title: A randomized trial of 4-aminopyridine in EA2 and related familial episodic ataxias.
abstract: OBJECTIVE
  The therapeutic effects of 4-aminopyridine (4AP) were investigated in a randomized, double-blind, crossover trial in 10 subjects with familial episodic ataxia with nystagmus.
  
  
  METHODS
  After randomization, placebo or 4AP (5 mg 3 times daily) was administered for 2 3-month-long treatment periods separated by a 1-month-long washout period. The primary outcome measure was the number of ataxia attacks per month; the secondary outcome measures were the attack duration and patient-reported quality of life (Vestibular Disorders Activities of Daily Living Scale [VDADL]). Nonparametric tests and a random-effects model were used for statistical analysis.
  
  
  RESULTS
  The diagnosis of episodic ataxia type 2 (EA2) was genetically confirmed in 7 subjects. Patients receiving placebo had a median monthly attack frequency of 6.50, whereas patients taking 4AP had a frequency of 1.65 (p = 0.03). Median monthly attack duration decreased from 13.65 hours with placebo to 4.45 hours with 4AP (p = 0.08). The VDADL score decreased from 6.00 to 1.50 (p = 0.02). 4AP was well-tolerated.
  
  
  CONCLUSIONS
  This controlled trial on EA2 and familial episodic ataxia with nystagmus demonstrated that 4AP decreases attack frequency and improves quality of life.
  
  
  METHODS
  This crossover study provides Class II evidence that 4AP decreases attack frequency and improves the patient-reported quality of life in patients with episodic ataxia and related familial ataxias.
authors: Department of Neurology, Friedrich-Baur-Institute and IFB(LMU), University of Munich, Campus Grosshadern, Marchioninistr. 15, 81377 Munich, Germany. michael.strupp@med.uni-muenchen.de
authors: M
authors: M
authors: Strupp
authors: R
authors: R
authors: Kalla
authors: J
authors: J
authors: Claassen
authors: C
authors: C
authors: Adrion
authors: U
authors: U
authors: Mansmann
authors: T
authors: T
authors: Klopstock
authors: T
authors: T
authors: Freilinger
authors: H
authors: H
authors: Neugebauer
authors: R
authors: R
authors: Spiegel
authors: M
authors: M
authors: Dichgans
authors: F
authors: F
authors: Lehmann-Horn
authors: K
authors: K
authors: Jurkat-Rott
authors: T
authors: T
authors: Brandt
authors: J C
authors: JC
authors: Jen
authors: K
authors: K
authors: Jahn
mesh_terms: D015761:4-Aminopyridine / Q000627:therapeutic use*; D000203:Activities of Daily Living; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001259:Ataxia / Q000188:drug therapy* / Q000235:genetics / Q000523:psychology; D015220:Calcium Channels / Q000235:genetics; D002648:Child; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005820:Genetic Testing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009759:Nystagmus, Pathologic / Q000188:drug therapy* / Q000235:genetics / Q000523:psychology; D017063:Outcome Assessment, Health Care; D026902:Potassium Channel Blockers / Q000627:therapeutic use*; D011788:Quality of Life; D055815:Young Adult; D020864:Calcium Channels, N-Type
chemical_list: D015761:4-Aminopyridine; D015220:Calcium Channels; D047908:Intracellular Signaling Peptides and Proteins; D026902:Potassium Channel Blockers; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type; C105159:SH3GL1 protein, human