Background
Clinical spectrum of immunoglobulin M (IgM) monoclonal gammopathy varies from IgM monoclonal gammopathy of unknown significance (IgM-MGUS) to hematological malignancies. We evaluated the clinical features, electrophysiological characteristics, and prognosis of patients with peripheral neuropathy associated with IgM monoclonal gammopathy (PN-IgM MG).
Methods
We retrospectively evaluated 25 patients with PN-IgM MG. Peripheral neuropathy was classified as axonal, demyelinating, or undetermined, based on electrophysiological studies. We classified the enrolled patients into the IgM-MGUS and malignancy groups, and compared the clinical and electrophysiological features between the groups.
Results
Fifteen patients had IgM-MGUS and 10 had hematologic malignancies (Waldenström’s macroglobulinemia: two and B-cell non-Hodgkin’s lymphoma: eight). In the electrophysiological evaluation, the nerve conduction study (NCS) criteria for demyelination were met in 86.7% of the IgM-MGUS group and 10.0% of the malignancy group. In particular, the distal latencies of the motor NCS in the IgM-MGUS group were significantly prolonged compared to those in the malignancy group (median, 9.1 ± 5.1 [IgM-MGUS], 4.2 ± 1.3 [malignancy], p = 0.003; ulnar, 5.4 ± 1.9 [IgM-MGUS], 2.9 ± 0.9 [malignancy], p = 0.001; fibular, 9.3 ± 5.1 [IgM-MGUS], 3.8 ± 0.3 [malignancy], p = 0.01; P-posterior tibial, 8.3 ± 5.4 [IgM-MGUS], 4.4 ± 1.0 [malignancy], p = 0.04). Overall treatment responses were significantly worse in the malignancy group than in the IgM-MGUS group (p = 0.004), and the modified Rankin Scale score at the last visit was higher in the malignancy group than in the IgM-MGUS group (2.0 ± 1.1 [IgM-MGUS], 4.2 ± 1.7 [malignancy], p = 0.001), although there was no significant difference at the initial assessment.
Conclusions
The risk of hematological malignancy should be carefully assessed in patients with PN-IgM MG without electrophysiological demyelination features.

Paraproteinemic neuropathy is a heterogeneous set of neuropathies characterized by the presence of homogeneous immunoglobulin in the serum. Most cases are associated with monoclonal gammopathy of undetermined significance. It might also occur in hematologic malignant and nonmalignant conditions. The association between neuropathy and monoclonal gammopathy requires appropriate neurological and hematological investigations. Treatment is mostly based on underlying hematologic disorders. In this review, we provide a clinically practical approach to clinical, laboratory, electrophysiological features and management of patients with paraproteinemic neuropathy.