy and 15 had cortical-amygdalohippocampectomy. One patient underwent reoperation. Total of 318 postoperative EEGs were analyzed (average four per patient; median = 3, range = 1–11). Postoperative seizure control was

036 SEIZURE-ASSOCIATION FIBERS IN PATIENTS WITH CHRONIC FOCAL SEIZURES: IN VIVO NEURAL CONNECTIVITY STUDY AND TENSOR IMAGING STUDY Chuang M-F, Hsin YL Hualien Tzu Chi Medical Center, Hualien, Taiwan, China


16 29th IEC Proceedings Purpose: To explore the seizure-association fibers that are involved in the propagation of epileptic discharges, we used cortico-cortical evoked potential (CCEP) study to identify the long association fibers between the different cortical gyri or lobes. Then we used MR tensor tractography to confirm the exitance of the associated fibers. Method: CCEPs were conducted extraoperatively in epilepsy patients who underwent staged epilepsy surgery. Two adjacent electrodes were stimulated with biphasic constant current pulses with 0.3 ms duration at a rate of 0.3 Hz. Stimulation current level was set at 80% of the intensity that produced afterdischarges during brain functional mapping investigation. By diffuse tensor images, various nerve-fiber tracts were depicted particularly from the electrodes of presumed seizure onset. Results: Not only large short-latency CCEPs were observed in the electrodes adjacent to the electrode pair of stimulation, but also remote CCEPs were recorded. By the ictal ECoGs, larger first-evoked wave of CCEPs could be found from the electrodes were involved in the seizure propagation. Nerve fibers were reconstructed over the seizure-association region to a tractography. Conclusion: By the ictal ECoGs, larger first-evoked wave of CCEPs could be found from the electrodes were involved in the seizure propagation. As compared with the contralateral normal cortices, lessen numbers of nerve fibers could be reconstructed a tractography. However, there were condensed tracts which connected the seizure onset zone with the principal propagated regions. Our CCEPs studies supported the existence of exclusive pathways for spreading of epileptic discharges in patients with chronic focal seizures. The proposed neural pathways were further validated with tensor tractography. Our findings may potentially help in preoperative planning.

Wednesday, 31 August 2011 14:30–16:00 Hall 2 Platform Session 7 Genes and mutations 037 WHOLE EXOME SEQUENCING IMPLICATES SLC25A22 AS A GENE FOR MMPEI Poduri A1,2, Heinzen EL3, Salih MA4, Chitsazzadeh V5, Hill RS6,7, Elhosary PC1, Barry BJ6,7, Partlow JN6,7, Ge D3, Shianna KV3, Bashiri FA4, Zeidan RM8, Elmalik SA9, Kabiraj MMU10, Stçdberg T11, Scheffer IE12, Barkovich AJ13, Goldstein D3, Walsh CA2,6,7 1 Department of Neurology, Children's Hospital Boston, Boston, MA, U.S.A., 2Department of Neurology, Harvard Medical School, Boston, MA, U.S.A., 3Center for Human Genome Variation, Duke University School of Medicine, Durham, NC, U.S.A., 4Division of Pediatric Neurology, College of Medicine and King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, 5University of Texas School of Medicine, Houston, TX, U.S.A., 6Division of Genetics, Manton Center for Orphan Disease Research, Children's Hospital Boston, Boston, MA, U.S.A., 7Howard Hughes Medical Institute, Chevy Chase, MD, U.S.A., 8Division of Neurology, Department of Medicine, College of Medicine and King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, 9Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia, 10Division of Clinical Neurophysiology, Department of Neuroscience, Armed Forces Hospital, Riyadh, Epilepsia, 52(Suppl. 6):4–22, 2011 doi: 10.1111/j.1528-1167.2011.03206.x

