Efficacy of zonisamide in a case of Parkinson’s disease with intractable resting and re-emergent tremor

Abstract

Sirs, Zonisamide (ZNS) was originally used as an anti-epileptic agent. ZNS has recently been shown to exert beneficial effects in patients with Parkinson s disease (PD) [1–6] and anti-tremor effects in patients with essential tremor and in tacrine-induced tremulous jaw movements in rats [7–11]. We report herein that intractable resting and re-emergent tremor [12] (resting tremor that re-emerges after a variable delay while maintaining posture) in patients with PD improved dramatically by ZNS. This case was a 73-year-old woman with PD who developed resting tremor and mild postural tremor on the right hand at the age of 68 years. The patient first took pramipexole, but the dosage could not be increased because of adverse effects of sleepiness, and so was kept at 1.5 mg/day. After 2 years, resting tremors expanded to all extremities, and postural tremor appeared on both upper hands. Levodopa/carbidopa at 500 mg/day, cabergoline and amantadine showed no efficacy against tremors. Trihexyphenidyl at 2 mg/day decreased tremors (Video S1), but induced somnolence. Alotinolol could not be used, as the patient was asthmatic. After 4 years, activities of daily living deteriorated because of severe resting and re-emergent tremors on both upper hands, as well as jaw and tongue tremors (Video S1). She was unable to change clothes or eat meals by herself even using daily doses of pramipexole at 1.5 mg, levodopa/carbidopa at 500 mg and trihexyphenidyl at 4 mg. ZNS was added at 50 mg/day, and tremors diminished slightly. Resting and re-emergent tremors improved markedly with ZNS at 100 mg/day (Video S2). Although mild sleepiness was observed, no severe additional adverse effects were noted during treatment with ZNS. Her