Myasthenia Gravis

  • Satish V. Khadilkar
  • Rakhil S. Yadav
  • Bhagyadhan A. Patel


Myasthenia gravis is the most common immunological disease of the neuromuscular junction. It affects young females and elderly males and is associated with other immunological diseases. A proportion of patients have thymoma. External ocular muscles, eyelids, muscles of mastication and swallowing are preferentially affected by the disease. Myasthenic crisis forms a medical emergency and urgent intensive therapy is required. The course is fluctuating; remissions and exacerbations are known. The type of antibody has some bearing on the presentation, course and therapy options. Long-term immunosuppression and medical monitoring are required for most patients. Advances in the intensive care and judicious use of available options in immunosuppression have improved the quality of life.


Myasthenia gravis Fluctuating Fatigability Ptosis Ophthalmoparesis Bulbar weakness AchR Decrement on RNS Thymoma Pyridostigmine Immunosuppressive agents 


  1. Andersen JB, Erik Gilhus N, Sanders DB. Factors affecting outcome in myasthenia gravis. Muscle Nerve. 2016;54(6):1041–9.CrossRefPubMedGoogle Scholar
  2. Barnett C, Katzberg H, Nabavi M, Bril V. The quantitative myasthenia gravis score: comparison with clinical, electrophysiological, and laboratory markers. J Clin Neuromuscul Dis. 2012;13(4):201–5.CrossRefPubMedGoogle Scholar
  3. Bedlack RS, Simel DL, Bosworth H, Samsa G, Tucker-Lipscomb B, Sanders DB. Quantitative myasthenia gravis score: assessment of responsiveness and longitudinal validity. Neurology. 2005;64(11):1968–70.CrossRefPubMedGoogle Scholar
  4. Benatar M. A systematic review of diagnostic studies in myasthenia gravis. Neuromuscul Disord. 2006;16:459–67.CrossRefPubMedGoogle Scholar
  5. Binks S, Vincent A, Palace J. Myasthenia gravis: a clinical-immunological update. J Neurol. 2016;263(4):826–34.CrossRefPubMedGoogle Scholar
  6. Bou Ali H, Salort-Campana E, Grapperon AM, Gallard J, Franques J, Sevy A, Delmont E, Verschueren A, Pouget J, Attarian S. New strategy for improving the diagnostic sensitivity of repetitive nerve stimulation in myasthenia gravis. Muscle Nerve. 2017;55(4):532–8.CrossRefPubMedGoogle Scholar
  7. Bouwyn JP, Magnier P, Bédat-Millet AL, Ahtoy P, Maltête D, Lefaucheur R. Anti-MuSK myasthenia gravis with prolonged remission. Neuromuscul Disord. 2016;26(7):453–4.CrossRefPubMedGoogle Scholar
  8. Burns TM, Sanders DB, Kaminski HJ, Wolfe GI, Narayanaswami P, Venitz J. Two steps forward, one step back: mycophenolate mofetil treatment for myasthenia gravis in the United States. Muscle Nerve. 2015;51(5):635–7.CrossRefPubMedGoogle Scholar
  9. Carr AS, Cardwell CR, McCarron PO, et al. A systematic review of population based epidemiological studies in myasthenia gravis. BMC Neurol. 2010;18(10):46.CrossRefGoogle Scholar
  10. Chen P, Feng H, Deng J, Luo Y, Qiu L, Ou C, Liu W. Leflunomide treatment in corticosteroid-dependent myasthenia gravis: an open-label pilot study. J Neurol. 2016;263(1):83–8.CrossRefPubMedGoogle Scholar
  11. Costa J, Evangelista T, Conceição I, de Carvalho M. Repetitive nerve stimulation in myasthenia gravis-relative sensitivity of different muscles. Clin Neurophysiol. 2004;115:2776–82.CrossRefPubMedGoogle Scholar
