Valproate-Induced Encephalopathy in Three Cases

Valproic acid-induced encephalopathy is a serious complication of valproate, rarely observed, and can lead to death if early diagnosis is not made. It is clinically presented as mental status changes that range from drowsiness to lethargy and coma, focal or bilateral neurological deficits, seizure, vomiting, and marked electroencephalography (EEG) background slowing, with or without hyperammonemia. It can also be properly managed by discontinuation of the drug. We present three cases who developed vomiting, disturbance in consciousness, EEG-slowing, and elevated serum ammonia levels. In all cases, symptoms resolved after termination of valproate. Most notably, these side effects occurred in the presence of normal liver enzymes and normal valproate concentrations. Development of unconsciousness and associated EEG slow waves are observed rarely in VPA-induced encephalopathy, and this is discussed together with a review of the literature. Serum ammonia level is an important parameter in the early diagnosis of this rare adverse event. The clinical symptomatology and EEG findings have significant importance in the differential diagnosis when encephalopathy occurs without hyperammonemia and with normal or slight increase in serum ammonia level.