Advertisement

Myasthenia Gravis and Pregnancy

  • Christyn Edmundson
  • Mohammad Kian SalajeghehEmail author
Chapter

Abstract

Myasthenia gravis (MG) is an autoimmune disorder characterized by fluctuating and fatigable weakness of skeletal muscle. MG is more common in women than in men, particularly in the second and third decades of life, resulting in a relatively high burden of MG in women of child bearing age. The disease and its treatment side effects may have considerable impact on women’s general and reproductive health. Hormonal changes during pregnancy can influence the presentation and severity of MG. MG and its treatments also carry implications for the fetus. This chapter reviews the existing literature on the presentation, disease course, treatment and possible complications of MG in women, with a focus on pregnancy, labor and delivery.

Keywords

Myasthenia gravis Neuromuscular junction Pregnancy Lactation 

References

  1. 1.
    Amato AA, Russell JA. Neuromuscular disorders. 2nd ed. New York: McGraw-Hill Medical; 2016.Google Scholar
  2. 2.
    Sanders DB, Wolfe GI, Benatar M, Evoli A, Gilhus NE, Illa I, et al. International consensus guidance for management of myasthenia gravis: executive summary. Neurology. 2016;87(4):419–25.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Cutolo M, Capellino S, Straub RH. Oestrogens in rheumatic diseases: friend or foe? Rheumatology (Oxford). 2008;47(Suppl 3):iii2–5.Google Scholar
  4. 4.
    Mays J, Butts CL. Intercommunication between the neuroendocrine and immune systems: focus on myasthenia gravis. Neuroimmunomodulation. 2011;18(5):320–7.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Leker RR, Karni A, Abramsky O. Exacerbation of myasthenia gravis during the menstrual period. J Neurol Sci. 1998;156(1):107–11.PubMedGoogle Scholar
  6. 6.
    Frenkel M. Treatment of myasthenia gravis by ovulatory suppression. Arch Neurol. 1964;11:613–7.PubMedGoogle Scholar
  7. 7.
    Stickler DE, Stickler LL. Single-fiber electromyography during menstrual exacerbation and ovulatory suppression in MuSK antibody-positive myasthenia gravis. Muscle Nerve. 2007;35(6):808–11.PubMedGoogle Scholar
  8. 8.
    Djelmis J, Sostarko M, Mayer D, Ivanisevic M. Myasthenia gravis in pregnancy: report on 69 cases. Eur J Obstet Gynecol Reprod Biol. 2002;104(1):21–5.PubMedGoogle Scholar
  9. 9.
    Delpy L, Douin-Echinard V, Garidou L, Bruand C, Saoudi A, Guery JC. Estrogen enhances susceptibility to experimental autoimmune myasthenia gravis by promoting type 1-polarized immune responses. J Immunol. 2005;175(8):5050–7.PubMedGoogle Scholar
  10. 10.
    Wu KH, Tobias ML, Kelley DB. Estrogen and laryngeal synaptic strength in Xenopus laevis: opposite effects of acute and chronic exposure. Neuroendocrinology. 2001;74(1):22–32.PubMedGoogle Scholar
  11. 11.
    Boldingh MI, Maniaol AH, Brunborg C, Weedon-Fekjaer H, Verschuuren JJ, Tallaksen CM. Increased risk for clinical onset of myasthenia gravis during the postpartum period. Neurology. 2016;87(20):2139–45.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Massey JM, De Jesus-Acosta C. Pregnancy and myasthenia gravis. Continuum (Minneap Minn). 2014;20(1):115–27.Google Scholar
  13. 13.
    Batocchi AP, Majolini L, Evoli A, Lino MM, Minisci C, Tonali P. Course and treatment of myasthenia gravis during pregnancy. Neurology. 1999;52(3):447–52.PubMedGoogle Scholar
