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Disorders of Neuromuscular Transmission

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Geriatric Diseases

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Abstract

Myasthenia gravis (MG) is an autoimmune disorder characterized by fluctuating muscle weakness and fatigue caused by antibodies directed against the nicotine acetylcholine (ACh) receptor (AChR) or against the muscle-specific tyrosine kinase (MuSK) receptor. The prevalence has increased over the past four to five decades, and the increase is mainly found in patients over the age of 50 years. Clinically and epidemiologically, it is possible to recognize two subtypes, the early-onset myasthenia gravis (EOMG) and the late-onset myasthenia gravis (LOMG). In MG, antibodies to the AChR cause a functional blockade of the binding site for ACh. Some MG patients do not have detectable AChR antibodies and are termed seronegative MG. In 2–3% of AChR-seronegative patients, there was seropositivity of anti-MuSK antibody. It had been reported that anti-AChR antibodies were seen in 65% with early-onset MG compared to 85% in the late-onset MG and elevated titers of anti-MuSK antibodies were similar. Ocular MG is more common in LOMG compared to EOMG so is myopathy. About 30% of late-onset MG patients without thymoma have antibodies to titin, whereas titin antibodies are uncommon in the early-onset MG. Significant therapeutic progress has been made in the treatment of MG and introduction of new modalities especially immunosuppressive, immunomodulating drugs, plasma exchange, and thymectomy. In Eaton-Lambert syndrome (E-LS), there is a reduction in the release of acetylcholine from the motor nerve terminals. There are substantial differences between E-LS and MG in the pathophysiology, clinical features, electromyographic changes, and treatment. More than half the patients with E-LS are associated with malignancies such as small cell lung cancer (SCLC) non-small cell lung cancer, and lymphoma, among others. The antibodies in E-LS prevent the opening of the calcium channels, and hence the release of ACh and voltage-gated calcium channels (VGCC) antibodies has been reported in 75–100% of patients with L-ES. Guanidine increases the release of ACh.

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References

  1. Montero-Odasso M. Dysphonia as first symptom of late onset myasthenia gravis. J Gen Intern Med. 2006;21:C4–C6.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Aarli JA. Late-onset myasthenia gravis: changing scene Arch Neurol. 1999;56:25–27.

    Article  CAS  PubMed  Google Scholar 

  3. Vincent A, Clover L, Buckley C, Evans JG, Rothwell PM. Evidence of underdiagnosis of myasthenia gravis in older people. J Neurol Neurosurg Psychiatry. 2003;74(8):1105–1108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Aarli JA. Myasthenia gravis in the elderly: Is it different. Ann NY Acad Sci. 2008;1132:238–243.

    Article  PubMed  Google Scholar 

  5. Aragones JM, Bolibar I, Bonfill X, Bufill E, Mummany A Alousef et al., Myasthenia, gravis: a higher than expected incidence in the elderly. Neurology. 2003;60(6):1024–1026.

    Article  CAS  PubMed  Google Scholar 

  6. Simpson JF, Westerberg MR, Magee KR. Myasthenia gravis : an analysis of 295 cases. Acta Neurol Scand. 1996;42(suppl 23):1–27.

    Google Scholar 

  7. Zivkovic SA, Clemens PR, Lacomis D. Characteristics of late-onset myasthenia gravis. J Neurol. 2012;259(10):2167–71.

    Article  PubMed  Google Scholar 

  8. Pourmand R. Myasthenia gravis. Dis Mon. 1997;43:65–109.

    Article  CAS  PubMed  Google Scholar 

  9. Somnier F, Trojaburg W. Neurophysiological evaluation in myasthenia gravis: a comprehensive study of a complete patient population. Electroencephhalogr Clin Neurophysiol. 1993;89:73–87.

    Article  CAS  Google Scholar 

  10. Chaudhuri A. Myasthenic crises. QJM 2014;102(2):97–107.

    Article  Google Scholar 

  11. Koneczay I, Cossins J, Vincent A. The role of muscle specific tyrosine kinase (MuSK) and mystery of MuSK myasthenia gravis. J Anatomy. 2014;224:21–35.

    Google Scholar 

  12. Lee JY, Sung JJ, Cho JY, Oh DH, Kim HJ, Park JH, et al. MuSK antibody positive, seronegative Myasthenia gravis in Korea J Clin Neurosci. 2006;13:353–355.

    Article  PubMed  Google Scholar 

  13. Evoli A, Blanchi MR, Riso R, Minicuci GM, Batocchi AP, Servidel S, et al. response to therapy in myasthenia gravis with antiMuSK antibodies. Ann NY Acad Sci. 2008;1132:76–83.

    Article  CAS  PubMed  Google Scholar 

  14. Chang T, Gunaratne P, Gamage R, Riffsy MTM, Vincent V. MuSK antoibody positive myasthenia gravis in South Asian population. J Neurol Sci. 2009;33:35.

