VALPROATE-ASSOCIATED CARNITINE DEFICIENCY AND MALIGNANT CEREBRAL EDEMA IN THE ABSENCE OF HEPATIC-FAILURE

We describe a 27-year-old woman who developed encephalopathy and cereb ral edema during treatment of refractory complex partial seizures that included acute administration of valproate (VPA) at a dosage of 35 mg /kg per day. Multiple random VPA levels were within therapeutic range, and results of liver function studies did not show evidence of hepati c failure. Cerebral computerized tomography (CT) showed evidence of ma ssive cerebral edema with central herniation. Just prior to death, pla sma levels of free and acyl carnitines were markedly decreased. Analys is of urinary organic acids showed increased excretion of lactate, but a normal distribution of VPA metabolites. Carnitine deficiency may pr edispose patients to the development of coma and life-threatening cere bral edema associated with acute administration of VPA, even in the ab sence of concomitant hepatic failure. We suggest specific guidelines f or the evaluation and management of altered consciousness in patients with seizures receiving VPA.