Monoclonal gammopathy–associated peripheral neuropathy (MGNS)

Authored by Manni Mohyuddin, published on 2026-04-28 02:03:02.0

The algorithm broadly aligns with current practice in separating neuropathy with an M-protein into (1) overt plasma cell disorders with clear causal mechanisms (AL amyloidosis, POEMS, Waldenström macroglobulinemia) where clone-directed therapy is indicated, versus (2) MGUS where causality is often uncertain and subtype-dependent. The emphasis that IgG/IgA MGUS is less likely causal than IgM, and that IgM-associated distal acquired demyelinating neuropathy (often anti-MAG mediated) is typically managed with immune therapy (IVIG, rituximab) is consistent with contemporary reviews and practice guidance. Evidence quality is mixed, with many recommendations based on observational data and small trials rather than large RCTs.

  1. M protein found during peripheral neuropathy eval
    • Amyloidosis or POEMS present?
      Amyloidosis => Isolated nerve involvement without heart/kidney extremely unlikely POEMS =>VEGF helpful
      • Yes
        • Treat plasma cell clone
      • No
        • IgG or IgA
          • Extremely unlikely to be causally associated
            If clone ↑ and neuropathy worsening can consider, but very unlikely to be helpful
        • IgM
          • If not Waldenstrom but presenting as distal acquired demyelinating neuropathy then treat
            Treat with IVIG; if no response try Rituximab
          • If Waldenstrom's (treat Waldenstrom)
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