    Google Scholar 

  15. Suzuki S, Utsugisawa K, Nagane Y, Satoh T, Kuwna M, Suzuki N, et al. Clinical and immunological differences between early and late-onset myasthenia gravis in Japan. Neuroimmunol. 2011;230(1–2):148–52.

    Article  CAS  Google Scholar 

  16. Romi F. Thymoma in myasthenia gravis: from diagnosis to treatment. Autoimmune Dis 2011;2011:474–512. https://doi.org/10.4061/2011/474512. Epub2011 Aug 10.

    Google Scholar 

  17. Gunji K, Skolnick C, Bednarczuk T, Benes S, Ackrell BHC, Cochran P, et al. Eye muscle antibodies in patients with ocular myasthenia gravis: possible mechanism for eye muscle inflammation in acetylcholine receptor antibody-negative patients. Clin Immunol Immunopathol. 1998;87(3):276–81.

    Article  CAS  PubMed  Google Scholar 

  18. Wang W, Hen YP, Wei DN. The clinical characteristics of early-oset versus late-onset types of myasthenia gravis. Zhonghua Nei Ke Za Zhi. 2011;50(6):496–8.

    PubMed  Google Scholar 

  19. Somnier FE. Myasthenia gravis. Dan Med Bull. 1996;43(1):1–10.

    CAS  PubMed  Google Scholar 

  20. Schon F, Drayson M,Thompson RA. Myasthenia gravis in elderly people. Age Ageing. 1996;25:56–58.

    Article  CAS  PubMed  Google Scholar 

  21. Maniaol AH, Elsais A, Lorentzen AR, Owe JK, Viken MH, Seether H, et al. Late onset myasthenia gravis is associated with HLA DRB1*15:01 in the Norwegian population. PLOS ONE 2012 May 09. https://doi.org/10.1371/journal pone.0036603.

  22. Aarli JA. Late-onset myasthenia gravis. Eur J Neurol. 1997;4:203–209.

    Article  Google Scholar 

  23. Barbaud A, Carlander B, Pages M. Late onset forms of myasthenia gravis. Comparison with early-onset myasthenia gravis. Rev Neurol (Paris). 2006;162(10):990–6.

    Article  CAS  PubMed  Google Scholar 

  24. Meriggioli MN, Sanders DB. Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol. 2009;8(5):475=490.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Howard JJ, Jr Clinical overview of myasthenia gravis. http://www.myasthenia.org/healthprofessionals/clinicaloverviewofmg-aspx retrieved on 1 July 2014.

  26. Keesey JC. Clinical evaluation and management of myasthenia gravis. Muscle Nerve. 2004;29:484–505.

    Article  PubMed  Google Scholar 

  27. Chaudhry V, Cornblath DR, Griffin KW, O’Brien R, Drachman DB. Mycophenolate mofetil: a safe and promising immunosuppressant in neuromuscular disorders. Neurology. 2001;56:94–96.

    Article  CAS  PubMed  Google Scholar 

  28. Donaldson DH, Ansker M, Horan S, Rutherford RP, Ringle SP. The relationship of age to outcome of myasthenia gravis. Neurology. 1990; 40:786–790.

    Article  CAS  PubMed  Google Scholar 

  29. Antonini G, Morino S, Gragnani F, Fiorelli M. Myasthenia gravis in the elderly. Acta Neurol Sci. 1996; 93:260–263.

    Google Scholar 

  30. Kuks JBM, Linsburg PG, Horst G, Oosterhuis HJGH. Antibodies to skeletal muscle in MG part 2. Prevalence in non-thymoma patients. J Neuro Sci. 1993;120:78.

    Article  CAS  Google Scholar 

  31. Szczudlik P, Szyluk B, Lipowska M, Ryniewicz B, Kubiszewska J, Dutkiewicz M, et al. Antititin antibody in early –and late-onset myasthenia gravis. Acta Neurol Scand. 2014;130(4):229–33.

    Article  CAS  PubMed  Google Scholar 

  32. Diagnosis-How is myasthenis gravis confirmed? www.myasthenia.org.au/background/diagnosis/ accessed 25 Aug 2016.

  33. Mantegazza R, Bonanno S, Camera G, Antozzi A. Current and emerging therapies for the treatment of myasthenia gravis. Neuropsychiatr Dis Treat. 2011;7:151–160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kawaguchi N. Immunosuppressive/immunomodulating therapies in myasthenia gravis-at present and in the near future. Brain Nerve. 2–11;63(7):737–43.

    Google Scholar 

  35. Sanders DB, Evoli, Immunosuppressive therapies in myasthenia gravis. Autoimmunity. 2010;43(5–6)428–35.

    Article  CAS  PubMed  Google Scholar 

  36. Newsom-Davis J. Therapy in myasthenia gravis and Lambert-Eaton myasthenic syndrome. Semin Neurol. 2003;23(2):191–8.

    Article  PubMed  Google Scholar 

  37. Kaminski HJ. Treatment of myasthenia gravis. In: Kaminski HHJ, editor. Myasthenia and related disorders. Totowa: Humana Press; 2003 p 197–221.

