Skip to main content

Advertisement

SpringerLink
Log in

IVIg in myasthenia gravis, Lambert Eaton myasthenic syndrome and inflammatory myopathies: current status

  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Intravenous immunoglobulin (IVIg) is an effective tool for the treatment of diseases with immune pathogenesis. This article reviews the current knowledge of the benefits of treating with IVIg patients with myasthenia gravis (MG), Lambert Eaton myasthenic syndrome (LEMS), dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM).

Myasthenia gravis

Treatment of MG with IVIg was reported to be beneficial in a number of case series and two randomised controlled trials, in which efficacy was measured by clinical improvement using myasthenic muscle score and decrease in anti-acetylcholine receptor antibodies (AchRAb). According to the results, IVIg could be recommended for crisis and severe exacerbation. In many other clinical conditions, such as response to treatment of mild or moderate exacerbation, changes in steroid dosage and before thymectomy, IVIg has also been reported to be helpful, but no controlled trials to confirm its efficacy have been performed.

Lambert-Eaton myasthenic syndrome

A placebo-controlled crossover study reported a significant clinical improvement in the amplitude of the resting CMAP following IVIg treatment. Further experience from case reports also indicates that IVIg is useful in patients with LEMS, both as a short- and long-term treatment, especially when immunosuppressive drugs are not fully effective.

Inflammatory myopathies/Dermatomyositis:

In a double-blind placebo-controlled crossover trial in patients with DM resistant to other treatments, IVIg was shown to produce a significant increase of muscle strength as well as a marked improvement in immunopathological parameters in repeated muscle biopsies (before and after IVIg). Thus, IVIg is an important therapy in patients with DM resistant to other conventional therapies.

Polymyositis:

No randomised trials have been undertaken. One study showed clinical improvement and a reduction in the need of prednisone in patients with chronic refractory PM.

Inclusion body myositis:

Three controlled trials showed some muscle strength improvement, although the changes did not reach statistical significance. However improvement in swallowing was repeatedly observed, suggesting that some patients with severe dysphagia may derive a modest benefit from IVIg therapy.

Conclusion

Controlled trials indicate that in MG, LEMS, and DM, IVIg at a total dose of 2 g/kg is a highly useful therapy. Uncontrolled trials and case reports indicate benefit in many different clinical situations, but further clinical investigation is required.

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

Access this article

Log in via an institution

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. Achiron A, Barak Y, Miron S, Sarova-Pinhas I (2000) Immunoglobulin treatment in refractory Myasthenia gravis. Muscle Nerve 23:551–555

    Article  CAS  PubMed  Google Scholar 

  2. Al-Mayouf SM, Laxer RM, Schneider R, Silverman ED, Feldman BM (2000) Intravenous immunoglobulin therapy for juvenile dermatomyositis: efficacy and safety. J Rheumatol 27:2498–2503

    CAS  PubMed  Google Scholar 

  3. Arsura EL, Bick A, Brunner NG, Grob D (1988) Effects of repeated doses of intravenous immunoglobulin in myasthenia gravis. Am J Med Sci 295:438–443

    CAS  PubMed  Google Scholar 

  4. Bain PG, Motomura M, Newsom-Davis J, Misbah SA, Chapel HM, Lee ML, Vincent A, Lang B (1996) Effects of intravenous immunoglobulin on muscle weakness and calcium-channel autoantibodies in the Lambert-Eaton myasthenic syndrome. Neurology 47:678–683

    CAS  PubMed  Google Scholar 

  5. Bird SJ (1992) Clinical and electrophysiologic improvement in Lambert-Eaton syndrome with intravenous immunoglobulin therapy. Neurology 42:1422–1423

    CAS  PubMed  Google Scholar 

  6. Cherin P, Herson S, Wechsler B, Piette JC, Bletry O, Coutellier A, Ziza JM, Godeau P (1991) Efficacy of intravenous gammaglobulin therapy in chronic refractory polymyositis and dermatomyositis: an open study with 20 adult patients. Am J Med 91:162–168

    Article  CAS  PubMed  Google Scholar 

  7. Cherin P, Pelletier S, Teixeira A, Laforet P, Genereau T, Simon A, Maisonobe T, Eymard B, Herson S (2002) Results and long-term follow-up of intravenous immunoglobulin infusions in chronic, refractory polymyositis: an open study with thirty-five adult patients. Arthritis Rheum 46:467–474

    Article  CAS  PubMed  Google Scholar 

  8. Cosi V, Lombardi M, Piccolo G, Erbetta A (1991) Treatment of myasthenia gravis with high-dose intravenous immunoglobulin. Acta Neurol Scand 84:81–84

