Neuropathy in Waldenström’s Macroglobulinaemia

Abstract

Neuropathy is the most common organ-specific complication of Waldenstrom’s macroglobulinemia (WM) and is observed at least in 40 % of patients. Paraproteinaemic IgM in WM and MGUS can possess activity against peripheral nerve epitopes, most typically Myelin-Associated Glycoprotein (MAG), but also GM1 and other gangliosides. Anti-MAG neuropathy is the commonest of the presentations. IgM can also act as a cryoglobulin and deposit in vessels resulting in vasculitis. Acquired AL amyloid can occur with deposition and polymerization of free light chains in numerous tissues, with a painful progressive motor and sensory axonal neuropathy with autonomic involvement. Even more rarely still WM cells invade the peripheral nerves sometimes without significant systemic load and can result in a presentation that looks like an inflammatory neuropathy but requires nervous system penetrating chemotherapy. An important consideration in the work up of a possible proprotein neuropathy (PPN) is whether electrophysiological tests, cerebrospinal fluid (CSF) examination, or a nerve biopsy are indicated. The presence of a symptomatic PPN will in its own right mandate the institution of therapy. If there is a causal link between WM and the PN, an improvement in the PN might be expected as a by-product of treating WM, provided neurotoxic agents have been avoided.