  14. 14.
    Braga AC, Pinto C, Santos E, Braga J. Myasthenia gravis in pregnancy: experience of a portuguese center. Muscle Nerve. 2016;54(4):715–20.PubMedGoogle Scholar
  15. 15.
    Ducci RD, Lorenzoni PJ, Kay CS, Werneck LC, Scola RH. Clinical follow-up of pregnancy in myasthenia gravis patients. Neuromuscul Disord. 2017;27(4):352–7.PubMedGoogle Scholar
  16. 16.
    Norwood F, Dhanjal M, Hill M, James N, Jungbluth H, Kyle P, et al. Myasthenia in pregnancy: best practice guidelines from a U.K. multispecialty working group. J Neurol Neurosurg Psychiatry. 2014;85(5):538–43.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Ohlraun S, Hoffmann S, Klehmet J, Kohler S, Grittner U, Schneider A, et al. Impact of myasthenia gravis on family planning: how do women with myasthenia gravis decide and why? Muscle Nerve. 2015;52(3):371–9.PubMedGoogle Scholar
  18. 18.
    US Food and Drug Administration pregnancy categories, drug safety and availability. www.accessdata.fda.gov/scripts/cder/daf/. Accessed 15 Nov 2017.
  19. 19.
    Park-Wyllie L, Mazzotta P, Pastuszak A, Moretti ME, Beique L, Hunnisett L, et al. Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology. 2000;62(6):385–92.PubMedGoogle Scholar
  20. 20.
    Carmichael SL, Shaw GM, Ma C, Werler MM, Rasmussen SA, Lammer EJ, et al. Maternal corticosteroid use and orofacial clefts. Am J Obstet Gynecol. 2007;197(6):585 e1–7. discussion 683–4, e1–7Google Scholar
  21. 21.
    Hviid A, Molgaard-Nielsen D. Corticosteroid use during pregnancy and risk of orofacial clefts. CMAJ. 2011;183(7):796–804.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Skuladottir H, Wilcox AJ, Ma C, Lammer EJ, Rasmussen SA, Werler MM, et al. Corticosteroid use and risk of orofacial clefts. Birth Defects Res A Clin Mol Teratol. 2014;100(6):499–506.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Guidon AC, Massey EW. Neuromuscular disorders in pregnancy. Neurol Clin. 2012;30(3):889–911.PubMedGoogle Scholar
  24. 24.
    Clark AL. Clinical uses of intravenous immunoglobulin in pregnancy. Clin Obstet Gynecol. 1999;42(2):368–80.PubMedGoogle Scholar
  25. 25.
    Ciafaloni E, Massey JM. Myasthenia gravis and pregnancy. Neurol Clin. 2004;22(4):771–82.PubMedGoogle Scholar
  26. 26.
    Hehir MK, Hobson-Webb LD, Benatar M, Barnett C, Silvestri NJ, Howard JF Jr, et al. Rituximab as treatment for anti-MuSK myasthenia gravis: multicenter blinded prospective review. Neurology. 2017;89(10):1069–77.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Stieglbauer K, Pichler R, Topakian R. 10-year-outcomes after rituximab for myasthenia gravis: efficacy, safety, costs of inhospital care, and impact on childbearing potential. J Neurol Sci. 2017;375:241–4.PubMedGoogle Scholar
  28. 28.
    Wolfe GI, Kaminski HJ, Aban IB, Minisman G, Kuo HC, Marx A, et al. Randomized trial of thymectomy in myasthenia gravis. N Engl J Med. 2016;375(6):511–22.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009;33(3):130–7.PubMedGoogle Scholar
  30. 30.
    Lake AJ, Al Khabbaz A, Keeney R. Severe preeclampsia in the setting of myasthenia gravis. Case Rep Obstet Gynecol. 2017;2017:9204930.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Ozcan J, Balson IF, Dennis AT. New diagnosis myasthenia gravis and preeclampsia in late pregnancy. BMJ Case Rep. 2015;1–4.Google Scholar
  32. 32.