    CAS  PubMed  Google Scholar 

  9. Dalakas MC (1991) Polymyositis, dermatomyositis and inclusion-body myositis. N Engl J Med 325:1487–1498

    CAS  Google Scholar 

  10. Dalakas MC (1998) Controlled studies with high-dose intravenous immunoglobulin in the treatment of dermatomyositis, inclusion body myositis, and polymyositis. Neurology 51:S37–S45

    CAS  PubMed  Google Scholar 

  11. Dalakas MC (1999) Intravenous immunoglobulin in the treatment of autoimmune neuromuscular diseases: present status and practical therapeutic guidelines. Muscle Nerve 22:1479–1497

    Article  CAS  PubMed  Google Scholar 

  12. Dalakas MC (2003) Therapeutic approaches in patients with inflammatory myopathies. Semin Neurol 23:199–206

    Article  PubMed  Google Scholar 

  13. Dalakas MC (2004) The molecular pathophysiology in inflammatory myopathies. Rev Med Interne 25(Suppl 1):S14–S16

    PubMed  Google Scholar 

  14. Dalakas MC, Hohlfeld R (2003) Polymyositis and dermatomyositis. Lancet 362:971–982

    CAS  PubMed  Google Scholar 

  15. Dalakas MC, Illa I, Dambrosia JM, Soueidan SA, Stein DP, Otero C, Dinsmore ST, McCrosky S (1993) A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis. N Engl J Med 329:1993–2000

    Article  CAS  PubMed  Google Scholar 

  16. Dalakas MC, Koffman B, Fujii M, Spector S, Sivakumar K, Cupler E (2001) A controlled study of intravenous immunoglobulin combined with prednisone in the treatment of IBM. Neurology 56:323–327

    CAS  PubMed  Google Scholar 

  17. Dalakas MC, Sonies B, Dambrosia J, Sekul E, Cupler E, Sivakumar K (1997) Treatment of inclusion-body myositis with IVIg: a double-blind, placebo-controlled study. Neurology 48:712–716

    CAS  PubMed  Google Scholar 

  18. Danieli MG, Malcangi G, Palmieri C, Logullo F, Salvi A, Piani M, Danieli G (2002) Cyclosporin A and intravenous immunoglobulin treatment in polymyositis/dermatomyositis. Ann Rheum Dis 61:37–41

    Article  CAS  PubMed  Google Scholar 

  19. Drachman DB (1994) Myasthenia gravis. N Engl J Med 330:1797–1810

    Article  CAS  PubMed  Google Scholar 

  20. Drachman DB, Jones RJ, Brodsky RA (2003) Treatment of refractory myasthenia: “rebooting” with high-dose cyclophosphamide. Ann Neurol 53:29–34

    Article  CAS  PubMed  Google Scholar 

  21. Fateh-Moghadam A, Wick M, Besinger U, Geursen RG (1984) High-dose intravenous gammaglobulin for myasthenia gravis. Lancet 1:848–849

    Article  CAS  Google Scholar 

  22. Gajdos P, Chevret S, Clair B, Tranchant C, Chastang C (1997) Clinical trial of plasma exchange and high-dose intravenous immunoglobulin in myasthenia gravis. Myasthenia Gravis Clinical Study Group. Ann Neurol 41:789–796

    Article  CAS  PubMed  Google Scholar 

  23. Gajdos P, Chevret S, Toyka K (2003) Intravenous immunoglobulin for myasthenia gravis. Cochrane Database Syst Rev:CD002277

    Google Scholar 

  24. Gronseth GS, Barohn RJ (2000) Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 55:7–15

    CAS  PubMed  Google Scholar 

  25. Hoch W, McConville J, Helms S, Newsom-Davis J, Melms A, Vincent A (2001) Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med 7:365–368

    Article  CAS  PubMed  Google Scholar 

  26. Hughes BW, Moro De Casillas ML, Kaminski HJ (2004) Pathophysiology of myasthenia gravis. Semin Neurol 24:21–30

    Article  PubMed  Google Scholar 

  27. Lang B, Newsom-Davis J, Wray D, Vincent A, Murray N (1981) Autoimmune aetiology for myasthenic (Eaton-Lambert) syndrome. Lancet 2:224–226

    Article  CAS  PubMed  Google Scholar 

  28. Mareska M, Gutmann L (2004) Lambert-Eaton myasthenic syndrome. Semin Neurol 24:149–153

    Article  PubMed  Google Scholar 

  29. Mastaglia FL, Phillips BA, Zilko PJ (1998) Immunoglobulin therapy in inflammatory myopathies. J Neurol Neurosurg Psychiatry 65:107–110

    CAS  PubMed  Google Scholar 

  30. McEvoy KM, Windebank AJ, Daube JR, Low PA (1989) 3.4-Diaminopyridine in the treatment of Lambert-Eaton myasthenic syndrome. N Engl J Med 321:1567–1571

