Abstract
Myasthenia gravis is an autoimmune disorder characterized by the presence of autoantibodies against the acetylcholine receptor present in the post-synaptic membrane of the neuromuscular junction impairing the muscle contraction and causing the patient suffering from the disorder to develop a myriad of muscular defects ranging from drooping of eyelids, blurred or double vision, shortness of breath, difficulty in swallowing, as well as weakness of limbs and arms. Myasthenia gravis is known as the disease of old men and young women but in contrast to the global scenario, in India, myasthenia gravis was found to be predominant in males with the ratio of 2.70:1. Though the disorder has been studied for centuries, the true reason for disease and its pathophysiology still eludes us. But recent advancement in molecular biology and diagnostic tools has enabled us to identify many targets for pharmacotherapy as well as for early diagnosis. Thus, improving the patient’s morbidity and quality of life. In this article, we are discussing the recent advancements made in diagnosis and therapy of the disease.
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References
Arsura E (1989) Experience with intravenous immunoglobulin in myasthenia gravis. Clin Immunol Immunopathol 53:S170–S179. https://doi.org/10.1016/0090-1229(89)90083-4
Bashuk RG, Krendel DA (1990) Myasthenia gravis presenting as weakness after magnesium administration. Muscle Nerve 13:708–712. https://doi.org/10.1002/mus.880130808
Berrih-Aknin S, Frenkian-Cuvelier M, Eymard B (2014) Diagnostic and clinical classification of autoimmune myasthenia gravis. J Autoimmun 48–49:143–148. https://doi.org/10.1016/j.jaut.2014.01.003
Bever CT, Chang HW, Penn AS, Jaffe IA, Bock E (1982) Penicillamine-induced myasthenia gravis: Effects of penicillamine on acetylcholine receptor. Neurology 32:1077–1077. https://doi.org/10.1212/WNL.32.10.1077
Budde JM, Morris CD, Gal AA, Mansour KA, Miller JI (2001) Predictors of outcome in thymectomy for myasthenia gravis. Ann Thorac Surg 72:197–202. https://doi.org/10.1016/S0003-4975(01)02678-9
Cadisch R, Streit E, Hartmann K (1996) Exacerbation of pseudoparalytic myasthenia gravis following azithromycin (Zithromax). Schweiz Med Wochenschr 126:308–310
Chiu H, Chen W, Yeh J (2000) The six year experience of plasmapheresis in patients with myasthenia gravis. Ther Apher 4:291–295. https://doi.org/10.1046/j.1526-0968.2000.004004291.x
Ciafaloni E (2005) Mycophenolate mofetil and myasthenia gravis. Lupus 14:46–49. https://doi.org/10.1191/0961203305LU2118OA
Conti-Fine BM, Milani M, Kaminski HJ (2006) Myasthenia gravis: past, present, and future. J Clin Investig 116:2843–2854. https://doi.org/10.1172/JCI29894
Datta S, Singh S, Govindarajan R (2020) Retrospective analysis of eculizumab in patients with acetylcholine receptor antibody-negative myasthenia gravis: a case series. J Neuro Dis 7(3):269–277. https://doi.org/10.3233/JND-190464
Engel AG (1961) Thyroid function and myasthenia gravis. Arch Neurol 4:663–674. https://doi.org/10.1001/archneur.1961.00450120077009
Etherington SJ, Everett AW (2004) Postsynaptic production of nitric oxide implicated in long-term depression at the mature amphibian (Bufo marinus) neuromuscular junction: NO-mediated synaptic depression. J Physiol 559:507–517. https://doi.org/10.1113/jphysiol.2004.066498
Evoli A, Batocchi AP, Palmisani MT, Lo Monaco M, Tonali P (1992) Long-term results of corticosteroid therapy in patients with myasthenia gravis. Eur Neurol 32:37–43. https://doi.org/10.1159/000116785
Farmakidis C et al (2018) Treatment of myasthenia gravis. Neuro Clin 36(2):311–337. https://doi.org/10.1016/j.ncl.2018.01.011
