SpringerLink
Log in

Myasthenia Gravis

  • Chapter
  • First Online:
Acquired Neuromuscular Disorders

  • 1326 Accesses

Abstract

Myasthenia gravis (MG) is an autoimmune disease, caused by IgG antibodies to postsynaptic proteins at the neuromuscular junction, including the acetylcholine receptor (AChR), the muscle-specific tyrosine kinase receptor (MuSK), and the low-density lipoprotein receptor-related protein 4 (Lrp4). With different mechanisms, these antibodies induce morphological and functional changes responsible for neuromuscular transmission failure. Thymus alterations and defects in immune tolerance play a role in the pathogenesis of MG with anti-AChR antibodies. The clinical hallmark of MG is fatigable weakness of striated muscles, with marked variability in symptom extension and severity. The diagnosis is based on antibody detection, electrophysiological findings of a postsynaptic defect of neuromuscular transmission, and clinical response to acetylcholinesterase inhibitors. MG heterogeneity should be taken into account in patients’ management. Treatment varies according to weakness pattern and severity, age of onset, thymus pathology, and antibody profile. Therapeutic options include symptomatic agents, thymectomy, plasma exchange, intravenous immunoglobulin, steroids, and immunosuppressants. Monoclonal antibodies, such as rituximab and eculizumab are promising, and other biological agents are currently under study.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (Canada)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (Canada)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (Canada)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Hughes BW, Kusner LL, Kaminski HJ (2006) Molecular architecture of the neuromuscular junction. Muscle Nerve 33:445–461

    Article  CAS  PubMed  Google Scholar 

  2. Ohno K, Ito M, Kawakami Y et al (2013) Specific binding of collagen Q to the neuromuscular junction is exploited to cure congenital myasthenia and to explore bases of myasthenia gravis. Chem Biol Interact 203:335–340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Burden SJ, Yumoto N, Zhang W (2013) The role of MuSK in synapse formation and neuromuscular disease. Cold Spring Harb Perspect Biol 5:a009167

    Article  PubMed  PubMed Central  Google Scholar 

  4. Meriggioli MN, Sanders DB (2012) Muscle autoantibodies in myasthenia gravis: beyond diagnosis? Expert Rev Clin Immunol 8:427–438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Carr AS, Cardwell CR, McCarron PO et al (2010) A systematic review of population based epidemiological studies in Myasthenia Gravis. BMC Neurol 10:46

    Article  PubMed  PubMed Central  Google Scholar 

  6. Oh SJ (2009) Muscle-specific receptor tyrosine kinase antibody positive myasthenia gravis current status. J Clin Neurol 5:53–64

    Article  PubMed  PubMed Central  Google Scholar 

  7. Zisimopoulou P, Evangelakou P, Tzartos J et al (2014) A comprehensive analysis of the epidemiology and clinical characteristics of anti-LRP4 in myasthenia gravis. J Autoimmun 52:139–145

    Article  CAS  PubMed  Google Scholar 

  8. Luo J, Taylor P, Losen M et al (2009) Main immunogenic region structure promotes binding of conformation-dependent myasthenia gravis autoantibodies, nicotinic acetylcholine receptor conformation maturation, and agonist sensitivity. J Neurosci 29:13898–13908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Marx A, Pfister F, Schalke B et al (2013) The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes. Autoimmun Rev 12:875–884

    Article  CAS  PubMed  Google Scholar 

  10. Berrih-Aknin S, Le Panse R (2014) Myasthenia gravis: a comprehensive review of immune dysregulation and etiological mechanisms. J Autoimmun 52:90–100

    Article  CAS  PubMed  Google Scholar 

  11. McConville J, Farrugia ME, Beeson D et al (2004) Detection and characterization of MuSK antibodies in seronegative myasthenia gravis. Ann Neurol 55:580–584

    Article  CAS  PubMed  Google Scholar 

  12. Niks EH, Van LY, Leite MI et al (2008) Clinical fluctuations in MuSK myasthenia gravis are related to antigen-specific IgG4 instead of IgG1. J Neuroimmunol 195:151–156

    Article  CAS  PubMed  Google Scholar 

  13. Klooster R, Plomp JJ, Huijbers MG et al (2012) Muscle-specific kinase myasthenia gravis IgG4 autoantibodies cause severe neuromuscular junction dysfunction in mice. Brain 135:1081–1101

