A randomized, controlled, double-blind, crossover trial of zonisamide in myoclonus-dystonia

作者：Hainque Elodie; Vidailhet Marie; Cozic Nathalie; Charbonnier Beaupel Fanny; Thobois Stephane; Tranchant Christine; Brochard Vanessa; Glibert Gerald; Drapier Sophie; Mutez Eugenie; De Maindreville Anne Doe; Lebouvier Thibaud; Hubsch Cecile; Degos Bertrand; Bonnet Cecilia; Grabli David; Legrand Andre Pierre; Meneret Aurelie; Azulay Jean Philippe; Bissery Anne; Zahr Noel; Clot Fabienne; Mallet Alain; Dupont Sophie; Apartis Emmanuelle; Corvol Jean Christophe

来源：Neurology, 2016, 86(18): 1729-1735.

DOI：10.1212/wnl.0000000000002631

Objective: To evaluate the efficacy and safety of zonisamide in patients with myoclonus-dystonia.
Methods: We conducted a randomized, double-blind, placebo-controlled crossover trial of zonisamide (300 mg/d) in 24 patients with myoclonus-dystonia. Each treatment period consisted of a 6-week titration phase followed by a 3-week fixed-dose phase. The periods were separated by a 5-week washout period. The co-primary outcomes were action myoclonus severity (section 4 of the Unified Myoclonus Rating Scale [UMRS 4]) and myoclonus-related functional disability (UMRS 5). Secondary outcomes included dystonia severity, assessed with the movement and disability subscales of the Burke-Fahn-Marsden-Dystonia Rating Scale (BFM), the Clinical Global Impression-Improvement scale (CGI), and safety measures. Wilcoxon signed-rank tests for paired data were used to analyze treatment effects.
Results: Twenty-three patients (11 men, 12 women) were analyzed in the intention-to-treat analysis. Zonisamide significantly improved both action myoclonus (median improvement [95% confidence limits] -5 [-9.25 to -1.44], p = 0.003) and myoclonus-related functional disability (median improvement [95% confidence limits] -2 [-2.58 to -2.46], p = 0.007) compared to placebo. Zonisamide also significantly improved dystonia (BFM movement) compared to placebo (median improvement [95% confidence limits] -3 [-8.46 to 0.03], p = 0.009). No difference was found between zonisamide and placebo with respect to the CGI (median improvement [95% confidence limits] -1 [-1.31 to 0.09], p = 0.1). Zonisamide was well-tolerated.
Conclusions: Zonisamide is well-tolerated and effective on the motor symptoms of myoclonusdystonia.
Classification of evidence: This study provides Class I evidence that zonisamide improves myoclonus and related disability in patients with myoclonus-dystonia.

• 出版日期2016-5-3