title: Update on the pharmacotherapy of cerebellar and central vestibular disorders.
abstract: 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.
authors.affiliation: Division of Cognitive and Restorative Neurology, Department of Neurology, University Hospital Bern, Freiburgstrasse 18, 3010, Bern, Switzerland. roger.kalla@insel.ch.
authors.forename: Roger
authors.initials: R
authors.lastname: Kalla
authors.affiliation: Department of Neurology and German Center for Vertigo and Balance Disorders, University Hospital Munich, Campus Grosshadern, Munich, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Teufel
authors.affiliation: Department of Neurology and German Center for Vertigo and Balance Disorders, University Hospital Munich, Campus Grosshadern, Munich, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Feil
authors.affiliation: Department of Neurology and German Center for Vertigo and Balance Disorders, University Hospital Munich, Campus Grosshadern, Munich, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Muth
authors.affiliation: Division of Cognitive and Restorative Neurology, Department of Neurology, University Hospital Bern, Freiburgstrasse 18, 3010, Bern, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Strupp
mesh_terms: D015761:4-Aminopyridine / Q000627:therapeutic use; D002526:Cerebellar Diseases / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D009759:Nystagmus, Pathologic / Q000188:drug therapy / Q000209:etiology; D026902:Potassium Channel Blockers / Q000627:therapeutic use*; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D015837:Vestibular Diseases / Q000150:complications / Q000188:drug therapy*
chemical_list: D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D015761:4-Aminopyridine; D007930:Leucine; C088117:acetylleucine
keywords: Aminopyridines; Central vestibular disorders; Cerebellar ataxia; Downbeat nystagmus; Episodic ataxia type 2; Vestibular migraine