    Haider B, von Oertzen J. Neurological disorders. Best Pract Res Clin Obstet Gynaecol. 2013;27(6):867–75.PubMedGoogle Scholar
  33. 33.
    Hoff JM, Daltveit AK, Gilhus NE. Myasthenia gravis in pregnancy and birth: identifying risk factors, optimising care. Eur J Neurol. 2007;14(1):38–43.PubMedGoogle Scholar
  34. 34.
    Ahlsten G, Lefvert AK, Osterman PO, Stalberg E, Safwenberg J. Follow-up study of muscle function in children of mothers with myasthenia gravis during pregnancy. J Child Neurol. 1992;7(3):264–9.PubMedGoogle Scholar
  35. 35.
    O’Carroll P, Bertorini TE, Jacob G, Mitchell CW, Graff J. Transient neonatal myasthenia gravis in a baby born to a mother with new-onset anti-MuSK-mediated myasthenia gravis. J Clin Neuromuscul Dis. 2009;11(2):69–71.PubMedGoogle Scholar
  36. 36.
    Niks EH, Verrips A, Semmekrot BA, Prick MJ, Vincent A, van Tol MJ, et al. A transient neonatal myasthenic syndrome with anti-musk antibodies. Neurology. 2008;70(14):1215–6.PubMedGoogle Scholar
  37. 37.
    Lee JY, Min JH, Han SH, Han J. Transient neonatal myasthenia gravis due to a mother with ocular onset of anti-muscle specific kinase myasthenia gravis. Neuromuscul Disord. 2017;27(7):655–7.PubMedGoogle Scholar
  38. 38.
    Townsel C, Keller R, Johnson K, Hussain N, Campbell WA. Seronegative maternal ocular myasthenia gravis and delayed transient neonatal myasthenia gravis. AJP Rep. 2016;6(1):e133–6.PubMedPubMedCentralGoogle Scholar
  39. 39.
    D’Amico A, Bertini E, Bianco F, Papacci P, Jacobson L, Vincent A, et al. Fetal acetylcholine receptor inactivation syndrome and maternal myasthenia gravis: a case report. Neuromuscul Disord. 2012;22(6):546–8.PubMedGoogle Scholar
  40. 40.
    Hacohen Y, Jacobson LW, Byrne S, Norwood F, Lall A, Robb S, et al. Fetal acetylcholine receptor inactivation syndrome: a myopathy due to maternal antibodies. Neurol Neuroimmunol Neuroinflamm. 2015;2(1):e57.PubMedGoogle Scholar
  41. 41.
    Ressel G. AAP updates statement for transfer of drugs and other chemicals into breast milk. American Academy of Pediatrics. Am Fam Physician. 2002;65(5):979–80.PubMedGoogle Scholar
  42. 42.
    American Academy of Pediatrics Committee on D. Transfer of drugs and other chemicals into human milk. Pediatrics. 2001;108(3):776–89.Google Scholar
  43. 43.
    Wakata N, Nemoto H, Sugimoto H, Nomoto N, Konno S, Hayashi N, et al. Bone density in myasthenia gravis patients receiving long-term prednisolone therapy. Clin Neurol Neurosurg. 2004;106(2):139–41.PubMedGoogle Scholar
  44. 44.
    Pouwels S, de Boer A, Javaid MK, Hilton-Jones D, Verschuuren J, Cooper C, et al. Fracture rate in patients with myasthenia gravis: the general practice research database. Osteoporos Int. 2013;24(2):467–76.PubMedGoogle Scholar
  45. 45.
    Yeh JH, Chen HJ, Chen YK, Chiu HC, Kao CH. Increased risk of osteoporosis in patients with myasthenia gravis: a population-based cohort study. Neurology. 2014;83(12):1075–9.PubMedGoogle Scholar
  46. 46.
    Grossman JM, Gordon R, Ranganath VK, Deal C, Caplan L, Chen W, et al. American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res. 2010;62(11):1515–26.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of Neuromuscular Medicine, Department of NeurologyHospital of the University of PennsylvaniaPhiladelphiaUSA
  2. 2.Neuromuscular Center & EMG Laboratory, Departmentof NeurologyVA Boston Healthcare System, Harvard Medical SchoolBostonUSA

Personalised recommendations