CC BY-NC-ND 4.0 · J Neuroanaesth Crit Care 2019; 06(02): 153-159
DOI: 10.1055/s-0039-1689739
Review Article
Indian Society of Neuroanaesthesiology and Critical Care

Management of Myasthenia Gravis

Sudhir Venkataramaiah
1   Department of Neuroanaesthesiology and Neurocritical Care, National Institute of Mental Health and Neurosciences, Hosur Road, Bengaluru, Karnataka, India
,
Sriganesh Kamath
1   Department of Neuroanaesthesiology and Neurocritical Care, National Institute of Mental Health and Neurosciences, Hosur Road, Bengaluru, Karnataka, India
› Author Affiliations
Further Information

Publication History

Received: 23 February 2019

Accepted after revision: 01 April 2019

Publication Date:
07 June 2019 (online)

Abstract

Myasthenia gravis (MG) apart from Guillain–Barré syndrome is one of the most common disorders presenting as respiratory failure secondary to muscle weakness in the modern world. MG is also one of the most researched and reasonably well understood autoimmune disorder of mankind. From the description of early cases of MG to the current day understanding, the progress in the management and therapeutics has advanced significantly. Diagnosis of MG can be accurately done either with traditional tests such as the edrophonium test or by advanced nerve conduction studies. Presence of demonstrable circulating autoantibodies against the acetyl choline receptors, muscle-specific tyrosine kinase, involvement of B and T cells in the pathogenesis, and tomographic evidence of the enlarged thymus gland in certain patients have led to designing specific treatment strategies. Removal of the circulating autoantibodies as much as possible by plasmapheresis supported by anticholinesterases and immunosuppression are the mainstay of targeted therapy. The advent of newer immunosuppressant drugs such as rituximab which targets the CD20 protein present on the surface of B cells and tacrolimus which is an interleukin 2 inhibitor has improved the therapeutic armamentarium of the physician. These agents in combination with time tested medications such as steroids and antimetabolites have rendered faster remission rates and improved outcomes in MG crisis. This article outlines the basic pathophysiology, specific and supportive management strategies in patients presenting with MG with or without crisis.

