Diagnosis and Treatment Methods of Autoimmune Myasthenia Gravis: A Systematic Review
Year 2022,
Volume: 4 Issue: 2, 104 - 116, 31.07.2022
Melike Nur Yangın
Yaşar Zorlu
Feride Severcan
Abstract
Myasthenia Gravis causes abnormalities in the neuromuscular junction, which is an autoimmune disorder and has a prevalence of 15-20 per 100,000 people. Although skeletal and extraocular muscles are commonly affected by the disease, approximately 10% of patients have severe involvement in the muscles necessary for respiration. A myasthenic crisis may cause life-threatening consequences. The prevalence and incidence of autoimmune MG increase with age. Women's disease incidence peaks between the ages of 30 and 40, while men's incidence peaks between the ages of 60 and 80. The existence of autoantibodies against postsynaptic membrane proteins is the most crucial indicator of myasthenia gravis. Anti-AChR (acetylcholine receptor antibody) positive is a distinct feature of MG (% 80). While anti-MuSK (muscle-specific kinase antibody) positivity is detected in 1-10% of all patients, LRP4 (low density lipoprotein receptor related protein 4) antibody positivity is seen in 3-25% of MG patients without AChR and MuSK antibodies (anti-LRP4). Despite many methods used in the diagnosis of Myasthenia Gravis, it is not possible to make the diagnosis in some patients because of conditions that may vary from patient to patient, such as fluctuation in symptoms and clinical findings. Rapid diagnosis is crucial in patients with Myasthenia Gravis, because effective treatment must begin as early as possible to prevent potentially fatal complications. Moreover, rapid diagnosis of patients and determination of the patient's subtype is an important step in the treatment process. Therefore, the aim of this study is to summarize the techniques used in the diagnosis and treatment of myasthenia gravis which is one of the rare diseases.
Supporting Institution
Tübitak; Altınbaş Üniversitesi
Project Number
TUBITAK-1003-SBAG-218S986; AYP2021-3
Thanks
Türkiye Bilimsel ve Teknik Araştırma Kurumu, TÜBİTAK-1003 SBAG-Proje no:218S986 ve Altınbaş Üniversitesi, AYP2021-3 projesine teşekkür ederiz.
References
- Beloor Suresh, A. and Asuncion, RMD. Myasthenia Gravis, StatPearls [Internet], 2021, Available from: https://www.ncbi.nlm.nih.gov/books/NBK559331/?report=classichttps://www.ncbi.nlm.nih.gov/books/NBK559331/
- Berrih-Aknin, S., Frenkian-Cuvelier, M. & Eymard, B. (2014). Diagnostic and clinical classification of autoimmune myasthenia gravis. J Autoimmun, 48-49:143-8.
- Conti-Fine, BM., Milani, M. & Kaminski, HJ. (2006). Myasthenia gravis: past, present, and future. J Clin Invest, 116(11):2843-54.
- Dincer, A. (2015) Expression of TRAIL/TRAIL Receptors in T-Cell Subtypes in the Clinical Presentations of Myasthenia Gravis (Dissertation for specialty in medicine). Retrived from Ulusal Tez Merkezi – Turkey & Adana. (426698)
- Evoli, A. and Padua, L. (2013). Diagnosis and therapy of myasthenia gravis with antibodies to muscle-specific kinase. Autoimmun. Rev, 12, 931–935.
- Frykman, H., Kumar, P., & Oger, J. (2020). Immunopathology of Autoimmune Myasthenia Gravis: Implications for Improved Testing Algorithms and Treatment Strategies. Frontiers in neurology, 11, 596621.
- Gilhus, N.E. & Verschuuren, J.J. (2015). Myasthenia gravis: Subgroup classification and therapeutic strategies. Lancet Neurol, 14, 1023–1036.
- Gilhus, N.E., Tzartos, S., Evoli, A., Palace, J., Burns, T.M. & Verschuuren, J.J.G.M. (2019). Myasthenia gravis. Nat. Rev. Dis. Prim., 5, 30.
- Gilhus, NE., Skeie, GO., Romi, F., Lazaridis, K., Zisimopoulou, P. & Tzartos, S. (2016). Myasthenia gravis autoantibody characteristics and their implicationsfor therapy. Nat Rev Neurol, 12:259- 268.
- Gronseth, G.S. and Barohn, R.J. (2000). Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 55:7-15.
