A randomised double-blind, cross-over trial of 4-aminopyridine for downbeat nystagmus--effects on slowphase eye velocity, postural stability, locomotion and symptoms

J Neurol Neurosurg Psychiatry. 2013 Dec;84(12):1392-9. doi: 10.1136/jnnp-2012-304736. Epub 2013 Jun 29.

Abstract

Objective: The effects of 4-aminopyridine (4-AP) on downbeat nystagmus (DBN) were analysed in terms of slow-phase velocity (SPV), stance, locomotion, visual acuity (VA), patient satisfaction and side effects using standardised questionnaires.

Methods: Twenty-seven patients with DBN received 5 mg 4-AP four times a day or placebo for 3 days and 10 mg 4-AP four times a day or placebo for 4 days. Recordings were done before the first, 60 min after the first and 60 min after the last drug administration.

Results: SPV decreased from 2.42 deg/s at baseline to 1.38 deg/s with 5 mg 4-AP and to 2.03 deg/s with 10 mg 4-AP (p<0.05; post hoc: 5 mg 4-AP: p=0.04). The rate of responders was 57%. Increasing age correlated with a 4-AP-related decrease in SPV (p<0.05). Patients improved in the 'get-up-and-go test' with 4-AP (p<0.001; post hoc: 5 mg: p=0.025; 10 mg: p<0.001). Tandem-walk time (both p<0.01) and tandem-walk error (4-AP: p=0.054; placebo: p=0.059) improved under 4-AP and placebo. Posturography showed that some patients improved with the 5 mg 4-AP dose, particularly older patients. Near VA increased from 0.59 at baseline to 0.66 with 5 mg 4-AP (p<0.05). Patients with idiopathic DBN had the greatest benefit from 4-AP. There were no differences between 4-AP and placebo regarding patient satisfaction and side effects.

Conclusions: 4-AP reduced SPV of DBN, improved near VA and some locomotor parameters. 4-AP is a useful medication for DBN syndrome, older patients in particular benefit from the effects of 5 mg 4-AP on nystagmus and postural stability.

Keywords: Eye movements; Neurootology; Pharmacology; Vertigo; Vision.

Publication types

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

MeSH terms

  • 4-Aminopyridine / adverse effects
  • 4-Aminopyridine / pharmacology*
  • 4-Aminopyridine / therapeutic use*
  • Adult
  • Age Factors
  • Aged
  • Cross-Over Studies
  • Double-Blind Method
  • Eye Movements / drug effects*
  • Female
  • Humans
  • Locomotion / drug effects*
  • Male
  • Middle Aged
  • Nystagmus, Pathologic / drug therapy*
  • Patient Satisfaction
  • Postural Balance / drug effects*
  • Symptom Assessment
  • Visual Acuity / drug effects

Substances

  • 4-Aminopyridine