Myasthenia gravis: a clinical-immunological update

Journal of Neurology

Volumn 263, Issue 4, 2016, Pages 826-834

  Binks, Sophie ^a   Vincent, Angela ^a   Palace, Jacqueline ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

Cell based assays; IgG4; LRP4; MuSK; Myasthenia gravis; Neuromuscular junction; Thymectomy

Indexed keywords

AGRIN; AQUAPORIN 4; AZATHIOPRINE; CHOLINERGIC RECEPTOR; COLLAGEN ANTIBODY; COLLAGEN Q ANTIBODY; CORTICOSTEROID; ECULIZUMAB; EPITOPE; IMMUNOGLOBULIN G4; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 4; METHOTREXATE; MUSCLE PROTEIN; MUSCLE SPECIFIC TYROSINE KINASE; OLIGODENDROCYTE MYELIN GLYCOPROTEIN; PROTEIN TYROSINE KINASE; PYRIDOSTIGMINE; RITUXIMAB; TIRASEMTIV; UNCLASSIFIED DRUG;

ADULT; ARTICLE; CLINICAL FEATURE; DEMYELINATING DISEASE; EMERGENCY TREATMENT; EPITOPE MAPPING; HUMAN; IMMUNOPATHOGENESIS; INCIDENCE; LIFE EXPECTANCY; MYASTHENIA GRAVIS; NEUROPATHOLOGY; PLASMAPHERESIS; PRACTICE GUIDELINE; PREVALENCE; PRIORITY JOURNAL; PROTEIN TARGETING; RADIOIMMUNOASSAY; THYMECTOMY; FEMALE; IMMUNOLOGY; MALE;

FEMALE; HUMANS; MALE; MYASTHENIA GRAVIS;

EID: 84951864169     PISSN: 03405354     EISSN: 14321459     Source Type: Journal    
DOI: 10.1007/s00415-015-7963-5     Document Type: Article

References (111)

1. Meriggioli MN, Sanders DB (2009) Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol 8(5):475–490
2. Hoch W, McConville J, Helms S et al (2001) Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med 7(3):365–368
3. McConville J, Farrugia ME, Beeson D et al (2004) Detection and characterization of MuSK antibodies in seronegative myasthenia gravis. Ann Neurol 55(4):580–584
4. Koneczny I, Cossins J, Waters P et al (2013) MuSK myasthenia gravis IgG4 disrupts the interaction of LRP4 with MuSK but both IgG4 and IgG1-3 can disperse preformed agrin-independent AChR clusters. PLoS One 8(11):e80695
5. 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(51):20783–20788
6. Leite MI, Jacob S, Viegas S et al (2008) IgG1 antibodies to acetylcholine receptors in ‘seronegative’ myasthenia gravis. Brain 131(Pt 7):1940–1952
7. 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(8):994–1001
8. Rodríguez Cruz PM, Al-Hajjar M, Huda S et al (2015) Clinical features and diagnostic usefulness of antibodies to clustered acetylcholine receptors in the diagnosis of seronegative myasthenia gravis. JAMA Neurol 72(6):642–649
9. Cossins J, Belaya K, Zoltowska K et al (2012) The search for new antigenic targets in myasthenia gravis. Ann N Y Acad Sci 1275:123–128
10. Carr AS, Cardwell CR, McCarron PO et al (2010) A systematic review of population based epidemiological studies in myasthenia gravis. BMC Neurol 18(10):46
11. Pakzad Z, Aziz T, Oger J (2011) Increasing incidence of myasthenia gravis among elderly in British Columbia, Canada. Neurology 76(17):1526–1528
12. Benatar M, Sanders DB, Burns TM et al (2012) Recommendations for myasthenia gravis clinical trials. Muscle Nerve 45(6):909–917
13. Benatar M, Sanders DB, Wolfe GI et al (2012) Design of the efficacy of prednisone in the treatment of ocular myasthenia (EPITOME) trial. Ann N Y Acad Sci 1275:17–22
14. Clinical trials.gov. Efficacy of prednisone in the treatment of ocular myasthenia (EPITOME). ClinicalTrials.gov identifier NCT00995722 [on-line]. Web-page last updated 2015 Jan 6. https://clinicaltrials.gov/ct2/show/NCT00995722?term=EPITOME&rank=1. Accessed 13 Aug 2015
15. Keung B, Robeson KR, DiCapua DB et al (2013) Long-term benefit of rituximab in MuSK autoantibody myasthenia gravis patients. J Neurol Neurosurg Psychiatry 84(12):1407–1409
16. Wolfe GI, Kaminski HJ, Jaretzki A et al (2003) Development of a thymectomy trial in nonthymomatous myasthenia gravis patients receiving immunosuppressive therapy. Ann N Y Acad Sci 998:473–480
17. Gronseth GS, Barohn RJ (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(1):7–15
18. Cea G, Benatar M, Verdugo RJ et al (2013) Thymectomy for non-thymomatous myasthenia gravis. Cochrane Database Syst Rev 10:CD008111
19. Norwood F, Dhanjal M, Hill M et al (2014) Myasthenia in pregnancy: best practice guidelines from a UK multispecialty working group. J Neurol Neurosurg Psychiatry 85(5):538–543
20. Kerty E, Elsais A, Argov Z et al (2014) EFNS/ENS Guidelines for the treatment of ocular myasthenia. Eur J Neurol 21(5):687–693
21. Sussman J, Farrugia ME, Maddison P et al (2015) Myasthenia gravis: association of British Neurologists’ management guidelines. Pract Neurol 15(3):199–206
22. Cruz PMR, Palace J, Beeson D (2014) Inherited disorders of the neuromuscular junction: an update. J Neurol. 261(11):2234–2243
23. Wong SH, Huda S, Vincent A et al (2014) Ocular myasthenia gravis: controversies and updates. Curr Neurol Neurosci Rep 14(1):421
24. Phillips LH, Torner JC (1996) Epidemiologic evidence for a changing natural history of myasthenia gravis. Neurology 47(5):1233–1238
25. Poulas K, Tisbri E, Kokla A et al (2001) Epidemiology of seropositive myasthenia gravis in Greece. J Neurol Neurosurg Psychiatry 71(3):352–356
26. Vincent A, Clover L, Buckley C et al (2003) Evidence of underdiagnosis of myasthenia gravis in older people. J Neurol Neurosurg Psychiatry 74(8):1105–1108
27. Matsui N, Nakane S, Nakagawa Y et al (2009) Increasing incidence of elderly onset patients with myasthenia gravis in a local area of Japan. J Neurol Neurosurg Psychiatry 80(10):1168–1171
28. Murai H, Yamashita N, Watanabe M et al (2011) Characteristics of myasthenia according to onset-age: Japanese nationwide survey. J Neurol Sci 305(1–2):97–102
29. Somnier FE (2005) Increasing incidence of late-onset anti-AChR antibody-seropositive myasthenia gravis. Neurology 65(6):928–930