Saudi Arabia, 11Department of Neuropediatrics, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden, 12Departments of Medicine and Paediatrics, University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Vic., Australia, 13Department of Radiology, University of California San Francisco, San Francisco, CA, U.S.A. Purpose: To identify a genetic cause for malignant migrating seizures in infancy (MMPEI). Method: We characterized a pedigree with MMPEI from Saudi Arabia and obtained DNA from leukocytes from affected and unaffected family members. We analyzed data from a single nucleotide polymorphism (SNP) 500K screen to identify regions with evidence for linkage. We performed whole exome sequencing and analyzed homozygous variants in the regions of linkage. Results: In a multiplex consanguineous pedigree with MMPEI in two affected individuals, we identified two regions of linkage, chromosome 4p16.1-p16.3 and chromosome 11p15.4-pter. Using whole exome sequencing, we identified eight novel homozygous variants in genes in these regions. Only one variant, c.G328C in SLC25A22, results in a change of a highly conserved amino acid (p.G110R) and was not present in control samples. SLC25A22 has been shown to have strong expression in the developing brain and has been implicated in an early onset epilepsy with a suppression burst pattern on EEG that is distinct from MMPEI. Conclusion: We have shown that MMPEI can be inherited and have identified a novel homozygous variant in SLC25A22 in the affected individuals. Taken together with our evidence for linkage and the presence of other SLC25A22 mutations in another severe epilepsy syndrome, our data strongly suggest that SLC25A22 is responsible for MMPEI, a severe condition with few known etiologies. We have demonstrated that a combination of linkage analysis and whole exome sequencing can be used to discover disease genes. Finally, we have expanded the phenotypic spectrum associated with SLC25A22.

038 CEREBRAL MICRODYSGENESIS IN REFRACTORY EPILEPSY PATIENTS WITH SCN1A MUTATIONS Skjei K, Harding B, Marsh E Children's Hospital of Philadelphia, Philadelphia, PA, U.S.A. Purpose: SCN1A mutations have been associated with a range of epilepsy phenotypes. Currently, pathologic mutations are believed to lead to epilepsy by alteration of sodium currents, particularly in interneurons. Targeted pharmacological management is often unsuccessful raising the question as to whether other pathophysiologic mechanisms may be involved. In this cases series, we describe the clinical features and surgical pathology of four patients with SCN1A mutations and refractory epilepsy who underwent focal cortical resection. Method: The medical records of four SCN1A mutation positive children with medically refractory epilepsy were reviewed retrospectively. Data extracted included clinical course, neuro-imaging and electroencephalographic reports, and SCN1A mutation type. Surgical pathology specimens were reviewed. Results: All patients carried diagnoses of intractable epilepsy with mixed seizure types. SCN1A mutations included one deletion, one missense mutation, one frame shift (insertion) leading to premature stop, and one novel mutation of unknown significance in a highly conserved region of the gene. Age at surgery ranged from 18 months to 20 years. All patients showed some clinical improvement immediately following surgery but subsequently continued seizing. Surgical histopathology showed a clear increase in the number of neurons in the white matter in

17 29th IEC Proceedings three of the subjects. One patient each showed indistinct cortical layers and multifocal intracortical neuron clusters. Conclusion: In this case series of children with SCN1A mutations who underwent focal resective surgery, three of four patients’ neuropathological specimens demonstrated cortical microdysgenesis. This raises the possibility that SCN1A mutatations’ epileptogenicity maybe due in part to disruption of normal brain development.

