The presence of MGUS in patients with peripheral neuropathy (PN) may be either coincidental or causal. Younger age group (<50 y) and the presence of IgM MGUS increase the likelihood of a causal relationship between MGUS and peripheral neuropathy. 1
The likelihood of a causal relationship is higher in the younger age group because of the very low prevalence of M proteins (less than 1.5%) in this population making coincidental presence of MGUS and PN much less likely. In contrast, this relationship may just be coincidental in older patients because of higher baseline prevalence of MGUS (7% in those over 70 y old). 1
Similarly, a causal relationship between MGUS and PN may be more likely when the M protein is IgM (vs IgG or IgA). In a study of patients with MGUS and peripheral neuropathy, 31% of patients with IgM MGUS had neuropathy vs 14% for IgA and 6% for IgG MGUS. In fact, among patients with PN without an obvious cause, the prevalence of an M protein may be as high as 10%.2 Whether the relationship between non-IgM MGUS and PN is causal remains unclear.3
Although the exact mechanism of MGUS-related PN is not known, pathologic studies in Waldenstrom macroglobulinemia and multiple myeloma have demonstrated demyelination and widened myelin lamellae associated with monoclonal IgM deposits.1
But before you implicate MGUS as the cause of PN, make sure to exclude common causes of PN, such as diabetes mellitus, alcoholism and potential drugs.
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- Chaudhry HM, Mauermann ML, Rajkumar SV. Monoclonal gammopathy—associated peripheral neuropathy: diagnosis and management. Mayo Clin Proc 2017; 92:838-50. https://www.mayoclinicproceedings.org/article/S0025-6196(17)30118-0/pdf
- Kelly JJ Jr, Kyle RA, O’Brien PC, et al. Prevalence of monoclonal protein in peripheral neuropathy. Neurology 1981;31:1480-83. https://www.ncbi.nlm.nih.gov/pubmed/6273767
- Nobile-Orazio E, Barbien L, Baldini L, et al. Peripheral neuropathy in monoclonal gammopathy of undetermined significance: prevalence and immunopathogenetic studies. Acta neurol Scand 1992;85:383-90. https://onlinelibrary.wiley.com/doi/10.1111/j.1600-0404.1992.tb06033.x