Skip to main content
Log in

Neuropathy associated with “benign” anti-myelin-associated glycoprotein IgM gammopathy: Clinical, immunological, neurophysiological pathological findings and response to treatment in 33 cases

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

We studied 33 patients presenting with a peripheral neuropathy associated with non-malignant anti-myelin-associated glycoprotein (MAG) IgM monoclonal gammopathy (MG) in an attempt to delineate their clinical, immunological, electrophysiological and pathological characteristics; we also reviewed our experience concerning long-term follow-up and therapy. Peripheral neuropathy associated with non-malignant anti-MAG IgM MG was observed mostly in males (sex ratio 7.2), and mean age at onset was 67 years (range 46–81). A predominantly sensory pattern was noted in more than 80% of cases, although some patients were affected by a predominantly motor peripheral neuropathy. Although disease progression was slow in most cases, 45% of patients suffered severe disability, and in 2 cases, the patient's death appeared to stem directly from the neuropathy. The electrophysiological findings were indicative of a demyelinating process in 90% of cases, and electron microscopic examination of nerve biopsy specimens demonstrated widening of the myelin lamellae in more than 95% of cases. Most of our patients showed a disappointing response to steroids and chemotherapy or plasma exchanges. Intravenous immune globulin, evaluated in 17 patients, had a transient, mostly subjective effect in 35% and led to a clear-cut improvement in 24% of cases. We did not observe any correlation between the severity of the clinical picture and the anti-sulphoglucuronyl paragloboside antibody titre; in individual cases, clinical improvement occurred without lowering of IgM levels. Although the severity and the rate of progression may greatly vary from patient to patient, the combination of clinical, electrophysiological and pathological features delineates a characteristic pattern in peripheral neuropathy associated with non-malignant anti-MAG IgM MG.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Antoine JC, Steck A, Michel D (1993) Neuropathie périph'erique mortelle à prédominance motrice associée à une IgM monoclonale anti-MAG. Rev Neurol (Paris) 149:496–499

    Google Scholar 

  2. Barbieri S, Nobile-Orazio E, Baldini L, Fayoumi Z, Manfredini E, Scarlato G (1987) Visual evoked potentials in patients with neuropathy and macroglobulinemia. Ann Neurol 22:663–666

    Google Scholar 

  3. Bosch EP, Smith BE (1993) Peripheral neuropathies associated with monoclonal proteins. Med Clin North Am 77:125–139

    Google Scholar 

  4. Bouche P, Bouchacourt E, Léger JM, Travers MA, Cathala HP (1985) les neuropathies périphériques associées aux gammopathies monoclonales. Intérêt des études électrophysiologiques. Rev EEG Neurophysiol 15:255–265

    Google Scholar 

  5. Braun PE, Frail D, Latov N (1982) MAG is the antigen for a monoclonal antibody in patients with a demyelinating neuropathy. J Neurochem 39:1261–1265

    Google Scholar 

  6. Bromberg MB, Albers JW (1993) Patterns of sensory nerve conduction abnormalities in demyelinating and axonal peripheral nerve disorders. Muscle Nerve 16:262–266

    Google Scholar 

  7. Burger D, Perruisseau G, Steck AJ (1991) Anti-myelin associated glycoprotein antibodies in patients with a monoclonal IgM gammopathy and polyneuropathy and a simplified method for the preparation of glycolipid antigens. J Immunol Methods 140:31–36

    Google Scholar 

  8. Cook D, Dalakas M, Galdi A, Biondi D, Porter H (1990) High-dose intravenous immunoglobulin in the treatment of demyelinating neuropathy associated with monoclonal gammopathy. Neurology 40:212–214

    Google Scholar 

  9. Dubas F, Pouplard-Barthelaix A, Delestre F, Emile J (1987) Polyneuropathies avec gammapathie monoclonale IgM. 12 cas. Rev Neurol (Paris) 143:670–683

    Google Scholar 

  10. Dyck PJ, Low PA, Windebank AJ, Jaradeh SS, Gosselin S, Bourque P, Smith BE, Kratz KM, Karnes JL, Evans BA, Pineda AA, O'Brien PC, Kyle RA (1991) Plasma exchange in polyneuropathy associated with monoclonal gammapathy of undetermined significance. N Engl J Med 325:1482–1486

