, Volume 5, Issue 4, pp 535–541 | Cite as

Current and future standards in treatment of myasthenia gravis

Review Article


Myasthenia gravis (MG) is a prototypic antibody-mediated neurological autoimmune disorder. Herein we characterize modern treatment algorithms that are adapted to disease severity, and introduce the current principles of escalating strategies for MG treatment. In non-thymoma patients younger than about 50 years of age and with generalized weakness, a complete early (but not urgent) thymectomy is considered as state-of-the-art on the basis of circumstantial evidence and expert opinion. In up to 10% of patients, MG is associated with a thymoma (i.e., is of paraneoplastic origin). The best surgical type of procedure is still under debate.

Myasthenic crisis is best treated by plasmapheresis, mostly combined with immunoabsorption techniques. Intravenous immunoglobulins are a reasonable alternative, but a shortage in supplies and high prices limit their use. In generalized MG, a wide array of immunosuppressive treatments has been established, although not formally tested in double-blind, prospective trials. With regard to immunosuppression, azathioprine is still the standard baseline treatment, often combined with initial corticosteroids. In rare patients with an inborn hepatic enzyme deficiency of thiomethylation, azathioprine may be substituted by mycophenolate mofetil. Severe cases may benefit from combined immunosuppression with corticosteroids, cyclosporine A, and even with moderate doses of methotrexate or cyclophosphamide. Tacrolimus is under investigation.

In refractory cases, immunoablation via high-dose cyclophosphamide followed by trophic factors such as granulocyte colony-stimulating factor has also been suggested. In the future we may face an increased use of novel, B-cell, or T-cell-directed monoclonal antibodies.

