IgM-monoclonal gammopathy neuropathy and tremor: A first epidemiologic case control study

Introduction: Small case series suggest tremor occurs frequently in IgM-monoclonal gammopathy of undetermined significance (IgM-MGUS) neuropathy. Epidemiologic study to confirm this association is lacking. Whether the neuropathy or another remote IgM-effect is causal remains unsettled. Materials and methods: An IgM-MGUS neuropathy case cohort (n= 207) was compared to age, gender, and neuropathy impairment score (NIS) matched, other-cause neuropathy controls (n= 414). Tremor details were extracted from structured neurologic evaluation. All patients underwent nerve conductions. Results: Tremor occurrence was significantly higher in IgM-MGUS case cohort (29%) than in control cohort (9.2%) (p= 0.001). In IgM-MGUS cases, tremor was associated with worse NIS (p= 0.025) and demyelinating nerve conductions (p= 0.020), but 11 of 60 (18%) IgM-MGUS cases with tremor had axonal neuropathy. In other-cause neuropathy controls, tremor was associated with axonal nerve conductions (p= 0.03) but not with NIS severity (p= 0.57). Tremor occurrence associated with older age in controls, (p= 0.004) but not in IgM-MGUS cases (p= 0.272). Most IgM-MGUS tremor cases (49/60) had a postural-kinetic tremor, 8 had rest tremor, 3 had mixed rest-action. Alternative causes of tremor was identified in 42% of IgM-MGUS cases, the most common type is inherited essential tremor 6/60 (p= 0.04). Conclusions: This first epidemiologic case-control study validates association between IgM-MGUS neuropathy and tremor. Among IgM-MGUS neuropathy cases, severity as well as type of neuropathy (demyelinating over axonal) correlated with tremor occurrence. IgM-MGUS paraproteinemia may increase tremor expression in persons recognized with common other risk factors for tremor.