title: 3,4-Diaminopyridine is more effective than placebo in a randomized, double-blind, cross-over drug study in LEMS.
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.affiliation: Department of Neurology, University of Alabama at Birmingham, Veterans Affairs Medical Center, UAB Station, Birmingham, Alabama 35294, USA. shinjoh@uab.edu
authors.forename: Shin J
authors.initials: SJ
authors.lastname: Oh
authors.forename: Gwendolyn G
authors.initials: GG
authors.lastname: Claussen
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hatanaka
authors.forename: Marla B
authors.initials: MB
authors.lastname: Morgan
mesh_terms: D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000077770:Amifampridine; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015624:Lambert-Eaton Myasthenic Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011446:Prospective Studies
chemical_list: D010919:Placebos; D015761:4-Aminopyridine; D000077770:Amifampridine