SummaryBackground-Carbamazepine is widely accepted as a drug of first choice for patients with partial onset seizures. Several newer drugs possess efficacy against these seizure types but previous randomised controlled trials have failed to inform a choice between these drugs. We aimed to assess efficacy with regards to longer-term outcomes, quality of life, and health economic outcomes.

SummaryBackground-Valproate is widely accepted as a drug of first choice for patients with generalised onset seizures, and its broad spectrum of efficacy means it is recommended for patients with seizures that are difficult to classify. Lamotrigine and topiramate are also thought to possess broad spectrum activity. The SANAD study aimed to compare the longer-term effects of these drugs in patients with generalised onset seizures or seizures that are difficult to classify.

Objectives: To determine the prevalence of cognitive delay and possible associated dysmorphic features in children exposed to antiepileptic drugs (AEDs) in utero. Design: Retrospective study of children born to mothers with epilepsy. Setting: Regional epilepsy clinics in Liverpool and Manchester, UK. Participants: Children aged between 6 months and 16 years born to mothers with epilepsy. Main outcome measures: Structured interviews, hospital records, clinical examination, and psychometric tests (Wechsler) were used to assess exposure and intelligence quotient (IQ). Blinded assessment of photographs was used to score children with characteristic dysmorphic features. Results: A total of 249 children aged 6 and over were studied: 41 were exposed to sodium valproate, 52 to carbamazepine, 21 to phenytoin, 49 to polytherapy, and 80 were unexposed. Mean verbal IQ was significantly lower in the valproate group compared to unexposed and other monotherapy groups. Multiple regression analysis showed that both valproate exposure and frequent tonic-clonic seizures in pregnancy were significantly associated with a lower verbal IQ despite adjusting for other confounding factors. There was a significant negative correlation between dysmorphic features and verbal IQ in children exposed to valproate. Conclusions: This study identifies valproate as a drug carrying potential risks for developmental delay and cognitive impairment and is the first to suggest that frequent tonic-clonic seizures have a similar effect. Our results need to be interpreted with caution given their retrospective nature. Women with epilepsy need careful counselling about individual risk benefit of AED treatment before pregnancy.

Objective-To assess the long term outcome of patients with methylmalonic acidaemia in a cross sectional study. Patients-All 35 patients with methylmalonic acidaemia seen at Great Ormond Street Hospital for Children in London, UK between 1970 and 1996 were studied. They were divided into cobalamin responsive (n = 6) and non-responsive (n = 29), and early and late onset groups.Results-There was a significant diVerence between cobalamin responsive and non-responsive groups in severity, survival, and incidence of neurological sequelae. Cobalamin responsive patients had mild disease, irrespective of age at presentation, their neurological complications were less severe, and they are all alive. The cobalamin non-responsive group comprised 19 early and nine late onset patients. The early onset patients had more severe disease at presentation and 14 have died; all late onset patients are alive. There was no significant diVerence in abnormal neurological signs, although early onset patients had a significantly reduced full scale intelligence quotient and poor cognitive outcome. In both groups, abnormal neurological signs continue to increase with age. Conclusions-Cobalamin responsive patients have a better long term outcome. The outcome in the non-responsive patients, particularly the early onset group, remains poor and alternative treatments should therefore be considered early in this group. (Arch Dis Child 1998;78:508-512)

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