Valproate-induced hyperammonemic encephalopathy: a brief review

Abstract

Although there are several case reports on VHE, this review is a comprehensive evaluation of its causes and potential mechanisms. Rapid diagnosis and management will help in reducing VHE-related morbidity.

Encephalopathy Induced by Combination Therapy with Valproic Acid and Topiramate: Challenging the Utility of Serum Ammonia Measurement

“…1,2,7 This patient's presentation was consistent with previous reports: the encephalopathy developed about 5 days after valproic acid was added to topiramate, and the EEG findings shortly after achievement of therapeutic valproic acid concentrations were consistent with drug-induced encephalopathy.…”

“…Monotherapy with either valproic acid or topiramate or combination therapy with the 2 drugs has frequently been reported to cause encephalopathy. [2][3][4][5][7][8][9] In a recent retrospective chart analysis, the odds ratio for development of encephalopathy was 10 for patients receiving valproic acid -topiramate combination therapy relative to patients receiving valproic acid alone. 1 In the case reported here, the patient's improved neurologic status after withdrawal of valproic acid suggested that this drug had a role in the development of encephalopathy.…”

“…[1][2][3][4][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…”

Case: Valproat-Induced Hyperammonemic Encephalopathy

“…Under VPA treatment over a few months, asymptomatic hyperammonaemia occurs in 16,2-52,3% of patients in the literature (2). Valproate induced hyperammonemic encephalopathy (VHE) is characterized by an acute onset of impaired consciousness, focal neurologic symptoms and increased seizure frequency (1,3). Different mechanisms have been implicated in VHE.…”

“…While VPA usage and related issues increase, numerous drug interactions and toxicities are reported. Severe toxicities include hepatic damage, pancreatitis, teratogenicity, bone marrow supression, coagulation disorders and hyperammonemic encephalopathy (1). Under VPA treatment over a few months, asymptomatic hyperammonaemia occurs in 16,2-52,3% of patients in the literature (2).…”