Key Words

Immunosuppression immunoglobulins plasmapheresis immunoadsorption acetylcholine receptor muscle specific kinase thymoma 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Drachman DB. Myasthenia gravis. N Engl J Med 1994;330: 1797–1810.PubMedCrossRefGoogle Scholar
  2. 2.
    Hohlfeld R, Wekerle H. The immunopathogenesis of myasthenia gravis. In: Engel AG, editor. Myasthenia gravis and myasthenic syndromes. Oxford: Oxford University Press;1999. pp. 87–110.Google Scholar
  3. 3.
    Vincent A, Bowen J, Newsom-Davis J, McConville J. Seronegative generalised myasthenia gravis: clinical features, antibodies and their targets. Lancet Neurol 2003;2: 99–106.PubMedCrossRefGoogle Scholar
  4. 4.
    Hohlfeld R, Melms A, Schneider C, Toyka KV, Drachman DB. Therapy of myasthenia gravis and myasthenic syndromes In: Brandt T, Caplan LR, Dichgans J, Diener HC, Kennard C, editors. Neurological disorders: course and treatment. Philadelphia: Elsevier; 2003. pp. 1341–1362.CrossRefGoogle Scholar
  5. 5.
    Wekerle H, Ketelsen UP. Intrathymic pathogenesis and dual genetic control of myasthenia gravis. Lancet 1977;1: 678–680.PubMedCrossRefGoogle Scholar
  6. 6.
    Kirchner T, Schalke B, Melms A, von Kugelgen T, Muller-Hermelink HK. Immunohistological patterns of non-neoplastic changes in the thymus in Myasthenia gravis. Virchows Arch B Cell Pathol Incl Mol Pathol 1986;52: 237–257.PubMedCrossRefGoogle Scholar
  7. 7.
    Farrugia ME, Robson MD, Clover L, et al. MRI and clinical studies of facial and bulbar muscle involvement in MuSK antibody-associated myasthenia gravis. Brain 2006;129: 1481–1492.PubMedCrossRefGoogle Scholar
  8. 8.
    Leite MI, Strobel P, Jones M, et al. Fewer thymic changes in MuSK antibody-positive than in MuSK antibody-negative MG. Ann Neurol 2005;57: 444–448.PubMedCrossRefGoogle Scholar
  9. 9.
    Strobel P, Bauer A, Puppe B, et al. Tumor recurrence and survival in patients treated for thymomas and thymic squamous cell carcinomas: a retrospective analysis. J Clin Oncol 2004;22: 1501–1509.PubMedCrossRefGoogle Scholar
  10. 10.
    Schneider-Gold C, Toyka KV. Myasthenia gravis: pathogenesis and immunotherapy (English). Dtsch Ä rzteblatt 2007;104: A420-A426.Google Scholar
  11. 11.
    Gold R, Dalakas MC, Toyka KV. Immunotherapy in autoimmune neuromuscular disorders. Lancet Neurol 2003;2: 22–32.PubMedCrossRefGoogle Scholar
  12. 12.
    Muller-Hermelink HK, Marx A. Thymoma. Curr Opin Oncol 2000;12: 426–433.PubMedCrossRefGoogle Scholar
  13. 13.
    Schneider-Gold C, Gajdos P, Toyka KV, Hohlfeld RR. Corticosteroids for myasthenia gravis. Cochrane Database Syst Rev 2005;CD002828.Google Scholar
  14. 14.
    Gronseth GS, Barohn RJ. Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence-based review)-Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000;55: 7–15.PubMedCrossRefGoogle Scholar
  15. 15.
    Mertens HG, Hertel G, Reuther P, Ricker K. Effect of immunosuppressive drugs (azathioprine). Ann N Y Acad Sci 1981;377: 691–699.PubMedCrossRefGoogle Scholar
  16. 16.
    Palace J, Newsom-Davis J, Lecky B; Myasthenia Gravis Study Group. A randomized double-blind trial of prednisolone alone or with azathioprine in myasthenia gravis. Neurology 1998;50: 1778–1783.PubMedCrossRefGoogle Scholar
  17. 17.
    Gold R, Toyka KV. Immuntherapie neurologischer Erkrankungen. UniMed Verlag; Bremen: 2006.Google Scholar
  18. 18.
    Hohlfeld R, Toyka KV, Besinger UA, Gerhold B, Heininger K. Myasthenia gravis: reactivation of clinical disease and of autoimmune factors after discontinuation of long-term azathioprine. Ann Neurol 1985;17: 238–242.PubMedCrossRefGoogle Scholar
  19. 19.
    Schneider-Gold C, Hartung HP, Gold R. Mycophenolate mofetil and tacrolimus: new therapeutic options in neuroimmunological diseases. Muscle & Nerve 2006;34: 284–291.CrossRefGoogle Scholar
  20. 20.
    Benatar M, Rowland LP. The muddle of mycophenolate mofetil in myasthenia. Neurology 2008;71: 390–391.PubMedCrossRefGoogle Scholar
  21. 21.
    Schneider C, Gold R, Reiners K, Toyka KV. Mycophenolate mofetil in the therapy of severe myasthenia gravis. Eur Neurol 2001;46: 79–82.PubMedCrossRefGoogle Scholar
  22. 22.
    Sanders DB, Hart IK, Mantegazza R, et al. An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis. Neurology 2008;71: 400–406.PubMedCrossRefGoogle Scholar
  23. 23.
    Gold R, Stangel M, Dalakas MC. Drug insight: the use of intravenous immunoglobulin in neurology-therapeutic considerations and practical issues. Nat Clin Pract Neurol 2007;3: 36–44.PubMedCrossRefGoogle Scholar
  24. 24.
    Gajdos P, Chevret S, Clair B, Tranchant C, Chastang C. Clinical trial of plasma exchange and high-dose intravenous immunoglobulin in myasthenia gravis. Ann Neurol 1997;41: 789–796.PubMedCrossRefGoogle Scholar
  25. 25.
    Gajdos P, Tranchant C, Clair B, et al. Treatment of myasthenia gravis exacerbation with intravenous immunoglobulin-a randomized double-blind clinical trial. Arch Neurol 2005;62: 1689–1693.PubMedCrossRefGoogle Scholar
  26. 26.
    Zinman L, Ng E, Bril V. IV immunoglobulin in patients with myasthenia gravis-a randomized controlled trial. Neurology 2007;68: 837–841.PubMedCrossRefGoogle Scholar
  27. 27.
    Lehmann HC, Hartung HP, Hetzel GR, Stuve O, Kieseier BC. Plasma exchange in neuroimmunological disorders: part 2. Treatment of neuromuscular disorders. Arch Neurol 2006;63: 1066–1071.PubMedCrossRefGoogle Scholar
  28. 28.
    Bufler J, Kahlert S, Tzartos S, Toyka KV, Maelicke A, Franke C. Activation and blockade of mouse muscle nicotinic channels by antibodies directed against the binding site of the acetylcholine receptor. J Physiol (Lond) 1996;492: 107–114.CrossRefGoogle Scholar
  29. 29.
    Heininger K, Hartung H-P, Toyka KV, Gaczkowski A, Borberg H. Therapeutic plasma exchange in myasthenia gravis: semiselective adsorption of Anti-AChR autoantibodies with tryptophane-linked polyvinylalcohol gels. Ann N Y Acad Sci 1987;505: 898–900.CrossRefGoogle Scholar
  30. 30.
    Flachenecker P, Taleghani BM, Gold R, Grossmann R, Wiebecke D, Toyka KV. Treatment of severe myasthenia gravis with protein A immunoadsorption and cyclophosphamide. Transfus Sci 1998;19(Suppl): 43–46.PubMedCrossRefGoogle Scholar
  31. 31.
    Hauser SL, Waubant E, Arnold DL, et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 2008;358: 676–688.PubMedCrossRefGoogle Scholar
  32. 32.
    Martin F, Chan AC. B cell immunobiology in disease: evolving concepts from the clinic. Annu Rev Immunol 2006;24: 467–496.PubMedCrossRefGoogle Scholar
  33. 33.
    Chan A, Lee DH, Linker R, Mohr A, Toyka KV, Gold R. Rescue therapy with anti-CD20 treatment in neuroimmunologic break-through disease. J Neurol 2007;254: 1604–1606.PubMedCrossRefGoogle Scholar
  34. 34.
    Thakre M, Inshasi J, Marashi M. Rituximab in refractory MuSK antibody myasthenia gravis. J Neurol 2007;254: 968–969.PubMedCrossRefGoogle Scholar
  35. 35.
    Hain B, Jordan K, Deschauer M, Zierz S. Successful treatment of musk antibody-positive myasthenia gravis with rituximab. Muscle & Nerve 2006;33: 575–580.CrossRefGoogle Scholar

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2008

Authors and Affiliations

  1. 1.Department of Neurology, St. Josef HospitalRuhr University BochumBochumGermany

Personalised recommendations