ABSTRACT

The association between peripheral neuropathy and paraproteinemia has been increasingly recognized in the past 25 years. The first descriptions concerned peripheral neuropathy associated with multiple myeloma, then Waldenström’s macroglobulinemia1. In 1978, Kyle2 proposed the term of monoclonal gammopathy of undetermined significance (MGUS) to regroup cases with ‘benign’ paraproteinemia, and Kelly and colleagues3 drew attention to the frequency of the association between MGUS and polyneuropathy. Finally, an activity of the M-protein directed to peripheral nerve antigens (myelin-associated glycoprotein: MAG; glycolipids: sulfate glucuronyl paragloboside, sulfate glucuronyl lactosaminyl paragloboside, sulfatides) has been demonstrated in a high proportion of paraproteinemic demyelinating neuropathies (PDNs) associated with immunoglobulin M (IgM) MGUS4-7, but has not been found in PDN associated with IgG and IgA MGUS. In this review the main characteristics of PDN, associated with either lymphoproliferative disorders or MGUS, are summarized, and the current place of therapies developed is discussed, with special attention to intravenous immunoglobulin (IVIG), which has been increasingly used in the treatment of immune-mediated neuromuscular diseases over the past decade (Table 1)8,9.