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Mitochondria have a crucial role in brain development and neurogenesis, both in embryonic and adult brains. Since the brain is the highest energy consuming organ, it is highly vulnerable to mitochondrial dysfunction. This has been implicated in a range of brain disorders including, neurodevelopmental conditions, psychiatric illnesses, and neurodegenerative diseases. Genetic variations in mitochondrial DNA (mtDNA), and nuclear DNA encoding mitochondrial proteins, have been associated with several cognitive disorders. However, it is not yet clear whether mitochondrial dysfunction is a primary cause of these conditions or a secondary effect. Our review article deals with this topic, and brings out recent advances in mitochondria-oriented therapies. Mitochondrial dysfunction could be involved in the pathogenesis of a subset of disorders involving cognitive impairment. In these patients, mitochondrial dysfunction could be the cause of the condition, rather than the consequence. There are vast areas in this topic that remains to be explored and elucidated.

In a prospective cohort of children (13-21 years) of women with epilepsy (CWWE), we compared those exposed to antiseizure medications (ASM) in utero to those without exposure to ASM regarding their language proficiency and intelligence. We also compared their educational performance with state-wide averages.Research staff blinded to the ASM exposure of CWWE administered the Clinical Evaluation of Language Fundamentals IV and the Wechsler Intelligence Scale for Children IV to test their language proficiency and intelligence. We assessed their educational performance with a questionnaire. CWWE without antenatal exposure to ASM served as comparators for language and intelligence tests. The educational performance of CWWE (regardless of ASM exposure) was compared with the state-wide averages published by the government.In total, 446 children (mean age 16.5 ± 2.2 years; 236 girls) participated in the study. Their ASM exposure involved monotherapy for 272 (61%), polytherapy for 133 (29.8%) and none for 41 (9.2%). The commonly used ASMs (monopolytherapy) were carbamazepine (n = 192), valproate (n = 124), phenobarbitone (n = 95), and phenytoin (n = 73). The full-scale intelligence quotient of CWWE (n = 146) with antenatal exposure to ASM (89.2 ± 21.5) was significantly lower (p = 0.03) than that of CWWE (n = 11) unexposed to ASM (96.9 ± 8.8). The CELF core language scaled score for the exposed CWWE (n = 132) was significantly lower than that of unexposed children (n = 12; 99.2 ± 19.9). Compared with state-wide averages, CWWE (n = 386) had delayed initiation of education (2.6% vs. 0.1%), increased dropout rates (1% vs. 0.11%), increased usage of special assistance during examinations (4.4% vs. 0.1%) and a lower rate (19.9% vs. 37%) of enrolment in universities.The language and intelligence functions of CWWE with exposure to older ASMs were lower than those of unexposed CWWE. Compared to state-wide averages, a significantly higher proportion of CWWE had difficulties with education, and only a smaller proportion enrolled in higher education.

We aim to report the major congenital malformation (MCM) rates for new and old anti-epileptic drugs (AED) exposures during the first trimester of pregnancy in women with epilepsy (WWE).We extracted relevant data on drug exposure and malformation rate from the records of a prospective observational registry (Kerala Registry of Epilepsy and Pregnancy) for all completed pregnancies between 1998 and 2019. A comprehensive and uniform criterion with detailed guideline was used for assessment of malformations. We employed generalised linear model to generate adjusted incidence rate ratios (aIRR) of MCM in AED exposed group as compared to AED unexposed group, after adjustment for age and educational status of mothers' and epilepsy classification.The unadjusted MCM rate was 6.2% for all the infants included in the study (148/2328); 4.7% for the unexposed group (16/340), and 6.6% for the exposed group (132/1988). The aIRR of MCM as compared to unexposed group was similar for all monotherapies; lamotrigine (0.50; 95% CI 0.07-3.68), levetiracetam (1.16; 0.43-3.11), oxcarbazepine (1.61; 0.62-4.21) valproate (1.71, 0.93-3.19), phenytoin (1.21, 0.51-2.90), carbamazepine (0.99, 0.54-1.82), and phenobarbitone (1.20, 0.52-2.74). However, the point estimates suggest least risk with lamotrigine and highest risk with valproate. Polytherapy with high-dose valproate carried significantly higher risk of MCM as compared to the unexposed group (aIRR=4.12; 2.18-7.79, p0.001). The aIRR of GTCS during pregnancy was 1.63 (95% CI 1.12-2.37, p = 0.011) for monotherapy with new AEDs (lamotrigine, levetiracetam or oxcarbazepine) as compared to old AEDs (phenobarbitone, phenytoin, carbamazepine, or valproate).The MCM risk was significantly higher for polytherapy with high dose valproate. It did not differ substantially between different AED monotherapies although point estimate was lowest with lamotrigine. Pregnant women on new AEDs report higher likelihood of GTCS than women on old AEDs during pregnancy.

