Hyperammonemic Encephalopathy: A Rare Presentation of Valproic Acid Toxicity in the Absence of Liver Impairment

Abstract

Hyperammonemia can occur due to a broad range of etiologies and is commonly found in the setting of liver impairment. However, the absence of liver pathology presents a diagnostic challenge. Valproic acid (Valproate) toxicity has been associated with hyperammonemic encephalopathy, but it is a rare occurrence and can be overlooked. Case 1) A 28-year-old woman presented with 3-days of altered mentation, elevated ammonia level and normal liver function. The patient's mentation improved with Lactulose therapy and was subsequently discharged. She had a readmission shortly thereafter with the same presentation. Patient was on Valproate for epilepsy treatment. Valproate levels were elevated, but discontinuing Valproate removed the inciting cause of encephalopathy. She improved with no further hospitalizations. Case 2) A 57-year-old woman presented with 2-hours of altered mentation after intentional overdose. Patient had elevated ammonia and Valproate levels without hepatic impairment. Discontinuation of Valproate and L-carnitine therapy improved patient's encephalopathy. These cases represent a rare complication of Valproate use. Its effect on urea cycle is thought to be one possible explanation for hyperammonemia. Management includes discontinuation of the drug and symptomatic treatment with Lactulose. We also highlight L-carnitine as proposed treatment for such toxicity. It is important for clinicians to be mindful of both hepatic and non-hepatic causes of hyperammonemia. These patients remind us to act with benevolence, utilizing a stepwise approach to diagnosis and treatment in order to improve patient outcomes. In retrospect, in our first case such consideration would have prompted earlier discontinuation of Valproate, potentially avoiding hospital readmission.