039 KCNQ2 MUTATIONS ARE A CAUSE OF NEONATAL EPILEPTIC ENCEPHALOPATHIES WITH A RECOGNIZABLE CLINICAL AND RADIOLOGICAL PHENOTYPE Weckhuysen S1,2,3, Mandelstam S4,5, Suls A1,2,6, Audenaert D1,2,6, Deconinck T1,2,6, Claes L1,2,6, Deprez L1,2,6, Smets K1,2,7, Hristova D8, Yordanova I9,10, Jordanova A1,2,6, Ceulemans B2,11, Jansen A12,13, Hasaerts D12, Roelens F14, Lagae L15, Yendle S16, Stanley T17, Heron S18, Mulley J18,19, Berkovic S16, Scheffer I16,20, De Jonghe P1,2,7 1 Neurogenetics Group, Department of Molecular Genetics, VIB, University of Antwerp, Antwerp, Belgium, 2University of Antwerp, Antwerp, Belgium, 3Epilepsy Centre Kempenhaeghe, Hans Berger Kliniek, Oosterhout, The Netherlands, 4Brain Research Institute, Austin Health, Melbourne, Vic., Australia, 5 Department of Radiology, Royal Children's Hospital, Melbourne, Vic., Australia, 6Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium, 7Department of Neurology, University Hospital of Antwerp, Antwerp, Belgium, 8 Tokuda Hospital-Sofia, Pediatrics clinic, Children neurology unit, Sofia, Bulgaria, 9National Genetics Laboratory, Medical University-Sofia, Sofia, Bulgaria, 10Molecular Medicine Center, Medical University-Sofia, Sofia, Bulgaria, 11Pediatric Neurology, Department of Neurology, University Hospital of Antwerp, Antwerp, Belgium, 12Pediatric Neurology Unit, Department of Pediatrics, UZ Brussel, Brussels, Belgium, 13 Department of Public Health, Vrije Universiteit Brussel, Brussels, Belgium, 14Department of Pediatrics, Heilig Hart Ziekenhuis, Roeselare, Belgium, 15Department of Pediatric Neurology, University Hospital Gasthuisberg, Leuven, Belgium, 16 Epilepsy Research Centre, Department of Medicine, University of Melbourne, Melbourne, Vic., Australia, 17 Department of Paediatrics, Wellington School of Medicine, University of Otago, Wellington, New Zealand, 18Epilepsy Research Program, SA Pathology at Women's and Children's Hospital, Adelaide, SA, Australia, 19School of Molecular and Biomedical Sciences, and School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia, 20Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Vic., Australia Purpose: KCNQ2 and KCNQ3 mutations are known to be responsible for Benign Familial Neonatal Seizures (BFNS). A few reports on patients with a KCNQ2 mutation with a more severe outcome exist, but a definite relationship has not been established. In this study we investigated whether KCNQ2/3 mutations are a frequent cause of epileptic encephalopathies with an early onset and whether patients present with a particular phenotype. Method: We analyzed 80 patients with unexplained neonatal or earlyinfantile seizures and associated psychomotor retardation for KCNQ2 and KCNQ3 mutations. Clinical and imaging data were reviewed in detail.

Results: We found seven different heterozygous KCNQ2 mutations in eight patients (8/80; 10%); six mutations were proven de novo. One parent with a milder phenotype was mosaic for the mutation. The eight patients had onset of intractable seizures in the first week of life with a prominent tonic component. Seizures generally resolved by age 3 years but the children had severe-profound intellectual disability with motor impairment. EEG at onset showed a burst suppression pattern or multifocal epileptic activity. Early MRI of the brain showed characteristic hyperintensities in the basal ganglia and thalamus that later resolved. Conclusion: KCNQ2 mutations are found in a substantial proportion of patients with a neonatal epileptic encephalopathy with a very distinct electro-clinical and radiological phenotype. This suggests that KCNQ2 screening should be included in the diagnostic workup of refractory neonatal seizures of unknown origin.

