ABSTRACT

Several medications can exacerbate or cause Restless Legs syndrome (RLS). Topiramate is an antiepileptic drug used to epilepsy and migraine treatment. In literature, number of case with topiramate induced RLS is very rare. Herein, we present the case with topiramate induced RLS, in which the case takes to topiramate for migraine prophylaxis. However, how topiramate causes RLS is exactly unknown. Probably, topiramate has an antidopaminergic effect.

Keywords: Topiramate, restless legs syndrome, antidopaminergic effect

Introduction

Restless Legs syndrome (RLS) is a common sensorimotor disorder that is characterized by an urge to move the legs (and, rarely, the arms as well) and peculiar, unpleasant sensations. The diagnosis is based on clinical criteria: an urge to move the legs, symptoms occurring during periods of rest; symptoms relieving by movement; and symptoms worsen in the evening or night (1). Several medications including antipsychotics, antidepressant, antihistamines, antiemetics and antiepileptics such as phenytoin, zonisamide can exacerbate or cause RLS (2). However, some antiepileptic drugs have been suggested as alternative to dopaminergic agents for RLS treatment (3,4). Topiramate (TPM) is an antiepileptic drug used in epilepsy and migraine treatment (5). We report one case with topiramate induced RLS.

Case

A 29 year old woman affected by migraine without aura started to use topiramate as prophylactic treatment. It was gradually titrated up to 100 mg bid. Migraine attacks were reduced, but at the third month of treatment, she reported numbness in her legs especially during inactivity and in the evening. Her complaint was relieved by movement. There were no similar symptoms in patient’s history before migraine prophylatic treatment with topiramate. Serum studies (blood count, electrolytes, liver and renal function, thyroid hormones, iron, iron binding capacity, ferritin and vitamin B12 levels) and electroneurography were normal. We applied to International RLS rating scale (IRLS) (6) and she had moderate RLS symptoms (IRLS score 18). After 2 weeks TPM had been terminated, IRLS was repeated (IRLS score 4).

Discussion

It is thought that basic pathology in RLS is dopaminergic deficiency. There are several cases with TPM induced RLS (7,8). TPM has been essentially used as a wide spectrum antiepileptic agent. However, in the other pathologies such as migraine, neuropathic pain, essential tremor and impulse control disorder, it has been effectively used. Action mechanism of TPM is multiple including gabaergic effect via GABA A receptor, antiglutamatergic effect via AMPA and kainate receptors, blockage of voltage gated sodium and calcium channels, and inhibition of carbonic anhydrase (9). It has been fully unknown relationship between TPM and dopaminergic system has not been reported before. However, in a study, TPM has showed to reduce levodopa induced dyskinesias in MPTP lesioned primates (10). This result has suggested that TPM has antidopaminergic effect.
TPM induced RLS can be possible with regard to dopaminergic deficiency in RLS and antidopaminergic effect of TPM. Thus, we have to keep alert for RLS when using drugs like TPM with wide effect spectrum.