  12. Cruz JL, Wolff ML, Vanderman AJ, Brown JN. The emerging role of tacrolimus in myasthenia gravis. Ther Adv Neurol Disord. 2015;8(2):92–103.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Dalakas MC. Future perspectives in target-specific immunotherapies of myasthenia gravis. Ther Adv Neurol Disord. 2015;8(6):316–27.CrossRefPubMedPubMedCentralGoogle Scholar
  14. De Feo LG, Schottlender J, Martelli NA, Molfino NA. Use of intravenous pulsed cyclophosphamide in severe, generalized myasthenia gravis. Muscle Nerve. 2002;26(1):31–6.CrossRefPubMedGoogle Scholar
  15. Díaz-Manera J, Rojas García R, Illa I. Treatment strategies for myasthenia gravis: an update. Expert Opin Pharmacother. 2012;13(13):1873–83.CrossRefPubMedGoogle Scholar
  16. Drachman DB. Myasthenia gravis. Semin Neurol. 2016a;36(5):419–24.CrossRefPubMedGoogle Scholar
  17. Drachman DB. Treatment for refractory myasthenia gravis-new lymphs for old. JAMA Neurol. 2016b;73(6):624–6.CrossRefPubMedGoogle Scholar
  18. El-Salem K, Yassin A, Al-Hayk K, Yahya S, Al-Shorafat D, Dahbour SS. Treatment of MuSK-associated myasthenia gravis. Curr Treat Options Neurol. 2014;16(4):283.CrossRefPubMedGoogle Scholar
  19. Farrugia ME, Vincent A. Autoimmune mediated neuromuscular junction defects. Curr Opin Neurol. 2010;23(5):489–95.CrossRefPubMedGoogle Scholar
  20. Fitzgerald MG, Shafritz AB. Distal myasthenia gravis. J Hand Surg Am. 2014;39(7):1419–20.CrossRefPubMedGoogle Scholar
  21. Gajdos P, Chevret S, Toyka K. Plasma exchange for myasthenia gravis. Cochrane Database Syst Rev. 2002;4:CD002275.Google Scholar
  22. Gajdos P, Chevret S, Toyka KV. Intravenous immunoglobulin for myasthenia gravis. Cochrane Database Syst Rev. 2012;12:CD002277.PubMedGoogle Scholar
  23. Gilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol. 2015;14(10):1023–36.CrossRefPubMedGoogle Scholar
  24. Gilhus NE, Skeie GO, Romi F, Lazaridis K, Zisimopoulou P, Tzartos S. Myasthenia gravis - autoantibody characteristics and their implications for therapy. Nat Rev Neurol. 2016;12(5):259–68.CrossRefPubMedGoogle Scholar
  25. Gotterer L, Li Y. Maintenance immunosuppression in myasthenia gravis. J Neurol Sci. 2016;369:294–302.CrossRefPubMedGoogle Scholar
  26. Guptill JT, Sanders DB, Evoli A. Anti-MuSK antibody myasthenia gravis: clinical findings and response to treatment in two large cohorts. Muscle Nerve. 2011;44(1):36–40.CrossRefPubMedGoogle Scholar
  27. Ha JC, Richman DP. Myasthenia gravis and related disorders: pathology and molecular pathogenesis. Biochim Biophys Acta. 2015;1852(4):651–7.CrossRefPubMedGoogle Scholar
  28. Hehir MK, Burns TM, Alpers J, Conaway MR, Sawa M, Sanders DB. Mycophenolate mofetil in AChR-antibody-positive myasthenia gravis: outcomes in 102 patients. Muscle Nerve. 2010;41(5):593–8.CrossRefPubMedGoogle Scholar
  29. Hughes T. The early history of myasthenia gravis. Neuromuscul Disord. 2005;15(12):878–86.CrossRefPubMedGoogle Scholar
  30. Iorio R, Damato V, Alboini PE, Evoli A. Efficacy and safety of rituximab for myasthenia gravis: a systematic review and meta-analysis. J Neurol. 2015;262(5):1115–9.CrossRefPubMedGoogle Scholar
  31. Jayam Trouth A, Dabi A, Solieman N, Kurukumbi M, Kalyanam J. Myasthenia gravis: a review. Autoimmune Dis. 2012;2012:874680, 10 pages.PubMedPubMedCentralGoogle Scholar
  32. Jolly F. UeberMyasthenia gravis pseudoparalytica, vol. 32. Berlin: Klin Wochenschr; 1895.Google Scholar