India is considered the diabetes capital of the world and has the highest burden of mucormycosis. Bacterial, viral and fungal co-infections are increasingly being reported in severe acute respiratory syndrome virus 2 (SARSCoV-2) infected patients. India is one of the worst affected countries during the second wave of the COVID-19 pandemic. This combination of diabetes mellitus, COVID-19 and mucormycosis has led to the drastic upsurge of COVID-19-associated mucormycosis (CAM) in India. Immunosuppression, iron disequilibrium, endothelial injury, ketoacidosis and hypoxia are some of the other COVID-19-related risk factors for CAM. There has been an increase in the proportion of mucormycosis affecting paranasal sinuses and central nervous system (CNS) in CAM compared to pre-COVID-19 literature due to the SARSCoV-2-related pathophysiological mechanisms, complications and treatment strategies. CAM is a medical and surgical emergency, and it can present with non-specific symptoms and signs initially resulting in diagnostic delay. High index of suspicion and regular screening for features of CAM are of paramount importance to prevent lethal consequences. Rapid action with a tripod approach consisting of withdrawal of immunomodulators, early antifungal therapy and extensive surgical debridement is considered the best possible treatment model. We review the published data to give a detailed account of the predisposing factors and their mechanisms, diagnostic work-up, treatment modalities and prevention strategies of CAM with special emphasis on CNS mucormycosis.

We aimed to determine a possible association between motor and mental development in infants of women with epilepsy and antenatal exposure to antiseizure medication (ASM).Developmental paediatricians who were blinded to antenatal ASM exposure evaluated motor and mental development of infants (12 months) using the Developmental Assessment Scale for Indian Infants (an Indian adaptation of the Bayley Scale of Infant Development). Motor (MODQ) and mental development quotients (MEDQ) were computed as ratios of respective developmental age to the chronological age of the child. We employed linear mixed models to study the relationship between antenatal exposure to ASM and the development quotients after adjustment for malformation status and age of the baby, maternal education and seizure type.We studied 1,357 infants with mean age of 15.3±4.0 months (71.2% of all eligible infants). Infants were classified as having monotherapy or polytherapy, or unexposed in 840, 407 and 110 participants, respectively. The MEDQ of the polytherapy (92.9±14.9) and monotherapy (96.9±13.9) groups was lower than that of unexposed infants (99.8 12.5). Similarly, the MODQ of polytherapy (91.1±19.3) and monotherapy (96.6±17.5) groups was lower than that of unexposed infants (97.6 16.6). The differences in adjusted mean MEDQ were -7.4 (-11.4 to -4.3, p=0.001), -9.6 (-11.3 to -6.0, p=0.001) and -6.4 (-9.2 to -3.7, p=0.001) for valproate monotherapy, polytherapy with valproate and polytherapy without valproate, respectively. The adjusted mean MODQ also showed a similar trend. Those exposed to levetiracetam (n=62) had higher or similar adjusted MODQ (110.4±14.3; p=0.001) and MEDQ (104.3±9.1; p=0.09), compared to unexposed infants. A dose-dependent decrease in developmental indicators was observed for valproate and phenobarbitone.Antenatal exposure to ASM, especially valproate and phenobarbitone, adversely affects motor and mental development of exposed infants. Early developmental screening of high-risk infants is desirable.

