Analysis of distribution and localization of proteins of the reelin signalling pathway in mesial temporal lobe epilepsy.

INTRODUCTION: Granule cell dispersion (GCD) is pathognomonic of hippocampal sclerosis seen in the mesial temporal lobe epilepsy (MTLE). Current animal studies indicate deficiency of Reelin is associated with abnormal granule cell migration leading to GCD. The present study aimed to evaluate complete Reelin signalling pathway to assess whether Reelin deficiency is related to MTLE. MATERIALS AND METHODS: Hippocampal sclerosis was confirmed by H and E stain. To explore the amount and cellular location of the Reelin cascade molecules, the hippocampal tissues from MTLE surgery and controls (n = 15 each) were studied using Immuno-histochemistry (IHC). Additionally, confocal imaging was used to validate the IHC findings by co-localization of different proteins. Quantification of IHC images was performed using histo-score and confocal images by Image J software. RESULTS: Immune expression of active Reelin was significantly reduced in patients. Reelin receptors were deranged, apolipoprotein E receptor 2 was increased while very low-density lipoprotein receptor was reduced. Disabled-1, a downstream molecule was significantly reduced in MTLE. Its ultimate target, cofilin was thus disinhibited and expressed more in MTLE. Reelin cleaving protease, matrix metalloprotease-9 (MMP-9) and MMP-9 inhibitor, tissue inhibitor of matrix protease-1, showed reduced expression in extracellular matrix. Semi-quantification of immunohistochemistry was done using Histo (H) score. H score of Reelin in diseased patients was 15 against 125 for control patients. These results were validated by confocal fluorescence microscopy. CONCLUSIONS: Reelin signalling cascade was deranged in chronic MTLE. Pharmacological manipulation of Reelin cascade can be done at various levels and it may provide novel treatment options for MTLE.

Exploring the genetic landscape of diphtheria, tetanus and pertussis vaccination-associated seizures or subsequent epilepsies.

Background: Diphtheria, Tetanus, and whole-cell Pertussis (DTwP) vaccination-associated seizures form the commonest type of serious adverse event following immunization in India and are an important reason for vaccine hesitancy. Our study explored the genetic explanation of DTwP vaccination-associated seizures or subsequent epilepsies. Methods: Between March 2017 and March 2019, we screened 67 children with DTwP vaccination-associated seizures or subsequent epilepsies, and of those, we studied 54 without prior seizures or neurodevelopmental deficits. Our study design was cross-sectional with a 1-year follow-up having both retrospective and prospective cases. We performed clinical exome sequencing focused on 157 epilepsy-associated genes and multiplex ligation-dependent probe amplification of the SCN1A gene at enrolment. We applied the Vineland Social Maturity Scale for neurodevelopmental assessment at follow-up. Findings: Of 54 children enrolled and underwent genetic testing (median age 37.5 months, interquartile range 7.7-67.2; diagnosis at enrolment: epilepsy 29, febrile seizure 21, and febrile seizure-plus 4), we found 33 pathogenic variants of 12 genes. Of 33 variants, 13 (39%) were novel. Most pathogenic variants were found in SCN1A gene (n = 21/33; 64%), SCN8A in 2 children, and 10 children had one variant in CDKL5, DEPDC5, GNAO1, KCNA2, KCNT1, KCNQ2, NPRL3, PCDH19, RHOBTB2, and SLC2A1. Five or more seizures (odds ratio [OR] = 5.3, confidence interval [CI]: 1.6-18.4, p = 0.006), drug-resistant epilepsy (OR = 9.8, 95% CI: 2.6-30.7, p = 0.001) and neurodevelopmental impairment (social quotient < 70) (OR = 5.6, 95% CI: 1.65-17.6, p = 0.006) were significant predictors of genetic diagnosis. Interpretation: Our study provides proof-of-concept for genetic aetiology in children with DTwP vaccination-associated seizures or subsequent epilepsies and has important implications for vaccination policies in developing countries. Funding: International Pediatric Association Foundation, Inc. (IPAF): Ihsan Dogramaci research award 2016/2017; Indian Council of Medical Research (ICMR), New Delhi, India: No.3/1/3/JRF-2016/HRD/LS/71/10940.

Expressional Study of Permeability Glycoprotein and Multidrug Resistance Protein 1 in Drug-resistant Mesial Temporal Lobe Epilepsy.

