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Association of IgM monoclonal gammopathy with progressive muscular atrophy and multifocal motor neuropathy: a case–control study

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Abstract

Monoclonal gammopathy in patients with amyotrophic lateral sclerosis (ALS) and related disorders has been reported in small studies but the validity of the reported associations remains uncertain. Presence of monoclonal gammopathy may indicate specific pathogenic pathways and may facilitate the development of novel treatment strategies. The objective of this large case–control study was to determine the prevalence of monoclonal gammopathy in motor neuron diseases (MND) and multifocal motor neuropathy (MMN). Monoclonal gammopathy was determined by immunoelectrophoresis and immunofixation in serum from 445 patients with ALS, 158 patients with progressive muscular atrophy (PMA), 60 patients with primary lateral sclerosis (PLS), 88 patients with MMN and in 430 matched healthy controls. Anti-ganglioside antibody titers were determined in sera from patients with MMN and PMA, and in ALS and PLS patients with monoclonal gammopathy. Logistic regression analysis was used to investigate associations of monoclonal gammopathy with motor neuron diseases and clinical characteristics. Neither ALS nor PLS was associated with monoclonal gammopathy. IgM monoclonal gammopathy was more frequent in patients with PMA (8 %) (OR = 4.2; p = 0.001) and MMN (7 %) (OR = 5.8; p = 0.002) than in controls (2 %). High titers of anti-GM1 IgM antibodies were present in 43 % of MMN patients and 7 % of PMA patients. Patients with PMA and IgM monoclonal gammopathy or anti-GM1 antibodies had a higher age at onset, more often weakness of upper legs and more severe outcome than patients with MMN. PMA and MMN, but not ALS and PLS, are significantly associated with IgM monoclonal gammopathy and anti-GM1 antibodies. These results may indicate that a subset of patients presenting with PMA share pathogenic mechanisms with MMN.

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Acknowledgments

This work was supported by the Prinses Beatrix Spierfonds; VSB fonds; Kersten Foundation; The Netherlands ALS Foundation; and the JR van Dijk and the Adessium Foundation. The research leading to these results has received funding from the European Community’s Health Seventh Framework Programme (FP7/2007–2013) under grant agreement number 259867.

Conflicts of interest

B. C. Jacobs received a travel grant from Baxter Biopharmaceutics and research support from the Netherlands Organization for Health Research and Development, Erasmus MC, Prinses Beatrix Spierfonds, Stichting Spieren voor Spieren, GBS-CIDP Foundation International and travel support from, and serves on the Editorial Board of the Journal of the Peripheral Nervous System. H. Franssen received grants from Baxter International Inc. and research support from the Prinses Beatrix Spierfonds. J. H. Veldink receives support from Thierry Latran Foundation and received travel grants from Baxter International Inc. W. L. van der Pol received travel grants from Baxter International Inc. and research support from the Prinses Beatrix Spierfonds and Stichting Spieren voor Spieren. L. H. van den Berg received travel grants and consultancy fees from Baxter; serves on scientific advisory boards for ARISLA (the Italian ALS Association), Prinses Beatrix Fonds, Thierry Latran Foundation, and Biogen Idec; serves on the editorial board of Amyotrophic Lateral Sclerosis; and receives research support from the Prinses Beatrix Spierfonds, Netherlands ALS Foundation, VSB Fonds, Adessium Foundation, and the European Union.

Ethical standard

The Medical Ethical Committee of the University Medical Center Utrecht approved the study protocol and therefore the study has been performed in accordance with the ethical standards laid down in the Declaration of Helsinki.

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Authors and Affiliations

  1. Department of Neurology and Neurosurgery, Brain Center Rudolph Magnus, University Medical Center Utrecht, Utrecht, The Netherlands

    Lotte Vlam, Sanne Piepers, Nadia A. Sutedja, Marloes Stam, Hessel Franssen, Jan H. Veldink, Elisabeth A. Cats, Nicolette C. Notermans, Renske I. Wadman, W.-Ludo van der Pol & Leonard H. van den Berg

  2. Department of Neurology and Immunology, Erasmus Medical Center, Rotterdam, The Netherlands

    Bart C. Jacobs & Anne P. Tio-Gillen

  3. Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands

    Andries C. Bloem

Authors
  1. Lotte Vlam
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  2. Sanne Piepers
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  3. Nadia A. Sutedja
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  4. Bart C. Jacobs
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  5. Anne P. Tio-Gillen
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  6. Marloes Stam
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  7. Hessel Franssen
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  8. Jan H. Veldink
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  9. Elisabeth A. Cats
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  10. Nicolette C. Notermans
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  11. Andries C. Bloem
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  12. Renske I. Wadman
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  13. W.-Ludo van der Pol
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  14. Leonard H. van den Berg
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Corresponding author

Correspondence to Leonard H. van den Berg.

Additional information

W.-L. van der Pol and L. H. van den Berg contributed equally to the manuscript.

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Vlam, L., Piepers, S., Sutedja, N.A. et al. Association of IgM monoclonal gammopathy with progressive muscular atrophy and multifocal motor neuropathy: a case–control study. J Neurol 262, 666–673 (2015). https://doi.org/10.1007/s00415-014-7612-4

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  • DOI: https://doi.org/10.1007/s00415-014-7612-4

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