 
  • References

  • 1 Zhang X, Yang M, Xu J. et al. Clinical and serological study of myasthenia gravis in HuBei Province, China. J Neurol Neurosurg Psychiatry 2007; 78 (04) 386-390
  • 2 Slater CR. The structure of human neuromuscular junctions: some unanswered molecular questions. Int J Mol Sci 2017; 18 (10) E2183
  • 3 Drachman DB, Adams RN, Stanley EF, Pestronk A. Mechanisms of acetylcholine receptor loss in myasthenia gravis. J Neurol Neurosurg Psychiatry 1980; 43 (07) 601-610
  • 4 Wallace B. scFvs get down to basics: how MuSK makes synapses. Nat Biotechnol 1997; 15 (08) 721-722
  • 5 Wickelgren I. Synapse-making molecules revealed. Science 1996; 272 (5265) 1100
  • 6 Drachman DB, McIntosh KR, Yang B. Factors that determine the severity of experimental myasthenia gravis. Ann N Y Acad Sci 1998; 841: 262-282
  • 7 Hughes BW, Moro De CasillasML, Kaminski HJ. Pathophysiology of myasthenia gravis. Semin Neurol 2004; 24 (01) 21-30
  • 8 Thanvi BR, Lo TC. Update on myasthenia gravis. Postgrad Med J 2004; 80 (950) 690-700
  • 9 Vincent A, Palace J, Hilton-Jones D. Myasthenia gravis. Lancet 2001; 357 (9274) 2122-2128
  • 10 Jayam TrouthA, Dabi A, Solieman N, Kurukumbi M, Kalyanam J. Myasthenia gravis: a review. Autoimmune Dis 2012; 2012: 874680
  • 11 Cheo SW, Low QJ, Mow WC, Yuen KangC. Ice pack test - an useful bedside test to diagnose myasthenia gravis. QJM. 2018
  • 12 Sanders DB, Howard Jr JF, Johns TR. Single-fiber electromyography in myasthenia gravis. Neurology 1979; 29 (01) 68-76
  • 13 Rabinstein AA. Acute Neuromuscular Respiratory Failure. Continuum (Minneap Minn) 2015; 21 (05) Neurocritical Care) 1324-1345
  • 14 Elsheikh B, Arnold WD, Gharibshahi S, Reynolds J, Freimer M, Kissel JT. Correlation of single-breath count test and neck flexor muscle strength with spirometry in myasthenia gravis. Muscle Nerve 2016; 53 (01) 134-136
  • 15 Rezania K, Goldenberg FD, White S. Neuromuscular disorders and acute respiratory failure: diagnosis and management. Neurol Clin 2012; 30 (01) 161-185 viii
  • 16 Seneviratne J, Mandrekar J, Wijdicks EF, Rabinstein AA. Noninvasive ventilation in myasthenic crisis. Arch Neurol 2008; 65 (01) 54-58
  • 17 Rabinstein A, Wijdicks EF. BiPAP in acute respiratory failure due to myasthenic crisis may prevent intubation. Neurology 2002; 59 (10) 1647-1649
  • 18 Godoy DA, Mello LJ, Masotti L, Di Napoli M. The myasthenic patient in crisis: an update of the management in neurointensive care unit. Arq Neuropsiquiatr 2013; 71 (9A) 627-639
  • 19 Kirmani JF, Yahia AM, Qureshi AI. Myasthenic crisis. Curr Treat Options Neurol 2004; 6 (01) 3-15
  • 20 Wendell LC, Levine JM. Myasthenic crisis. Neurohospitalist 2011; 1 (01) 16-22
  • 21 Seneviratne J, Mandrekar J, Wijdicks EF, Rabinstein A. Predictors of extubation failure in myasthenic crisis. Arch Neurol 2008; 65 (07) 929-933
  • 22 Rabinstein AA, Mueller-Kronast N. Risk of extubation failure in patients with myasthenic crisis. Neurocrit Care 2005; 3 (03) 213-215
  • 23 Varelas PN, Chua HC, Natterman J. et al. Ventilatory care in myasthenia gravis crisis: assessing the baseline adverse event rate. Crit Care Med 2002; 30 (12) 2663-2668
  • 24 Panegyres PK, Squier M, Mills KR, Newsom-Davis J. Acute myopathy associated with large parenteral dose of corticosteroid in myasthenia gravis. J Neurol Neurosurg Psychiatry 1993; 56 (06) 702-704
  • 25 Vallet B, Fourrier F, Hurtevent JF, Parent M, Chopin C. Myasthenia gravis and steroid-induced myopathy of the respiratory muscles. Intensive Care Med 1992; 18 (07) 424-426
  • 26 Sussman J, Farrugia ME, Maddison P, Hill M, Leite MI, Hilton-Jones D. The Association of British Neurologists’ myasthenia gravis guidelines. Ann N Y Acad Sci 2018; 1412 (01) 166-169
  • 27 Sanders DB, Wolfe GI, Benatar M. et al. International consensus guidance for management of myasthenia gravis: executive summary. Neurology 2016; 87 (04) 419-425
  • 28 Sanders DB, Wolfe GI, Narayanaswami P. MGFA Task Force on MG Treatment Guidance. Developing treatment guidelines for myasthenia gravis. Ann N Y Acad Sci 2018; 1412 (01) 95-101
  • 29 Jones LA, Robertson NP. An update on treatments in myasthenia gravis. J Neurol 2017; 264 (01) 205-207
  • 30 Li Y, Arora Y, Levin K. Myasthenia gravis: newer therapies offer sustained improvement. Cleve Clin J Med 2013; 80 (11) 711-721
  • 31 Barth D, Nabavi NouriM, Ng E, Nwe P, Bril V. Comparison of IVIg and PLEX in patients with myasthenia gravis. Neurology 2011; 76 (23) 2017-2023
  • 32 Dhawan PS, Goodman BP, Harper CM. et al. IVIG versus PLEX in the treatment of worsening myasthenia gravis: what is the evidence?: a critically appraised topic. Neurologist 2015; 19 (05) 145-148
  • 33 Mertens HG, Hertel G, Reuther P, Ricker K. Effect of immunosuppressive drugs (azathioprine). Ann N Y Acad Sci 1981; 377: 691-699
  • 34 Relling MV, Gardner EE, Sandborn WJ. et al; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clin Pharmacol Ther 2011; 89 (03) 387-391
  • 35 Meriggioli MN, Ciafaloni E, Al-Hayk KA. et al. Mycophenolate mofetil for myasthenia gravis: an analysis of efficacy, safety, and tolerability. Neurology 2003; 61 (10) 1438-1440
  • 36 Sanders DB, Hart IK, Mantegazza R. et al. An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis. Neurology 2008; 71 (06) 400-406
  • 37 Heckmann JM, Rawoot A, Bateman K, Renison R, Badri M. A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis. BMC Neurol 2011; 11: 97
  • 38 Pasnoor M, He J, Herbelin L. et al; Methotrexate in MG Investigators of the Muscle Study Group. A randomized controlled trial of methotrexate for patients with generalized myasthenia gravis. Neurology 2016; 87 (01) 57-64
  • 39 Díaz-Manera J, Martínez-Hernández E, Querol L. et al. Long-lasting treatment effect of rituximab in MuSK myasthenia. Neurology 2012; 78 (03) 189-193
  • 40 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) 1909-1914
  • 41 Zhang Z, Yang C, Zhang L, Yi Q, Hao Z. Efficacy and safety of tacrolimus in myasthenia gravis: a systematic review and meta-analysis. Ann Indian Acad Neurol 2017; 20 (04) 341-347
  • 42 Chen P, Feng H, Deng J. et al. Leflunomide treatment in corticosteroid-dependent myasthenia gravis: an open-label pilot study. J Neurol 2016; 263 (01) 83-88
  • 43 Cataneo AJM, Felisberto G, Cataneo Jr DC. Thymectomy in nonthymomatous myasthenia gravis - systematic review and meta-analysis. Orphanet J Rare Dis 2018; 13 (01) 99
  • 44 Kumar V, Kaminski HJ. Treatment of myasthenia gravis. Curr Neurol Neurosci Rep 2011; 11 (01) 89-96
  • 45 Jordan A, Freimer M. Recent advances in understanding and managing myasthenia gravis. F1000 Res 2018; 7: 7