Introduction: About 30% of patients with epilepsy do not respond to anti-epileptic drugs, leading to refractory seizures. The pathogenesis of drug-resistance in mesial temporal lobe epilepsy (MTLE) is not completely understood. Increased activity of drug-efflux transporters might be involved, resulting in subclinical concentrations of the drug at the target site. The major drug-efflux transporters are permeability glycoprotein (P-gp) and multidrug-resistance associated protein-1 (MRP-1). The major drawback so far is the expressional analysis of transporters in equal numbers of drug-resistant epileptic tissue and age-matched non-epileptic tissue. Methods: We have studied P-gp and MRP-1 drug-efflux transporters in the sclerotic hippocampal tissues resected from the epilepsy surgery patients (n=15) and compared their expression profile with the tissues resected from non-epileptic autopsy cases (n=15). Results: Statistically significant over expression of both P-gp (P<0.0001) and MRP-1 (P=0.01) at gene and protein levels were found in the MTLE cases. The fold change of P-gp was more pronounced than MRP-1. Immunohistochemistry of the patient group showed increased immunoreactivity of P-gp at blood-brain barrier and increased reactivity of MRP-1 in the parenchyma. The results were confirmed by confocal immunofluorescence microscopy. Conclusion: Our results suggested that P-gp in association with MRP-1 might be responsible for the multi-drug resistance in epilepsy. P-gp and MRP-1 could be important determinants of bio availability and tissue distribution of anti-epileptic drugs in the brain which can pharmacologically inhibited to achieve optimal drug penetration to target site.

Satisfaction and effectiveness of tele-medicine in follow-up of people with epilepsy in a resource-poor setting during COVID-19.

BACKGROUND: Effectiveness of different tele-medicine strategies varies in different medical conditions. Use of basic tele-medicine strategy like mobile health (m-health) can be an effective option in different medical conditions in a resource-poor setting. AIMS: To study effectiveness and satisfaction of tele-medicine among persons with epilepsy (PWE) in a developing nation during COVID-19 pandemic. METHODS: Persons with epilepsy aged 18 years or more who have attended epilepsy clinic at least once physically and were asked for regular follow-up were included. A cross-sectional telephonic survey was conducted to assess effectiveness of tele-medicine over past 1 year. Satisfaction was assessed by tele-medicine satisfaction questionnaire. RESULT: 31.9% of PWE have used tele-medicine facility in last 1 year and 58.2% were unaware of the availability of such a facility. Among those who utilized tele-medicine, 95.3% were able to explain their concerns satisfactorily during tele-consultation and change in prescription was done in 42.8%. None experienced any new adverse event. Overall, more than 95% were satisfied with tele-consultation and more than 80% wanted to use it again. CONCLUSION: Even basic tele-medicine strategies can be a very effective and satisfactory mode of follow-up for PWE in resource-poor settings. Steps should be undertaken to make people aware of the availability of such a facility.

Knowledge, attitude, and barriers for epilepsy surgery: A survey among resident doctors in a tertiary care center in India.

BACKGROUND: Knowledge and attitude of doctors toward epilepsy surgery are essential for management and timely referral of people with Drug refractory epilepsy (DRE). This study aimed at analyzing knowledge, attitude, and barriers for epilepsy surgery among medical residents. METHODS: A survey consisting of 16 statements in a Likert-like scale and one open-ended question was conducted among residents joining different postgraduate courses after MBBS (GR) and super-specialty courses after MD (PG) within 2 months of joining the institute. PGs with a postgraduate degree in internal medicine, pediatrics, or psychiatry were included. Demographic data were analyzed using descriptive statistics. Difference in response to the survey statements was analyzed using independent t test. RESULTS: 115 participated in the survey of which 97 were GRs. Participants belonged to 22 different states and 3 were foreign nationals. 45% of participants did not know the definition of DRE. There was a difference of opinion among GRs and PGs regarding surgery as a treatment option for epilepsy and feasibility of epilepsy surgery in children (p < .05). PGs were more confident in treating PWE and preferred to refer people with DRE to a higher center early (p < .05). Lack of knowledge was the commonest barrier for epilepsy surgery. CONCLUSION: A substantial number of participants lacked the basic knowledge of DRE and epilepsy surgery. Lack of knowledge was perceived to be the commonest barrier for epilepsy surgery. Dissemination of basic knowledge and development of protocols for identification and referral of people with DRE are the need of the hour.

Temporal lobe epilepsy with amygdala enlargement: A systematic review.

