Tremor and Movement Slowness Are Two Unrelated Adverse Effects Induced by Valproate Intake

Background To date, only a few clinical and neurophysiological studies have assessed the features of valproate-induced tremor (VIT), and whether valproate (VPA) affects voluntary movements is underinvestigated. Objective To better characterize the clinical and neurophysiological features of VIT in patients with epilepsy and the effect of VPA on the execution of voluntary movement. Methods We tested 29 patients with VIT (13 taking VPA alone and 16 taking VPA plus other antiepileptics). Patients underwent a neurological examination, video recordings and kinematic assessments of postural, kinetic, and resting upper limb tremor using a motion analysis system. Movement execution was tested by kinematic assessment of finger tapping. Data of patients with VIT were compared with those of 13 patients with epilepsy taking VPA but without tremor, 13 patients with epilepsy who were not on VPA treatment, 20 patients with Parkinson's disease (PD), and 20 healthy controls (HCs). Results Clinical and kinematic evaluations showed that tremor in patients taking VPA alone was less severe than tremor in patients taking VPA plus other antiepileptics. All patients taking VPA, regardless of the presence of tremor, performed slower finger tapping compared with HCs, similar to what was observed in PD, although with no sequence effect. Patients with epilepsy without VPA showed a normal motor performance. Conclusions Tremor and movement slowness are motor signs induced by VPA. VIT severity is exacerbated when VPA is taken in combination with other antiepileptics. VPA-induced slowness occurs regardless of tremor, may precede tremor development, and is not attributed to epilepsy.