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

Abstract

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.

Insight Into the Relationship Between Motor and Cognitive Symptoms in Essential Tremor

“…Additionally, various studies have highlighted associations between degenerative cerebellar disease, cerebellar tumours, ischemic lesions, and movement slowness in ET [3]. Further supporting the role of the cerebellum in altered voluntary movement execution, we have recently demonstrated that patients with tremor induced by valproate may also present movement slowness which re ect a cerebellar network disruption due to valproate [37]. Moreover, cerebellar dysfunction may give rise to various cognitive dysfunctions, including the Cognitive Affective Cerebellar Syndrome (CCAS), as postulated by Schmahmann et al in the '90s.…”

“…Re ective markers were strategically placed on the dominant hand, and on the distal phalanx of the index nger and thumb. We recorded postural tremors in two different arm positions: arms outstretched in front of the chest (Posture 1 -P1) and arms exed at the elbows in a lateral "wing beating" posture (Posture 2 -P2) [8, 5,7,37,6,4,39,40]. Three 45-second recordings were obtained for each position.…”

“…Fast Fourier Transform was also applied to the accelerometry traces to calculate the power spectrum, and the tremor frequency peak (expressed in Hz) [8,5,7,37,6,4,39,40]. [8,5,7,37,6,4]Patients' mean values from the right and left sides were considered for the analyses. We utilized a specialized algorithm for the analysis of kinetic tremors during arm movement.…”

“…Speci cally, we computed the curvature index (CI) of the arm endpoint trajectory [8, 5,7,37,6,4,39,40]. The CI indicates movement homogeneity, with higher values indicating the greater kinetic tremor [8, 5,7,37,6,4,39,40]. Regarding postural tremor data, we averaged data from P1 and P2.…”

“…The assessment was conducted as in previous works [8,5,7,37,6,4,[38][39][40]. We used a 3-D optoelectronic system (SMART motion system, BTS, Milan, Italy) with three infrared cameras detecting movement in three-dimensional space, and the analysis was carried out o ine using dedicated software (SMART Analyzer, BTS Engineering, Italy).…”