Temporal lobe epilepsy (TLE) with enlargement of the amygdala (AE) is a distinct clinical entity with contrasting clinical features from TLE with hippocampal sclerosis (HS). The objectives of this systematic analysis were to study the clinical characteristics and treatment outcome of people with TLE with AE. Pubmed, Embase, Cochrane, Web of Science, Scopus, and Medline were searched using the keywords amygdala enlargement, temporal lobe epilepsy, epilepsy, and seizure in November 2020. We found 18 studies that satisfied the inclusion criteria. A total of 361 patients were included in this analysis. The mean age of onset was 36.2 years, and febrile seizure was uncommon compared to TLE with HS subjects. The type of aura and automatism was similar to TLE with HS, though less prevalent. Electroencephalography (EEG) was usually concordant with the side of AE. Anti-seizure medications (ASM), surgical, and immunotherapy were used in different studies. 86 patients underwent surgery with Engel I outcome in 69.7%. Histopathology of the resected samples was predominantly dysplasia and gliosis. A group of patients that responded well to immunotherapy with subsequent reduction of amygdala volume (AMV) purported an autoimmune etiology of AE. Heterogeneity was the main drawback that prevented comparability among the studies. The methods of measurement of AMV also differed widely in the included studies, and standardization of its method is still lacking. This analysis suggests TLE with AE as a distinctive group of patients either due to a developmental anomaly or autoimmune etiology.

Carbamazepine versus levetiracetam in epilepsy due to neurocysticercosis.

BACKGROUND: The choice of antiepileptic drug (AED) in newly diagnosed neurocysticercosis (NCC) patients with epilepsy continues to be arbitrary. We compared efficacy and side effect profile of levetiracetam (LEV) and carbamazepine (CBZ) for the treatment of seizures in newly diagnosed patients with NCC. PATIENTS AND METHODS: This was an open-labeled randomized comparative monotherapy study including newly diagnosed drug naïve patients of NCC (n = 99) presenting with seizures who were randomized in 1:1 ratio using computed generated numbers. All patients were followed up for at least six months after start of treatment. The primary outcome measure was seizure control over six months following start of AEDs. RESULTS: Fifteen (15.2%) patients [CBZ- 4(8.2%); LEV- 11(22%)] developed recurrence of seizures. A trend (p = 0.09) was found toward better control of seizures in CBZ compared to LEV. Two (4%) patients in LEV group and 17 (34.6%) patients in CBZ group developed drug-related minor side effects (p < 0.0001). Three patients in CBZ group needed discontinuation of therapy due to skin rash. Eleven patients who relapsed while on LEV did not have any recurrence of seizures after switching over to CBZ. Out of 3 patients who relapsed while receiving CBZ and were changed to LEV, two developed seizures during follow-up. CONCLUSION: CBZ and LEV could be used as alternatives in newly diagnosed patients of NCC at the behest of minor side effects in the CBZ group.

Presence of allele CYP3A4*16 does not have any bearing on carbamazepine-induced adverse drug reactions in North Indian people with epilepsy.

OBJECTIVES: The objectives of this study were to determine the relationship between genetic polymorphisms in gene encodings for CYP3A4 and carbamazepine (CBZ)-induced dose-related side effects in North Indian people with epilepsy. PATIENTS AND METHODS: The current prospective study included 37 patients with CBZ-induced dose-related side effects and 102 patients who did not experience side effects while on CBZ. The genotyping for CYP3A4 allele (CYP3A4*16) was done using real-time polymerase chain reaction (RT-PCR) in Applied Biosystems 7500 RT-PCR System (USA). CBZ was administered in all patients at a dose varying from 15 to 20 mg/kg daily. RESULTS: Various demographic variables were comparable between the groups except that control of seizures was far better in controls. After testing, it was found that none of our patients had the presence of CYP3A4*16 allele. CONCLUSION: CYP3A4*16 allele is not represented significantly in North Indian people with CBZ-induced dose-related side effects.

Functional MRI in epilepsy - Comparison of Lateralization index and language scoring.

