Paraproteinaemic neuropathies

In this article, we review the main clinical and pathological features of p araproteinaemic neuropathies and discuss recent experimental findings, Furt her knowledge of the disease process at the molecular level has allowed a b etter characterization of clinical syndromes and has given new insights int o their pathogenesis. The most convincing evidence for a causal relationshi p can be drawn from IgM monoclonal gammopathies with specificities directed against carbohydrate determinants of the myelin associated glycoprotein (M AG). There remain however, many unresolved questions, such as how monoclona l anti-MAG IgM antibodies cross the blood-nerve barrier and trigger a chron ic demyelinating polyneuropathy while the central nervous system is essenti ally spared, IgM paraproteins with specificity for other molecules, such as neurofilaments, sulphatide, gangliosides, chondroitin sulphate and tubulin , have also been identified, but their pathogenetic importance remains to b e elucidated. Other paraproteinaemic neuropathies such as IgG and IgA neuropathies have t o be considered separately, The paraneoplastic endocrine and cytokine manif estations of rare osteosclerotic myelomas provide valuable insights into th e interaction between the immune and the nervous system, The antigen-specif icity of IgG and IgA monoclonal antibodies are only poorly characterized bu t some have been found to be directed against endoneurial determinants and a few against axonal proteins such as neurofilaments.