Distinct patterns of small-fiber dysfunction in anti-myelin-associated glycoprotein-positive and negative paraproteinemic neuropathies

Objective. IgM paraproteinemic neuropathies are traditionally considered large-fiber disorders, while small-fiber involvement remains poorly investigated. We assessed small-fiber dysfunction using thermal quantitative sensory testing in IgM paraproteinemic neuropathies, comparing anti-myelin-associated glycoprotein-positive and negative patients, and explored relationships with nerve conduction studies, disability, quality of life, and serum neurofilament light chain. Methods. Thirty-nine patients (24 anti-myelin-associated glycoprotein-positive, 15 negative) and 20 healthy volunteers underwent thermal quantitative sensory testing at the hand and foot, clinical and quality-of-life assessment, and serum neurofilament light chain measurement. A 12-month clinical, quantitative sensory testing, and electrophysiological follow-up was available in a subgroup. Results. Both patient groups showed cold detection threshold abnormalities at the foot, consistent with length-dependent Aδ-fiber dysfunction. Only anti-myelin-associated glycoprotein-negative patients showed significant warm detection and heat pain threshold abnormalities, with a non-length-dependent pattern suggestive of broader C-fiber involvement. In anti-myelin-associated glycoprotein-negative neuropathy, cold detection thresholds strongly correlated with sensory impairment, disability, and quality of life. In anti-myelin-associated glycoprotein-positive patients, thermal thresholds were associated mainly with sensory deficits. Distinct correlations between quantitative sensory testing and nerve conduction studies suggested heterogeneous involvement of nerve compartments. No correlation was found with serum neurofilament light chain, and longitudinal changes were limited. Conclusions. Small-fiber dysfunction occurs in IgM paraproteinemic neuropathies with distinct patterns according to anti-myelin-associated glycoprotein status, with broader abnormalities in anti-myelin-associated glycoprotein-negative patients. Significance. These findings support quantitative sensory testing as a complementary tool to electrophysiological studies for characterizing small-fiber involvement in IgM paraproteinemic neuropathies.