Skip to main content

Revisiting the spectrum of IgM-related neuropathies in a large cohort of IgM monoclonal gammopathy

Abstract

Introduction

A significant number of patients with a peripheral neuropathy have IgM monoclonal gammopathy (IgM-MG). In this work, we encompassed the spectrum and outcome of IgM-related neuropathies (IgM-NP) in a large monocentric cohort of patients with IgM-MG.

Methods

We retrospectively reviewed the neurological and hematological findings and the course of neuropathy in all patients with IgM-MG over a five-year period in our center (Henri Mondor hospital, Assistance Publique Hôpitaux de Paris (APHP), France).

Results

Among 550 patients with IgM-MG, 83 patients (15%) had IgM-NP (55 males, mean age 67 y.o.). The median serum level of IgM-MG was 3.4 g/L, mostly kappa light chain component. The hematological diagnosis was Monoclonal Gammopathy of Undetermined Significance (MGUS) in 62 patients. Anti-MAG antibodies were detected in 38 patients with heterogeneous clinical and neurophysiological features. Four patients had neurolymphomatosis presenting as a non-length dependent predominantly motor neuropathy, which occurred long after the finding of IgM-MG and was responsive to hematological treatment. Five patients had an AL amyloid neuropathy revealed by a small fiber neuropathy. Finally, 30 patients were classified as “Neuropathy of Uncertain Relationship with the IgM” (NURIM) with characteristics close to those of an anti-MAG-NP at the time of diagnosis, except for the neurophysiological features with a predominant axonal pattern.

Conclusion

This study emphasizes the wide spectrum of IgM-NP associated with a variety of hematological diagnoses. In particular, the course and prognosis vary considerably. In this setting, further studies are needed to unravel the group of patients classified as NURIM.

This is a preview of subscription content, access via your institution.

Fig. 1

References

  1. Kelly JJ, Kyle RA, O’Brien PC, Dyck PJ (1981) Prevalence of monoclonal protein in peripheral neuropathy. Neurology 31:1480–1483

    Article  Google Scholar 

  2. Ramchandren S, Lewis RA (2012) An update on monoclonal gammopathy and neuropathy. Curr Neurol Neurosci Rep 12:102–110. https://doi.org/10.1007/s11910-011-0237-4

    CAS  Article  PubMed  Google Scholar 

  3. Vallat J-M, Duchesne M, Corcia P, Richard L, Ghorab K, Magy L, Mathis S (2021) The wide spectrum of pathophysiologic mechanisms of paraproteinemic neuropathy. Neurology 96:214–225. https://doi.org/10.1212/WNL.0000000000011324

    Article  PubMed  Google Scholar 

  4. Joint Task Force of the EFNS and the PNS (2010) European Federation of neurological societies/peripheral nerve society guideline on management of paraproteinemic demyelinating neuropathies. Report of a joint task force of the European federation of neurological societies and the peripheral nerve society—first revision. J Peripher Nerv Syst 15:185–195. https://doi.org/10.1111/j.1529-8027.2010.00278.x

    Article  Google Scholar 

  5. Yamamoto S, Wilczek HE, Nowak G, Larsson M, Oksanen A, Iwata T, Gjertsen H, Söderdahl G, Wikström L, Ando Y et al (2007) Liver transplantation for Familial Amyloidotic Polyneuropathy (FAP): a single-center experience over 16 years. Am J Transplant 7:2597–2604. https://doi.org/10.1111/j.1600-6143.2007.01969.x

    CAS  Article  PubMed  Google Scholar 

  6. Owen RG, Kyle RA, Stone MJ, Rawstron AC, Leblond V, Merlini G, Garcia-Sanz R, Ocio EM, Morra E, Morel P et al (2013) Response assessment in Waldenström macroglobulinaemia: update from the VIth international workshop. Br J Haematol 160:171–176. https://doi.org/10.1111/bjh.12102

    Article  PubMed  Google Scholar 

  7. Liberatore G, Giannotta C, Sajeev BP, Morenghi E, Terenghi F, Gallia F, Doneddu PE, Manganelli F, Cocito D, Filosto M et al (2020) Sensitivity and specificity of a commercial ELISA test for anti-MAG antibodies in patients with Neuropathy. J Neuroimmunol 345:577288. https://doi.org/10.1016/j.jneuroim.2020.577288