  33. Juel VC. Evaluation of neuromuscular junction disorders in the electromyography laboratory. Neurol Clin. 2012;30(2):621–39.CrossRefPubMedGoogle Scholar
  34. Juel VC, Massey JM. Myasthenia gravis. Orphanet J Rare Dis. 2007;2:44.CrossRefPubMedPubMedCentralGoogle Scholar
  35. Kalita J, Kohat AK, Misra UK. Predictors of outcome of myasthenic crisis. Neurol Sci. 2014;35(7):1109–14.CrossRefPubMedGoogle Scholar
  36. Kerty E, Elsais A, Argov Z, Evoli A, Gilhus NE. EFNS/ENS guidelines for the treatment of ocular myasthenia. Eur J Neurol. 2014;21(5):687–93.CrossRefPubMedGoogle Scholar
  37. Khadilkar SV, Chaudhari CR, Patil TR, Desai ND, Jagiasi KA, Bhutada AG. Once myasthenic, always myasthenic? Observations on the behavior and prognosis of myasthenia gravis in a cohort of 100 patients. Neurol India. 2014;62(5):492–7.CrossRefPubMedGoogle Scholar
  38. Kubis KC, Danesh-Meyer HV, Savino PJ, Sergott RC. The ice test versus the rest test in myasthenia gravis. Ophthalmology. 2000;107(11):1995–8.CrossRefPubMedGoogle Scholar
  39. Kumar R, Nagappa M, Sinha S, Taly AB, Rao S. MG-QoL-15 scores in treated myasthenia gravis: experience from a university hospital in India. Neurol India. 2016;64(3):405–10.CrossRefPubMedGoogle Scholar
  40. Larner AJ. The place of the ice pack test in the diagnosis of myasthenia gravis. Int J Clin Pract. 2004a;58(9):887–8.CrossRefPubMedGoogle Scholar
  41. Larner AJ. The place of the ice pack test in the diagnosis of myasthenia gravis. Int J Clin Pract. 2004b;58(9):887–8.CrossRefPubMedGoogle Scholar
  42. Mantegazza R, Antozzi C, Peluchetti D, Sghirlanzoni A, Cornelio F. Azathioprine as a single drug or in combination with steroids in the treatment of myasthenia gravis. J Neurol. 1988;235(8):449–53.CrossRefPubMedGoogle Scholar
  43. Melzer N, Ruck T, Fuhr P, Gold R, Hohlfeld R, Marx A, Melms A, Tackenberg B, Schalke B, Schneider-Gold C, Zimprich F, Meuth SG, Wiendl H. Clinical features, pathogenesis, and treatment of myasthenia gravis: a supplement to the guidelines of the German Neurological Society. J Neurol. 2016;263(8):1473–94.CrossRefPubMedPubMedCentralGoogle Scholar
  44. Murthy JM. Thymectomy in myasthenia gravis. Neurol India. 2009;57(4):363–5.CrossRefPubMedGoogle Scholar
  45. Murthy JM, Meena AK, Chowdary GV, Naryanan JT. Myasthenic crisis: clinical features, complications and mortality. Neurol India. 2005;53(1):37–40.CrossRefPubMedGoogle Scholar
  46. Nagappa M, Netravathi M, Taly AB, Sinha S, Bindu PS, Mahadevan A. Long-term efficacy and limitations of cyclophosphamide in myasthenia gravis. J Clin Neurosci. 2014;21(11):1909–14.CrossRefPubMedGoogle Scholar
  47. Nastuk WL, Strauss AJL, Osserman KE. Search for a neuromuscular blocking agent in the blood of patients with myasthenia gravis. Am J Med. 1959;26(3):394–409.CrossRefPubMedGoogle Scholar
  48. Nikolić AV, Bačić GG, Daković MŽ, Lavrnić SĐ, Rakočević Stojanović VM, Basta IZ, Lavrnić DV. Myopathy, muscle atrophy and tongue lipid composition in MuSK myasthenia gravis. Acta Neurol Belg. 2015;115(3):361–5.CrossRefPubMedGoogle Scholar
  49. Oger J, Frykman H. An update on laboratory diagnosis in myasthenia gravis. Clin Chim Acta. 2015;449:43–8.CrossRefPubMedGoogle Scholar
  50. Pascuzzi RM. The history of myasthenia gravis. Neurol Clin. 1994;12(2):231–42.PubMedGoogle Scholar