040 EPILEPTIC AND NONEPILEPTIC FEATURES IN PATIENTS WITH EARLY ONSET EPILEPTIC ENCEPHALOPATHY AND STXBP1 MUTATIONS Milh M1, Villeneuve N2, Mondher C3, Kaminska A4, Larroche C5, Gitiaux C6, Borges-Correia A7, Cacciagli P7, Mignon-Ravix C7, Cuberos H7, Chabrol B1, Villard L7 1 INSERM U910, Service de Neuropdiatrie, Marseille, France, 2 Service de Neuropdiatrie, Hopital de la Timone, CINAPSE, Marseille, France, 3CHU, Service de Pdiatrie, Dijon, France, 4APHP, Service d’lectrophysiologie Clinique, Necker, Paris, France, 5CHU, Service de Pdiatrie, Limoges, France, 6APHP, Service d’lectrophysiologie Clinique, Service de Neuropdiatrie, Necker, Paris, France, 7INSERM U910, Universit de la Mditerrane, Marseille, France Purpose: STXBP1 has been associated with various types of epileptic syndromes, mostly beginning early in life. In order to refine the phenotype associated with MUNC18-1/STXBP1 aberrations in early onset epileptic syndromes, we studied this gene in a cohort of patients with early onset epileptic encephalopathy. Methods: STXBP1 was screened in 51 patients with early onset epilepsy, normal brain MRI and negative metabolic screening. Three groups of patients could be defined in this cohort: (1) Ohtahara syndrome (n = 37); (2) Early myoclonic encephalopathy (n = 7) and (3) Early onset epileptic encephalopathy that did not fit with any recognizable syndrome (n = 7). Each patient was recorded with several video/EEG. Key findings: We found five novel STXBP1 mutations, in patients in which video/EEG recordings could be reviewed from the beginning of the illness. All the patients mutated had Ohtahara syndrome, with some particular clinical and EEG features : the first seizures were clonic in two patients, with a first EEG showing relatively low amplitude burst of activity before evolving into a typical suppression-burst pattern, while the two other had epileptic spasms and typical suppression-burst pattern from the beginning. Epilepsy dramatically improved after 6 months and finally disappeared before the end of the first year of life for three patients, and at 18 months for the last one. At the same time, EEG paroxysmal abnormalities disappeared, giving place to continuous activity with posterior fast rythms. Each patients displayed frequent non epileptic movement disorders that could easily be mistaken for epileptic seizures. Significance: We confirm that STXBP1 is a major gene to screen in cases of Ohtahara syndrome, since it is mutated in more than 10% of the patient with Ohtahara in our cohort. This gene should particularly be tested in case of surprising evolution with disappearance of epileptic seizures and EEG paroxysmal activity at the end of the first year of age; and appearance of posterior fast rythms after 1 year of age. Epilepsia, 52(Suppl. 6):4–22, 2011 doi: 10.1111/j.1528-1167.2011.03206.x

18 29th IEC Proceedings 041 EXPANSION OF THE PHENOTYPE ASSOCIATED WITH PCDH19 MUTATIONS Hjalgrim H1,2, Dibbens LM3, Scheffer IE4, Olofsson K1, Nikanorova M1, Jepsen B1, Møller RS1 1 Danish Epilepsy Center, Dianalund, Denmark, 2University of Southern Denmark, Odense, Denmark, 3Epilepsy Research Program, University of South Australia, SA, Australia, 4Epilepsy Research Centre, Departments of Medicine and Paediatrics, University of Melbourne, Austin Health and Royal Children's Hospital, Vic., Australia Purpose: Mutations in the gene encoding protocadherin 19, PCDH19, cause Epilepsy and Mental Retardation limited to Females (EFMR). This study aimed to identify and phenotype patients with PCDH19 mutations. Method: Eighteen unrelated females with a wide spectrum of epilepsies with onset before the age of 20 months, were screened for mutations in PCDH19. Detailed phenotyping was performed in the patients and six affected relatives. 15/18 probands had previously tested negative for mutations or rearrangements in SCN1A. Results: Six (33.3%) novel PCDH19 mutations were identified in two sporadic and four familial cases. Each of the mutations is located in the extracellular portion of the protein and the missense mutations alter conserved residues. Family studies revealed mutations in six affected females, two unaffected females and two unaffected males. The predominant clinical features were clusters of seizures and aggressive behavior, with marked variability. Autonomic seizures were also seen. Seizure onset ranged from 6 months to 6 years of age. Affected females had normal development prior to seizure onset but >70% had neurocognitive and/or psychiatric problems at 2–3 years of age. Psychiatric problems included a catatonic/Parkinson like state in one affected relative. Conclusion: PCDH19 mutations are a relative frequent cause of idiopathic early onset epilepsy in Danish females. Here we extend the phenotype of EFMR to include later onset than previously reported (6 years) and a catatonic/Parkinson like state. PCDH19 should be screened in females with onset of epilepsy 80 years showed myoclonus interfering with autonomous walking. Myoclonus severity was correlated with disease duration (p < 0.001) and patients’ age (p = 0.001). Six patients (42.8%) experienced seizures, usually between the second and sixth decades of life. Evaluation of EEG long-term evolution revealed progressive slowing of background activity in parallel with the gradual worsening of myoclonus. In contrast, paroxysmal activity and photosensitivity were particularly evident during the intermediate phases of the disease. In addition, psychiatric and neuropsychological dysfunction occurred in more than one-third of the patients. Conclusion: We provide data for a slight age-dependent progression and the presence of neuropsychiatric and neuropsychological dysfunction in this unique syndrome, for which the definition of familial or autosomal dominant cortical tremor, myoclonus, and epilepsy (FCTME/ADCME) seems to be, therefore, more appropriate.