    CAS  Article  PubMed  Google Scholar 

  8. Van den Bergh PYK, van Doorn PA, Hadden RDM, Avau B, Vankrunkelsven P, Allen JA, Attarian S, Blomkwist-Markens PH, Cornblath DR, Eftimov F et al (2021) European academy of neurology/peripheral nerve society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force—second revision. J Peripher Nerv Syst JPNS 26:242–268. https://doi.org/10.1111/jns.12455

    CAS  Article  PubMed  Google Scholar 

  9. Campagnolo M, Zambello R, Nobile-Orazio E, Benedetti L, Marfia GA, Riva N, Castellani F, Bianco M, Salvalaggio A, Garnero M et al (2017) IgM MGUS and Waldenstrom-associated anti-MAG neuropathies display similar response to rituximab therapy. J Neurol Neurosurg Psychiatry 88:1094–1097. https://doi.org/10.1136/jnnp-2017-315736

    Article  PubMed  Google Scholar 

  10. Kyle RA, Garton JP (1987) The Spectrum of IgM monoclonal gammopathy in 430 cases. Mayo Clin Proc 62:719–731

    CAS  Article  Google Scholar 

  11. Cao X-X, Meng Q, Mao Y-Y, Su W, Zhen J-F, Shen K-N, Zhang C-L, Huang X-F, Duan M-H, Zhang W et al (2016) The clinical spectrum of IgM monoclonal gammopathy: a single center retrospective study of 377 patients. Leuk Res 46:85–88. https://doi.org/10.1016/j.leukres.2016.05.002

    Article  PubMed  Google Scholar 

  12. Magy L, Kaboré R, Mathis S, Lebeau P, Ghorab K, Caudie C, Vallat JM (2015) Heterogeneity of polyneuropathy associated with anti-MAG antibodies. J Immunol Res. https://doi.org/10.1155/2015/450391

    Article  PubMed  PubMed Central  Google Scholar 

  13. Svahn J, Petiot P, Antoine J-C, Vial C, Delmont E, Viala K, Steck AJ, Magot A, Cauquil C, Zarea A et al (2018) Anti-MAG antibodies in 202 patients: clinicopathological and therapeutic features. J Neurol Neurosurg Psychiatry 89:499–505. https://doi.org/10.1136/jnnp-2017-316715

    Article  PubMed  Google Scholar 

  14. Chaudhry HM, Mauermann ML, Rajkumar SV (2017) Monoclonal gammopathy-associated peripheral neuropathy: diagnosis and management. Mayo Clin Proc 92:838–850. https://doi.org/10.1016/j.mayocp.2017.02.003

    Article  PubMed  Google Scholar 

  15. Bourque PR, Masson-Roy J, Warman-Chardon J, Massie R, Melanson M, Brooks J, Breiner A (2021) Temporal evolution of nerve conduction study abnormalities in anti-myelin-associated glycoprotein neuropathy. Muscle Nerve 63:401–404. https://doi.org/10.1002/mus.27134

    CAS  Article  PubMed  Google Scholar 

  16. Hänggi P, Aliu B, Martin K, Herrendorff R, Steck AJ (2022) Decrease in serum anti-MAG autoantibodies is associated with therapy response in patients with anti-MAG neuropathy: retrospective study. Neurol Neuroimmunol Neuroinflammation 9:e1109. https://doi.org/10.1212/NXI.0000000000001109

    Article  Google Scholar 

Download references

Funding

This study received no funding.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Benjamin Bardel.

Ethics declarations

Conflicts of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical standard statement

The study was entirely based on register data and was approved by the French data inspection agency (Commission nationale de l’informatique et des libertés, CNIL 1685786 v 0). The participants gave their non-objection consent to the use of these data collected in the context of clinical practice, according to the French law requirement regarding ethical approval of register-based research.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Bardel, B., Molinier-Frenkel, V., Le Bras, F. et al. Revisiting the spectrum of IgM-related neuropathies in a large cohort of IgM monoclonal gammopathy. J Neurol (2022). https://doi.org/10.1007/s00415-022-11139-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00415-022-11139-2

Keywords

  • Peripheral neuropathy
  • IgM-related neuropathy
  • Anti-MAG neuropathy
  • IgM-monoclonal gammopathy
  • Paraproteinemic neuropathy