The neuropathies of Waldenström's macroglobulinemia (WM) and IgM-MGUS

Abstract

Background: Neuropathy is common in Waldenström's macroglobulinemia (WM, an IgM-associated lymphoplasmacytic lymphoma) and in IgM-monoclonal gammopathy of undetermined significance (IgM-MGUS). Paraneoplastic or paraimmune mechanisms are thought to be involved in the pathogenesis of these neuropathies. Attempts at distinguishing WM and IgM-MGUS neuropathies are lacking especially among bone marrow (BM) confirmed patients.

Methods: Retrospective analyses were performed on BM confirmed WM (N=30) and IgM-MGUS (N=73) neuropathy patients with neurologic assessments and hematologic features.

Results: The presence of anemia and quantity of IgM monoclonal protein were significantly greater in WM. Based on multiple neurologic assessments differences were not found for: 1) length of time from neurologic symptom onset to evaluation; 2) chief complaint of painless loss of feeling in the feet, Romberg's sign and tremor; and 3) clinical motor, sensory and reflex abnormalities. Autonomic testing was normal in both diseases. Using nerve conduction (NCS) criteria for demyelination, 62% of IgM-MGUS and 27% of WM met this criteria (p=0.013). IgM MGUS patients had greater terminal conduction slowing by ulnar residual latency calculation (<0.01). The degree of axonal loss as measured by summated compound muscle action potentials and available nerve biopsy was not significantly different between diseases.

Conclusion: Although WM and IgM-MGUS must be distinguished for hematologic prognosis and treatment, clinical neuropathy presentations of WM and IgM-MGUS are similar and likely related to comparable axonal loss in both conditions. Despite these similarities, evidence of demyelination was found by electrophysiologic studies much more commonly in IgM-MGUS. This difference may reflect varied immune mechanism(s) in the two disorders.

Figure

Teased and epoxy embedded sections from representative sural nerve biopsies of a patient with IgM-MGUS (a, b) and Waldenström’s macroglobulinemia (WM) (c, d) neuropathy. Both biopsies show combination axonal fiber loss and degeneration (black arrows) with de and remyelination (open arrows). By the electrophysiologic criteria the shown IgM-MGUS patient had demyelinating features with axonal loss whereas the WM patient had axonal nerve conductions despite occasional demyelinating teased fibers. Both these patients presented with insidious onset sensory gait ataxia without pain or significant weakness.