3,4-Diaminopyridine is more effective than placebo in a randomized, double-blind, cross-over drug study in LEMS.

Academic Article

Abstract

  • The purpose of this study was to investigate the clinical and electrophysiological efficacy of 3,4-diaminopyridine (DAP) in patients with Lambert-Eaton myasthenic syndrome (LEMS) in a randomized, double-blind, cross-over drug trial. The diagnosis of LEMS was made based on the combination of fluctuating muscle weakness, diminished or absent reflexes, and more than 60% increment of the compound muscle action potential (CMAP) amplitude after brief exercise or 50-HZ stimulation on a repetitive nerve stimulation (RNS) test. Evaluations were done at baseline, with placebo, and with 3,4-DAP (up to 75-80 mg/day). Assignment of placebo or 3,4-DAP was done in a double-blinded manner. Measurements included subjective symptoms score, objective clinical measurements [LEMS classification, muscle strength score, quantitative myasthenia gravis (QMG) score] and RNS test and single-fiber electromyography (SFEMG). The differences between placebo and baseline values (placebo change) were compared with the differences between 3,4-DAP and baseline or placebo values (DAP change). Seven patients with LEMS (QMG score >9) participated in the study. One patient had major side-effects with 3,4-DAP and withdrew from the study. Statistically significant efficacy was noted with DAP change (N = 13) compared with placebo change (N = 7) according to the subjective symptoms score (P = 0.01), LEMS classification (P < 0.001), muscle strength score (P < 0.006), QMG score (P = 0.02), and CMAP (P = 0.03). For long-term treatment, 2 patients preferred 3,4-DAP, 1 chose guanidine hydrochloride, 1 preferred pyridostigmine, and 2 chose no treatment. A randomized, double-blind, cross-over drug trial of 3,4-DAP showed significant efficacy over placebo in patients with LEMS. As a long-term treatment, however, not all patients preferred this drug.
  • Authors

    Published In

  • Muscle and Nerve  Journal
  • Keywords

  • 4-Aminopyridine, Adult, Aged, Amifampridine, Cross-Over Studies, Double-Blind Method, Female, Humans, Lambert-Eaton Myasthenic Syndrome, Male, Middle Aged, Placebos, Prospective Studies
  • Digital Object Identifier (doi)

    Authorlist

  • Oh SJ; Claussen GG; Hatanaka Y; Morgan MB
  • Start Page

  • 795
  • End Page

  • 800
  • Volume

  • 40
  • Issue

  • 5