    CAS  PubMed  Google Scholar 

  31. Meriggioli MN, Ciafaloni E, Al-Hayk KA, Rowin J, Tucker-Lipscomb B, Massey JM, Sanders DB (2003) Mycophenolate mofetil for myasthenia gravis: an analysis of efficacy, safety, and tolerability. Neurology 61:1438–1440

    CAS  PubMed  Google Scholar 

  32. Muchnik S, Losavio AS, Vidal A, Cura L, Mazia C (1997) Long-term follow-up of Lambert-Eaton syndrome treated with intravenous immunoglobulin. Muscle Nerve 20:674–678

    Article  CAS  PubMed  Google Scholar 

  33. Newsom-Davis J (2004) Lambert-Eaton myasthenic syndrome. Rev Neurol (Paris) 160:177–180

    CAS  PubMed  Google Scholar 

  34. Palace J, Newsom-Davis J, Lecky B (1998) A randomized double-blind trial of prednisolone alone or with azathioprine in myasthenia gravis. Myasthenia Gravis Study Group. Neurology 50:1778–1783

    CAS  PubMed  Google Scholar 

  35. Perez Nellar J, Dominguez AM, Llorens-Figueroa JA, Ferra-Betancourt A, Pardo A, Quiala M, Gali Z (2001) A comparative study of intravenous immunoglobulin and plasmapheresis preoperatively in myasthenia. Rev Neurol 33:413–416

    CAS  PubMed  Google Scholar 

  36. Qureshi AI, Choudhry MA, Akbar MS, Mohammad Y, Chua HC, Yahia AM, Ulatowski JA, Krendel DA, Leshner RT (1999) Plasma exchange versus intravenous immunoglobulin treatment in myasthenic crisis. Neurology 52:629–632

    CAS  PubMed  Google Scholar 

  37. Richman DP, Agius MA (2003) Treatment of autoimmune myasthenia gravis. Neurology 61:1652–1661

    CAS  PubMed  Google Scholar 

  38. Ronager J, Ravnborg M, Hermansen I, Vorstrup S (2001) Immunoglobulin treatment versus plasma exchange in patients with chronic moderate to severe myasthenia gravis. Artif Organs 25:967–973

    Article  CAS  PubMed  Google Scholar 

  39. Sanders DB, Massey JM, Sanders LL, Edwards LJ (2000) A randomized trial of 3,4-diaminopyridine in Lambert-Eaton myasthenic syndrome. Neurology 54:603–607

    CAS  PubMed  Google Scholar 

  40. Takano H, Tanaka M, Koike R, Nagai H, Arakawa M, Tsuji S (1994) Effect of intravenous immunoglobulin in Lambert-Eaton myasthenic syndrome with small-cell lung cancer: correlation with the titer of anti-voltage-gated calcium channel antibody. Muscle Nerve 17:1073–1075

    Article  CAS  PubMed  Google Scholar 

  41. Vincent A, Bowen J, Newsom-Davis J, McConville J (2003) Seronegative generalised myasthenia gravis: clinical features, antibodies, and their targets. Lancet Neurol 2:99–106

    Article  PubMed  Google Scholar 

  42. Vincent A, McConville J, Farrugia ME, Bowen J, Plested P, Tang T, Evoli A, Matthews I, Sims G, Dalton P, Jacobson L, Polizzi A, Blaes F, Lang B, Beeson D, Willcox N, Newsom-Davis J, Hoch W (2003) Antibodies in myasthenia gravis and related disorders. Ann N Y Acad Sci 998:324–335

    Article  CAS  PubMed  Google Scholar 

  43. Walter MC, Lochmuller H, Toepfer M, Schlotter B, Reilich P, Schroder M, Muller-Felber W, Pongratz D (2000) High-dose immunoglobulin therapy in sporadic inclusion body myositis: a double-blind, placebo-controlled study. J Neurol 247:22–28

    Article  CAS  PubMed  Google Scholar 

  44. Wolfe GI, Barohn RJ, Foster BM, Jackson CE, Kissel JT, Day JW, Thornton CA, Nations SP, Bryan WW, Amato AA, Freimer ML, Parry GJ (2002) Randomized, controlled trial of intravenous immunoglobulin in myasthenia gravis. Muscle Nerve 26:549–552

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Chief Neuromuscular Diseases Unit, Servei Neurologia, Hospital Sta Creu i Sant Pau, Universitat Autonoma de Barcelona, Avda Pare Claret #167, 08025, Barcelona, Spain

    Isabel Illa

Authors
  1. Isabel Illa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Isabel Illa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Illa, I. IVIg in myasthenia gravis, Lambert Eaton myasthenic syndrome and inflammatory myopathies: current status. J Neurol 252 (Suppl 1), i14–i18 (2005). https://doi.org/10.1007/s00415-005-1104-5

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-005-1104-5

Key words

Search

Navigation