051 STORMY ONSET EPILEPSY IN GIRLS WITH DE NOVO PROTOCADHERIN 19 MUTATIONS Specchio N1, Terracciano A2, Marini C3, Mei D3, Trivisano M4, Sicca F5, Fusco L1, Granata T6, Freri E6, Cusmai R1, Darra F7, Dalla Bernardina B7, Guerrini R3, Bertini E2, Vigevano F1 1 Division of Neurology, Bambino Ges Children's Hospital, IRCCS, Rome, Italy, 2Unit of Molecular Medicine for Neuromuscular and Neurodegenerative diseases, Rome, Italy, 3 Child Neurology Unit and Laboratories, Pediatric Hospital A. Meyer, University of Florence, Florence, Italy, 4Clinic for Nervous System Diseases, University of Foggia, Foggia, Italy, 5 Child Neurology and Psychiatric Unit, IRCCS Stella Maris, Calambrone, Pisa, Italy, 6Neurological Institute ‘‘Besta’’, Milan, Italy, 7Child Neuropsychiatry Unit, University of Verona, Verona, Italy Purpose: To describe clinical, and neuropsychological features of 13 consecutive sporadic girls with PCDH19 mutations. Mutations of

protocadherin 19 (PCDH19) were originally associated to epilepsy with mental retardation limited to females (EFMR). The spectrum of phenotypes associated to PCDH19, de novo or familial mutations, has been extended to include female patients with early onset epileptic encephalopathies resembling Dravet Syndrome (DS) or focal epilepsy with or without mental retardation. Method: We sequenced PCDH19 gene in patients with infantile or early-childhood seizures with either focal or generalized onset, without an obvious aetiology. Results: Mean age at the time of the study was 13.5 € 11 years. Mean age at seizure onset was 15.5 € 11 months (range 9–38). All patients experienced clusters of either focal or generalized seizures, precipitated during febrile illness in five. Attacks, were very frequent at onset, but became less numerous during follow-up Ictal EEG showed temporal lobes involvement in five patients. Perictal EEG showed focal or multifocal epileptiform and slow abnormalities. Cognitive impairment became obvious, after seizure onset, in three patients and was associated with autistic features in two. Genetic analysis revealed ten new and three known de novo, PCDH19 mutations that were missense in nine, and frameshift in four. Conclusion: Our findings emphasize that de novo PCDH19 mutations are associated with infantile or early childhood onset of febrile or afebrile seizures often occurring in clusters. Cognitive impairment is not constantly present and autistic features are observed in some patients. Most patients have a ‘‘stormy’’ seizure onset, often related to fever still seizures severity does not clearly correlate with the degree of cognitive deficit. PCDH19 is likely a major epilepsy gene, phenotypes associated with mutations of this gene range from epileptic encephalopathies to mild epilepsy yet large series of patients will be necessary to fully delineate phenotypic spectrum.