  51. Pascuzzi RM. The edrophonium test. Semin Neurol. 2003;23(1):83–8.CrossRefPubMedGoogle Scholar
  52. Pascuzzi RM, Coslett HB, Johns TR. Long-term corticosteroid treatment of myasthenia gravis: report of 116 patients. Ann Neurol. 1984;15(3):291–8.CrossRefPubMedGoogle Scholar
  53. Pasnoor M, He J, Herbelin L, Burns TM, Nations S, Bril V, Wang AK, Elsheikh BH, Kissel JT, Saperstein D, Shaibani JA, Jackson C, Swenson A, Howard JF Jr, Goyal N, David W, Wicklund M, Pulley M, Becker M, Mozaffar T, Benatar M, Pazcuzzi R, Simpson E, Rosenfeld J, Dimachkie MM, Statland JM, Barohn RJ, Methotrexate in MG Investigators of the Muscle Study Group. A randomized controlled trial of methotrexate for patients with generalized myasthenia gravis. Neurology. 2016;87(1):57–64.CrossRefPubMedPubMedCentralGoogle Scholar
  54. Patil SA, Bokoliya SC, Nagappa M, Taly AB. Diagnosis of myasthenia gravis: comparison of anti-nicotinic acetyl choline receptor antibodies, repetitive nerve stimulation and neostigmine tests at a tertiary neuro care centre in India, a tenyear study. J Neuroimmunol. 2016a;292:81–4.CrossRefPubMedGoogle Scholar
  55. Patil SA, Bokoliya SC, Nagappa M, Taly AB. Diagnosis of myasthenia gravis: comparison of anti-nicotinic acetyl choline receptor antibodies, repetitive nerve stimulation and neostigmine tests at a tertiary neuro care centre in India, a ten year study. J Neuroimmunol. 2016b;292:81–4.CrossRefPubMedGoogle Scholar
  56. Patrick J, Lindstrom J. Autoimmune response to acetylcholine receptor. Science. 1973;180(4088):871–2.CrossRefPubMedGoogle Scholar
  57. Romi F. Thymoma in myasthenia gravis: from diagnosis to treatment. Autoimmune Dis. 2011;2011:474512.PubMedPubMedCentralGoogle Scholar
  58. Sanders DB, Siddiqi ZA. Lessons from two trials of mycophenolate mofetil in myasthenia gravis. Ann N Y Acad Sci. 2008;1132:249–53.CrossRefPubMedGoogle Scholar
  59. Sanders DB, Wolfe GI, Benatar M, Evoli A, Gilhus NE, Illa I, Kuntz N, Massey JM, Melms A, Murai H, Nicolle M, Palace J, Richman DP, Verschuuren J, Narayanaswami P. International consensus guidance for management of myasthenia gravis: executive summary. Neurology. 2016;87(4):419–25.CrossRefPubMedPubMedCentralGoogle Scholar
  60. Shah PA, Wadia PM. Reversible man-in-the-barrel syndrome in myasthenia gravis. Ann Indian Acad Neurol. 2016;19(1):99–101.CrossRefPubMedPubMedCentralGoogle Scholar
  61. Sharma S, Lal V, Prabhakar S, Agarwal R. Clinical profile and outcome of myasthenic crisis in a tertiary care hospital: a prospective study. Ann Indian Acad Neurol. 2013;16(2):203–7.CrossRefPubMedPubMedCentralGoogle Scholar
  62. Silvestri NJ, Wolfe GI. Myasthenia gravis. Semin Neurol. 2012;32(3):215–26.CrossRefPubMedGoogle Scholar
  63. Silvestri NJ, Wolfe GI. Treatment-refractory myasthenia gravis. J Clin Neuromuscul Dis. 2014a;15(4):167–78.CrossRefPubMedGoogle Scholar
  64. Silvestri NJ, Wolfe GI. Treatment-refractory myasthenia gravis. J Clin Neuromuscul Dis. 2014b;15(4):167–78.CrossRefPubMedGoogle Scholar
  65. Simpson JA. Myasthenia gravis, a new hypothesis. Scott Medical. 1960;5:419–36.CrossRefGoogle Scholar
  66. Singhal BS, Bhatia NS, Umesh T, Menon S. Myasthenia gravis: a study from India. Neurol India. 2008;56(3):352–5.CrossRefPubMedGoogle Scholar
