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.

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.

• Authors: M Strupp, R Kalla, J Claassen, C Adrion, U Mansmann, T Klopstock, T Freilinger, H Neugebauer, R Spiegel, M Dichgans, F Lehmann-Horn, K Jurkat-Rott, T Brandt, J C Jen, K Jahn
• Journal: Neurology (Neurology) Vol. 77 Issue 3 Pg. 269-75 (Jul 19 2011) ISSN: 1526-632X [Electronic] United States
• PMID: 21734179 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 4-Aminopyridine (therapeutic use)
• Activities of Daily Living
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Ataxia (drug therapy, genetics, 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, genetics, psychology)
• Outcome Assessment, Health Care
• Potassium Channel Blockers (therapeutic use)
• Quality of Life
• Young Adult