Ataxias: Hereditary, Acquired, and Reversible Etiologies

Abstract

A variety of etiologies can cause cerebellar dysfunction, leading to ataxia symptoms. Therefore, the accurate diagnosis of the cause for cerebellar ataxia can be challenging. A step-wise investigation will reveal underlying causes, including nutritional, toxin, immune-mediated, genetic, and degenerative disorders. Recent advances in genetics have identified new genes for both autosomal dominant and autosomal recessive ataxias, and new therapies are on the horizon for targeting specific biological pathways. New diagnostic criteria for degenerative ataxias have been proposed, specifically for multiple system atrophy, which will have a broad impact on the future clinical research in ataxia. In this article, we aim to provide a review focus on symptoms, laboratory testing, neuroimaging, and genetic testing for the diagnosis of cerebellar ataxia causes, with a special emphasis on recent advances. Strategies for the management of cerebellar ataxia is also discussed.

Fig. 1

Characteristic structural MRI features of multiple system atrophy. The hot crossed bun sign in multiple system atrophy cerebellar type, a feature as a result of the olivopontocerebellar system degeneration (A), and T2 hyperintense external striatal signals, implying putaminal degeneration in multiple system atrophy parkinsonian type (B). MRI, magnetic resonance imaging.

Fig. 2

The recommended diagnostic algorithm for cerebellar ataxia. CANVAS, cerebellar ataxia, neuropathy, vestibular areflexia syndrome; CJD, Creutzfeldt–Jakob disease; FXTAS, fragile X tremor and ataxia associated syndrome; ILOCA, idiopathic late-onset cerebellar ataxia; MSA, multiple system atrophy.