Aminopyridines for symptomatic treatment in multiple sclerosis.

BACKGROUND: The potassium channel blockers 4-aminopyridine (AP) and 3,4-diaminopyridine (DAP) increase nerve conduction in demyelinated nerve fibers, and have been proposed as a symptomatic therapy for people with multiple sclerosis (MS). OBJECTIVES: To determine the efficacy and safety of aminopyridines for neurological deficits in MS people. SEARCH STRATEGY: We searched CENTRAL (Issue 2, 2002), MEDLINE (January 1966-July 2002), EMBASE (1974-July 2002), and the Cochrane MS Group's Specialised Register. We hand searched bibliographic references from retrieved studies and recent MS symposia reports, and contacted known studies' investigators. SELECTION CRITERIA: We included trials fulfilling all following criteria: randomised controlled trials (RCTs); adults with MS, out of exacerbation; AP or DAP treatment versus placebo; clinical endpoints. DATA COLLECTION AND ANALYSIS: We identified 26 potentially pertinent studies. Three reviewers independently extracted data and assessed trial quality from 17 full-paper studies. MAIN RESULTS: Six studies (eight publications, 198 participants, all crossover trials) were considered. Five studies assessed the efficacy of AP versus placebo, one compared DAP with active placebo. Treatment duration ranged from hours to six months. Median quality score of the studies was 3. Heterogeneity of outcome assessment and absence of information on individual study periods allowed quantitative pooling of results for few categorical variables. Of the 198 treated patients, there were six major side effects: one acute encephalopathy, three episodes of confusion, and two seizures. Three studies (54 patients) assessed manual muscle testing, with 29 patients (54%) improving in at least one muscular district during study treatment versus four patients (7%) during placebo (odds ratio [OR] 14.5, 95% confidence interval [CI] 4.7-43.7). Nine out of 54 participants (17%) improved in ambulation during study treatment versus none during placebo (p