AIMS: To evaluate the role of functional magnetic resonance imaging (fMRI) in epilepsy management and to ascertain whether laterality index (LI) derived from fMRI data, using routinely utilized paradigms, can serve as an adjunct to/or replace preoperative neuropsychological testing for evaluation of language lateralization and impairment. MATERIALS AND METHODS: This was a prospective study which included 20 consecutive patients with a clinical diagnosis of temporal lobe epilepsy over a period of 1 year. Neuropsychological assessment included oral word association test and animal names test. The scores of both tests were compared with normographic data provided in the NIMHANS neuropsychology battery. Three fMRI paradigms were used, namely, picture naming, word generation, and sentence completion. Processing and statistical analysis were performed subsequently. RESULTS AND CONCLUSION: Right temporal lobe epilepsy (RTLE) was seen in 12 patients and left temporal lobe epilepsy (LTLE) in 8 patients. All patients were right handed. The activation pattern was predominantly left lateralized. Language lateralization varied with the type of paradigm. The overall percentage of patients showing left lateralization ranged from 44.00% for the picture naming task to 75% for the sentence completion. Reduced left lateralization was noted in both LTLE and RTLE patients. A negative correlation was observed in LTLE patients between performance in the verbal fluency and the lateralization index in the temporal and parietal regions of interest (ROI) in the word generation paradigm, suggesting that increased left lateralization was associated with a poorer score on neuropsychological tests. In RTLE patients, however, there was no significant correlation between performance in neuropsychological tests and LI. In conclusion, language lateralization using LI can serve as an adjunct during preoperative evaluation. However, it cannot replace neuropsychological testing.

Prevalence of Epilepsy and its Association with Exposure to Toxocara canis: A Community Based, Case-control Study from Rural Northern India.

OBJECTIVES: Many community-based and hospital-based studies across the world have yielded contradictory results regarding association of positive Toxocara canis serology and epilepsy. The present study was planned to analyze disease burden of epilepsy in rural community of North India and its association with exposure to T. canis in this part of the world. METHODS: A door-to-door screening survey was carried out in the rural community using a validated questionnaire for epilepsy by trained field workers, which was finally confirmed by trained neurologists. The risk factors for epilepsy and for predisposing infections were also enquired. The results were compared with an equal number of age- and sex-matched healthy controls enrolled from the same community. Serologic evaluation was carried out to detect antibodies against T. canis. RESULTS: A total of 41,973 persons from the rural community in 49 villages were enrolled in the study. Two hundred and eleven persons were confirmed to be suffering from active epilepsy, resulting in a crude prevalence of 5 per 1000 population. More than 50% of people with epilepsy were in the second or third decade of life. The prevalence of antibodies to T. canis was similar in people with epilepsy (13.7%; 29 of 211 individuals) and controls (9.95%; 21 of 211 individuals). Of the 151 persons with epilepsy, who underwent CT scan, 34 people (22.3%) had evidence of inflammatory granuloma, thereby confirming high incidence of this infestation in rural Northern India. SIGNIFICANCE: Our study does not support the association between epilepsy and exposure to T. canis in rural Northern Indian population.

N-acetyltransferase 2 (NAT2) gene polymorphism as a predisposing factor for phenytoin intoxication in tuberculous meningitis or tuberculoma patients having seizures - A pilot study.

BACKGROUND & OBJECTIVES: Simultaneous administration of phenytoin and isoniazid (INH) in tuberculous meningitis (TBM) or tuberculoma patients with seizures results in higher plasma phenytoin level and thus phenytoin intoxication. N-acetyltransferase 2 (NAT2) enzyme catalyses two acetylation reactions in INH metabolism and NAT2 gene polymorphism leads to slow and rapid acetylators. The present study was aimed to evaluate the effect of allelic variants of N-acetyltransferase 2 (NAT2) gene as a predisposing factor for phenytoin toxicity in patients with TBM or tuberculoma having seizures, and taking INH and phenytoin simultaneously. METHODS: Sixty patients with TBM or tuberculoma with seizures and taking INH and phenytoin simultaneously for a minimum period of seven days were included in study. Plasma phenytoin was measured by high performance liquid chromatography. NAT2 gene polymorphism was studied using restriction fragment length polymorphism and allele specific PCR. RESULTS: The patients were grouped into those having phenytoin intoxication and those with normal phenytoin level, and also classified as rapid or slow acetylators by NAT2 genotyping. Genotypic analysis showed that of the seven SNPs (single nucleotide polymorphisms) of NAT2 gene studied, six mutations were found to be associated with phenytoin intoxication. For rs1041983 (C282T), rs1799929 (C481T), rs1799931 (G857A), rs1799930 (G590A), rs1208 (A803G) and rs1801280 (T341C) allelic variants, the proportion of homozygous mutant was higher in phenytoin intoxicated group than in phenytoin non-intoxicated group. INTERPRETATION & CONCLUSIONS: Homozygous mutant allele of NAT2 gene at 481site may act as a predisposing factor for phenytoin intoxication among TBM or tuberculoma patients having seizures.

