Major advances in our knowledge concerning autoimmune and paraneoplastic cerebellar ataxias have occurred in the last 20 years. The discovery of several neural antibodies represents an undeniable contribution to this field, especially those serving as good biomarkers of paraneoplastic neurological syndromes and those showing direct pathogenic effects. Yet, many patients still lack detectable or known antibodies, and also many antibodies have only been reported in few patients, which makes it difficult to define in detail their clinical value. Nevertheless, a notable progress has additionally been made in the clinical characterization of patients with the main neural antibodies, which, although typically present with a subacute pancerebellar syndrome, may also show either hyperacute or chronic onsets that complicate the differential diagnoses. However, prodromal and transient features could be useful clues for an early recognition, and extracerebellar involvement may also be highly indicative of the associated antibody. Moreover, important advances in our understanding of the pathogenesis of cerebellar ataxias include the description of antibody effects, especially those targeting cell-surface antigens, and first attempts to isolate antigen-specific T-cells. Furthermore, genetic predisposition seems relevant, although differently involved according to cancer association, with particular HLA observed in non-paraneoplastic cases and genetic abnormalities in the tumor cells in paraneoplastic ones. Finally, immune checkpoint inhibitors used as cancer immunotherapy may rarely induce cerebellar ataxias, but even this undesirable effect may in turn serve to shed some light on their physiopathology. Herein, we review the principal novelties of the last 20 years regarding autoimmune and paraneoplastic cerebellar ataxias.
