Valproic Acid-Induced Hyperammonemia with Encephalopathy (VIHE): A Case Report

Abstract

Valproic acid (VPA) is a wide spectrum antiepileptic medication indicated for seizure prophylaxis across the spectrum of epilepsy. Since coming into clinical use, VPA has also been recommended for the management of a variety of other pathologies, including, most notably, mood stabilization in the manic patient.VPA's common adverse effects include gastrointestinal, influenza-like symptoms, headache, and difficulties with sleep; nonetheless, in rare instances, VPA has been noted to cause the severe and potentially lethal condition of hyperammonemia with encephalopathy (VIHE).VIHE is the result of a dose-independent increase in ammonia levels. Often the patient is asymptomatic; if symptoms reach clinical threshold, lethargy is most common, though seizures, focal neurologic deficits and even coma are possible. VIHE can occur in patients despite normal hepatic function, normal loading doses, chronic stable doses and normal free serum drug levels. Once the diagnosis is confirmed, the first approach for symptomatic patients is to discontinue VPA, start alternative mood stabilizer as indicated, and supplement hyperammonemia treatment with lactulose, carnitine or carglumic acid. Below is a case report of VIHE that developed in an adolescent girl with a history of Bipolar I Disorder who was hospitalized in our facility for stabilization of mania. As demonstrated below, early diagnosis of VIHE is pivotal in reducing morbidity and ultimately can be life-saving.

Valproate Induced Hyperammonemic Encephalopathy

“…Up to 50% cases can be asymptomatic. 1 Treatment for valproate induced encephalopathy is mainly supportive along with withholding valproate. The aim is to reduce ammonia production by stopping catabolism.…”

Valproic acid rechallenge after valproate-induced hyperammonemic encephalopathy

“…1 VIHE, presenting with lethargy, confusion, frank delirium, blurred vision, seizures, or coma, is most commonly treated by discontinuing the drug and adding a substance to diminish ammonia levels, including lactulose or rifaximin/neomycin; however, current research has proposed mechanisms of prevention, treatment, and maintenance therapy to allow for the continuation of VPA using supplementation of levocarnitine or carglumic acid. [2][3][4][5] Studies have shown that individuals with a past medical history of VIHE may continue VPA with the addition of supplementation, but continuation of VPA without supplementation in a patient with a past medical history of VIHE has not previously been reported.…”