title: IgM-monoclonal gammopathy neuropathy and tremor: a first epidemiologic case control study.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Peripheral Nerve Research Laboratory, Mayo Clinic, Department of Neurology, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Ahlskog
authors.forename: Neeraj
authors.initials: N
authors.lastname: Kumar
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Mauermann
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Klein
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D003711:Demyelinating Diseases / Q000150:complications*; D005260:Female; D006801:Humans; D007075:Immunoglobulin M; D008297:Male; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000150:complications* / Q000276:immunology; D009431:Neural Conduction; D011115:Polyneuropathies / Q000150:complications*; D014202:Tremor / Q000150:complications* / Q000453:epidemiology* / Q000276:immunology
chemical_list: D007075:Immunoglobulin M