Purpose To study if one can conceptualize the scalp ictal onset pattern through analysis of interictal spike domain analysis in temporal lobe epilepsy (TLE). Methods Seventy-four patients with unilateral mesial temporal sclerosis (MTS) were categorized into "type A" interictal epileptiform discharges (IEDs) with negativity over infero-lateral scalp electrodes over temporal region and contralateral central region showing positivity; all IEDs other than type A were categorized as type B. The ictal electrographic patterns was termed "focal" when confined to side of MTS, was "regional" when lateralized to the ipsilateral hemisphere; "diffuse" if nonlateralized/localized; and ictal onset contralateral to MTS termed as "discordant." Results A total of 377 seizures and 5,476 spikes were studied. These were divided into four types: (1) type A IEDs ipsilateral to MTS (44 patients), (2) type A IEDs bitemporally (16 patients), (3) type A IEDs contralaterally (7 patients) and type B IEDs ipsilaterally, and (4) bilateral type B IEDs (7 patients). The ictal pattern was either focal or regional in 51 of 60 patients (85%) with type A IEDs; it was "diffuse" in 9 patients (15%). Diffuse ictal onset was seen in 12 of 14 (86%) with either ipsilateral/bitemporal type B IEDs. Ictal onset on the opposite hemisphere was noted in 2 (14%). Conclusions Type A IEDs signify a focal ictal onset and type B IEDs suggest a diffuse ictal onset in patients with MTS on one side. Significance Interictal spike domain analysis helps predicting ictal patterns in temporal lobe epilepsy.

Aim: The aim is to study survival outcome and sudden unexpected death in epilepsy (SUDEP) of people with epilepsy who underwent epilepsy monitoring. Subjects and Methods: Between 2000 and 2004, 558 persons were admitted to the epilepsy monitoring unit of SCTIMST who fulfilled the selection criteria. Their survival status as on December 31, 2013, was ascertained by clinic attendance record and by mail or telephone contact. Results: Five hundred and fifty-eight persons with epilepsy (males 319, 6408 person-years) were included in this study. There had been 20 deaths till December 31, 2013, and 5 additional deaths were reported when followed up till May 2016. The standardized mortality ratio was 5.35 and higher for males (6.25) than for females (3.52). Those with generalized seizures (tonic and myoclonic seizures), electroencephalography (EEG) showing multifocal and generalized interictal discharges, and polypharmacy had a higher risk of mortality. SUDEP accounted for 5 deaths. Conclusion: People with refractory epilepsy who had undergone presurgical video EEG monitoring had higher mortality risk. Generalized or myoclonic seizures, multifocal or generalized interictal discharges, and polypharmacy independently increased their risk of mortality. SUDEP is an important cause of death.

Purpose The objective of the study was to evaluate the frequency, clinical, and video-electroencephalographic (VEEG) predictors of convlusive status epilepticus (CSE) in the epilepsy-monitoring unit (EMU). Methods The data of all patients who had CSE in our EMU between 2008 and 2017 were reviewed. For each case, two age- and diagnosis-matched subjects who underwent VEEG and did not develop CSE were taken as internal controls. Electro-clinical data of both the groups were compared. Predictors of CSE were assessed using logistic regression analysis. Results Out of 11,188 video-telemetries were conducted between 2008-17, forty-three events of CSE (0.38%) were recorded. On comparisons with 86 internal controls no differences were apparent on prevalence of cognitive impairment, structural lesion, number of baseline anti-seizure medications (ASM), ASM taper schedule, ictal patterns, and duration of VEEG monitoring. Inter-ictal rhythmic periodic patterns had significantly higher prevalence in cases (p = 0.028). Logistic regression analysis revealed that odds of CSE were higher with past history of SE [p = 0.008; adjusted odds ratio (OR) = 5.48 (confidence intervals {CI} 1.55–19.28)] and in presence of rhythmic spike and wave discharges [p = 0.016, OR = 33.518(CI = 1.93–581.4)]; the odds were lower if the first two seizures recorded did not evolve into CSE [p = 0.009, OR = 0.247 (CI = 0.08–0.70)] and if there was prior history of daily seizures [p = 0.02, OR = 0.250 (CI = 0.07–0.84)]. Conclusion CSE is a rare yet important adverse event in EMU. Clinical predictors are more relevant in comparison to EEG variables. Extent of ASM withdrawal may not directly account for occurrence of CSE; factors inherent to a patient’s epilepsy are deterministic.

