Abstract
Over the past 40 years Dr. Robert Lisak has made important contributions to our understanding of the
pathophysiology and therapy of myasthenia gravis. This review will touch upon some
of his work as it discusses current therapies and the potential for new treatments
based on the evolving knowledge of the underlying basis of the disease. The recognition
of different immune mechanisms that can cause the phenotype that we acknowledge as
myasthenia gravis coincides with the introduction of monoclonal antibodies and other
new therapies that can target specific aspects of the disease. This has raised our
hopes for treatments that will have less side effects and be more effective. In some
cases these hopes have been realized. In other instances, the situation remains a
“work in progress”. Dr. Lisak's work and teachings remain cogent to our modern approach
to this classic immunologic disease.
Keywords
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References
- LRP4 serves as a coreceptor of agrin.Neuron. 2008; 60: 285-297
- Autoimmune response to acetylcholine receptor.Science. 1973; 180: 871-872
- Ocular myasthenia gravis in an academic neuro-ophthalmology clinic: clinical features and therapeutic response.J Clin Neuromuscul Dis. 2011; 13: 46-52
- Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies.Nat Med. 2001; 7: 365-368
- IgG1 antibodies to acetylcholine receptors in ‘seronegative’ myasthenia gravis.Brain. 2008; 131: 1940-1952
- Presence and pathogenic relevance of antibodies to clustered acetylcholine receptor in ocular and generalized myasthenia gravis.Arch Neurol. 2012; 69: 994-1001
- Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis.Brain. 2003; 126: 2304-2311
- Clinical aspects of MuSK antibody positive seronegative MG.Neurology. 2003; 60: 1978-1980
- Autoantibodies to lipoprotein-related protein 4 in patients with double-seronegative myasthenia gravis.Arch Neurol. 2012; 69: 445-451
- Nonresponsiveness to anticholinesterase agents in patients with MuSK-antibody-positive MG.Neurology. 2005; 65: 1605-1606
- Treatment of ocular symptoms in myasthenia gravis.Neurology. 2008; 71: 1335-1341
- Evidence report: the medical treatment of ocular myasthenia (an evidence-based review); report of the Quality Standards Subcommittee of the American Academy of Neurology.Neurology. 2007; 68: 2144-2149
- Acetylcholinesterase inhibitor treatment for myasthenia gravis.Cochrane Database Syst Rev. 2011; : CD006986
- Cholinergic neuromuscular hyperactivity in patients with myasthenia gravis seropositive for MuSK antibody.Muscle Nerve. 2006; 34: 111-115
- The early history of myasthenia gravis.Neuromuscul Disord. 2005; 15: 878-886
- The history of myasthenia gravis.Neurol Clin. 1994; 12: 231-242
- Fewer thymic changes in MuSK antibody-positive than in MuSK antibody-negative MG.Ann Neurol. 2005; 57: 444-448
- The thymus in myasthenia gravis: site of “innate autoimmunity”?.Muscle Nerve. 2011; 44: 467-484
- Greatly increased autoantibody production in myasthenia gravis by thymocyte suspensions prepared with proteolytic enzymes.Clin Exp Immunol. 1983; 54: 378-386
- Antibodies to acetylcholine receptor and tetanus toxoid: in vitro synthesis by thymic lymphocytes.J Immunol. 1986; 137: 1221-1225
- 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
- Guidelines for treating autoimmune neuromuscular transmission disorders.Eur J Neurol. 2010; 17: 893-902
- Remission of myasthenia gravis following plasma exchange.Lancet. 1976; 2: 1373-1376
- Plasmapheresis and immunosuppressive drug therapy in myasthenia gravis.N Engl J Med. 1977; 297: 1134-1140
- Symposium on therapeutic controversies. Myasthenia gravis. Plasmapheresis in the treatment of myasthenia gravis.Trans Am Neurol Assoc. 1978; 103: 292-302
- Safety of plasma exchange therapy in patients with myasthenia gravis.Muscle Nerve. Apr 2013; 47: 510-514
- Comparison of IVIg and PLEX in patients with myasthenia gravis.Neurology. 2011; 76: 2017-2023
- Intravenous immunoglobulin for myasthenia gravis.Cochrane Database Syst Rev. 2012; : CD002277https://doi.org/10.1002/14651858.CD002277
- Immunosuppressive agents for myasthenia gravis.Cochrane Database Syst Rev. 2007; : CD005224
- Azathioprine in the treatment of myasthenia gravis.Ann Neurol. 1984; 15: 602-605
- A randomized double-blind trial of prednisolone alone or with azathioprine in myasthenia gravis. Myasthenia Gravis Study Group.Neurology. 1998; 50: 1778-1783
- A randomized clinical trial comparing prednisolone and azathioprine in myasthenia gravis. Results of a second interim analysis.J Neurol Neurosurg Psychiatry. 1993; 56: 1157-1163
- Successful treatment of myasthenia gravis with tacrolimus.Muscle Nerve. 2002; 25: 111-114
- Clinical study of FK506 in patients with myasthenia gravis.Muscle Nerve. 2003; 28: 570-574
- An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis.Neurology. 2008; 71: 400-406
- Use of intravenous pulsed cyclophosphamide in severe, generalized myasthenia gravis.Muscle Nerve. 2002; 26: 31-36
- Treatment of refractory myasthenia: “rebooting” with high-dose cyclophosphamide.Ann Neurol. 2003; 53: 29-34
- Rebooting the immune system in myasthenia gravis: taking risks for a cure?.Editorial Ann. Neurol. 2003; 53: 7-9
- Biologics and other novel approaches as new therapeutic options in myasthenia gravis: a view to the future.Ann N Y Acad Sci. 2012; 1274: 1-8
- Induction of myasthenia gravis by immunization against muscle-specific kinase.J Clin Invest. 2006; 116: 1016-1024
- Response of patients with refractory myasthenia gravis to rituximab: a retrospective study.Ther Adv Neurol Disord. 2010; 4: 259-266
- Long-lasting treatment effect of rituximab in MuSK myasthenia.Neurology. 2012; 78: 189-193
- A potential role of B-cell activating factor in the pathogenesis of autoimmune MG.Arch Neurol. 2008; 65: 1358-1362
- The role of B cell-activating factor in autoimmune myasthenia gravis.Ann N Y Acad Sci. 2012; 1274: 60-67
- Suppressor T cells in myasthenia gravis and antibodies to acetylcholine receptor.Ann Neurol. 1986; 19: 87-89
- A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis.Muscle Nerve. March 20 2013; ([Epub ahead of print])https://doi.org/10.1002/mus.23839
- The thymus in myasthenia gravis. Evidence for altered cell population.N Engl J Med. 1974; 291: 1271-1275
- Thymic and peripheral blood T- and B-cell levels in myasthenia gravis.Neurology. 1978; 28: 1298-1301
- Regulatory T cells induced by GM-CSF suppress ongoing experimental myasthenia gravis.Clin Immunol. 2008; 128: 172-180
- Strategies for treating autoimmunity: novel insights from experimental myasthenia gravis.Ann N Y Acad Sci. 2008; 1132: 276-282
- Granulocyte macrophage colony-stimulating factor treatment of a patient in myasthenic crisis: effects on regulatory T cells.Muscle Nerve. 2012; 46: 449-453
Article info
Publication history
Published online: August 12, 2013
Accepted:
June 18,
2013
Received in revised form:
June 16,
2013
Received:
April 8,
2013
Identification
Copyright
© 2013 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