    Article  PubMed  Google Scholar 

  14. Kawakami Y, Ito M, Hirayama M et al (2011) Anti-MuSK autoantibodies block binding of collagen Q to MuSK. Neurology 77:1819–1826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Huijbers MG, Zhang W, Klooster R et al (2013) MuSK IgG4 autoantibodies cause myasthenia gravis by inhibiting binding between MuSK and Lrp4. Proc Natl Acad Sci USA 110:20783–20788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Yumoto N, Kim N, Burden SJ (2012) Lrp4 is a retrograde signal for presynaptic differentiation at neuromuscular synapses. Nature 489:438–442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhang W, Coldefy A-S, Hubbard SR et al (2011) Agrin binds to the N-terminal region of Lrp4 protein and stimulates association between Lrp4 and the first immunoglobulin-like domain in muscle-specific kinase (MuSK). J Biol Chem 286:40624–40630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Higuchi O, Hamuro J, Motomura M et al (2011) Autoantibodies to low-density lipoprotein receptor-related protein 4 in myasthenia gravis. Ann Neurol 69:418–422

    Article  CAS  PubMed  Google Scholar 

  19. Shen C, Lu Y, Zhang B et al (2013) Antibodies against low-density lipoprotein receptor-related protein 4 induce myasthenia gravis. J Clin Invest 123:5190–5202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gasperi C, Melms A, Schoser B et al (2014) Anti-agrin autoantibodies in myasthenia gravis. Neurology 82:1976–1983

    Article  CAS  PubMed  Google Scholar 

  21. Zoltowska Katarzyna M, Belaya K, Leite M et al (2015) Collagen Q – a potential target for autoantibodies in myasthenia gravis. J Neurol Sci 348:241–244

    Article  CAS  PubMed  Google Scholar 

  22. Gallardo E, Martínez-Hernández E, Titulaer MJ et al (2014) Cortactin autoantibodies in myasthenia gravis. Autoimmun Rev 13:1003–1007

    Article  CAS  PubMed  Google Scholar 

  23. Luchanok U, Kaminski HJ (2008) Ocular myasthenia: diagnostic and treatment recommendations and the evidence base. Curr Opin Neurol 21:8–15

    Article  PubMed  Google Scholar 

  24. Alshekhlee A, Miles JD, Katirji B et al (2009) Incidence and mortality rate of myasthenia gravis and myasthenic crisis in US hospitals. Neurology 72:1548–1554

    Article  CAS  PubMed  Google Scholar 

  25. Guptill JT, Sanders DB, Evoli A (2011) Anti-MuSK antibody myasthenia gravis: clinical findings and response to treatment in two large cohorts. Muscle Nerve 44:36–40

    Article  PubMed  Google Scholar 

  26. Evoli A, Padua L (2013) Diagnosis and therapy of myasthenia gravis with antibodies to muscle-specific kinase. Autoimmun Rev 12:931–935

    Article  CAS  PubMed  Google Scholar 

  27. Meriggioli MN, Sanders DB (2009) Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol 8:475–490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Jacob S, Viegas S, Leite MI et al (2012) Presence and pathogenic relevance of antibodies to clustered acetylcholine receptor in ocular and generalized myasthenia gravis. Arch Neurol 69:994–1001

    Article  PubMed  Google Scholar 

  29. Tzartos JS, Zisimopolou P, Rentzos M et al (2014) LRP4 antibodies in serum and CSF from amyotrophic lateral sclerosis patients. Ann Clin Transl Neurol 1:80–87

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Skeie GO, Aarli JA, Gilhus NE (2006) Titin and ryanodine receptor antibodies in myasthenia gravis. Acta Neurol Scand 113(S183):19–23

    Article  Google Scholar 

  31. Suzuki S, Baba A, Kaida K et al (2014) Cardiac involvements in myasthenia gravis associated with anti-Kv1.4 antibodies. Eur J Neurol 21:223–230

    Article  CAS  PubMed  Google Scholar 

  32. Howard JF Jr (2013) Electrodiagnosis of disorders of neuromuscular transmission. Phys Med Rehabil Clin N Am 24:169–192

    Article  PubMed  Google Scholar 

  33. Oh SJ, Hatanaka Y, Hemmi S et al (2006) Repetitive nerve stimulation of facial muscles in MuSK antibody-positive myasthenia gravis. Muscle Nerve 33:500–504