Objective This is an audit of the use of valproate (VPA) during pregnancy in women with epilepsy (WWE). Methods We identified all pregnancies exposed to VPA in the Kerala Registry of Epilepsy and Pregnancy between January 2010 and December 2019. Subjects' past usage of antiepileptic drugs (AEDs), seizure count before and during pregnancy, fetal outcome, and major congenital malformations (MCMs) were abstracted from the registry records. The presumed reason for usage of VPA was deducted from the clinical records. Results There were 221 pregnancies (17.75%) exposed to VPA (monotherapy, n = 149) during the audit period. The MCM rate for the completed pregnancies exposed to VPA was higher (n = 20, 10.36%) than that of VPA-unexposed pregnancies (n = 39, 4.96%). The relative risk for MCM with VPA exposure was 2.1 (95% confidence interval = 1.24-3.48, number needed to treat with VPA to result in MCM = 19). Reasons for using VPA during pregnancy (some women had more than one reason) were (1) VPA was the first AED prescribed and was effective (68, 29.06%), (2) other AEDs were ineffective (128, 54.70%), and (3) other AEDs were discontinued due to adverse effects (17, 7.28%). Other reasons (21, 8.97%) were (1) VPA was selected after the epilepsy classification was revised (3, 1.28%), (2) other AEDs were expensive (2, .85%), and (3) patient switched to VPA from other AEDs for unspecified reason (16, 6.83%). VPA was discontinued during pregnancy for 6 (2.71%) persons. Less than 10% of women were tried on lamotrigine or levetiracetam before switching to VPA. Significance Nine MCMs per thousand pregnancies can be avoided if VPA is not used in WWE. Safe and effective AEDs as alternatives to VPA are the need of the hour. Professional bodies and regulatory authorities need to implement updated guidelines on AED usage in girls and women.

Introduction. To study whether voltage topographic analysis of interictal epileptiform discharges (IEDs) in temporal lobe epilepsy (TLE) help to predict the type of scalp ictal onset pattern. Methods. IEDs from 74 patients with drug resistant TLE and unilateral mesial temporal sclerosis (MTS) who underwent presurgical evaluation were categorized according to dipolar fields into Types A and B temporal IEDs. Type A IEDs were defined as those with dipolar fields (tangential/ vertical) with sharply defined negativity over the infero-lateral temporal scalp and positivity over contra lateral centro-parietal scalp. Type B IEDs included all other IEDs other than Type A. Scalp ictal electrographic patterns were classified into rhythms confined to temporal lobe ipsilateral to MTS (“focal”), lateralized to the hemisphere (“regional”), and diffuse, nonlateralized and non-localized rhythms (“diffuse”) and ictal onset to the contra lateral side of MTS (“discordant”). Results. A total of 5476 IEDs and 377 seizures were analyzed. They were divided into four categories based on the side of MTS: 1) Type A IEDs ipsilateral to MTS (44 patients); 2) bilateral Type A IEDs (16 patients); 3) Type B IEDs ipsilateral and Type A IEDs contra laterally (7 patients); 4) Bilateral type B IEDs (7 patients). In 51 of 60 (85%) patients with Type A IEDs (either ipsilateral and/or bilateral to MTS), the ictal pattern was either focal or regional and only in 9 patients (15%) it was “diffuse”.12 of 14 (86%) patients with either ipsilateral or bilateral Type B IEDs showed a diffuse ictal onset, whereas 2 (14%) showed a contralateral ictal onset. Conclusion. In MTS, Type A IEDs are associated with clearly localized ictal onset and Type B IEDs with diffuse ictal onset. A spikevoltage topographic analysis is sufficient for selection of cases for antero-medial temporal lobe resection. Additional home-video recordings of seizures can rule out psychogenic non-epileptiform events.

Women with epilepsy (WWE) and their care providers are equally concerned about the risk of seizures and adverse effects of using antiepileptic drugs (AED) during pregnancy to the mother and the baby. The risk of death or other complications during the pregnancy period is high when WWE continue to have seizures. Antenatal exposure to valproate and several other AEDs as monotherapy and polytherapy is associated with a higher risk of Major Congenital Malformations (MCM). The risk of MCM is dose dependent for valproate and several other AEDs. Children who were exposed to AEDs in the antenatal period demonstrate impaired intelligence and language functions when examined in early childhood, and this effect endures into the second decade of life also. There is considerable difficulty in communicating the complexities of the benefits and risks of using AEDs during the preconception period and pregnancy to the women and their relatives. In this technical note, we are presenting the grid-based preconception counseling of the risk and benefits of different treatment options to facilitate shared decision making. The clinician elicits the preferences and concerns of WWE in the first column of the grid. The potential outcomes of different treatment options concerning these preferences and concerns are presented in the remaining columns of the grid so that a shared decision can be reached. This option grid provides an opportunity to the WWE to review the options holistically and make appropriate decisions.