- Guo, F., Wang, C. Y., Wang, S., Zhang, J., Yan, Y. J., Guan, Z. Y., & Meng, F. J. (2019). Alteration in gene expression profile of thymomas with or without myasthenia gravis linked with the nuclear factor-kappaB/autoimmune regulator pathway to myasthenia gravis pathogenesis. Thoracic cancer, 10(3), 564–570.
- Gwathmey, K.G. & Burns, T.M. (2015). Myasthenia Gravis Semin Neurol, 35 (4):327-39.
- Ingelfinger, F., Krishnarajah, S., Kramer, M., Utz, S. G., Galli, E., Lutz, M., Zwicky, P., Akarca, A. U., Jurado, N. P., Ulutekin, C., Bamert, D., Widmer, C. C., Piccoli, L., Sallusto, F., Núñez, N. G., Marafioti, T., Schneiter, D., Opitz, I., Lanzavecchia, A., Jung, H. H., … Becher, B. (2021). Single-cell profiling of myasthenia gravis identifies a pathogenic T cell signature. Acta neuropathologica, 141(6), 901–915.
- Jayam Trouth, A., Dabi, A., Solieman, N., Kurukumbi, M., & Kalyanam, J. (2012). Myasthenia gravis: a review. Autoimmune diseases, 2012, 874680.
- Lazaridis, K. & Tzartos, S.J. (2020). Autoantibody Specificities in Myasthenia Gravis; Implications for Improved Diagnostics and Therapeutics. Front. Immunol, 11, 212.
- Lennon, V.A. (1997). Serologic profile of myasthenia gravis and distinction from the Lambert- Eaton myasthenic syndrome. Neurology, 48:S23–S27.
- Lleo, A., Invernizzi, P., Gao, B., Podda, M., Gershwin, M.E. (2010). Definition of human autoimmunity--autoantibodies versus autoimmune disease. Autoimmun Rev, 9(5):A259-66.
- Lushchekina, S., Kots, E., Kharlamova, A., Petrov, K., Masson, P. (2015). Molecular modeling of mechanism of action of anti-myasthenia gravis slow-binding inhibitor of acetylcholinesterase. Int J Risk Saf Med.;27 Suppl 1:S74-5
- Marx, A., Pfister, F., Schalke, B., Saruhan-Direskeneli, G., Melms, A. & Ströbel, P. (2013). The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes. Autoimmun Rev, 12: 875–84.
- Melzer, N., Ruck, T., Fuhr, P., Gold, R., Hohlfeld, R., Marx, A., Melms, A., Tackenberg, B., Schalke, B., Schneider-Gold, C., Zimprich, F., Meuth, S. G., & Wiendl, H. (2016). Clinical features, pathogenesis, and treatment of myasthenia gravis: a supplement to the Guidelines of the German Neurological Society. Journal of neurology, 263(8), 1473–1494.
- Meriggioli, M.N. and Sanders, D.B. (2004). Myasthenia Gravis: Diagnosis. Semin. Neurol, 24, 31–39.
- Montero-Odasso, M. (2006). Dysphonia as first symptom of late-onset myasthenia gravis. J Gen Intern Med, 21(6):C4-6.
- Murai, H., Noda, T., Himeno, E., Kawano, Y., Ohyagi, Y., Shiraishi, H., Motomura, M. & Kira, J. (2006). Infantile onset myasthenia gravis with MuSK antibodies. Neurology, 67(1):174
Ngo, S.T., Steyn, F.J., McCombe, P.A.(2014). Gender differences in autoimmune disease. Front Neuroendocrinol, 35(3):347-69.
- Oh, S.J., Kim, D.E., Kuruoglu, R., Bradley, R.J. and Dwyer, D. (1992). Diagnostic sensitivity of the laboratory tests in myasthenia gravis. Muscle and Nerve, 15:720–724.
Pascuzzi, RM. (2003). The edrophonium test. Semin Neurol, 23:83-8.
- Pasnoor, M., Dimachkie, M.M., Farmakidis, C. & Barohn, R.J. (2018). Diagnosis of Myasthenia Gravis. Neurol. Clin, 36, 261–274.
- Remes-Troche, J.M., Téllez-Zenteno, J.F., Estañol, B., Garduño-Espinoza, J. & García-Ramos, G. (2002). Thymectomy in Myasthenia Gravis: Response, Complications, and Associated Conditions. Arch Med Res 33: 545-51.
- Rousseff, R.T. (2021). Diagnosis of Myasthenia Gravis. J Clin Med, 16; 10(8):1736.
