Improvement of cervico-trunco-brachial segmental dystonia with topiramate.

Sirs: Topiramate (Topamax, Ortho-McNeil Pharmaceuticals, Raritan, NJ), a sulfamate-substituted monosaccharide, was approved in 1995 (1996 in the United States) for the treatment of epileptic disorders (including epileptic myoclonus [9]). Since then it was also approved for the prevention of migraine and its off label use has gained popularity as a weight reduction agent, in the treatment bipolar disorder [10], neuropathic pain [4] and in hyperkinetic movement disorders [3]. We report a patient with segmental cervicotrunco-brachial dystonia who experienced symptomatic benefit after treatment with topiramate. A 47-year-old ambidextrous male was initially evaluated in our Movement Disorders clinic (at the age of 40 years) for administration of botulinum toxin injections for his segmental dystonia which started about the age of 8 following a varicella-zoster viral infection. His dystonic symptoms involved the neck and shoulder muscles as well as the trunk and both upper extremities (left > right). His abnormal movements consisted of side-to-side trunk flexion associated with mild-moderate head tremors, shoulder elevation and action-induced upper limb dystonia of moderate intensity, mainly of the extensors of the wrist (left > right). The neck and shoulder dystonia has been highly responsive to botulinum toxin injections (usually about 300 units in both trapezius and splenius capitis and right sternocleidomastoid muscles) which had been given continuously since the age of 35 (every 4 months). The patient has also tried different combinations of lorazepam, clonazepam, propranolol, sodium valproate and baclofen with mild symptomatic benefit. He has a family history in which his sister has laryngeal dystonia and his father suffers from Parkinson’s disease. However, no genetic tests were performed. Neurological examination has consistently revealed trunk flexion movements associated with mild to moderate amplitude head tremors for the most part rotational with a tendency for the head to be mildmoderately rotated to the left, and a moderate left shoulder elevation. When he stretched out the upper extremities, there was mild dystonic posturing of both, left more than right. Sustained postural holding or task performance (writing, eating etc.) elicited dystonic activity of both upper extremities. EEG, brain MRI and copper studies were normal. The patient was gradually started on topiramate (up to 200 mg/day) at the age of 46 and experienced a marked improvement of his trunk and upper limb dystonic component, with marked reduction in trunk flexion and action-induced wrist extension. The patient did not report an improvement of his symptoms at lower doses of topiramate (100 mg–150 mg/day). However, about two months later he started complaining of a significant amount of eye pain associated with eye redness, blurred vision (which was diagnosed as angle closure glaucoma) as well as weight loss and occasional word-finding difficulty. After gradually discontinuing the topiramate all these symptoms (all known side-effects of topiramate [2, 8]) subsided. However, there was considerable deterioration of the dystonic features. There are limited data on the efficacy of topiramate on hyperkinetic movement disorders. It has been found to reduce symptoms of essential [3] and cerebellar tremor [11], and was reported to be effective in single cases of spinal myoclonus [14], Tourette’s syndrome [1] and vascular hemichorea/hemiballism [5]. Furthermore, topiramate has been reported to reduce levodopa-induced dyskinesia (without affecting the antiparkinsonian action of levodopa) in the MPTP-lesioned marmoset model of Parkinson’s disease (PD) [13]. The exact mechanism of action of topiramate in hyperkinetic movement disorders is unknown. It has been postulated that hyperkinetic disorders may be caused by decreased GABAergic transmission in the indirect basal ganglion pathway [7]. Consistent with that theory, it seems reasonable to believe that drugs that increase GABAergic neurotransmission would be beneficial. Topiramate has been proven to enhance GABA activity [12]. Topiramate has also AMPA receptor antagonistic properties [6]. Since overactive AMPA receptormediated transmission has been implicated in the development of hyperkinetic movement disorders (i. e. levodopa-induced dyskinesia) in animal models [13] it could provide a useful treatment for other hyperkinetic movement disorders like dystonia. In summary, there are reports (including the present one) that suggest the possible beneficial role of topiramate in the treatment of hyperkinetic movement disorders. However, one should always be aware of its potential side effects LETTER TO THE EDITORS