The ILAE Task Force on Women and Pregnancy conducted a survey among ILAE Chapters of their use of guidelines or recommendations for the management of women with epilepsy during pregnancy. A web-based questionnaire including 10 questions was sent to the 118 ILAE Chapters in December 2017 with repeated reminders until the end of February 2018. In total, 77 chapters (65%) responded, although not to all questions. Out of those responding, 68% reported having guidelines or recommendations, 34% of which were from 2014 or earlier. At least 20% of the guidelines did not include information on possible risk to cognitive development, information regarding specific risks with specific antiepileptic drugs, nor recommendations regarding selection of antiepileptic drugs. Among those responding to the question, 91% reported that recommendations were made regarding folate supplementation, but the recommended dose ranged from 0.4 mg/d to 4 mg/d or more; 34% did not include recommendations regarding drug level monitoring during pregnancy, and 19% did not include guidelines on breastfeeding. Our survey demonstrates that there is a need for the development of up-to-date, globally applicable recommendations for the management of epilepsy during pregnancy. Fil: Tomson, Torbjörn. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia. Karolinska University Hospital. Department of Neurology; Suecia Fil: Battino, Dina. Fondazione IRCCS Istituto Neurologico Carlo Besta. Department of Neurophysiology and Experimental Epileptology. Epilepsy Center; Italia Fil: Bromley, Rebecca. Central Manchester University Hospitals NHS Foundation Trust; Reino Unido. University of Manchester; Reino Unido Fil: Kochen, Sara Silvia. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina Fil: Meador, Kimford J.. University of Stanford; Estados Unidos Fil: Pennell, Page B.. Brigham and Women's Hospital. Harvard Medical School. Department of Neurology. Divisions of Epilepsy and Women's Health; Estados Unidos Fil: Thomas, Sanjeev V.. Sree Chitra Tirunal Institute of Medical Sciences and Technology. Department of Neurology; India

Special considerations are required for women with epilepsy. These include issues such as catamenial exacerbation, concerns for contraception, teratogenesis (including both anatomical and neurodevelopmental effects), and other concerns for pregnancy complications such as increased seizures or adverse obstetric outcomes. In this manuscript, several cases are presented and discussed addressing some of the important issues in the management of women with epilepsy.

Background: The COVID-19 infection outbreak has aroused increasing attention and affected thousands of people nationwide. The long incubation period, high infectious rate, varied manifestation, and absence of effective treatment make it difficult to manage the disease transmission. Objective: The intended goals are to encourage efficient management of neurological and neurosurgical patients, resource utilization, and protecting the healthcare provider during the COVID-19 epidemic. Herein, we present a consensus statement from various centers in India Methodology: In addition to the literature review, recommendations were included from neurologists and neurosurgeons from various centers in India. Results: Every patient presenting for treatment should be treated as a potential asymptomatic infected case. Patients should be categorized based upon the priority as acute (require immediate treatment/surgery within 24 h), sub-acute (requiring treatment within a maximum of 7–10 days), or chronic (requiring treatment within a month). Non-essential elective surgeries and outpatient clinics should be avoided after informing the patient(s). There is a high risk of aerosol dispersion during intubation and certain neurosurgical procedures particularly those involving drills and endoscopes. These procedures should be performed wearing full personal protective equipment. The workflow of the operating rooms should also be modified significantly. Minor modifications in personal and professional lifestyles and routine training to use the PPE will ensure efficient management of resources. Conclusion: These recommendations could be used to mitigate the risks and reduce exposure to other patients, public, and healthcare staff.