- Samuelsson, A., Towers, T.L. & Ravetch, J.V. (2001). Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor. Science, 19;291(5503):484-6.
- Shelly, S., Paul, P., Bi, H., Dubey, D., Milone, M., Sorenson, E.J., Crum, B.A., Laughlin, R.S., Liewluck, T., Mandrekar, J., Pittock, S.J., Zekeridou, A., McKeon, A., Harper, M.C., Mills, J.R. & Klein, C.J. (2020). Improving accuracy of myasthenia gravis autoantibody testing by reflex algorithm. Neurology, 95, e3002–e3011.
- Sieb, J. P. (2014). Myasthenia gravis: an update for the clinician. Clinical and experimental immunology, 175(3), 408–418.
- Skeie, G. O., Apostolski, S., Evoli, A., Gilhus, N. E., Illa, I., Harms, L. & Horge, H. W. (2010). Guidelines for treatment of autoimmune neuromuscular transmission disorders. European Journal of Neurology, 17(7), 893–902.
- Vincent, A. & Newsom-Davis, J. (1985). Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays. Journal of Neurology Neurosurgery and Psychiatry, 48:1246–52.
- Vincent, A., Bowen, J., Newsom-Davis, J., & McConville, J. (2003). Seronegative generalised myasthenia gravis: clinical features, antibodies, and their targets. The Lancet Neurology. 2(2), 99–106.
- Vincent, A., Huda, S., Cao, M., Cetin, H., Koneczny, I., Cruz, P.M.R., Jacobson, L., Viegas, S., Jacob, S., Woodhall, M., Nagaishi, A., Maniaol, A., Damato, V., Leite, M.I., Cossins, J., Webster, R., Palace, J. & Beeson, D. (2018). Serological and experimental studies in different forms of myasthenia gravis. Ann. N. Y. Acad. Sci, 1413, 143–153.
- Yavuz, Z. (2019). Myastenia Gravis Klinik ve Demografik Özellikleri (Dissertation for specialty in medicine). Retrived from Ulusal Tez Merkezi – Turkey & Ankara. (602539)
- Zhang, B., Tzartos, J.S., Belimezi, M., Ragheb, S., Bealmear, B., Lewis, R.A., Xiong, W.C., Lisak, R.P., Tzartos, S.J. & Mei, L. (2012). Autoantibodies to lipoprotein-related protein 4 in patients with double-seronegative myasthenia gravis. Arch Neurol, 69(4):445-51.
Diagnosis and Treatment Methods of Autoimmune Myasthenia Gravis: A Systematic Review
Year 2022,
Volume: 4 Issue: 2, 104 - 116, 31.07.2022
Melike Nur Yangın
Yaşar Zorlu
Feride Severcan
Abstract
Myasthenia Gravis causes abnormalities in the neuromuscular junction, which is an autoimmune disorder and has a prevalence of 15-20 per 100,000 people. Although skeletal and extraocular muscles are commonly affected by the disease, approximately 10% of patients have severe involvement in the muscles necessary for respiration. A myasthenic crisis may cause life-threatening consequences. The prevalence and incidence of autoimmune MG increase with age. Women's disease incidence peaks between the ages of 30 and 40, while men's incidence peaks between the ages of 60 and 80. The existence of autoantibodies against postsynaptic membrane proteins is the most crucial indicator of myasthenia gravis. Anti-AChR (acetylcholine receptor antibody) positive is a distinct feature of MG (% 80). While anti-MuSK (muscle-specific kinase antibody) positivity is detected in 1-10% of all patients, LRP4 (low density lipoprotein receptor related protein 4) antibody positivity is seen in 3-25% of MG patients without AChR and MuSK antibodies (anti-LRP4). Despite many methods used in the diagnosis of Myasthenia Gravis, it is not possible to make the diagnosis in some patients because of conditions that may vary from patient to patient, such as fluctuation in symptoms and clinical findings. Rapid diagnosis is crucial in patients with Myasthenia Gravis, because effective treatment must begin as early as possible to prevent potentially fatal complications. Moreover, rapid diagnosis of patients and determination of the patient's subtype is an important step in the treatment process. Therefore, the aim of this study is to summarize the techniques used in the diagnosis and treatment of myasthenia gravis which is one of the rare diseases.
