Paraneoplastic neurologic syndromes: pathogenesis and physiopathology.
Since 1965 when the first paraneoplastic antineuronal antibody was reported by Wilkinson and Zeromski (55), the number of immunological responses detected in association with paraneoplastic syndromes of the nervous system has steadily increased. These responses are characterized by the presence of antineuronal antibodies in serum and CSF and/or infiltrates of T-cells in the tumor and nervous system. A few syndromes are mediated by antibodies; they include those resulting from dysfunction of the neuromuscular junction at the pre- or post-synaptic level (Lambert-Eaton myasthenic syndrome, myasthenia gravis) or ion channel dysfunction in the peripheral nervous system (i.e, Voltage-gated potassium channel and neuromyotonia). In most other paraneoplastic syndromes, including those involving the central nervous system, the pathogenic role of highly specific antineuronal antibodies (anti-Hu, anti-Yo, etc.) has not been established; nevertheless these antibodies should be regarded as useful markers of specific paraneoplastic syndromes and tumors. Moreover, there is increasing evidence that in some of these syndromes T-cell mediated mechanisms can cause the neurologic dysfunction and contribute to tumor rejection. Some paraneoplastic syndromes are caused by the tumor secretion of antibodies (macroglobulinemia and MAG antibodies), hormones, and cytokines. In other instances, the tumor may compete with the nervous system for an essential substrate (glucose, tryptophan) and result in neurologic dysfunction.
Dalmau
J
J
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10021, USA. dalmauj@mskcc.org
Gultekin
H S
HS
Posner
J B
JB
D006801:Humans; D009422:Nervous System Diseases / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D009468:Neuromuscular Diseases / Q000473:pathology / Q000503:physiopathology; D010257:Paraneoplastic Syndromes / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D010523:Peripheral Nervous System Diseases / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology