Myasthenia gravis classification

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Charmaine Patel, M.D. [2]

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Myasthenia gravis may be classified into 4 sub types based on presence of autoantibodies: Pure ocular form, generalized form with anti-AChR antibodies, the forms without classical anti-AChR antibodies, neonatal MG, congenital.


Myasthenia gravis may be classified into 4 sub types based on presence of autoantibodies.

Pure ocular form

  • Ocular symptoms are the initial symptom in most of the MG cases.
  • In about 15 percent of these patients this initial symptom will not progress to generalized disease after 2 years and they will classify as pure ocular form of the Myasthenia gravis.
  • In approximately 50 percent of these patients we can’t detect antibodies by classical assay and we need to detect them through cell-based assay.[1]

Generalized form with anti-AChR antibodies

About 85 percent of MG patients develop generalized disease with autoantibody against AchR.[2] These antibodies are IgG1 and IgG3 subclasses which can bind to complement.[3] Thymic abnormalities are more common in this group, especially thymic follicular hyperplasia.[4] this subtype can be further divided into 2 groups:

  • Early onset myasthenia gravis (onset of the disease before the age of 50 (EOMG)): In this group we have female predominance with the ratio of 3/1. Thymic follicular hyperplasia is more common in this group and is believed to be related to deregulation of sex hormones and their receptors on thymic cells.[5][6]
  • These patients can have other autoimmune diseases like Hashimoto’s disease.[7]
  • Late onset myasthenia gravis (onset of the disease after the age of 50 (LOMG)): Patients with this type of the disease can present with thymoma, a tumor of thymic epithelial cells.[8] In almost 50 percent of them we can find other antibodies like anti-ryanodine antibody, anti-titin antibody and anti-striated muscle antibody.[9] most of the patients in this group have severe symptoms like bulbar involvement.[10]

The forms without classical anti-AChR antibodies

This subtype can be further divided into 3 groups

Neonatal MG

  • 10-20 percent of mothers with MG may have infants who display a transient neonatal myasthenia (TNM) for few days to 3 months.
  • The cause of this condition is passive transfer of antibodies to the neonate.[19]



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  3. Verschuuren JJ, Huijbers MG, Plomp JJ, Niks EH, Molenaar PC, Martinez-Martinez P, Gomez AM, De Baets MH, Losen M (July 2013). "Pathophysiology of myasthenia gravis with antibodies to the acetylcholine receptor, muscle-specific kinase and low-density lipoprotein receptor-related protein 4". Autoimmun Rev. 12 (9): 918–23. doi:10.1016/j.autrev.2013.03.001. PMID 23535160.
  4. Berrih S, Morel E, Gaud C, Raimond F, Le Brigand H, Bach JF (January 1984). "Anti-AChR antibodies, thymic histology, and T cell subsets in myasthenia gravis". Neurology. 34 (1): 66–71. PMID 6228745.
  5. Eymard B, Berrih-Aknin S (January 1995). "[Role of the thymus in the physiopathology of myasthenia]". Rev. Neurol. (Paris) (in French). 151 (1): 6–15. PMID 7676132.
  6. Nancy P, Berrih-Aknin S (May 2005). "Differential estrogen receptor expression in autoimmune myasthenia gravis". Endocrinology. 146 (5): 2345–53. doi:10.1210/en.2004-1003. PMC 1839841. PMID 15661863.
  7. Klein R, Marx A, Ströbel P, Schalke B, Nix W, Willcox N (September 2013). "Autoimmune associations and autoantibody screening show focused recognition in patient subgroups with generalized myasthenia gravis". Hum. Immunol. 74 (9): 1184–93. doi:10.1016/j.humimm.2013.06.020. PMID 23792059.
  8. Marx A, Pfister F, Schalke B, Saruhan-Direskeneli G, Melms A, Ströbel P (July 2013). "The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes". Autoimmun Rev. 12 (9): 875–84. doi:10.1016/j.autrev.2013.03.007. PMID 23535159.
  9. Suzuki S, Utsugisawa K, Nagane Y, Suzuki N (2011). "Three types of striational antibodies in myasthenia gravis". Autoimmune Dis. 2011: 740583. doi:10.4061/2011/740583. PMC 3139883. PMID 21785709.
  10. Romi F, Aarli JA, Gilhus NE (June 2007). "Myasthenia gravis patients with ryanodine receptor antibodies have distinctive clinical features". Eur. J. Neurol. 14 (6): 617–20. doi:10.1111/j.1468-1331.2007.01785.x. PMID 17539937.
  11. 11.0 11.1 Evoli A, Tonali PA, Padua L, Monaco ML, Scuderi F, Batocchi AP, Marino M, Bartoccioni E (October 2003). "Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis". Brain. 126 (Pt 10): 2304–11. doi:10.1093/brain/awg223. PMID 12821509.
  12. McConville J, Farrugia ME, Beeson D, Kishore U, Metcalfe R, Newsom-Davis J, Vincent A (April 2004). "Detection and characterization of MuSK antibodies in seronegative myasthenia gravis". Ann. Neurol. 55 (4): 580–4. doi:10.1002/ana.20061. PMID 15048899.
  13. Leite MI, Ströbel P, Jones M, Micklem K, Moritz R, Gold R, Niks EH, Berrih-Aknin S, Scaravilli F, Canelhas A, Marx A, Newsom-Davis J, Willcox N, Vincent A (March 2005). "Fewer thymic changes in MuSK antibody-positive than in MuSK antibody-negative MG". Ann. Neurol. 57 (3): 444–8. doi:10.1002/ana.20386. PMID 15732104.
  14. Le Panse R, Berrih-Aknin S (October 2013). "Autoimmune myasthenia gravis: autoantibody mechanisms and new developments on immune regulation". Curr. Opin. Neurol. 26 (5): 569–76. doi:10.1097/WCO.0b013e328364d6cd. PMID 23995274.
  15. Bartoccioni E, Scuderi F, Minicuci GM, Marino M, Ciaraffa F, Evoli A (August 2006). "Anti-MuSK antibodies: correlation with myasthenia gravis severity". Neurology. 67 (3): 505–7. doi:10.1212/01.wnl.0000228225.23349.5d. PMID 16894117.
  16. Higuchi O, Hamuro J, Motomura M, Yamanashi Y (February 2011). "Autoantibodies to low-density lipoprotein receptor-related protein 4 in myasthenia gravis". Ann. Neurol. 69 (2): 418–22. doi:10.1002/ana.22312. PMID 21387385.
  17. Pevzner A, Schoser B, Peters K, Cosma NC, Karakatsani A, Schalke B, Melms A, Kröger S (March 2012). "Anti-LRP4 autoantibodies in AChR- and MuSK-antibody-negative myasthenia gravis". J. Neurol. 259 (3): 427–35. doi:10.1007/s00415-011-6194-7. PMID 21814823.
  18. Zhang B, Tzartos JS, Belimezi M, Ragheb S, Bealmear B, Lewis RA, Xiong WC, Lisak RP, Tzartos SJ, Mei L (April 2012). "Autoantibodies to lipoprotein-related protein 4 in patients with double-seronegative myasthenia gravis". Arch. Neurol. 69 (4): 445–51. doi:10.1001/archneurol.2011.2393. PMID 22158716.
  19. Béhin A, Mayer M, Kassis-Makhoul B, Jugie M, Espil-Taris C, Ferrer X, Chatenoud L, Laforêt P, Eymard B (June 2008). "Severe neonatal myasthenia due to maternal anti-MuSK antibodies". Neuromuscul. Disord. 18 (6): 443–6. doi:10.1016/j.nmd.2008.03.006. PMID 18434154.
  20. Engel AG, Sine SM (June 2005). "Current understanding of congenital myasthenic syndromes". Curr Opin Pharmacol. 5 (3): 308–21. doi:10.1016/j.coph.2004.12.007. PMID 15907919.

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