Valproate induces non-hyperammonemic encephalopathy below a standard serum concentration range: A case report

Valproate (VPA)-induced encephalopathy may present with consciousness disturbance, epilepsy, and psychiatric disorders after acute or long-term VPA use. VPA-induced encephalopathy typically occurs in the setting of either or both hyperammonemia and low serum L-carnitine levels, however, it may also develop without hyperammonemia or decreased serum L-carnitine levels.

We herein describe a 71-year-old male with VPA-induced nonhyperammonemic encephalopathy with a history of long-term VPA therapy for a corticosteroid-induced mood disorder. He presented with persistent consciousness disturbance.

Serum levels of ammonia and carnitine were within the normal ranges, while that of VPA was below the standard range. A cerebral spinal fluid analysis revealed elevated protein with a normal white cell count. Mild brain atrophy was observed on brain magnetic resonance images and mild periventricular hyperintensity on fluid-attenuated inversion recovery images. Electroencephalography showed semirhythmic delta activity in the parieto-occipital area, and sharp transients in the bifrontal area. The patient was diagnosed with VPA-induced nonhyperammonemic encephalopathy.

The patient was discontinued from VPA.

After the discontinuation of VPA, the patient's consciousness was gradually restored, and electroencephalographic findings also improved. After discharge, he has not had consciousness disturbance, or obvious cognitive impairment.

VPA-induced encephalopathy needs to be considered when patients treated with VPA exhibit neurological symptoms, even if their serum concentration of VPA is below the standard range, and they do not have hyperammonemia or carnitine deficiency. In such cases, treatment with VPA needs to be ceased immediately because neurological symptoms may be alleviated by its discontinuation.