Encephalopathy induced by combination therapy with valproic Acid and topiramate: challenging the utility of serum ammonia measurement.

The combination of valproic acid and topiramate has been shown to increase the risk of encephalopathy.1-5 Certain authors have proposed that this combination evokes a synergistic mechanism that produces hyperammonemia, which in turn results in encephalopathy.2,6 Described here is a case of encephalopathy potentially induced by the combination of valproic acid and topiramate, in which serial serum ammonia measurements suggested that encephalopathy may occur before hyperammonemia. This case challenges the proposed mechanism in this clinical situation and the utility of measuring serum ammonia concentration