TREATMENT WITH ORAL 3,4-DIAMINOPYRIDINE IMPROVES LEG STRENGTH IN MULTIPLE-SCLEROSIS PATIENTS - RESULTS OF A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSSOVER TRIAL

To examine the efficacy and toxicity of oral 3,4 diaminopyridine (DAP) in dosages up to 100 mg/day, 36 patients with multiple sclerosis (MS) enrolled in a randomized, double-blind, placebo-controlled, crossover trial. The primary outcome measure was improvement of a prospectively defined neurologic deficit, which was leg weakness in 34 patients. Se condary outcome measures included the patient's subjective response, s cored manual motor testing (MMT) of leg strength, scored leg strength from videotaped motor testing (VMT), quadriceps and hamstrings strengt h (QMT) measured by isometric dynamometry, neuropsychological testing (NPT), ambulation index (AI), and Expanded Disability Status Scale (ED SS) score. Paresthesias and abdominal pain were common and were dose l imiting in eight patients. Three patients had episodes of confusion, a nd one patient had a seizure while on DAP. Eight patients withdrew fro m the study, leaving 28 evaluable patients for the efficacy analysis. The prospectively defined neurologic deficit improved in 24 patients-2 2 on DAP and 2 on placebo (p = 0.0005). All improvements were in leg w eakness. Subjective response and measures of leg strength and function (MMT, VMT, QMT, and Al) improved on DAP compared with placebo. Neithe r NPT nor EDSS scores improved. DAP treatment can induce improvements in leg strength in MS patients, but toxicity is limiting in many patie nts.