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Prognostic factor of poor outcome in anti-MAG neuropathy: clinical and electrophysiological analysis of a French Cohort

  • Marie-Ange Hoang Tang
  • Stéphane Mathis
  • Pierre Duffau
  • Philippe Cazenave
  • Guilhem Solé
  • Fanny Duval
  • Antoine Soulages
  • Gwendal Le MassonEmail author
Original Communication
  • 39 Downloads

Abstract

Background

Anti-MAG polyneuropathy (anti-MAG PN) is an immune-mediated peripheral sensorimotor neuropathy characterized by distal demyelination and ataxia. However, this disorder, unlike other immune-mediated neuropathies, is difficult to treat in most cases.

Method

We retrospectively collected all anti-MAG PN patients followed in two hospitals for a period of 12 years to determine prognostic factors, especially those that indicated a good response to the various therapeutic strategies used.

Results

Forty-seven patients were included in the study; of these, 61% had a classical ‘distal demyelinating pattern’, 34.2% had a ‘CIDP-like pattern’, and the others had an ‘axonal pattern’. The most commonly used treatments were intravenous immunoglobulin (IVIg) as the first-line treatment and rituximab as the second- or third-line treatment. No prognostic factor was identified for IVIg, but electrophysiological parameters at onset were better in patients with a good response to rituximab than in non-responder patients, even though mild or high disability was observed in nearly half the patients at last examination.

Conclusion

Even though disability seems to progress in most cases despite the treatments used, our results suggest that an early electrophysiological reduction in sensory nerves could be considered a ‘red flag’ for the prompt initiation of rituximab to try to delay long-term disability.

Keywords

MAG Neuropathy Prognosis Sural nerve Rituximab 

Notes

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Compliance with ethical standards

Conflicts of interest

The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.

Ethical standards

This study was in compliance with the ethical principles of the conference of Helsinki.

Supplementary material

415_2019_9618_MOESM1_ESM.docx (13 kb)
Supplementary material 1 (DOCX 13 kb)