Sleep disturbances in drug naïve Parkinson's disease (PD) patients and effect of levodopa on sleep.

CONTEXT: Parkinson's disease (PD) is associated with sleep disturbances, attributed to the neurodegenerative process and therapeutic drugs. Studies have found levodopa to increase wakefulness in some patients while increasing sleepiness in others. AIMS: To confirm sleep disturbances in drug naïve PD patients and understand the impact of levodopa on their sleep. MATERIALS AND METHODS: Twenty-three drug naïve PD patients and 31 age-gender matched controls were compared using the Parkinson's Disease Sleep Scale (PDSS) and Epworth Sleepiness Scale (ESS). A polysomnogram objectively compared sleep quality. Of the 23 patients, the 12 initiated on levodopa were reassessed subjectively and through polysomnography after 2 months of therapy. STATISTICAL ANALYSIS: Data was expressed as mean ± standard deviation, median, and range. Continuous variables were analyzed by Student's T test for normally distributed data and Mann-Whitney U test for skewed data. Discrete variables were compared by Chi Square tests (Pearson Chi square Test or Fisher's Exact Test). Wilcoxon signed ranks test was applied in the analysis of paired data pre- and post-levodopa. A P value < 0.05 was considered as statistically significant. Statistical analysis of the data was done using the Statistical Package for the Social Sciences (SPSS) version 12. RESULTS: Drug naïve PD patients had lower PDSS scores than controls. The sleep architecture changes observed on polysomnogram were reduced NREM Stage III and REM sleep and increased sleep latency and wake after sleep onset time. Following levodopa, improved sleep efficiency with reduced sleep latency and wake after sleep onset time was noted, coupled with improved PDSS scores. However, NREM Stage III and REM sleep duration did not increase. DISCUSSION: PD patients take longer to fall asleep and have difficulty in sleep maintenance. Sleep maintenance is affected by nocturia, REM behavioral disorder, nocturnal cramps, akinesia, and tremors, as observed in PDSS scores. Levodopa improves sleep efficiency by improving motor scores without altering sleep architecture. CONCLUSIONS: Poor sleep quality and sleep architecture changes occur secondary to the neurodegenerative process in PD patients. Though levodopa improves sleep quality by reducing rigidity and tremor, it does not reverse sleep architecture changes.

Acute Flaccid paralysis in adults: Our experience.

UNLABELLED: Acute flaccid paralysis (AFP) is a complex clinical syndrome with a broad array of potential etiologies that vary with age. We present our experience of acute onset lower motor neuron paralysis. MATERIALS AND METHODS: One hundred and thirty-three consecutive adult patients presenting with weakness of duration less than four weeks over 12 months period were enrolled. Detailed history, clinical examination, and relevant investigations according to a pre-defined diagnostic algorithm were carried out. The patients were followed through their hospital stay till discharge or death. RESULTS: The mean age was 33.27 (range 13-89) years with male preponderance (67.7%). The most common etiology was neuroparalytic snake envenomation (51.9%), followed by Guillain Barre syndrome (33.1%), constituting 85% of all patients. Hypokalemic paralysis (7.5%) and acute intermittent porphyria (4.5%) were the other important conditions. We did not encounter any case of acute polio mylitis in adults. In-hospital mortality due to respiratory paralysis was 9%. CONCLUSION: Neuroparalytic snakebite and Guillain Barre syndrome were the most common causes of acute flaccid paralysis in adults in our study.

Status epilepticus: Our experience in a tertiary care centre in Northwestern India.

