To compare the efficacy of fampridine and acetazolamide with placebo for the prophylactic treatment of episodic ataxia type 2 (EA2).  

Episodic ataxia type 2 (EA2) is characterized by recurrent attacks of vertigo, imbalance, ataxia, dysarthria, and ocular motor disturbance. Two treatment options are currently recommended: 4-aminopyridine and acetazolamide. However, there has been no RCT for acetazolamide and only one for the non-sustained release form of 4-aminopyridine.

30 patients affected by EA2 (eight female; aged 20-71 years; 18 genetically confirmed, four with positive family history, eight with the clinical diagnosis), were enrolled in this phase III, randomised, double-blind, placebo-controlled, three-period crossover trial. Each period lasted 12 weeks with a four-week washout period. Each patient received a random sequence of 20 mg/d fampridine, 750 mg/d acetazolamide, and placebo. The primary endpoint was the number of attacks during the last 30 days within the 12-week treatment period. The trial was registered with DRKS.de (DRKS00005258) and EudraCT (2013-000107-17).

Compared to placebo both agents significantly reduced the number of attacks: fampridine to 63% (95% CI 54%-74%) and acetazolamide to 52% (95% CI 46-60%). Thirty-nine (26.5 %) adverse events occurred under treatment with fampridine and 66 (44.9 %) under acetazolamide, and 42 (28.6 %) under placebo. After the study, 24 patients continued the treatment with 4-AP and only three with acetazolamide.

 Fampridine as well as acetazolamide significantly reduce the number of attacks of patients affected by EA2 compared to placebo. In consideration of the side effects and the post-study observation of the patients preferences, treatment with fampridine 10 mg twice daily is potentially safer and better tolerated compared to the treatment with acetazolamide 250 mg three times daily.