Introduction A paucity of literature exists on genotype- phenotype correlates of ‘unknown-etiology’ infantile-onset developmental-epileptic encephalopathies (DEE) from India. The primary objective was to explore the yield of genetic testing in identifying potential disease causing variants in electro-clinical phenotypes of DEE Methods An observational hospital-based study was undertaken on children with unexplained refractory seizure-onset ≤12 months age and developmental delay, whose families consented and underwent genetic testing during a three year time period (2016–2018) by next-generation sequencing (NGS) or multiplex ligand protein amplification. Yield was considered based on demonstration of pathogenic/likely pathogenic variants only and variants of unknown significance (VUS) were documented. Results Pathogenic/likely pathogenic variants were identified in 26 (31.7 %) out of 82 children with DEE. These included those variants responsible for primarily DEE- 21(76.7 %); neuro-metabolic disorders- 3(18.6 %) and chromosomal deletions- 2(4.7 %). Of these patients, early-infantile epilepsy onset ≤ 6 months age was noted in 22(84.6 %). The DEE studied included Ohtahara syndrome associated with STXBP1 and SCN8A variants with yield of 50 % (2/4 tested); early myoclonic encephalopathy (no yield in 2); West syndrome with CDKL5, yield of 13.3 % (2/15 tested); epilepsy of infancy with migrating partial seizures due to CACNA1A and KCNT1 variants, yield of 67 % (2/3 tested); DEE-unclassified with KCNQ2, AP3B2, ZEB2, metabolic variants (SUOX, ALDH7A1, GLDC) and chromosome deletions (chr 1p36, chr2q24.3); yield of 32 % (8/25 tested). Patients with Dravet syndrome/Dravet-like phenotypes (N = 33) had variants in SCN1A (N = 10), SCN1B, CHD2; yield of 36.4 % (12/33 tested; 57.1 % from NGS). Eighteen patients with potential variants (SCN1A, SCN2A, SCN8A, KCNQ2, ALDH7A1 which also included VUS) could be offered targeted therapy. Conclusions Our study confirms a good yield of genetic testing in neonatal and infantile-onset DEE provided robust phenotyping of infants is attempted with prognostic and therapeutic implications, particularly relevant to centres with resource constraints.

Purpose The success of epilepsy surgery lies in identifying the ictal onset zone accurately. The significance of auras has little been explored on surgical outcome in drug-resistant epilepsy. This study focuses on the clinicopathological correlation of aura(s) and its role in predicting surgical outcome in drug-resistant temporal lobe epilepsy (TLE). We compared surgical outcome in TLE between patients with and without aura and identified the clinico-pathological, radiological and surgical differences between the two groups. Methods Consecutive patients who underwent presurgical evaluation from January 2009 to December 2014 for drug-resistant TLE who underwent anterior temporal lobectomy (ATL) were included. Patients were followed up at 3months, 12 months and then annually. Results Among 456 patients, 344(75%) had aura. Multivariate logistic regression showed that prototype EEG pattern at ictal onset (OR 2.12, 95% CI 1.18–3.06, p = 0.012) and right sided epileptogenic zone (OR 1.82 95% CI 1.18–3.78, p = 0.007) were significantly associated with presence of aura. There was no difference in surgical outcome between those with and without aura. But patients with auditory aura (OR 7.28, CI 2.80–18.95, p = 0.0002) and vertiginous aura (OR 3.01, CI 1.55–7.85, p = 0.028) had a poor surgical outcome. Bivariate analysis showed that normal MRI (p = 0.028) and normal/indeterminate pathology (p = 0.001) were significantly more common with auditory/vertiginous auras. Conclusions Mere presence of aura does not affect outcome after TLE surgery. However, auditory and vertiginous auras are predictors of poor surgical outcome. These patients require more extensive screening for an ictal onset zone beyond standard limits of ATL before surgery.

Objective The management of Women With Epilepsy (WWE) in pregnancy is a challenge that demands balancing the risks of Major Congenital Malformation (MCM) on one hand with adequate seizure control on the other. While most studies have analysed the risks of Anti-Epileptic Drugs (AED) exposure in the first trimester, AED changes during the second and third trimester and their effects on fetal outcome has not been studied adequately. Materials and Methods Data of WWE who were prospectively followed up and completed pregnancy with live birth under the Kerala registry of epilepsy and pregnancy (KREP) between 1998 and 2014 were analysed. The AED addition, dose escalation, unchanged continuation, dose reduction or stoppage during the second or third trimester in comparison to the first trimester was tabulated for each drug. The outcome measures evaluated were malformation status and Developmental Quotient (DQ) at one year as extracted from the clinical records of the registry. Results The first trimester AED exposure was nil for 231, monotherapy for 925 and polytherapy for 391 WWE. WWE on monotherapy in first trimester were more likely to remain on the same number of AEDs in second or third trimester than those who were on polytherapy (OR 3.1, 95% CI 2.2 – 4.46). AED naive women had a higher likelihood (OR 16.7; 95% CI 10.9–25.8) of being started on AED than women on monotherapy being switched to polytherapy. At least one AED was reduced or stopped during second or third trimester more often in women on polytherapy (15.1%) than in women on monotherapy (3.7%) (OR 4.7; 95% CI 2.9–7.2). Malformation rates for the infants of women whose AED dosage was increased or added were not significantly different from those of others. There was no statistically significant change in DQ with increase in dose or addition of drugs in the second or third trimester. Conclusion AEDs were reduced in a significant proportion of patients on polytherapy while more than a third of women who were not on AEDs in the first trimester were subsequently started on AEDs. Increase in dose or addition of AEDs after the first trimester is unlikely to influence malformation outcome but the potential adverse effect on the DQ needs to be explored on a larger set of data.