30. Parr JR, Andrew MJ, Finnis M et al (2014) How common is childhood myasthenia? The UK incidence and prevalence of autoimmune and congenital myasthenia. Arch Dis Child 99(6):539–542
31. Alkhawajah N, Oger J (2013) Late-onset myasthenia gravis: a review when incidence in older adults keeps increasing. Muscle Nerve 48(5):705–710
32. de Meel RH, Lipka AF, van Zwet EW et al (2015) Prognostic factors for exacerbations and emergency treatments in myasthenia gravis. J Neuroimmunol 15(282):123–125
33. Evoli A, Batocchi AP, Minisci C et al (2000) Clinical characteristics and prognosis of myasthenia gravis in older people. J Am Geriatr Soc 48(11):1442–1448
34. Živković SA, Clemens PR, Lacomis D (2012) Characteristics of late-onset myasthenia gravis. J Neurol 259(10):2167–2171
35. Compston DA, Vincent A, Newsom-Davis J et al (1980) Clinical, pathological, HLA antigen and immunological evidence for disease heterogeneity in myasthenia gravis. Brain 103(3):579–601
36. Linton PJ, Dorshkind K (2004) Age-related changes in lymphocyte development and function. Nat Immunol 5(2):133–139
37. Uzawa A, Kawaguchi N, Kanai T et al (2015) Two-year outcome of thymectomy in non-thymomatous late-onset myasthenia gravis. J Neurol 262(4):1019–1023
38. Tsuchida M, Yamoto Y, Souma T et al (1999) Efficacy and safety of extended thymectomy for elderly patients with myasthenia gravis. Ann Thorac Surg 67(6):1563–1567
39. UK clinical research network study portfolio. A prospective study of late-onset myasthenia gravis. UKCRN 13582 [on-line]. http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=13582. Accessed 13 Aug 2015
40. Phillips LH, Juel VC (1999) Myasthenia gravis in the tenth decade. Muscle Nerve 22(9):1297–1298
41. Alshekhlee A, Miles JD, Katirji B et al (2009) Incidence and mortality rates of myasthenia gravis and myasthenic crisis in US hospitals. Neurology 72(18):1548–1554
42. Punga AR, Sawada M, Stalberg EV (2008) Electrophysiological signs and the prevalence of adverse effects of acetylcholinesterase inhibitors in patients with myasthenia gravis. Muscle Nerve 37(3):300–307
43. Sanders DB, El-Salem K, Massey JM et al (2003) Clinical aspects of MuSK antibody positive seronegative MG. Neurology 60(12):1978–1980
44. Evoli A, Tonali PA, Padua L et al (2003) Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis. Brain 126(Pt 10):2304–2311
45. 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(1):36–40
46. Lavrnic D, Losen M, Vujic A et al (2005) The features of myasthenia gravis with autoantibodies to MuSK. J Neurol Neurosurg Psychiatry 76(8):1099–1102
47. Pasnoor M, Wolfe GI, Nations S et al (2010) Clinical findings in MuSK-antibody positive myasthenia gravis: a US experience. Muscle Nerve 41(3):370–374
48. Vincent A, Leite MI (2005) Neuromuscular junction autoimmune disease: muscle specific kinase antibodies and treatments for myasthenia gravis. Curr Opin Neurol 18(5):519–525
49. Yeh JH, Chen WH, Chiu HC et al (2004) Low frequency of MuSK antibody in generalized seronegative myasthenia gravis among Chinese. Neurology 62(11):2131–2132
50. Tsiamalos P, Kordas G, Kokla A et al (2009) Epidemiological and immunological profile of muscle-specific kinase myasthenia gravis in Greece. Eur J Neurol 16(8):925–930
51. Niks EH, Kuks JB, Verschuuren JJ (2007) Epidemiology of myasthenia gravis with anti-muscle specific kinase antibodies in the Netherlands. J Neurol Neurosurg Psychiatry 78(4):417–418
52. Niks EH, Kuks JB, Roep BO et al (2006) Strong association of MuSK antibody–positive myasthenia gravis and HLA-DR14-DQ5. Neurology 66(11):1772–1774
53. Bartoccioni E, Scuderi F, Augugliaro et al (2009) HLA class II allele analysis in MuSK-positive myasthenia gravis suggests a role for DQ5. Neurology 72(2):195–197
54. Alahgholi-Hajibehzad M, Yilmaz V, Gülsen-Parman Y et al (2013) Association of HLA-DRB*1, -DRB*16 and -DQB1*05 with MuSK-myasthenia gravis in patients from Turkey. Hum Immunol 74(12):1633–1635
55. Waters P, McKeon A, Leite MI et al (2012) Serologic diagnosis of NMO. A multicenter comparison of aquaporin-4-IgG assays. Neurology 78(9):665–671
56. Rodríguez Cruz PM, Huda S, López-Ruiz P et al (2015) Use of cell-based assays in myasthenia gravis and other antibody-mediated diseases. Exp Neurol 270:66–71
57. Devic P, Petiot P, Simonet T et al (2014) Antibodies to clustered acetylcholine receptor: expanding the phenotype. Eur J Neurol 21(1):130–134
58. Tsonis AI, Zisimopoulou P, Lazaridis K et al (2015) MuSK autoantibodies in myasthenia gravis detected by cell based assay—a multinational study. J Neuroimmunol 15(284):10–17
59. Koneczny I, Cossins J, Vincent A (2014) The role of muscle-specific tyrosine kinase (MuSK) and mystery of MuSK myasthenia gravis. J Anat 224(1):29–35
60. Kim N, Steigler AL, Cameron TO et al (2008) Lrp4 is a receptor for agrin and forms a complex with MuSK. Cell 135(2):334–342
61. Zhang B, Luo S, Wang Q et al (2008) LRP4 serves as a coreceptor of agrin. Neuron 60(2):285–297
62. Huijbers MG, Querol LA, Niks EH et al (2015) The expanding field of IgG4-mediated neurological autoimmune disorders. Eur J Neurol 22(8):1151–1161
63. Bartoccioni E, Scuderi F, Minicuci GM et al (2006) Anti-MuSK antibodies: correlation with myasthenia gravis severity. Neurology 67(3):505–507
64. Niks EH, van Leeuwen Y, Leite MI et al (2008) Clinical fluctuations in MuSK myasthenia gravis are related to antigen-specific IgG4 instead of IgG1. J Neuroimmunol 195(1–2):151–156
65. 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(Pt 4):1081–1101
66. Viegas S, Jacobson L, Waters P et al (2012) Passive and active immunization models of MuSK-Ab positive myasthenia: electrophysiological evidence for pre and postsynaptic defects. Exp Neurol 234(2):506–512
67. Yumoto N, Kim N, Burden S (2012) Lrp4 is a retrograde signal for presynaptic differentiation at neuromuscular synapses. Nature 489(7416):438–442
68. Higuchi O, Hamuro J, Motomura M et al (2011) Autoantibodies to low-density lipoprotein receptor–related protein 4 in Myasthenia Gravis. Ann Neurol 69(2):418–422
69. Pevzner A, Schoser B, Peters K et al (2012) Anti-LRP4 autoantibodies in AChR- and MuSK-antibody negative myasthenia gravis. J Neurol 259(3):427–435
70. Zhang B, Tzartos JS, Belimezi M et al (2012) Autoantibodies to lipoprotein-related protein 4 in patients with double-seronegative myasthenia gravis. Arch Neurol 69(4):445–451
71. 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
72. Zhang B, Shen C, Bealmear B et al (2014) Autoantibodies to agrin in myasthenia gravis patients. PLoS One 9(3):e91816
73. Gasperi C, Melms A, Schoser B et al (2014) Anti-agrin autoantibodies in myasthenia gravis. Neurology 82(22):1976–1983
74. Cartaud A, Strochlic L, Guerra M et al (2004) MuSK is required for anchoring acetylcholinesterase at the neuromuscular junction. J Cell Biol 165(4):505–515
75. Katarzyna M, Belaya K, Leite M et al (2015) Collagen Q—a potential target for autoantibodies in myasthenia gravis. J Neurol Sci 348(1–2):241–244
76. Leite MI, Coutinho E, Lana-Peixoto M et al (2012) Myasthenia gravis and neuromyelitis optica spectrum disorder. A multicenter study of 16 patients. Neurology 78(20):1601–1607
77. Gotkine M, Fellig Y, Abramsky O (2006) Occurrence of CNS demyelinating disease in patients with myasthenia gravis. Neurology 67(5):881–883
78. Isbister CM, Mackenzie PJ, Anderson D (2003) Co-occurrence of multiple sclerosis and myasthenia gravis in British Columbia. Mult Scler 9(6):550–553
79. Spillane J, Christofi G, Sidle KC et al (2013) Myasthenia gravis and neuromyelitis optica: a causal link. Mult Scler Relat Disord 2(3):233–237
80. Bever CT, Aquino AV, Penn AS et al (1983) Prognosis of ocular myasthenia. Ann Neurol 14(5):516–519
81. Sommer N, Sigg B, Melms A et al (1997) Ocular myasthenia gravis: response to long term immunosuppressive treatment. J Neurol Neurosurg Psychiatry 62(2):156–162
82. Kupersmith MJ (2009) Ocular myasthenia gravis: treatment successes and failures in patients with long-term follow-up. J Neurol 256(8):1314–1320
83. Wong SH, Plant GT, Cornblath W (2015) Does treatment of ocular myasthenia gravis with early immunosuppressive therapy prevent secondarily generalization and should it be offered to all such patients? J Neuroophthalmol [Epub ahead of print]
84. Mee J, Paine M, Byrne E et al (2003) Immunotherapy of ocular myasthenia gravis reduces conversion to generalized myasthenia gravis. J Neuroophthalmol 23(4):251–255
85. Grob D, Brunner N, Namba T et al (2008) Lifetime course of myasthenia gravis. Muscle Nerve 37(2):141–149
86. Wong S, Petrie A, Plant G (2015) Ocular MG: towards a risk of generalisation (‘ROG’) score. In: Association of British Neurologists (ABN) annual meeting, final programme and abstract book, 2015 May 20-2; Harrogate, UK: ABN; 2015 p 48
87. Kumar V, Kaminski HJ (2011) Treatment of myasthenia gravis. Curr Neurol Neurosci Rep 11(1):89–96
88. Palace J, Newsom-Davis J, Lecky B et al (1998) A randomized double-blind trial of prednisolone alone or with azathioprine in myasthenia gravis. Neurology 50(6):1778–1783
89. Heckmann J, 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 5(11):97
90. Zhou L, McConville J, Chaudhry V et al (2004) Clinical comparison of muscle-specific tyrosine kinase (MuSK) antibody-positive and -negative myasthenic patients. Muscle Nerve 30(1):55–60
91. Maddison P, McConville J, Farrugia ME et al (2011) The use of rituximab in myasthenia gravis and Lambert Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry 82(6):671–673
92. Díaz-Manera J, Martínez-Hernández E, Querol L et al (2012) Long-lasting treatment effect of rituximab in MuSK myasthenia. Neurology 78(3):189–193
93. Iorio R, Damato V, Aboini PE et al (2015) Efficacy and safety of rituximab for myasthenia gravis: a systematic review and meta-analysis. J Neurol 262(5):1115–1119
94. Catzola V, Battaglia A, Buzzonetti A et al (2013) Changes in regulatory T-cells after rituximab in two patients with refractory myasthenia gravis. J Neurol 260(8):2163–2165
95. Howard JF, Barohn RJ, Cutter GR et al (2013) A randomized, double-blind, placebo-controlled phase II trial of eculizumab in patients with refractory generalized myasthenia gravis. Muscle Nerve 48(1):76–84
96. Clinical trials.gov. Safety and efficacy of eculizumab in refractory generalized myasthenia gravis (REGAIN study). ClinicalTrials.gov identifier NCT01997229 [on-line]. Web-page last updated 2015 July 6. https://clinicaltrials.gov/ct2/show/NCT01997229. Accessed 13 Aug 2015
97. Argov Z, McKee D, Agus S et al (2007) Treatment of human myasthenia with oral antisense suppression of acetylcholinesterase. Neurology 69(7):699–700
98. Sussman J, Argov Z, Wirguin Y et al (2012) Further developments with antisense treatment for myasthenia gravis. Ann N Y Acad Sci 1275:13–16
99. Sanders DB, Rosenfeld J, Dimachkie MM et al (2015) A double-blinded, randomized, placebo-controlled trial to evaluate efficacy, safety, and tolerability of single doses of Tirasemtiv in patients with acetylcholine receptor-binding antibody-positive myasthenia gravis. Neurotherapeutics 12(2):455–460
100. Barth D, Nouri MN, Ng E et al (2011) Comparison of IVIg and PLEX in patients with myasthenia gravis. Neurology 76(23):2017–2023
101. Bril V, Barnett-Tapia C, Barth D et al (2012) IVIg and PLEX in the treatment of myasthenia gravis. Ann N Y Acad Sci 1275:1–6
102. Marx A, Pfister F, Schalke B et al (2012) Thymus pathology observed in the MGTX trial. Ann N Y Acad Sci 1275:92–100
103. Lauriola L, Ranelletti F, Maggiano N et al (2005) Thymus changes in anti-MuSK-positive and -negative myasthenia gravis. Neurology 64(3):536–538
104. Leite MI, Ströbel P, Jones M et al (2005) Fewer thymic changes in MuSK antibody-positive than in MuSK antibody-negative MG. Ann Neurol 57(3):444–448
105. Saka E, Topcuoglu MA, Akkaya B et al (2005) Thymus changes in anti-MuSK-positive and -negative myasthenia gravis. Neurology 65(5):782–783 (author reply 782–3)
106. Shrager JB (2010) Extended transcervical thymectomy: the ultimate minimally invasive approach. Ann Thorac Surg 89(6):S2128–S2134
107. Freeman RK, Ascioti AJ, van Woerkom JM et al (2011) Long-term follow-up after robotic thymectomy for nonthymomatous myasthenia gravis. Ann Thorac Surg 92(3):1018–1022 (discussion 1022–3)
108. Marulli G, Schiavon M, Perissinotto E et al (2013) Surgical and neurologic outcomes after robotic thymectomy in 100 consecutive patients with myasthenia gravis. J Thorac Cardiovasc Surg 145(3):730–735 (discussion 735–6)
109. Spillane J, Hayward M, Hirsch NP et al (2013) Thymectomy: role in the treatment of myasthenia gravis. J Neurol 260(7):1798–1801
110. Keijzers M, de Baets M, Hochstenbag M et al (2015) Robotic thymectomy in patients with myasthenia gravis: neurological and surgical outcomes. Eur J Cardiothorac Surg 48(1):40–45
111. Rückert JC, Swierzy M, Ismail M (2011) Comparison of robotic and nonrobotic thoracoscopic thymectomy: a cohort study. J Thorac Cardiovasc Surg 141(3):673–677