References

  1. 1.
    International Myeloma Working Group (2003) Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 121:749–757CrossRefGoogle Scholar
  2. 2.
    Crow RS (1956) Peripheral neuritis in myelomatosis. Br Med J 2:802–804CrossRefGoogle Scholar
  3. 3.
    Victor M, Banker BQ, Adams RD (1955–1956) The neuropathy of multiple myeloma. Trans Am Neurol Assoc 99–102Google Scholar
  4. 4.
    Garcin R, Mallarmé J, Rondot P (1958) Forme névritique de la macroglobulinémie de Waldenström. Bull Mem Soc Med Hop Paris 74:562–573PubMedGoogle Scholar
  5. 5.
    Nobile-Orazio E, Casellato C, Di Troia A (2002) Neuropathies associated with IgG and IgA monoclonal gammopathy. Rev Neurol (Paris) 158:979–987Google Scholar
  6. 6.
    Magy L, Kaboré R, Mathis S, Lebeau P, Ghorab K, Caudie C et al (2015) Heterogeneity of polyneuropathy associated with anti-MAG antibodies. J Immunol Res 2015:450391CrossRefGoogle Scholar
  7. 7.
    Latov N, Sherman WH, Nemni R, Galassi G, Shyong JS, Penn AS et al (1980) Plasma-cell dyscrasia and peripheral neuropathy with a monoclonal antibody to peripheral-nerve myelin. N Engl J Med 303:618–621CrossRefGoogle Scholar
  8. 8.
    Smith IS, Kahn SN, Lacey BW, King RH, Eames RA, Whybrew DJ et al (1983) Chronic demyelinating neuropathy associated with benign IgM paraproteinaemia. Brain 106:169–195CrossRefGoogle Scholar
  9. 9.
    Mathis S, Magy L, Le Masson G, Richard L, Soulages A, Solé G et al (2018) Value of nerve biopsy in the management of peripheral neuropathies. Expert Rev Neurother 18:589–602CrossRefGoogle Scholar
  10. 10.
    Quarles RH (2007) Myelin-associated glycoprotein (MAG): past, present and beyond. J Neurochem 100:1431–1448PubMedGoogle Scholar
  11. 11.
    Vallat JM, Magy L, Ciron J, Corcia P, Le Masson G, Mathis S (2016) Therapeutic options and management of polyneuropathy associated with anti-MAG antibodies. Expert Rev Neurother 16:1111–1119CrossRefGoogle Scholar
  12. 12.
    Falzone YM, Campagnolo M, Bianco M, Dacci P, Martinelli D, Ruiz M et al (2018) Functioning and quality of life in patients with neuropathy associated with anti-MAG antibodies. J Neurol 265:2927–2933CrossRefGoogle Scholar
  13. 13.
    Caudie C, Kaygisiz F, Jaquet P, Petiot P, Gonnaud PM, Antoine JC et al (2006) Les autoanticorps IgM anti-MAG par Elisa Buhlmann: apport diagnostique dans 117 neuropathies périphériques auto-immunes associées à une IgM monoclonale à activité anti-SGPG/SGLPG. Ann Biol Clin (Paris) 64:353–359Google Scholar
  14. 14.
    Farrell B, Godwin J, Richards S, Warlow C (1991) The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results. J Neurol Neurosurg Psychiatry 54:1044–1054CrossRefGoogle Scholar
  15. 15.
    Cocito D, Isoardo G, Ciaramitaro P, Migliaretti G, Pipieri A, Barbero P et al (2001) Terminal latency index in polyneuropathy with IgM paraproteinemia and anti-MAG antibody. Muscle Nerve 24:1278–1282CrossRefGoogle Scholar
  16. 16.
    Delmont E, Jeandel PY, Hubert AM, Marcq L, Boucraut J, Desnuelle C (2010) Successful treatment with rituximab of one patient with CANOMAD neuropathy. J Neurol 257:655–657CrossRefGoogle Scholar
  17. 17.
    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 15:185–195CrossRefGoogle Scholar
  18. 18.
    Joint Task Force of the EFNS and the PNS (2010) European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society—first revision. J Peripher Nerv Syst 15:1–9CrossRefGoogle Scholar
  19. 19.
    Nobile-Orazio E, Meucci N, Baldini L, Di Troia A, Scarlato G (2000) Long-term prognosis of neuropathy associated with anti-MAG IgM M-proteins and its relationship to immune therapies. Brain 123:710–717CrossRefGoogle Scholar
  20. 20.
    Ellie E, Vital A, Steck A, Boiron JM, Vital C, Julien J (1996) Neuropathy associated with “benign” anti-myelin-associated glycoprotein IgM gammopathy: clinical, immunological, neurophysiological pathological findings and response to treatment in 33 cases. J Neurol 243:34–43CrossRefGoogle Scholar
  21. 21.
