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 dete cted in association with paraneoplastic syndromes of the nervous system has steadily increased, These responses are characterized by the presence of a ntineuronal antibodies in serum and CSF and/or infiltrates of T-cells in th e tumor and nervous system, A few syndromes are mediated by antibodies; the y include those resulting from dysfunction of the neuromuscular junction at the pre- or post-synaptic level (Lambert-Eaton myasthenic syndrome, myasth enia gravis) or ion channel dysfunction in the peripheral nervous system (i .e, Voltage-gated potassium channel and neuromyotonia), In most other paran eoplastic syndromes, including those involving the central nervous system, the pathogenic role of highly specific antineuronal antibodies (anti-Hu, an ti-Yo, etc) has not been established; nevertheless these antibodies should be regarded as useful markers of specific paraneoplastic syndromes and tumo rs, Moreover, there is increasing evidence that in some of these syndromes T-cell mediated mechanisms can cause the neurologic dysfunction and contrib ute to tumor rejection. Some paraneoplastic syndromes are caused by the tum or 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 neur ologic dysfunction.