From tremor to myoclonus associated with valproate: Clinical insights and polymyographic evaluation

Abstract

Objectives: We aimed to perform clinical and polymyography analyses in patients with epilepsy to assess characteristics of involuntary movements associated with valproate.

Method: All consecutive patients who used valproate for epilepsy were included in the study. We performed a detailed examination and polymyography recordings on the upper extremities at rest, with arms outstretched, during loading, action, and fine hand movements. We determined the type and characteristics of abnormal movements, as well as the clinical findings associated with these movements.

Results: We included 63 patients in the study, identifying 45 (71.2%) with tremor and 20 (31.7%) with myoclonus. All patients with myoclonus also had tremor. Valproate-induced tremor was postural, mild, and associated with low- dose valproate, compared to patients without tremor (n=18). Although mild to moderate, a positive correlation was found between tremor severity, as measured by the Fahn-Tolosa-Marin tremor rating scale, and the duration of valproate use (p=0.026, r=0.328). Distal myoclonus was prominent and appeared in repetitive bursts (polyminimyoclonus), clinically mimicking tremor. It was equally present in patients with focal epilepsy. Patients with myoclonus had higher serum valproate levels than those without myoclonus.

Conclusions: Tremor was common, primarily mild and postural, and associated with low-dose valproate. The severity increased with the more prolonged use. Higher serum levels of valproate triggered myoclonus, even in patients with focal epilepsy. Polymyography is needed to distinguish tremor and myoclonus.