Update on the pharmacotherapy of cerebellar and central vestibular disorders

J Neurol. 2016 Apr:263 Suppl 1:S24-9. doi: 10.1007/s00415-015-7987-x. Epub 2016 Apr 15.


An overview of the current pharmacotherapy of central vestibular syndromes and the most common forms of central nystagmus as well as cerebellar disorders is given. 4-aminopyridine (4-AP) is recommended for the treatment of downbeat nystagmus, a frequent form of acquired persisting fixation nystagmus, and upbeat nystagmus. Animal studies showed that this non-selective blocker of voltage-gated potassium channels increases Purkinje cell excitability and normalizes the irregular firing rate, so that the inhibitory influence of the cerebellar cortex on vestibular and deep cerebellar nuclei is restored. The efficacy of 4-AP in episodic ataxia type 2, which is most often caused by mutations of the PQ-calcium channel, was demonstrated in a randomized controlled trial. It was also shown in an animal model (the tottering mouse) of episodic ataxia type 2. In a case series, chlorzoxazone, a non-selective activator of small-conductance calcium-activated potassium channels, was shown to reduce the DBN. The efficacy of acetyl-DL-leucine as a potential new symptomatic treatment for cerebellar diseases has been demonstrated in three case series. The ongoing randomized controlled trials on episodic ataxia type 2 (sustained-release form of 4-aminopyridine vs. acetazolamide vs. placebo; EAT2TREAT), vestibular migraine with metoprolol (PROVEMIG-trial), cerebellar gait disorders (sustained-release form of 4-aminopyridine vs. placebo; FACEG) and cerebellar ataxia (acetyl-DL-leucine vs. placebo; ALCAT) will provide new insights into the pharmacotherapy of cerebellar and central vestibular disorders.

Keywords: Aminopyridines; Central vestibular disorders; Cerebellar ataxia; Downbeat nystagmus; Episodic ataxia type 2; Vestibular migraine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 4-Aminopyridine / therapeutic use
  • Cerebellar Diseases / complications
  • Cerebellar Diseases / drug therapy*
  • Humans
  • Leucine / analogs & derivatives*
  • Leucine / therapeutic use
  • Male
  • Nystagmus, Pathologic / drug therapy
  • Nystagmus, Pathologic / etiology
  • Potassium Channel Blockers / therapeutic use*
  • Potassium Channels, Voltage-Gated / genetics
  • Vestibular Diseases / complications
  • Vestibular Diseases / drug therapy*


  • Potassium Channel Blockers
  • Potassium Channels, Voltage-Gated
  • 4-Aminopyridine
  • Leucine
  • acetylleucine