Zonisamide relieves myoclonus dystonia motor symptoms

By Eleanor McDermid

A randomised crossover trial shows that zonisamide significantly improves motor symptoms and related disability in adults with myoclonus dystonia.

Myoclonus dystonia is very rare, and Marie Vidailhet (Hôpital Pitié-Salpêtrière, Paris, France) and co-researchers stress that their study "is the first controlled therapeutic trial to be conducted in this setting."

It involved 23 patients with myoclonus dystonia who were randomly assigned to receive the benzisoxazole derivative zonisamide (up to 300 mg/day) or placebo for a 6-week dose-escalation period followed by 3 weeks at the highest tolerated dose. After a 5-week washout period, the patients were switched to the other treatment.

From a baseline of 28 points on the Unified Myoclonus Rating Scale (UMRS) section 4, the severity of action myoclonus improved by a median of 5 points during the zonisamide treatment period relative to the placebo period. And from a baseline of 7 points on the UMRS section 5, myoclonus-related functional disability improved by a significant 2 points with zonisamide relative to placebo. Both of these differences were statistically significant.

Patients also had significantly improved dystonia, by 3 points on the Burke-Fahn-Marsden Dystonia Rating Scale, during zonisamide versus placebo treatment, although related disability was unaffected.

"Zonisamide may thus be considered as a therapeutic option for patients with mild to moderate [myoclonus dystonia] and for patients with severe forms who refuse or are not eligible for deep brain stimulation", write the researchers in Neurology.

They note that the benefits observed with zonisamide in their study are less than those reported for deep-brain stimulation.

Adverse events were reported by 83% of patients during the zonisamide treatment period and by 74% during the placebo period. Asthenia was more common during the zonisamide versus placebo phases (65 vs 17%), as were mood swings (35 vs 26%).

The researchers note that patients only received 9 weeks of treatment in their study, leaving the longer-term benefits and safety profile to be determined.

And they add that, because myoclonus dystonia "usually starts before age 10, the use of zonisamide in children will need to be addressed, although studies in epilepsy show that zonisamide is well-tolerated in this age group."

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