    Google Scholar 

  11. Ellie E, Vital A, Steck AJ, Julien J, Henry P, Vital C (1995) High-grade B-cell cerebral lymphoma in a patient with anti-myelin-associated glycoprotein IgM paraproteinemic neuropathy. Neurology 45: 378–381

    Google Scholar 

  12. Ernerudh JH, Vrethem M, Andresen O, Lindberg C, Berlin G (1992) Immunochemical and clinical effects of immunosuppressive treatment in monoclonal IgM neuropathy. J Neurol Neurosurg Psychiatry 55:930–934

    Google Scholar 

  13. Gosselin S, Kyle RA, Dyck PJ (1991) Neuropathy associated with monoclonal gammopathies of undetermined significance. Ann Neurol 30:54–61

    Google Scholar 

  14. Gosselin S, Kyle RA, Dyck PJ (1992) Monoclonal gammopathy and neuropathy. Ann Neurol 31:690–691

    Google Scholar 

  15. Haas DC, Tatum AH (1988) Plasmapheresis alleviates neuropathy accompanying IgM anti-myelin-associated glycoprotein paraproteinemia. Ann Neurol 23:394–396

    Google Scholar 

  16. Hays AP, Latov N, Takatsu M, Sherman WH (1987) Experimental demyelination of nerve induced by serum of patients with neuropathy and an anti-MAG IgM M-protein. Neurology 37:242–256

    Google Scholar 

  17. Hoang-Xuan K, Léger JM, BenYounes-Chennoufi A, Saidi H, Bouche P, Baumann N, Brunet P (1993) Traitement des neuropathies dysimmunitaires par immunoglobulines polyvalentes intraveineuses. Rev Neurol (Paris) 149: 385–392

    Google Scholar 

  18. Kaku DA, England JD, Sumner AJ (1994) Distal accentuation of conduction slowing in polyneuropathy associated with antibodies to myelin-associated glycoprotein and sulphated glucuronyl paragloboside. Brain 117:941–947

    Google Scholar 

  19. Kelly JJ (1990) The electrodiagnostic findings in polyneuropathies associated with IgM monoclonal gammopathies. Muscle Nerve 13:1113–1117

    Google Scholar 

  20. Kelly JJ, Adelman LS, Berkman E, Bhan I (1988) Polyneuropathies associated with IgM monoclonal gammopathies. Arch Neurol 45:1355–1359

    Google Scholar 

  21. Kimura J (1989) Electrodiagnosis in diseases of nerve and muscle: principles and practice. Davis, Philadelphia.

    Google Scholar 

  22. Latov N (1992) Monoclonal gammopathy and neuropathy. Ann Neurol 31: 690

    Google Scholar 

  23. Latov N, Hays AP, Sherman WH (1988) Peripheral neuropathy and anti-MAG antibodies. Crit Rev Neurobiol 3:301–332

    Google Scholar 

  24. Léger JM, Ben Younes-Chennoufi A, Zuber M, Bouche P, Jauberteau MO, Dormont D, Danon F, Baumann N, Brunet P (1992) Frequency of central lesions in polyneuropathy associated with IgM monoclonal gammopathy: an MRI, neurophysiological and immunochemical study. J Neurol Neurosurg Psychiatry 55:112–115

    Google Scholar 

  25. Léger JM, Oksenhendler E, Ben Younes-Chennoufi A, Bussel A, Chastang C, Danon F, Bouche P, Brouet JC and the French Cooperative Study Group (1992) Chlorambucil with/without plasma exchanges in polyneuropathy associated with monoclonal IgM: a prospective randomized control study in 44 patients. J Neurol 239 [Suppl 2] Sll-S12

    Google Scholar 

  26. Melmed C, Frail D, Duncari I, Braun P, Danoff D, Finlayson M, Stewart J (1983) Peripheral neuropathy with IgM kappa monoclonal immunoglobulin directed against myelin-associated glycoprotein. Neurology 33:1397–1405

    Google Scholar 

  27. Nobile-Orazio E, Marmiroli P, Baldini L, Spagnol G, Barbieri S, Moggio M, Polli N, Polli E, Scarlato G (1987) Peripheral neuropathy in macroglobulinemia: incidence and antigen-specificity of M-proteins. Neurology 37:1506–1514

