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.