Monoclonal Gammopathy of Neurological Significance: Toward an Integrated Hematologic-Neurologic Perspective-A...

Monoclonal gammopathies of clinical significance (MGCSs) are entities in which a small hematological clone produces a monoclonal immunoglobulin capable of causing organ damage. Neurological involvement remains difficult to diagnose and treat, especially in the context of incidental monoclonal gammopathy of undetermined significance (MGUS)-peripheral neuropathy (PN) associations. We conducted a single-center retrospective study at Fundeni Clinical Institute, Bucharest, from January 2015 to December 2025. The reference population included 300 patients with MGUS. The diagnosis of MGNS was established clinically and/or electrophysiologically, with the exclusion of alternative causes of neuropathy. In total, 35 patients with MGNS were identified (prevalence 11.7%). Neuropathy was more common in IgM MGUS (36.7%) compared to IgG (15%), IgA (14.3%), or light chain MGUS (16.7%), with an increased risk for IgM (OR 3.27, p < 0.001). A total of 88.5% of patients received hematological treatment; neurological response was noted in the majority of treated patients. Mortality was 14.3%, and median OS was not reached. Our findings confirm the dissociation between low clonal load and the severity of organ involvement. IgM MGUS is associated with a significantly increased risk of neuropathy, supporting the need for systematic screening for MGUS in patients with PN and for a multidisciplinary approach.