A randomized trial of 4-aminopyridine in EA2 and related familial episodic ataxias

Neurology. 2011 Jul 19;77(3):269-75. doi: 10.1212/WNL.0b013e318225ab07. Epub 2011 Jul 6.


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.

Level of evidence: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / therapeutic use*
  • Activities of Daily Living
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Ataxia / drug therapy*
  • Ataxia / genetics
  • Ataxia / psychology
  • Calcium Channels / genetics
  • Child
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Genetic Testing
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Middle Aged
  • Mutation / genetics
  • Nystagmus, Pathologic / drug therapy*
  • Nystagmus, Pathologic / genetics
  • Nystagmus, Pathologic / psychology
  • Outcome Assessment, Health Care
  • Potassium Channel Blockers / therapeutic use*
  • Quality of Life
  • Young Adult


  • CACNA1A protein, human
  • Calcium Channels
  • Intracellular Signaling Peptides and Proteins
  • Potassium Channel Blockers
  • SH3GL1 protein, human
  • 4-Aminopyridine

Supplementary concepts

  • Episodic Ataxia, Type 2