Cerebellar Ataxia

The cerebellum, is a unique brain structure with distinctly organized neuronal circuits, is critical for motor and cognitive functions. The cerebellum has dense neuronal connections with almost all regions of the cerebral cortex and brainstem, and can serve as a “hub” to regulate the many brain functions. While cerebellar dysfunction has been implicated in tremor, dystonia, and autism, the prototypical disorder of the cerebellum is cerebellar ataxia, a clinical sign that can have a variety of causes, including nutritional deficiency, immunological dysfunction, vascular and degenerative etiologies, and genetic mutations. Searching for genetic causes for ataxia is particularly relevant because its the high frequency among degenerative ataxias and the diagnostic specificity of the known mutations. The diagnosis of cerebellar ataxia can often appear complicated to neurologists. To simplify and streamline the search for the causes of cerebellar ataxia, this chapter aims to provide a step-by-step approach. Complex environmental and genetic interactions, epigenetic alterations, or regional genetic somatic mosaicism might explain some of these cases; these remain underexplored areas in cerebellar ataxia diagnosis. Identifying a handful of progressive ataxic disorders that are treatable is an important goal in management of ataxia. This chapter describes clinical features, imaging findings, and genetics for the differential diagnoses of cerebellar ataxia, providing a guide for clinicians. The detailed genetic diagnosis of cerebellar ataxia can be very extensive, and is beyond the scope of this chapter. Instead, this chapter includes only the common causes of genetic ataxia. However, understanding the nature of disease mechanism caused by each genetic mutation is important for development of future therapeutic approaches.