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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.

SUBMITTER: Kalla R

PROVIDER: S-EPMC4833819 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Update on the pharmacotherapy of cerebellar and central vestibular disorders.

Kalla Roger R Teufel Julian J Feil Katharina K Muth Caroline C Strupp Michael M

Journal of neurology 20160415

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 ...[more]

PMID: 27083881

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Project description:ObjectivesGalvanic vestibular stimulation (GVS) has shown positive outcomes in various neurological and psychiatric disorders, such as enhancing postural balance and cognitive functions. In order to expedite the practical application of GVS in clinical settings, our objective was to determine the best GVS parameters for patients with vestibulopathy and cerebellar disorders using optimal design calculation.MethodsA total of 31 patients (26 males, mean age 57.03 ± 14.75 years, age range 22-82 years) with either unilateral or bilateral vestibulopathy (n = 18) or cerebellar ataxia (n = 13) were enrolled in the study. The GVS intervention included three parameters, waveform (sinusoidal, direct current [DC], and noisy), amplitude (0.4, 0.8, and 1.2 mA), and duration of stimulation (5 and 30 min), resulting in a total of 18 GVS intervention modes as input variables. To evaluate the effectiveness of GVS, clinical vertigo and gait assessments were conducted using the Dizziness Visual Analogue Scale (D-VAS), Activities-specific Balance Confidence Scale (ABC), and Scale for Assessment and Rating of Ataxia (SARA) as output variables. Optimal design and local sensitivity analysis were employed to determine the most optimal GVS modes.ResultsPatients with unilateral vestibulopathy experienced the most favorable results with either noisy or sinusoidal GVS at 0.4 mA amplitude for 30 min, followed by DC GVS at 0.8 mA amplitude for 5 min. Noisy GVS at 0.8 or 0.4 mA amplitude for 30 min demonstrated the most beneficial effects in patients with bilateral vestibulopathy. For patients with cerebellar ataxia, the optimal choices were noisy GVS with 0.8 or 0.4 mA amplitude for 5 or 30 min.ConclusionsThis study is the first to utilize design optimization methods to identify the GVS stimulation parameters that are tailored to individual-specific characteristics of dizziness and imbalance. A sensitivity analysis was carried out along with the optimal design to offset the constraints of a limited sample size, resulting in the identification of the most efficient GVS modes for patients suffering from vestibular and cerebellar disorders.

Dataset Information

Update on the pharmacotherapy of cerebellar and central vestibular disorders.

Publications

Update on the pharmacotherapy of cerebellar and central vestibular disorders.

Similar Datasets

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