Gilhus NE (2016) Myasthenia gravis. N Engl J Med 375:2570–2581. https://doi.org/10.1056/NEJMra1602678
Gilhus NE, Verschuuren JJ (2015) Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol 14:1023–1036. https://doi.org/10.1016/S1474-4422(15)00145-3
Gold R, Schneider-Gold C (2008) Current and future standards in treatment of myasthenia gravis. Neurotherapeutics 5:535–541. https://doi.org/10.1016/j.nurt.2008.08.011
Heatwole C (2008) Mycophenolate mofetil for myasthenia gravis: a clear and present controversy. NDT. https://doi.org/10.2147/NDT.S3309
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. https://doi.org/10.1038/85520
Hughes B, De Casillas M, Kaminski H (2004) Pathophysiology of myasthenia gravis. Semin Neurol 24:21–30. https://doi.org/10.1055/s-2004-829585
Hughes BW, Kusner LL, Kaminski HJ (2006) Molecular architecture of the neuromuscular junction. Muscle Nerve 33:445–461. https://doi.org/10.1002/mus.20440
Hussain N, Hussain F, Haque D, Chittivelu S (2018) A diagnosis of late-onset myasthenia gravis unmasked by topical antibiotics. J Community Hosp Intern Med Perspect 8:230–232. https://doi.org/10.1080/20009666.2018.1487245
Johnston JD (2005) Special section on myasthenia: the contributions of Dr. Mary Walker towards myasthenia gravis and periodic paralysis whilst working in Poor Law Hospitals in London. J Hist Neurosci 14:121–137. https://doi.org/10.1080/096470490512580
Kornfeld P, Horowitz SH, Genkins G, Papatestas AE (1976) Myasthenia gravis unmasked by antiarrhythmic agents. Mt Sinai J Med 43:10–14
Lindstrom JM, Seybold ME, Lennon VA, Whittingham S, Duane DD (1976) Antibody to acetylcholine receptor in myasthenia gravis: prevalence, clinical correlates, and diagnostic value. Neurology 26:1054–1054. https://doi.org/10.1212/WNL.26.11.1054
Link H, Sun J-B, Lu C-Z, Xiao B-G, Fredrikson S, Höjeberg B, Olson T (1992) Myasthenia gravis: T and B cell reactivities to the β-bungarotoxin binding protein presynaptic membrane receptor. J Neurol Sci 109:173–181. https://doi.org/10.1016/0022-510X(92)90165-H
Lisak RP, Richman DP (2020) Thymectomy and myasthenia gravis. Proc Natl Acad Sci USA 117:32195–32196. https://doi.org/10.1073/pnas.2022901117
Mehndiratta MM, Pandey S, Kuntzer T (2014) Acetylcholinesterase inhibitor treatment for myasthenia gravis. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD006986.pub3
Mehta A, Morris S (1995) Myasthenia gravis and sensitivity to muscle relaxants. Anaesthesia 50:574. https://doi.org/10.1111/j.1365-2044.1995.tb06080.x
Menon D, Barnett C, Bril V (2020) Novel treatments in myasthenia gravis. Front Neurol 11:538. https://doi.org/10.3389/fneur.2020.00538
Meriggioli MN, Sanders DB (2005) Advances in the diagnosis of neuromuscular junction disorders. Am J Phys Med Rehabil 84:627–638. https://doi.org/10.1097/01.phm.0000171169.79816.4c
Nacu A, Andersen JB, Lisnic V, Owe JF, Gilhus NE (2015) Complicating autoimmune diseases in myasthenia gravis: a review. Autoimmunity 48:362–368. https://doi.org/10.3109/08916934.2015.1030614
Oh SJ et al (1992) Diagnostic sensitivity of the laboratory tests in myasthenia gravis. Muscle Nerve 15(6):720–724. https://doi.org/10.1002/mus.880150616
Oosterhuis HJGH et al (1983) Anti-acetylcholine receptor antibodies in myasthenia gravis. J Neurol Sci 58(3):371–385. https://doi.org/10.1016/0022-510X(83)90096-5
Palace J, Newsom-Davis J, Lecky B, Myasthenia Gravis Study Group (1998) A randomized double-blind trial of prednisolone alone or with azathioprine in myasthenia gravis. Neurology 50:1778–1783. https://doi.org/10.1212/WNL.50.6.1778