    Google Scholar 

  28. Nobile-Orazio E, Baldini L, Barbieri S, Marmiroli P, Spagnol G, Francomano E, Scarlato G (1988) Treatment of patients with neuropathy and anti-MAG IgM M-proteins. Ann Neurol 24:93–97

    Google Scholar 

  29. Nobile-Orazio E, Manfredini E, Carpo M, Meucci N, Monaco S, Ferrari S, Bonetti B, Cavaletti G, Gemignani F, Durelli L, Barbieri S, Allaria S, Sgarzi M, Scarlato G (1994) Frequency and clinical correlates of anti-neural IgM antibodies in neuropathy associated with IgM monoclonal gammopathy. Ann Neurol 36:416–424

    Google Scholar 

  30. Norton WT, Poduslo SE (1973) Myelination in rat brain: method of myelin isolation. J Neurochem 21:749–757

    Google Scholar 

  31. Notermans NC, Wokke JHJ, Lokhorst HM, Franssen H, Vandergraaf Y, Jennekens FGI (1994) Polyneuropathy associated with monoclonal gammopathy of undetermined significance. A prospective study of the prognostic value of clinical and laboratory abnormalities. Brain 117:1385–1393

    Google Scholar 

  32. Pestronk A (1992) Monoclonal gammopathy and neuropathy. Ann Neurol 31:689

    Google Scholar 

  33. Prineas J (1970) Polyneuropathies of undetermined cause. Acta Neurol Scand 46 [Suppl 44]:14–15

    Google Scholar 

  34. Smith IS (1994) The natural history of chronic demyelinating neuropathy associated with benign IgM paraproteinemia. A clinical and neurophysiological study. Brain 117:949–957

    Google Scholar 

  35. Smith IS, Kahn SN, Lacey BW, King RHM, Eames RA, Whybrew DJ, Thomas PK (1983) Chronic demyelinating neuropathy associated with benign IgM paraproteinemia. Brain 106: 169–195

    Google Scholar 

  36. Steck AJ, Murray N, Meier C, Page N, Perruisseau G (1983) Demyelinating neuropathy and monoclonal IgM antibody to myelin associated glycoprotein. Neurology 33:19–23

    Google Scholar 

  37. Steck AJ, Murray N, Dellagi K, Brouet JC, Seligmann M (1987) Peripheral neuropathy associated with monoclonal IgM autoantibody. Ann Neurol 22:764–767

    Google Scholar 

  38. Takatsu M, Hays AP, Latov N, Abrams GM, Nemni R, Sherman WH, Nobile-Orazio E, Saito T, Freddo L (1985) Immunofluorescence study of patients with neuropathy and IgM M proteins. Ann Neurol 18:173–181

    Google Scholar 

  39. Tatum AH (1993) Experimental paraprotein neuropathy, demyelination by passive transfer of human IgM antimyelin-associated glycoprotein. Ann Neurol 33:502–506

    Google Scholar 

  40. Vital A, Vital C, Julien J, Baquey A, Steck AJ (1989) Polyneuropathy associated with IgM monoclonal gammopathy. Immunological and pathological study in 31 patients. Acta Neuropathol (Berl) 79:160–167

    Google Scholar 

  41. Vrethem M, Ernerudh J, Cruz M, Olerup O, Solders G, Ekstedt B, Anderson O, Hillert J (1993) Susceptibility to demyelinating polyneuropathy in plasma cell dyscrasia may be influenced by amino acid position 9 of the HLA-DRB chain. J Neuroimmunol 43: 139–144

    Google Scholar 

  42. Willison HJ, Trapp BD, Bacher JD, Dalakas MC, Griffin JW, Quarles RH (1988) Demyelination induced by intraneural injection of human antimyelin-associated glycoprotein antibodies. Muscle Nerve 11: 1169–1176

    Google Scholar 

  43. Yeung KB, Thomas PK, King RHM, Waddy H, Will RG, Hughes RAC, Gregson NA, Leibowitz S (1991) The clinical spectrum of peripheral neuropathies associated with benign monoclonal IgM, IgG and IgA paraproteinemia. Comparative clinical, immunological and nerve biopsy findings. J Neurol 238: 383–391

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ellie, E., Vital, A., Steck, A. et al. 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, 34–43 (1996). https://doi.org/10.1007/BF00878529

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00878529

Key words

Navigation