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Research paper
A randomised double-blind, cross-over trial of 4-aminopyridine for downbeat nystagmus—effects on slowphase eye velocity, postural stability, locomotion and symptoms
  1. Jens Claassen1,
  2. Rainer Spiegel1,
  3. Roger Kalla1,
  4. Mary Faldon2,
  5. Christopher Kennard2,
  6. Chotipat Danchaivijitr2,
  7. Stanislaw Bardins1,
  8. Nicole Rettinger1,
  9. Erich Schneider1,
  10. Thomas Brandt1,
  11. Klaus Jahn1,
  12. Julian Teufel1,
  13. Michael Strupp1,
  14. Adolfo Bronstein2
  1. 1Department of Neurology and German Center for Vertigo and Balance Disorders (IFBLMU), University Hospital Munich, Campus Großhadern, Munich, Bavaria, Germany
  2. 2Division of Brain Sciences, Imperial College London, Charing Cross Hospital, London, UK
  1. Correspondence to Professor Michael Strupp, FANA, Department of Neurology and German Center for Vertigo and Balance Disorders (IFBLMU), University Hospital Munich, Campus Großhadern, Marchioninistr 15, Munich, Bavaria 81377, Germany; michael.strupp{at} and Professor Adolfo M Bronstein, Division of Brain Sciences (Neuro-otology Unit), Imperial College London (Charing Cross Hospital), London W6 8RF, UK; a.bronstein{at}


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.

  • Neurootology
  • Eye movements
  • Vision
  • Vertigo
  • Pharmacology

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