Penn AS, Low BW, Jaffe IA, Luo L, Jacques JJ (1998) Drug-induced autoimmune myasthenia gravis. Ann N Y Acad Sci 841:433–449. https://doi.org/10.1111/j.1749-6632.1998.tb10961.x
Phillips L (2004) The epidemiology of myasthenia gravis. Semin Neurol 24:17–20. https://doi.org/10.1055/s-2004-829593
Ponseti JM, Azem J, Fort JM, Codina A, Montoro JB, Armengol M (2005) Benefits of FK506 (tacrolimus) for residual, cyclosporin- and prednisone-resistant myasthenia gravis: one-year follow-up of an open-label study. Clin Neurol Neurosurg 107:187–190. https://doi.org/10.1016/j.clineuro.2004.07.013
Sanders DB, Howard JF, Johns TR (1979) Single-fiber electromyography in myasthenia gravis. Neurology 29(1):68–68. https://doi.org/10.1212/WNL.29.1.68
Singhal B, Bhatia N, Umesh T, Menon S (2008) Myasthenia gravis: a study from India. Neurol India 56:352. https://doi.org/10.4103/0028-3886.43455
Somnier FE, Trojaborg W (1993) Neurophysiological evaluation in myasthenia gravis. A comprehensive study of a complete patient population. Electroencephalogr Clin Neurophysiol/Evoked Potentials Sect 89(2):73–87. https://doi.org/10.1016/0168-5597(93)90088-7
Tansey EM (2006) Henry Dale and the discovery of acetylcholine. CR Biol 329:419–425. https://doi.org/10.1016/j.crvi.2006.03.012
Téllez-Zenteno JF, Hernández-Ronquillo L, Salinas V, Estanol B, da Silva O (2004) Myasthenia gravis and pregnancy: clinical implications and neonatal outcome. BMC Musculoskelet Disord 5:42. https://doi.org/10.1186/1471-2474-5-42
Thanvi BR (2004) Update on myasthenia gravis. Postgrad Med J 80:690–700. https://doi.org/10.1136/pgmj.2004.018903
Thanvi BR, Lo TCN (2004) Update on myasthenia gravis. Postgrad Med J 80:690. https://doi.org/10.1136/pgmj.2004.018903
Tindall RSA, Rollins JA, Phillips JT, Greenlee RG, Wells L, Belendiuk G (1987) Preliminary results of a double-blind, randomized, placebo-controlled trial of cyclosporine in myasthenia gravis. N Engl J Med 316:719–724. https://doi.org/10.1056/NEJM198703193161205
Tindall RSA, Phillips JT, Rollins JA, Wells L, Hall K (1993) A clinical therapeutic trial of cyclosporine in myasthenia gravis. Ann NY Acad Sci 681:539–551. https://doi.org/10.1111/j.1749-6632.1993.tb22937.x
Ubogu EE, Ruff RL (2009) Neuromuscular junction physiology and pathophysiology. Myasthenia gravis and related disorders. Humana Press, Totowa, pp 1–12
Vincent A (2003) Evidence of underdiagnosis of myasthenia gravis in older people. J Neurol Neurosurg Psychiatry 74:1105–1108. https://doi.org/10.1136/jnnp.74.8.1105
Vincent A, Leite MI (2005) Neuromuscular junction autoimmune disease: muscle specific kinase antibodies and treatments for myasthenia gravis. Curr Opin Neurol 18(5):519–525. https://doi.org/10.1097/01.wco.0000180660.57801.3f
Vincent A, Palace J, Hilton-Jones D (2001) Myasthenia gravis. Lancet 357:2122–2128. https://doi.org/10.1016/S0140-6736(00)05186-2
Whiting PJ, Vincent A, Newsom-Davis J (1983) Acetylcholine receptor antibody characteristics in myasthenia gravis. Fractionation of alpha-bungarotoxin binding site antibodies and their relationship to IgG subclass. J Neuroimmunol 5:1–9. https://doi.org/10.1016/0165-5728(83)90022-x
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We are grateful to Dr. Sabitha M, Principal, Amrita School of Pharmacy, Kerala, India for providing assistance and resources for this work.
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Binu, A., Kumar, S.S., Padma, U.D. et al. Pathophysiological basis in the management of myasthenia gravis: a mini review. Inflammopharmacol 30, 61–71 (2022). https://doi.org/10.1007/s10787-021-00905-9
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DOI: https://doi.org/10.1007/s10787-021-00905-9