Pharmacotherapy of cerebellar and vestibular disorders

Abstract

Purpose of reviewMajor therapeutic advances have been made in patients with episodic and progressive cerebellar ataxias, downbeat nystagmus and some vestibular disorders. We provide an update review on this subject highlighting important research findings from the last two years. Recent findingsRecently, the use of omaveloxolone for 2 years significantly improved upright stability in Friedreich's ataxia patients. In an open-label study, N-acetyl-L-leucine administered for 6-weeks significantly improved clinical impression of change, ataxia, and quality of life in patients with Niemann-Pick disease type C1. A 12week treatment with dalfampridine was associated with improved standing balance in a subgroup of patients with multiple sclerosis. A gluten-free diet alone improved ataxia in half of patients with antiglutamic acid decarboxylase (GAD) ataxia, suggesting that gluten sensitivity might be part of the underlying pathogenesis in anti-GAD ataxia. In a head-to-head trial, both prolonged-release 4-aminopyridine (4-AP) and acetazolamide effectively reduced the attacks up to 60% in patients with episodic ataxia type 2 (EA2), albeit 4-AP had fewer adverse effects. Small observational studies have shown that patients with episodic vestibular syndrome who cannot be diagnosed as definite or probable vestibular migraine, might still improve vestibular symptoms following preventive treatment for migraine. The use of vitamin D supplementation in benign paroxysmal positional vertigo, steroids in acute unilateral vestibulopathy, and betahistine in Me ´nie `re's disease patients remains controversial. SummaryAlthough the use of several therapies is being established in the treatment of cerebellar and vestibular disorders, there is an urgent need for prospective controlled therapeutic trials.

Periodic vertigo and downbeat nystagmus while supine: Dysfunction of Purkinje cells coding gravity

“…Furthermore, the duration and interval of periodic vertigo and nystagmus are too short for the cerebellar adaptation to occur because periodic alternating nystagmus, in which cerebellar adaptation is involved, changes direction every 2 min 5 . Medications such as baclofen and clonazepam, potentially effective in periodic alternating nystagmus, 8,9 were ineffective in our patient. Hence, we favored periodic neuronal discharges as the mechanism, and the suppression of vertigo and nystagmus with phenytoin administration further supported this idea.…”

Loss of Flocculus Purkinje Cell Firing Precision Leads to Impaired Gaze Stabilization in a Mouse Model of Spinocerebellar Ataxia Type 6 (SCA6)

“…SCA6 is not the only disease that affects the P/Q channel alpha subunit: deletion mutations of the same gene underlie episodic ataxia type 2 (EA2) in patients, which also demonstrate gaze impairments [ 38 ]. ( Together these findings provide insight into the consequences of P/Q channelopathy on behavior.…”