The effect of a protein-rich meal (45 g protein) before and after L-carnitine (50 mg/kg/day) for 7 days in 11 epileptic children treated with valproate (VPA) was studied in relation to the magnitude and duration of the VPA-induced hyperammonemia at the University of Wisconsin School of Pharmacy and Department of Neurology, Madison, WI. After a protein meal, the 2-hour plasma ammonia level was increased by 86% over baseline before carnitine administration compared to 38% after carnitine. Ammonia levels approached baseline at 4 hours after a protein meal and were not related to changes in VPA concentrations. 
COMMENT. VPA increases plasma ammonia in almost 50% of children treated. The degree of hyperammonemia is related to diet. It is exacerbated by a protein rich meal, and the postprandial transient elevation of plasma ammonia is significantly reduced by L-carnitine administration and is unrelated to changes in VPA concentration. Both fasting and 2-hour postprandial plasma ammonia levels should be measured to determine the magnitude of a VPA-induced hyperammonemia.
Valproate-induced liver failure is reported in one of two siblings with Alpers disease treated at the University of Minnesota, Minneapolis . Both were developmentally delayed and suffered from seizures from 5 years of age. The proband receiving VPA for only 5 days had minimal liver abnormalities at autopsy at age 8 years. The younger brother treated with VPA for 4 weeks developed acute liver necrosis and died 5 weeks after admission. VPA is not recommended in children with suspected Alpers disease, characterized by developmental delay, ataxia, and epilepsia partialis continua.