Objectives To explore the effect of duration of epilepsy and delay in surgery on seizure outcome in patients operated for drug-resistant temporal lobe epilepsy (TLE). Materials & methods A total of 664 consecutive patients who underwent anterior temporal lobectomy (ATL) for TLE from 1995 to 2008 formed the study cohort. We divided them into two, one as seizure-free with or without antiepileptic drugs after ATL as "good outcome" (Engel class I a) and seizures of any type, any time after surgery as "poor outcome." The probability of seizure freedom/seizure recurrence based on the duration of epilepsy was compared using Kaplan-Meier curves, univariate Cox regression survival analysis, and multivariate Cox proportional hazards regression model. Results A total of 136 children and 528 adults underwent ATL during this period. Mean duration of epilepsy pre-ATL was 17.1 + 9.4 years. At mean follow-up of 8.5 years, 331 patients (49.8%) had good outcome and 333 (50.2%) had poor outcome. The hazard of seizure recurrence linearly increased with duration of epilepsy pre-ATL, from 1.5 (duration of epilepsy, 5-10 years) to 1.9 (duration of epilepsy, 10-15 years) to 2 (duration of epilepsy over 15 years). In addition, encephalitis as antecedent, bilateral mesial temporal sclerosis in MRI, normal histopathology, and spikes in postoperative EEG at 3 months and 1 year predicted poor seizure outcome. Conclusions "Epilepsy duration" independently predicted both short- and long-term seizure outcome after surgery in TLE. "Lost years" translate into poor seizure outcome after ATL. Therefore, all cases of drug-resistant TLE should be referred to a surgical center at the earliest.

Background: Evidence for the comparative teratogenic risk of antiepileptic drugs is insufficient, particularly in relation to the dosage used. Therefore, we aimed to compare the occurrence of major congenital malformations following prenatal exposure to the eight most commonly used antiepileptic drugs in monotherapy. Methods: We did a longitudinal, prospective cohort study based on the EURAP international registry. We included data from pregnancies in women who were exposed to antiepileptic drug monotherapy at conception, prospectively identified from 42 countries contributing to EURAP. Follow-up data were obtained after each trimester, at birth, and 1 year after birth. The primary objective was to compare the risk of major congenital malformations assessed at 1 year after birth in offspring exposed prenatally to one of eight commonly used antiepileptic drugs (carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, and valproate) and, whenever a dose dependency was identified, to compare the risks at different dose ranges. Logistic regression was used to make direct comparisons between treatments after adjustment for potential confounders and prognostic factors. Findings: Between June 20, 1999, and May 20, 2016, 7555 prospective pregnancies met the eligibility criteria. Of those eligible, 7355 pregnancies were exposed to one of the eight antiepileptic drugs for which the prevalence of major congenital malformations was 142 (10·3%) of 1381 pregnancies for valproate, 19 (6·5%) of 294 for phenobarbital, eight (6·4%) of 125 for phenytoin, 107 (5·5%) of 1957 for carbamazepine, six (3·9%) of 152 for topiramate, ten (3·0%) of 333 for oxcarbazepine, 74 (2·9%) of 2514 for lamotrigine, and 17 (2·8%) of 599 for levetiracetam. The prevalence of major congenital malformations increased with the dose at time of conception for carbamazepine (p=0·0140), lamotrigine (p=0·0145), phenobarbital (p=0·0390), and valproate (p

Background: FMRI is a noninvasive tool for mapping language networks, especially in children. We conducted FMRI studies in children in the age group 8- 12 years using 2 different paradigms for assessing language networks and lateralization. Aim: To map language networks in pre-adolescent children and to calculate lateralization index using two different visual paradigms. Methods and Materials: The study was conducted in normal right handed children in the age group 8-12 years. Sixteen normal subjects underwent FMRI using 2 paradigms- visual verb generation (VVG), word pairs paradigm (WPP) to stimulate language areas. FMRI data analysis was done using SPM8 (statistical parametric Mapping) software. Total activated voxels were calculated for each hemispheres in the pre-defined ROIs for both paradigms. Results: FMRI showed left language lateralization in 13 out of 16 children with both VVG and WPP and bilateral language lateralization in two subjects. With VVG there was more significant activation in the left inferior triangular gyrus (ITG) (P < 0.001), left inferior opercular gyrus (IOG) (P < 0.01), left middle frontal gyrus (MFG) (P < 0.05), left and right dorsolateral prefrontal cortex (P < 0.05). Left posterior superior temporal gyrus (STG or WA) (P < 0.001), Left AG (P < 0.03), Left SMG (P < 0.05) were significantly activated with WP paradigm. Conclusion: Our FMRI studies showed that VGP predominantly activated frontal language areas and WPP predominantly activated temperoparietal language areas. Several other brain regions were also involved in language processing apart from the classical language areas.

