J Clin Neurol.  2011 Dec;7(4):173-183. 10.3988/jcn.2011.7.4.173.

Treatment of Myasthenia Gravis Based on Its Immunopathogenesis

• Kim JY
• Park KD
• Richman DP

• KMID: 2179002
• DOI: http://doi.org/10.3988/jcn.2011.7.4.173

Abstract

The prognosis of myasthenia gravis (MG) has improved dramatically due to advances in critical-care medicine and symptomatic treatments. Its immunopathogenesis is fundamentally a T-cell-dependent autoimmune process resulting from loss of tolerance toward self-antigens in the thymus. Thymectomy is based on this immunological background. For MG patients who are inadequately controlled with sufficient symptomatic treatment or fail to achieve remission after thymectomy, remission is usually achieved through the addition of other immunotherapies. These immunotherapies can be classified into two groups: rapid induction and long-term maintenance. Rapid induction therapy includes intravenous immunoglobulin (IVIg) and plasma exchange (PE). These produce improvement within a few days after initiation, and so are useful for acute exacerbation including myasthenic crisis or in the perioperative period. High-dose prednisone has been more universally preferred for remission induction, but it acts more slowly than IVIg and PE, commonly only after a delay of several weeks. Slow tapering of steroids after a high-dose pulse offers a method of maintaining the state of remission. However, because of significant side effects, other immunosuppressants (ISs) are frequently added as "steroid-sparing agents". The currently available ISs exert their immunosuppressive effects by three mechanisms: 1) blocking the synthesis of DNA and RNA, 2) inhibiting T-cell activation and 3) depleting the B-cell population. In addition, newer drugs including antisense molecule, tumor necrosis factor alpha receptor blocker and complement inhibitors are currently under investigation to confirm their effectiveness. Until now, the treatment of MG has been based primarily on experience rather than gold-standard evidence from randomized controlled trials. It is hoped that well-organized studies and newer experimental trials will lead to improved treatments.

Keyword

myasthenia gravis; immunosuppressive agents; immunotherapy

MeSH Terms

Autoantigens
B-Lymphocytes
Complement System Proteins
DNA
Humans
Immunoglobulins
Immunoglobulins, Intravenous
Immunosuppressive Agents
Immunotherapy
Myasthenia Gravis
Perioperative Period
Plasma Exchange
Prednisone
Prognosis
Remission Induction
RNA
Steroids
T-Lymphocytes
Thymectomy
Thymus Gland
Tumor Necrosis Factor-alpha
Autoantigens
Complement System Proteins
DNA
Immunoglobulins
Immunoglobulins, Intravenous
Immunosuppressive Agents
Prednisone
RNA
Steroids
Tumor Necrosis Factor-alpha

Figure

• 

  Fig. 1 The management of MG according to symptoms. MG: myasthenia gravis, ISs: immunosuppressants, AZA: azathioprine, MyM: mycophenolate mofetil, CP: cyclophosphamide, CyA: cyclosporine, IVIg: intravenous immunoglobulin, RTM: rituximab.

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