Immunotherapy for paraneoplastic neurological disorders

Abstract

Paraneoplastic disorders may affect any part of the central or peripheral nervous systems. Although relatively uncommon, these disorders are a significant cause of severe neurological disability among cancer patients. Most, if not all, neurological paraneoplastic disorders are believed to be autoimmune diseases in which an antitumour immune response also attacks neurons that express shared neuronal tumour antigens. Affected patients often have one or more circulating antineuronal antibodies, which serve as a diagnostic marker for the paraneoplastic condition, and in some cases are the direct mediators of neuronal injury. The exact immunopathogenesis and relative contributions of humoral or cellular immune effectors for most paraneoplastic syndromes are not well understood. Some patients have a gratifying neurological response to tumour treatment and/or immunotherapy, especially if the diagnosis is made early and treatment is initiated promptly. Unfortunately, many patients are left with severe and permanent neurological deficits despite aggressive treatment. This review summarises the current understanding of the clinical immunology of paraneoplastic disorders, and outlines immunotherapy options and outcomes.