Fetal exposure to sodium valproate increases the risk of language impairment. This should be taken into account when making treatment decisions for women with epilepsy of childbearing age.

Objective: To determine clinical and EEG features that might help identify patients with epilepsy harboring small, intrinsically epileptogenic, surgically treatable, bottom-of-sulcus dysplasias (BOSDs).Methods: Retrospective review of clinical records, EEG, MRI, and histopathology in 32 patients with drug-resistant epilepsy and MRI-positive (72% 3.0 tesla), pathologically proven (type 2B cortical dysplasia) BOSDs operated at our centers during 2005-2013. Results: Localization of BOSDs was frontal in 19, insula in 5, parietal in 5, and temporal in 3, on the convexity or interhemispheric surfaces. BOSDs were missed on initial MRI at our centers in 22% of patients. Patients presented with focal seizures during infancy in 9, preschool years in 15, and school years in 8 (median age 5 years). Seizures were stereotyped, predominantly nocturnal, and typically nonconvulsive, with semiology referable to the fronto-central or perisylvian regions. Seizures occurred at high frequency during active periods, but often went into prolonged remission with carbamazepine or phenytoin. Intellect was normal or borderline, except in patients with seizure onset during infancy. Scalp EEG frequently revealed localized interictal epileptiform discharges and ictal rhythms. Patients underwent lesionectomy (median age 14 years) guided by electrocorticography and MRI, with prior intracranial EEG monitoring in only one patient. Twentyeight patients (88%) became seizure-free, and 20 discontinued antiepileptic medication (median follow-up 4.1 years). Conclusions:In patients with cryptogenic focal epilepsy, this clinical presentation and course should prompt review of or repeat MRI, looking for a BOSD in the frontal, parietal, or insula cortex. If a BOSD is identified, the patient might be considered for single-stage lesionectomy. Bottom-of-sulcus dysplasia (BOSD)1 is a localized variety of type 2 focal cortical dysplasia (FCD) in which the dysplastic features are maximal at the sulcal depth, tapering to a relatively normal gyral crown.2,3 Pathologically, BOSDs are characterized by neuronal dyslamination and dysmorphology, with or without balloon cells, at the bottom of the sulcus, with hypomyelination in the underlying white matter. 2,4,5 The characteristic MRI features of BOSD are cortical thickening, gray-white junction blurring, and subcortical T2 hyperintensity, often tapering to the ventricle as a "transmantle sign." [6][7][8][9] Straightening and elongation of the dysplastic sulcus, and depression or unusual sulcation of the overlying cerebral surface, may also be appreciated. 8,10,11 BOSDs are typically found in the frontal and parietal lobes.

Summary Purpose The association between autism spectrum disorders (ASDs) and prenatal anticonvulsant exposure is increasingly investigated, but comprehensive, blinded assessment using a validated instrument for autism within a well‐characterized prospective cohort has not been conducted. Thus, existing studies may represent an underestimate of the true risk. Herein we present a prospective cohort study in children exposed to anticonvulsants during pregnancy, with all assessments conducted by examiners who were blinded to drug‐exposure status. Methods Participants were 105 Australian children aged 6–8 years who were recruited via the Australian Pregnancy Register for Women on Antiepileptic Medication. Maternal epilepsy, pregnancy, and medical history data were obtained prospectively. Autism traits were assessed using the Childhood Autism Rating Scale (CARS). Results Eleven children (10.5%) had elevated CARS scores. Two were exposed to valproate monotherapy (2/26; 7.7%), two to carbamazepine monotherapy (2/34; 5.9%), and seven to valproate in polytherapy (7/15; 46.7%). Linear regression analysis showed that the mean valproate dose during pregnancy was a significant predictor of CARS scores after controlling for polytherapy, mean carbamazepine dose, folic acid use, seizures during pregnancy, tobacco and marijuana use, maternal intelligence quotient (IQ), and socioeconomic status. First trimester folic acid supplementation and marijuana use were also significant predictors of CARS scores. Significance Using direct assessment of children in our prospective study, we found an elevated rate of autism traits across the sample. The most important determinant of association with autistic traits was higher doses of sodium valproate exposure. The use of valproate in women who may become pregnant is now generally avoided; however, there are insufficient data regarding the risk of ASD with low‐dose valproate. If this risk is no greater than with other antiepileptic drugs (AED)s, it may enable women with genetic generalized epilepsy to retain optimal seizure control as well as minimize harm to their unborn child.

Prenatal exposure to sodium valproate (VPA) and polytherapy has been linked with increased risk of birth defects and cognitive impairment in young children. We evaluated the cognitive impact of prenatal exposure to VPA and polytherapy in school-aged children. Fifty-seven children exposed to VPA (n 5 23), polytherapy with VPA (n 5 15), or polytherapy without VPA (n 5 19) were assessed using the Wechsler Intelligence Scale for Children-Fourth Edition. Information on maternal epilepsy, pregnancy, and medical history was obtained prospectively through the Australian Pregnancy Register for Women with Epilepsy and Allied Disorders. All groups had elevated frequencies of Extremely Low (,70) or Borderline (70-79) Full-Scale IQ (15.8-40.0%). Verbal Comprehension and Working Memory scores in all groups fell significantly below the standardized test mean, while Perceptual Reasoning and Processing Speed scores were relatively intact. Multivariate analysis of covariance analysis revealed significant main effects of VPA on Verbal Comprehension and Working Memory, and of polytherapy on Verbal Comprehension and Processing Speed. Our results suggest that VPA has a dose-dependent negative impact on verbal intellectual abilities, and may also affect working memory. The possibility that inclusion of VPA in many polytherapy regimens may underlie reduced mean scores of polytherapyexposed children is discussed. (JINS, 2011, 17, 133-142)