Immune-mediated acquired ataxias

Abstract

The cerebellum, and in particular the Purkinje cells within it, appear to be a frequent immunological target in the context of some systemic diseases. This is perhaps more often the case with the cerebellum by comparison to other structures within the central nervous system. This observation may relate to the fact that the cerebellum is one of the largest, oldest, and most structurally conserved structures in the vertebrate nervous system and/or that Purkinje cells possess good and multiple antigenic targets. Immune-mediated ataxias include paraneoplastic cerebellar degeneration and post-infective cerebellitis, but these will be discussed elsewhere. This chapter covers in detail the epidemiology, clinical characteristics, pathophysiology, and treatment of some other examples of immune-mediated ataxias, including gluten ataxia and ataxia associated with anti-GAD antibodies. There is particular emphasis on gluten ataxia as this is one of the commonest immune-mediated cerebellar ataxias and one of the few ataxias that are potentially treatable. The chapter also introduces the concept of primary autoimmune cerebellar ataxia as a form of organ-specific autoimmune disease for the first time. The pathophysiology leading to cerebellar damage, loss of Purkinje cells, and the development of ataxia remains speculative, but existing clues are discussed in detail.