Objective To access the effect of vagus nerve stimulation (VNS) on the outcome of pregnancy. Methods We used the International Registry of Antiepileptic Drugs and Pregnancy (EURAP) and its network to search for women receiving adjunctive VNS during pregnancy. Data on maternal and fetal outcomes were extracted from the registry databases and outcomes were evaluated. Results Twenty-six pregnancies were identified in 25 women. All women were exposed to a relative high VNS stimulation level (mean duty cycle 18%, range 5%–51%). Most women had seizures during pregnancy and almost 70% were on antiepileptic drug (AED) polytherapy. The proportion of women with obstetrical interventions was 53.9% (95% confidence interval [CI] 33.4%–73.4%) which was higher compared to the EURAP average (48.2%; 95% CI 47.2%–49.1%). One infant (3.9%; 95% CI 0.1%–19.6%) was born with a major malformation (unilateral congenital glaucoma), which is within the range expected among offspring of AED-treated women. Conclusion Although the present series of VNS-exposed pregnancies is the largest reported to date, the sample size is insufficient to draw any firm conclusions on the safety of VNS in pregnancy but the findings suggest an increased rate of obstetrical interventions, and no clear signal of VNS-related teratogenicity.

Aim To study the clinical, electrophysiological and imaging characteristics of patients with unilateral mesial temporal lobe epilepsy (MTLE) with contralateral ictal onset on scalp EEG, viz. ‘burned-out hippocampus’ syndrome (MTLE-BHS). Methods MTLE-BHS was defined as TLE with unilateral hippocampal sclerosis (HS) without any dual pathology on MRI and contralateral ictal onset on scalp EEG, unlike in classical hippocampal sclerosis (HS). Consecutive “MTLE-BHS” patients evaluated at our Centre for Comprehensive Epilepsy Care from January 2005 to July 2014 were studied. Twenty-five cases of classic MTLE-HS operated during the same period were also analyzed for comparison. Results Seventeen patients were diagnosed to have MTLE-BHS. Mean age of seizure onset was 9.5 ± 7.7 years and the mean duration of epilepsy was18.2 ± 7.3 years. Epigastric aura was more common in MTLE-HS and fear, secondary generalized seizures and temporal polar changes on MRI were more prevalent in the MTLE-BHS subgroup. In the latter group, five (29%) exhibited seizure semiology and 2 (12%) had interictal discharges discordant to the side of MTS. Eight (47%) patients in the MTLE-BHS sub-group had normal medial temporal volume on Scheltens scale. Eight patients among MTLE-BHS underwent surgery (4 following intracranial monitoring that localized to the side of HS) with Engel class I outcome at 1 year follow-up in 6 and Engel class II outcome in 2. Conclusion Attenuation of ipsilateral fast ictal rhythms on scalp EEG as well as neocortical changes are likely to be deterministic factors for MTLE-BHS as opposed to the severity of hippocampal atrophy. Considering good post-operative outcomes, intracranial monitoring for surgical selection is not mandatory in MTLE-BHS despite discordant semiology and ictal onset, in the presence of inter-ictal, functional imaging and neuropsychology data concordant to the side of HS.

OBJECTIVES To estimate the prevalence of personality disorders in patients with temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS) and compare it with general population and analyze their implications on treatment outcome. MATERIALS AND METHODS TLE was diagnosed based on clinical history, MRI, and Video EEG data. IPDE-ICD10 screening questionnaire was applied to investigate personality disorder in 120 subjects, 60 cases, and 60 normal controls. Bear-Fedio inventory (BFI) was used to study different behavior traits in patients with TLE and controls. RESULTS Prevalence of personality disorders was higher (71.7% in cases versus 38.3% in controls) in patients with TLE compared to controls (P