Paraneoplastic neurologic syndromes : Up–to–Date

Abstract

Paraneoplastic neurologic syndromes (PNS) are a group of neurological disorders possibly caused by immunological mechanisms triggered by the underlying tumor that involve every part of the nervous system. Most antibodies associated with PNS (onconeural antibodies) are excellent diagnostic markers for the neurological syndromes and underlying tumors which were categorized as high–risk antibodies for cancer detection. These antibodies bind to intracellular proteins without functional roles for neuronal loss, instead, the direct effector for neuronal damage is thought to be cytotoxic T cells. While antibodies against cell surface antigens are less likely linked to cancer and those having these antibodies are usually responsive to immune–therapies. Frequently associated symptoms are limbic encephalitis, cerebellar ataxia and sensory neuronopathy. Associated tumors are mainly small cell lung cancer, breast/ovary/uterus cancers and thymoma. Timely diagnosis, prompt immunotherapy, and treatment of the underlying tumor are essential components of management of these cases. However, we need to be cautious for high frequency of false–positive/negative results of antibody–detection using commercial antibody–tests which alerts the importance of careful evaluation of clinical features. Recently, PNS emerged after immune check point inhibitor administration became a subject of attention to explore the pathogenesis of PNS. Other basic research for understanding immunological background of PNS has been progressing.