Project Number
TUBITAK-1003-SBAG-218S986; AYP2021-3
References
- Beloor Suresh, A. and Asuncion, RMD. Myasthenia Gravis, StatPearls [Internet], 2021, Available from: https://www.ncbi.nlm.nih.gov/books/NBK559331/?report=classichttps://www.ncbi.nlm.nih.gov/books/NBK559331/
- Berrih-Aknin, S., Frenkian-Cuvelier, M. & Eymard, B. (2014). Diagnostic and clinical classification of autoimmune myasthenia gravis. J Autoimmun, 48-49:143-8.
- Conti-Fine, BM., Milani, M. & Kaminski, HJ. (2006). Myasthenia gravis: past, present, and future. J Clin Invest, 116(11):2843-54.
- Dincer, A. (2015) Expression of TRAIL/TRAIL Receptors in T-Cell Subtypes in the Clinical Presentations of Myasthenia Gravis (Dissertation for specialty in medicine). Retrived from Ulusal Tez Merkezi – Turkey & Adana. (426698)
- Evoli, A. and Padua, L. (2013). Diagnosis and therapy of myasthenia gravis with antibodies to muscle-specific kinase. Autoimmun. Rev, 12, 931–935.
- Frykman, H., Kumar, P., & Oger, J. (2020). Immunopathology of Autoimmune Myasthenia Gravis: Implications for Improved Testing Algorithms and Treatment Strategies. Frontiers in neurology, 11, 596621.
- Gilhus, N.E. & Verschuuren, J.J. (2015). Myasthenia gravis: Subgroup classification and therapeutic strategies. Lancet Neurol, 14, 1023–1036.
- Gilhus, N.E., Tzartos, S., Evoli, A., Palace, J., Burns, T.M. & Verschuuren, J.J.G.M. (2019). Myasthenia gravis. Nat. Rev. Dis. Prim., 5, 30.
- Gilhus, NE., Skeie, GO., Romi, F., Lazaridis, K., Zisimopoulou, P. & Tzartos, S. (2016). Myasthenia gravis autoantibody characteristics and their implicationsfor therapy. Nat Rev Neurol, 12:259- 268.
- Gronseth, G.S. and Barohn, R.J. (2000). Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 55:7-15.
- Guo, F., Wang, C. Y., Wang, S., Zhang, J., Yan, Y. J., Guan, Z. Y., & Meng, F. J. (2019). Alteration in gene expression profile of thymomas with or without myasthenia gravis linked with the nuclear factor-kappaB/autoimmune regulator pathway to myasthenia gravis pathogenesis. Thoracic cancer, 10(3), 564–570.
- Gwathmey, K.G. & Burns, T.M. (2015). Myasthenia Gravis Semin Neurol, 35 (4):327-39.
- Ingelfinger, F., Krishnarajah, S., Kramer, M., Utz, S. G., Galli, E., Lutz, M., Zwicky, P., Akarca, A. U., Jurado, N. P., Ulutekin, C., Bamert, D., Widmer, C. C., Piccoli, L., Sallusto, F., Núñez, N. G., Marafioti, T., Schneiter, D., Opitz, I., Lanzavecchia, A., Jung, H. H., … Becher, B. (2021). Single-cell profiling of myasthenia gravis identifies a pathogenic T cell signature. Acta neuropathologica, 141(6), 901–915.
- Jayam Trouth, A., Dabi, A., Solieman, N., Kurukumbi, M., & Kalyanam, J. (2012). Myasthenia gravis: a review. Autoimmune diseases, 2012, 874680.
- Lazaridis, K. & Tzartos, S.J. (2020). Autoantibody Specificities in Myasthenia Gravis; Implications for Improved Diagnostics and Therapeutics. Front. Immunol, 11, 212.
- Lennon, V.A. (1997). Serologic profile of myasthenia gravis and distinction from the Lambert- Eaton myasthenic syndrome. Neurology, 48:S23–S27.
- Lleo, A., Invernizzi, P., Gao, B., Podda, M., Gershwin, M.E. (2010). Definition of human autoimmunity--autoantibodies versus autoimmune disease. Autoimmun Rev, 9(5):A259-66.
- Lushchekina, S., Kots, E., Kharlamova, A., Petrov, K., Masson, P. (2015). Molecular modeling of mechanism of action of anti-myasthenia gravis slow-binding inhibitor of acetylcholinesterase. Int J Risk Saf Med.;27 Suppl 1:S74-5
- Marx, A., Pfister, F., Schalke, B., Saruhan-Direskeneli, G., Melms, A. & Ströbel, P. (2013). The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes. Autoimmun Rev, 12: 875–84.