    Article  PubMed  Google Scholar 

  34. Sanders DB (2002) The clinical impact of single-fiber electromyography. Muscle Nerve 11:S15–S20

    Article  PubMed  Google Scholar 

  35. Phillips LH II, Melnick PA (1990) Diagnosis of myasthenia gravis in the 1990s. Semin Neurol 10:62–69

    Article  PubMed  Google Scholar 

  36. Oh SJ, Cho HK (1990) Edrophonium responsiveness not necessarily diagnostic of myasthenia gravis. Muscle Nerve 13:187–191

    Article  CAS  PubMed  Google Scholar 

  37. Hatanaka Y, Hemmi S, Morgan MB et al (2005) Nonresponsiveness to anticholinesterase agents in patients with MuSK-antibody-positive MG. Neurology 65:1508–1509

    Article  CAS  PubMed  Google Scholar 

  38. Reddel SW, Morsch M, Phillips WD (2014) Clinical and scientific aspects of muscle-specific tyrosine kinase-related myasthenia gravis. Curr Opin Neurol 27:558–565

    Article  CAS  PubMed  Google Scholar 

  39. Evoli A, Alboini PE, Damato V, Iorio R. 3,4-diaminopyridine may improve myasthenia gravis with MuSK antibodies. Neurology. 2016 Feb 12. pii: 10.1212/WNL.0000000000002466)

    Google Scholar 

  40. Gronseth GS, Barohn RJ (2002) Thymectomy for Myasthenia Gravis. Curr Treat Options Neurol 4:203–209

    Article  PubMed  Google Scholar 

  41. Gajdos P, Chevret S, Clair B et al (1997) Clinical trial of plasma exchange and high-dose intravenous immunoglobulin in myasthenia gravis. Myasthenia Gravis Clinical Study Group. Ann Neurol 41:789–796

    Article  CAS  PubMed  Google Scholar 

  42. Barth D, Nabavi Nouri M, Ng E et al (2011) Comparison of IVIg and PLEX in patients with myasthenia gravis. Neurology 76:2017–2023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Guptill JT, Oakley D, Kuchibhatla M et al (2013) A retrospective study of complications of therapeutic plasma exchange in myasthenia. Muscle Nerve 47:170–176

    Article  PubMed  Google Scholar 

  44. Pierce LR, Jain N (2003) Risks associated with the use of intravenous immunoglobulin. Transfus Med Rev 17:241–251

    Article  PubMed  Google Scholar 

  45. Mantegazza R, Bonanno S, Camera G et al (2011) Current and emerging therapies for the treatment of myasthenia gravis. Neuropsychiatr Dis Treat 7:151–160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Sathasivam S (2011) Current and emerging treatments for the management of myasthenia gravis. Ther Clin Risk Manag 7:313–323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Sanders DB, Hart IK, Mantegazza R et al (2008) An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis. Neurology 71:400–406

    Article  CAS  PubMed  Google Scholar 

  48. Muscle Study Group (2008) A trial of mycophenolate mofetil with prednisone as initial immunotherapy in myasthenia gravis. Neurology 71:394–399

    Article  Google Scholar 

  49. Heckmann JM, Rawoot A, Bateman K et al (2011) A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis. BMC Neurol 11:97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Iorio R, Damato V, Alboini PE et al (2015) Efficacy and safety of rituximab for myasthenia gravis: a systematic review and meta-analysis. J Neurol 262(5):1115–1119

    Article  CAS  PubMed  Google Scholar 

  51. Howard JF Jr, Barohn RJ, Cutter GR et al (2013) A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis. Muscle Nerve 48:76–84

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Neurology, Catholic University, Largo F. Vito 1, Rome, 00168, Italy

    Amelia Evoli & Raffaele Iorio

Authors
  1. Amelia Evoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raffaele Iorio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amelia Evoli .

Editor information

Editors and Affiliations

  1. Neuromuscular Center, IRCCS Fondazione San Camillo Hospit, Venice, Italy

    Corrado Angelini

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Evoli, A., Iorio, R. (2016). Myasthenia Gravis. In: Angelini, C. (eds) Acquired Neuromuscular Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-29514-5_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-29514-5_9

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-29512-1

  • Online ISBN: 978-3-319-29514-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation