Therapeutic Strategies in Immune-Mediated Cerebellar Ataxias

Abstract

Immune-mediated cerebellar ataxias (IMCAs) include diverse etiologies, suggesting that the cerebellum can be the target of many types of autoimmune responses with different pathophysiological mechanisms. When a known factor triggers autoimmunity, the first line of therapy is removal of the triggering factor, for example gluten-free diet in gluten ataxia, and surgical excision or chemotherapy of the neoplasm in paraneoplastic cerebellar degeneration (PCD). Certain conditions (e.g., post-infectious cerebellitis, Miller Fisher syndrome, and post-infectious opsoclonus myoclonus syndrome) are self-limiting presumably because exposure of antigen is transient. However, due to persistent stimulation by autoantigens (if the cancer cannot be eradicated), PCD requires subsequent combinations of immunotherapies that on the whole tend to be ineffective. For other types of IMCAs, such as anti-glutamic acid decarboxylase (anti-GAD) ataxia and primary autoimmune cerebellar ataxia (PACA), immediate immunotherapy is recommended. The cerebellum, a vulnerable autoimmune target of the nervous system, has remarkable capacity (collectively known as the cerebellar reserve, closely linked to plasticity) to compensate and restore function following various pathological insults. Therefore, a good recovery is expected when immune-mediated therapeutic interventions are applied during the early stages when the cerebellar reserve can be preserved, halting the progression and the development of significant disability. We recommend careful examination of the autoimmune profile in all patients presenting with progressive ataxia. This chapter does not discuss the topic of multiple sclerosis (MS).