A randomized trial of 3,4-diaminopyridine in Lambert-Eaton myasthenic syndrome

Objectives: The authors report the results of a prospective, placebo-contro lled, randomized study to evaluate the effectiveness of 3,4-diaminopyridine (DAP) in patients with Lambert-Eaton myasthenic syndrome (LEMS) and to det ermine the acute and long-term side effects of DAP.:Methods: Twenty-six pat ients with LEMS completed a two-arm parallel treatment protocol in which DA P, 20 mg three times' daily, or placebo was given blindly for 6 days, and a quantitative examination of muscle strength (the quantitative myasthenia g ravis [QMG] score) was used as the primary measure of efficacy. After the b linded study, patients were given open-label DAP and monitored for side eff ects as long as there was symptomatic improvement. Results: Twelve patients took DAP, and 14 took placebo. There was no difference in the age of LEMS onset, gender distribution, incidence of lung cancer, or baseline muscle st rength between the patients who were randomly assigned to receive placebo a nd those randomly assigned to DAP. Statistical analysis using the Wilcoxon' s rank sum test demonstrated that patients who received DAP had a significa ntly greater improvement in the QMG score and in the summated amplitude of compound muscle action potentials recorded from three sentinel limb muscles . All but one LEMS patient had significant symptomatic improvement from sub sequent open-label DAP. Side effects of DAP were negligible, consisting of perioral and digital paresthesia. Laboratory measurements demonstrated no e vidence of toxicity affecting liver, renal, hematologic, endocrinologic, en cephalographic, or electrocardiologic function acutely or after 6 months of open-label DAP. Conclusions: This study corroborates previous studies and many years of clinical experience showing that DAP is an effective and safe treatment for LEMS.