052 PROSPECTIVE ANALYSIS OF FAMILIAL MESIAL TEMPORAL LOBE EPILEPSY Morita ME, Yasuda CL, Betting LEG, Costa ALF, Kobayashi E, Lopes-Cendes I, Cendes F University of Campinas (Unicamp), Campinas, Brazil Purpose: Prospective evaluation of seizure outcome and clinical characteristics in familial mesial temporal lobe epilepsy (FMTLE). Method: Fifty-one individuals with FMTLE from 17 families were classified according to seizure outcome: (1) Remission: seizure-free for at least 2 years; (2) Benign: less than three complex partial seizures (CPS)/ year and no more than two secondary generalizations/year; and (3) Refractory: more than three CPS/year. We collected clinical data including EEG abnormalities, use of antiepileptic drugs (AED) and age at seizure onset. Results: Mean follow up was 94.8 € 23.5 months (31.1–155.1 months). The mean duration of epilepsy was 34.8 € 14.4 years (1–70 years). At baseline 15 patients were classified as benign, 20 as remission and 16 as refractory. At last follow up 8/15 (53.3%) benign patients remained classified as benign, 3/15 (20%) became refractory, 4/15 (26.7%) became seizure-free. In the remission subgroup 16/20 (80%) remained seizurefree and 4/20 (20%) were reclassified as benign. All refractory patients remained refractory, and 9/16 (56.1%) underwent surgery. At baseline, 7 (35%) of the remission group, 12 (80%) of the benign and 16 (100%) of the refractory group were using AEDs. At last follow up the use of AEDs was similar; 8 (40%) from the remission group, 11 (73.3%) from the benign. Four (25%) refractory patients who underwent surgery were not using AEDs. The frequency of EEG epileptiform discharges (ED) was higher in the refractory group n = 16 (100%) compared to the benign n = 9 (69.2%) and the remission group n = 1 (11.1%). Fischer exact test comparing benign and remission with the refractory group showed an association between presence EEG ED and seizure frequency at baseline (p = 0.0003). Epilepsia, 52(Suppl. 6):4–22, 2011 doi: 10.1111/j.1528-1167.2011.03206.x

22 29th IEC Proceedings Conclusion: Presence of EEG ED is more frequent in refractory FMTLE patients. Prospective follow up of more than 7 years revealed that patients with benign FMTLE for more than 1 year seem to remain in the same clinical status throughout the following years (either remission or infrequent seizures), even without medication in some cases. Refractory patients are unlikely to achieve seizure control unless surgery is performed. Supported by FAPESP.

053 MALFORMATIONS OF CORTICAL DEVELOPMENT AND EPILEPSY: CLINICAL, ELECTROPHYSIOLOGICAL, RADIOLOGICAL PROFILE AND PREDICTORS OF REMISSION Sattaluri SJ1, Krishna M2, Panigrahi M1, Ram Mohan V3, Varma R1 1 Krishna Institute of Medical Sciences, Secunderabad, India, 2 NIMS, Hyderabad, India, 3Vijaya Diagnostic Centre, Hyderabad, India Purpose: To study the clinical, EEG and imaging profile of patients with malformation of cortical development (MCD) and to determine the predictors of remission. Method: All patients with epilepsy, having at least one routine EEG, MRI Brain suggestive of MCD and at least 1 year follow-up were included. Results: There were 280 patients and MCDs accounted for 8.3% of all epilepsies; 160 were males. The age of onset of epilepsy ranged from birth to 45 years (