Clinical Presentation and Mechanisms of Immune-Mediated Cerebellar Ataxia

Abstract

The brain has traditionally been regarded as immunologically privileged because of the existence of the blood-brain barrier, the absence of conventional lymphatic drainage and the unusual tolerance of the brain to transplanted tissue. However, over the last decades, clinical evidence has accumulated indicating that the immune system may play an important role in some central nervous system diseases usually regarded as degenerative. The best-known example is paraneo-plastic cerebellar ataxia (PCA), which is thought to involve autoimmune cross-reaction between tumour and nervous system antigens. In the past 15 years, several antibodies directed against neuronal and tumoral antigens have been described in association with PCA, leading to the definition of different subtypes of PCA based on their associated antibodies, the clinical evolution and the type of tumour. Circulating antibodies have also been described in patients with non-paraneoplastic cerebellar ataxia (N-PCA), suggesting that the immune system may be involved in certain cases of sporadic cerebellar ataxia. In this review, the clinical presentation of the different subtypes of potentially immune-mediated PCA and N-PCA will be described, and the experimental approaches that have been developed in order to understand the pathogenic role of the immune system in these ataxias will be discussed.