  67. Skeie GO, Apostolski S, Evoli A, Gilhus NE, Illa I, Harms L, Hilton-Jones D, Melms A, Verschuuren J, Horge HW, European Federation of Neurological Societies. Guidelines for treatment of autoimmune neuromuscular transmission disorders. Eur J Neurol. 2010;17(7):893–902.CrossRefPubMedGoogle Scholar
  68. Soliven B, Rezania K, Gundogdu B, Harding-Clay B, Oger J, Arnason BG. Terbutaline in myasthenia gravis: a pilot study. J Neurol Sci. 2009;277(1–2):150–4.CrossRefPubMedGoogle Scholar
  69. Sudulagunta SR, Sepehrar M, Sodalagunta MB, Settikere Nataraju A, Bangalore Raja SK, Sathyanarayana D, Gummadi S, Burra HK. Refractory myasthenia gravis - clinical profile, comorbidities and response to rituximab. Ger Med Sci. 2016;14:Doc12.PubMedPubMedCentralGoogle Scholar
  70. Tindall RS, Phillips JT, Rollins JA, Wells L, Hall K. A clinical therapeutic trial of cyclosporine in myasthenia gravis. Ann N Y Acad Sci. 1993;681:539–51.CrossRefPubMedGoogle Scholar
  71. Vaphiades MS, Bhatti MT, Lesser RL. Ocular myasthenia gravis. Curr Opin Ophthalmol. 2012;23(6):537–42.CrossRefPubMedGoogle Scholar
  72. Vincent A. Unravelling the pathogenesis of myasthenia gravis. Nat Rev Immunol. 2002;2(10):797–804.CrossRefPubMedGoogle Scholar
  73. Vincent A, Leite MI. Neuromuscular junction autoimmune disease: muscle specific kinase antibodies and treatments for myasthenia gravis. Curr Opin Neurol. 2005;18(5):519–25.CrossRefPubMedGoogle Scholar
  74. Vincent A, Palace J, Hilton-Jones D. Myasthenia gravis. Lancet. 2001;357(9274):2122–8.CrossRefPubMedGoogle Scholar
  75. Walker MB. Case showing the effect of prostigmin on myasthenia gravis. J R Soc Med. 1935;28:759–61.Google Scholar
  76. Werner P, Kiechl S, Löscher W, Poewe W, Willeit J. Distal myasthenia gravis frequency and clinical course in a large prospective series. Acta Neurol Scand. 2003;108(3):209–11.CrossRefPubMedGoogle Scholar
  77. Witoonpanich R, Dejthevaporn C, Sriphrapradang A, Pulkes T. Electrophysiological and immunological study in myasthenia gravis: diagnostic sensitivity and correlation. Clin Neurophysiol. 2011;122:1873–7.CrossRefPubMedGoogle Scholar
  78. Witte AS, Cornblath DR, Parry GJ, Lisak RP, Schatz NJ. Azathioprine in the treatment of myasthenia gravis. Ann Neurol. 1984;15(6):602–5.CrossRefPubMedGoogle Scholar
  79. Wolfe GI, Kaminski HJ, Aban IB, Minisman G, Kuo HC, Marx A, Ströbel P, Mazia C, Oger J, Cea JG, Heckmann JM, Evoli A, Nix W, Ciafaloni E, Antonini G, Witoonpanich R, King JO, Beydoun SR, Chalk CH, Barboi AC, Amato AA, Shaibani AI, Katirji B, Lecky BR, Buckley C, Vincent A, Dias-Tosta E, Yoshikawa H, Waddington-Cruz M, Pulley MT, Rivner MH, Kostera-Pruszczyk A, Pascuzzi RM, Jackson CE, Garcia Ramos GS, Verschuuren JJ, Massey JM, Kissel JT, Werneck LC, Benatar M, Barohn RJ, Tandan R, Mozaffar T, Conwit R, Odenkirchen J, Sonett JR, Jaretzki A 3rd, Newsom-Davis J, Cutter GR, MGTX Study Group. Randomized trial of thymectomy in myasthenia gravis. N Engl J Med. 2016;375(6):511–22.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Satish V. Khadilkar
    • 1
  • Rakhil S. Yadav
    • 2
  • Bhagyadhan A. Patel
    • 3
  1. 1.Department of NeurologyBombay Hospital Institute of Medical SciencesMumbaiIndia
  2. 2.Consultant NeurologistSuyog Neurology Clinic, NH Multispeciality HospitalAhmedabadIndia
  3. 3.Consultant NeurologistTN Medical College and Nair HospitalMumbaiIndia

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