Etiology of Ataxia: A Mechanistic Insight of Autoimmune, Toxicity, and Genetic Approach

Ataxia is a diverse neurological disorders characterized by impaired coordination of voluntary muscle movements. Most often, affected parts of the nervous system are the cerebellum and the spinal cord. Ataxia etiology is associated with an extensive variation in acquired and genetic factors. Therefore, this chapter provides an overview of the background of ataxia and categorizes it into acquired and genetic based on the underlying causes of this neurological disorder, using advanced molecular and genetic techniques. The acquired ataxias include varied neurological ailments due to autoimmune responses, sensitivity, infections, vitamin deficiency, and vascular anomalies. The genetic form of ataxias has been grouped further into autosomal dominant, autosomal recessive, and X-linked ataxias. Furthermore, several genetic factors are integral to cause the variation in genetic ataxia, which include pathogenic repeat extensions (CAG, CTG, GAA), DNA repair anomalies, gene-sequence alteration, point mutations, and mode of inheritance transmission. Additionally, the role of degenerative ataxia concerning multiple system atrophy and idiopathic late-onset cerebellar ataxia-related neurological manifestations have also been important in diagnosis and treatment drives. Several diagnostic tests are used to assess ataxia, including biochemical laboratory tests such as blood alcohol levels, heavy metal levels, and high fetoprotein in the brain. Additionally, brain CT scan and advanced brain MRI are implemented along with genetic testing viz. CAG, CTG, GAA expansions, whole exosomes, and gene sequencing for advanced clinical manifestations. Thus, the etiology of ataxia is the first to be considered focused on acquired followed by genetic and degenerative factors that seem to be perfect diagnostic approaches for the treatment of ataxia. Therefore, successful clinical diagnosis requires a detailed follow-up history and disease progression, neurological examination, and proper diagnostic tests which are considered as gold standard tactics for unveiling the ataxia etiology, diagnosis, and treatment regimes.