Paraneoplastic neurological syndromes and onconeural antibodies: clinical and immunological aspects

Paraneoplastic neurological syndromes (PNS) are infrequent disorders that are associated with cancer. The syndromes are highly heterogeneous and often affect several areas of the nervous system. Among the most well-known syndromes are paraneoplastic encephalomyelitis, cerebellar degeneration, sensory neuronopathy, and Lambert-Eaton myastenic syndrome. There are various associated tumors, in particular small cell lung cancer, cancer of the breast and ovary, and thymoma. The onset of neurological symptoms often precedes the cancer diagnosis, and the recognition of a paraneoplastic syndrome should lead to immediate search for cancer. The etiology of the paraneoplastic syndromes is believed to be autoimmune. Antibodies to onconeural antigens, expressed in the tumor of the affected individual and in normal neurons, are found in many of the patients. These antibodies are useful markers for paraneoplastic etiology. The pathogenesis of the PNS is uncertain, but cellular immune responses are thought to be the main effector mechanism. The cornerstone of therapy is the identification and treatment of the underlying malignancy. In some of the disorders, immunosuppressive therapy is of additional benefit. The prognosis of the different PNS varies depending on the level of affection and the degree of neuronal death.