INTRODUCTION: Status epilepticus (SE) is a medical emergency. Aim of this study was to examine the etiology and outcome of adult patients in status epilepticus presenting to our center. PATIENTS AND METHODS: A prospective study was conducted from January 2009 to December 2010. Newly diagnosed patients as well as known case of seizure disorder presenting with status epilepticus were included. Detailed history, clinical examination, baseline investigation, neuroimaging electroencephalogram findings were recorded. Patients were treated using a standard protocol and were followed-up for 2 weeks after discharge. Quantification of precipitating factors was done using proportion, mean and standard deviation. RESULTS: 80 consecutive patients were studied. Mean age was 38.43 ± 16.56 years (range 13 to 78 years). Male to female ratio was 4:1. 57.5% were known cases of seizure disorders. Generalized tonic-clonic seizure was commonest presentation in 91.30%. Majority (97.5%) had convulsive SE. Poor drug compliance was found to be the commonest precipitant (50% patients), followed by central nervous system infection (20% patients. Alcohol intake contributed in 12.5% cases, whereas, precipitating factor couldn't be traced in 7.5% patients'. In 55% patients, SE was controlled with no recurrence or complication and in 25% there was recurrence after control of SE. 15% patients ended up with persistent sequel (cognitive and psychosomatic dysfunction, neurological deficit etc.) lasting for 2 weeks or more. The mortality was 5%. CONCLUSION: Poor compliance with drugs (in established cases of seizure disorders) and central nervous systems infections/structural lesions (in new onset cases) were commonest causes of SE in our study group. Conventional first line antiepileptics were able to control seizures in only 55% patients.

Phenotypic interaction of simultaneously administered isoniazid and phenytoin in patients with tuberculous meningitis or tuberculoma having seizures.

Treatment of tuberculous meningitis or tuberculoma has become complicated because of adverse drug interactions found amongst antitubercular and anticonvulsant drugs. The aim of the study is to evaluate the effect of simultaneously administered isoniazid (300 mg/day) and phenytoin (300 mg/day) on 60 patients with tuberculous meningitis or tuberculoma having seizures. Plasma samples were analyzed for isoniazid, acetylated-isoniazid (AcINH) and phenytoin levels by high performance liquid chromatography at 3h of drugs administration and patients were classified as rapid or slow acetylator on the basis of metabolic ratio of isoniazid (Rm) and percentage of acetylated-isoniazid (%AcINH). Out of 60 patients studied, 23 were slow acetylators and 37 were rapid acetylators. Slow acetylators revealed higher plasma isoniazid levels and lower plasma AcINH levels, metabolic ratio and %AcINH as compared to rapid acetylators. Plasma phenytoin levels were found to be significantly higher (above therapeutic range) in slow acetylators as compared to rapid acetylators. Plasma phenytoin concentration was moderately strong, negatively correlated with metabolic ratio (r=-0.439, P<0.001) and %AcINH (r=-0.729, P<0.001). Eight comatose patients (34.8%) also showed significantly higher plasma phenytoin levels. Our results suggest that assessment of acetylator status and plasma phenytoin level is critical for dose optimization of isoniazid and phenytoin and to predict the patients at risk of intoxication.

Seizure type, antiepileptic drugs, and reproductive endocrine dysfunction in Indian women with epilepsy: a cross-sectional study.

BACKGROUND: There is paucity of data regarding occurrence of reproductive endocrine disorders in Asian women with epilepsy (WWE) on antiepileptic drug (AED) therapy. PURPOSE: To determine the occurrence of reproductive endocrine disorders in Indian WWE, by seizure type and the AED use. METHODS: Consecutive 427 reproductive age WWE receiving various AEDs were screened for the occurrence of menstrual abnormalities, weight change, and hirsutism. Of these, 53 WWE with menstrual disturbances and/or hirsutism were further evaluated for ovarian morphology and reproductive hormonal profile. RESULTS: Menstrual abnormalities and/or hirsutism were observed in 83 of 427 (19.4%) WWE irrespective of epileptic seizure type; of these, 50 (60.2%) received valproate, 21 (25.3%) received carbamazepine, 11 (13.3%) received phenytoin, and one (1.2%) received phenobarbitone as the primary AED. Almost half of valproate-treated women had significant weight gain and obesity. Among 53 of 83 women evaluated further, 23.5% and 63.6% of valproate-treated women, 25% and 58.3% of carbamazepine-treated women, and none and 20% of phenytoin-treated women had polycystic ovaries (PCO) and hyperandrogenemia (HA), respectively. Valproate-treated women had significantly higher frequency of polycystic ovarian syndrome (PCOS) (11.8% vs. 2.5%, p < 0.0001) and mean serum testrosterone levels (1.78 vs. 1.36 ng/ml, p = 0.03), compared with women treated with other AEDs. LIMITATIONS: Limitations include small number of women in antiepileptic subgroups and a high drop out rate in women who underwent ultrasound and endocrinological investigations. CONCLUSION: Menstrual abnormalities, weight gain, obesity, and PCOS are frequent and significantly higher in WWE receiving valproate, independent of seizure type.