- Melzer, N., Ruck, T., Fuhr, P., Gold, R., Hohlfeld, R., Marx, A., Melms, A., Tackenberg, B., Schalke, B., Schneider-Gold, C., Zimprich, F., Meuth, S. G., & Wiendl, H. (2016). Clinical features, pathogenesis, and treatment of myasthenia gravis: a supplement to the Guidelines of the German Neurological Society. Journal of neurology, 263(8), 1473–1494.
- Meriggioli, M.N. and Sanders, D.B. (2004). Myasthenia Gravis: Diagnosis. Semin. Neurol, 24, 31–39.
- Montero-Odasso, M. (2006). Dysphonia as first symptom of late-onset myasthenia gravis. J Gen Intern Med, 21(6):C4-6.
- Murai, H., Noda, T., Himeno, E., Kawano, Y., Ohyagi, Y., Shiraishi, H., Motomura, M. & Kira, J. (2006). Infantile onset myasthenia gravis with MuSK antibodies. Neurology, 67(1):174
Ngo, S.T., Steyn, F.J., McCombe, P.A.(2014). Gender differences in autoimmune disease. Front Neuroendocrinol, 35(3):347-69.
- Oh, S.J., Kim, D.E., Kuruoglu, R., Bradley, R.J. and Dwyer, D. (1992). Diagnostic sensitivity of the laboratory tests in myasthenia gravis. Muscle and Nerve, 15:720–724.
Pascuzzi, RM. (2003). The edrophonium test. Semin Neurol, 23:83-8.
- Pasnoor, M., Dimachkie, M.M., Farmakidis, C. & Barohn, R.J. (2018). Diagnosis of Myasthenia Gravis. Neurol. Clin, 36, 261–274.
- Remes-Troche, J.M., Téllez-Zenteno, J.F., Estañol, B., Garduño-Espinoza, J. & García-Ramos, G. (2002). Thymectomy in Myasthenia Gravis: Response, Complications, and Associated Conditions. Arch Med Res 33: 545-51.
- Rousseff, R.T. (2021). Diagnosis of Myasthenia Gravis. J Clin Med, 16; 10(8):1736.
- Samuelsson, A., Towers, T.L. & Ravetch, J.V. (2001). Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor. Science, 19;291(5503):484-6.
- Shelly, S., Paul, P., Bi, H., Dubey, D., Milone, M., Sorenson, E.J., Crum, B.A., Laughlin, R.S., Liewluck, T., Mandrekar, J., Pittock, S.J., Zekeridou, A., McKeon, A., Harper, M.C., Mills, J.R. & Klein, C.J. (2020). Improving accuracy of myasthenia gravis autoantibody testing by reflex algorithm. Neurology, 95, e3002–e3011.
- Sieb, J. P. (2014). Myasthenia gravis: an update for the clinician. Clinical and experimental immunology, 175(3), 408–418.
- Skeie, G. O., Apostolski, S., Evoli, A., Gilhus, N. E., Illa, I., Harms, L. & Horge, H. W. (2010). Guidelines for treatment of autoimmune neuromuscular transmission disorders. European Journal of Neurology, 17(7), 893–902.
- Vincent, A. & Newsom-Davis, J. (1985). Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays. Journal of Neurology Neurosurgery and Psychiatry, 48:1246–52.
- Vincent, A., Bowen, J., Newsom-Davis, J., & McConville, J. (2003). Seronegative generalised myasthenia gravis: clinical features, antibodies, and their targets. The Lancet Neurology. 2(2), 99–106.
- Vincent, A., Huda, S., Cao, M., Cetin, H., Koneczny, I., Cruz, P.M.R., Jacobson, L., Viegas, S., Jacob, S., Woodhall, M., Nagaishi, A., Maniaol, A., Damato, V., Leite, M.I., Cossins, J., Webster, R., Palace, J. & Beeson, D. (2018). Serological and experimental studies in different forms of myasthenia gravis. Ann. N. Y. Acad. Sci, 1413, 143–153.
- Yavuz, Z. (2019). Myastenia Gravis Klinik ve Demografik Özellikleri (Dissertation for specialty in medicine). Retrived from Ulusal Tez Merkezi – Turkey & Ankara. (602539)
- Zhang, B., Tzartos, J.S., Belimezi, M., Ragheb, S., Bealmear, B., Lewis, R.A., Xiong, W.C., Lisak, R.P., Tzartos, S.J. & Mei, L. (2012). Autoantibodies to lipoprotein-related protein 4 in patients with double-seronegative myasthenia gravis. Arch Neurol, 69(4):445-51.