    Svahn J, Petiot P, Antoine JC, Vial C, Delmont E, Viala K et al (2018) Anti-MAG antibodies in 202 patients: clinicopathological and therapeutic features. J Neurol Neurosurg Psychiatry 89:499–505CrossRefGoogle Scholar
  22. 22.
    Chassande B, Léger JM, Younes-Chennoufi AB, Bengoufa D, Maisonobe T, Bouche P et al (1998) Peripheral neuropathy associated with IgM monoclonal gammopathy: correlations between M-protein antibody activity and clinical/electrophysiological features in 40 cases. Muscle Nerve 21:55–62CrossRefGoogle Scholar
  23. 23.
    Yeung KB, Thomas PK, King RH, Waddy H, Will RG, Hughes RA et al (1991) The clinical spectrum of peripheral neuropathies associated with benign monoclonal IgM, IgG and IgA paraproteinaemia. Comparative clinical, immunological and nerve biopsy findings. J Neurol 238:383–391CrossRefGoogle Scholar
  24. 24.
    Nobile-Orazio E, Manfredini E, Carpo M, Meucci N, Monaco S, Ferrari S et al (1994) Frequency and clinical correlates of anti-neural IgM antibodies in neuropathy associated with IgM monoclonal gammopathy. Ann Neurol 36:416–424CrossRefGoogle Scholar
  25. 25.
    Launay M, Delmont E, Benaim C, Sacconi S, Butori C, Desnuelle C (2009) Les polyneuropathies avec IgM monoclonale anti-MAG: étude descriptive clinique, biologique, électrophysiologique et anatomopathologique d’une cohorte de 13 patients. Rev Neurol (Paris) 165:1071–1079CrossRefGoogle Scholar
  26. 26.
    Rajabally YA, Delmont E, Hiew FL, Aube-Nathier AC, Grapperon AM, Cassereau J et al (2018) Prevalence, correlates and impact of pain and cramps in anti-MAG neuropathy: a multicentre European study. Eur J Neurol 25:135–141CrossRefGoogle Scholar
  27. 27.
    Boukhris S, Magy L, Khalil M, Sindou P, Vallat JM (2007) Pain as the presenting symptom of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). J Neurol Sci 254:33–38CrossRefGoogle Scholar
  28. 28.
    Michaelides A, Hadden RDM, Sarrigiannis PG, Hadjivassiliou M, Zis P (2019) Pain in chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review and meta-analysis. Pain Ther.  https://doi.org/10.1007/s40122-019-0128-y CrossRefPubMedGoogle Scholar
  29. 29.
    Dalakas MC, Rakocevic G, Salajegheh M, Dambrosia JM, Hahn AF, Raju R et al (2009) Placebo-controlled trial of rituximab in IgM anti-myelin-associated glycoprotein antibody demyelinating neuropathy. Ann Neurol 65:286–293CrossRefGoogle Scholar
  30. 30.
    Gazzola S, Delmont E, Franques J, Boucraut J, Salort-Campana E, Verschueren A et al (2017) Predictive factors of efficacy of rituximab in patients with anti-MAG neuropathy. J Neurol Sci 377:144–148CrossRefGoogle Scholar
  31. 31.
    Léger JM, Viala K, Nicolas G, Créange A, Vallat JM, Pouget J et al (2013) Placebo-controlled trial of rituximab in IgM anti-myelin-associated glycoprotein neuropathy. Neurology 80:2217–2225CrossRefGoogle Scholar
  32. 32.
    Comi G, Roveri L, Swan A, Willison H, Bojar M, Illa I et al (2002) A randomised controlled trial of intravenous immunoglobulin in IgM paraprotein associated demyelinating neuropathy. J Neurol 249:1370–1377CrossRefGoogle Scholar
  33. 33.
    Fatehi F, Delmont E, Grapperon AM, Salort-Campana E, Sevy A, Verschueren A et al (2017) Motor unit number index (MUNIX) in patients with anti-MAG neuropathy. Clin Neurophysiol 128:1264–1269CrossRefGoogle Scholar
  34. 34.
    Galassi G, Tondelli M, Ariatti A, Benuzzi F, Nichelli P, Valzania F (2017) Long-term disability and prognostic factors in polyneuropathy associated with anti-myelin-associated glycoprotein (MAG) antibodies. Int J Neurosci 127:439–447CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neurology, Nerve-Muscle Unit, CHU Bordeaux (Groupe Hospitalier Pellegrin)University of BordeauxBordeauxFrance
  2. 2.Centre de Référence des Pathologies Neuromusculaires, CHU Bordeaux (Groupe Hospitalier Pellegrin)University of BordeauxBordeauxFrance
  3. 3.Department of Internal Medicine and Clinical Immunology, CHU Bordeaux (Groupe Hospitalier Saint-André)University of BordeauxBordeauxFrance
  4. 4.Department of NeurologyRobert Boulin HospitalLibourneFrance

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