    Google Scholar 

  38. Ciafaloni E, Nikhar NK, Massey JM, Sanders DM. Retrospective analysis of the use of cyclosporine in myasthenia gravis. Neurology. 2000;448–450.

    Google Scholar 

  39. Skeie GO, Aarli JA, Gilhus NE. Titin and ryanodine receptor antibodies in myasthenia gravis. Acta Neurol Scand. Suppl 2006;183:19–23.

    Article  CAS  PubMed  Google Scholar 

  40. Shah AK. Excerpt from myasthenia gravis. e medicine –Myasthenia gravis http://www.emediine.com/neuro/byname/myasthenia-gravis.htm.

  41. Suzuki S. Lambert-Eaton myasthenia syndrome (LEMS). Brain Nerve. 2010;62(4):419–26.

    PubMed  Google Scholar 

  42. Bekircan-Kurt CE, DerleCiftci E, Kurne AT, Anlar B. Voltage gated calcium antibody-related neurological diseases. World J Clin Cases. 2015;3(3):293–300.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Motomura M, Fukuda T. Lambert-Eaton myasthenic syndrome. Brain Nerve. 2011;63(7):745–54.

    PubMed  Google Scholar 

  44. Sakai W, Nakane S, Matsuo H. Autoantibody against the presynaptic P/Q- type voltage-gated calcium channel in Lambert-Eaton myasthenic syndrome. Brain Nerve. 2013;65(4):441–8.

    CAS  PubMed  Google Scholar 

  45. Writz PN, Nijnuis MG, Sotodeh M, Willems LN, Brahim JJ, Putter H, et al. The epidemiology of myasthenia gravis. Lambert-Eaton myasthenia gravis and their associated tumours in the northern part of the province of South Holland. J Neurol. 2003;250(6):698–7.

    Article  Google Scholar 

  46. Newsom-Davis J. Therapy in myasthenia gravis and Lambert-Eaton myasthenic syndrome. Semin Neurol. 2003;2(2):191–8.

    Google Scholar 

  47. Lorenzoni PJ, Scola RH, Kay CSK. Non-neoplastic Lambert-Eaton myasthenia gravis. Arq Neuropsyquiatr. 2010;68(6):849–854.

    Article  Google Scholar 

  48. Titulaer MJ, Wirtz PW, Kuks JB, Schelhs HJ, van der Kooi AJ, Faber EG, et al. The Lambert-Eaton myasthenia gravis 1988–2008: a clinical picture of 97 patients. J Neurol immunol. 2008;201–202:153–58.

    Google Scholar 

  49. Gilhus NE, Lambert-Eaton myasthenia gravis. Pathophysiology diagnosis and therapy. Autoimmun Dis. vol 2011. https://doi.org/10.4061/2011/973808.

  50. Strikler DE, Sanders DB. Lambert-Eaton Myasthenic Syndrome. e-medicine Updated Jan 10, 2007.

    Google Scholar 

  51. Sanders DB. Lambert-Eaton Myasthenic syndrome. Clinical diagnosis, immune –mediated mechanisms and update therapies. Ann Neurol. 1995;37(S1):S63.

    Article  PubMed  Google Scholar 

  52. Keogh M, Sedehizadehs S, Maddison P. Treatment for lambert-Eaton myasthenia gravis. Cochrane summaries https://doi.org/10.1002/14651858:CD003279pub3.

  53. Sanders DB, Kim YI, Howard JF, Jr, Goetsch A. Eaton-Lambert syndrome: clinical and electrophysiological study of a patient with 4-aminopyridine. J Neurol Neurosurg Psychiatry. 1980;43:978–985.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Trouth JA, Dabi A, Solieman N, Kurukumbi M, Klyanam J. Myasthenia gravis: a review. Autoimmune Dis 2012;2012:874680. https://doi.org/10.1155/2012/874680. Epub2012 Oct 31.

  55. Paul RH, Cohen RA, Goldstein JM, Gilchrist JM. Fatigue and its impact on patients with myasthenia gravis. Muscle Nerve. 23(9):1402–6.

    Google Scholar 

  56. Aarli JA. Late-onset myasthenia gravis. Neurol Rev. 1999;56(2):25–27.

    CAS  Google Scholar 

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Authors and Affiliations

  1. The University of Sydney, Westmead Clinical School, Westmead, NSW, Australia

    Nages Nagaratnam & Kujan Nagaratnam

  2. Rehabilitation and Aged Care Service, Blacktown-Mt Druitt Hospital, Mount Druitt, NSW, Australia

    Gary Cheuk

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  1. Nages Nagaratnam
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Nagaratnam, N., Nagaratnam, K., Cheuk, G. (2018). Disorders of Neuromuscular Transmission. In: Geriatric Diseases. Springer, Cham. https://doi.org/10.1007/978-3-319-33434-9_39

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  • DOI: https://doi.org/10.1007/978-3-319-33434-9_39

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