Neurologie up2date 2024; 07(01): 12-26
DOI: 10.1055/a-2116-0102
Schritt für Schritt

Myasthenia gravis – Schritt für Schritt

Meret Herdick
,
Hannah Preßler
,
Andreas Meisel

Die Myasthenia gravis wird durch eine autoantikörpervermittelte Übertragungsstörung an der neuromuskulären Endplatte hervorgerufen. Leitsymptom ist eine belastungsabhängige Muskelschwäche. Diagnostisch haben der Nachweis von typischen Autoantikörpern und die elektrophysiologische Untersuchung einen hohen Stellenwert. Symptomatische und immunmodulierende medikamentöse Therapien stehen zur Verfügung, für bestimmte Patienten auch die Thymektomie. Die Prognose wird durch myasthene Krisen bestimmt, die mit einer erhöhten Mortalität einhergehen.



Publication History

Article published online:
05 March 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • Literatur

  • 1 Breiner A, Widdifield J, Katzberg HD. et al. Epidemiology of myasthenia gravis in Ontario, Canada. Neuromuscul Disord 2016; 26: 41-46
  • 2 Carr AS, Cardwell CR, McCarron PO. et al. A systematic review of population based epidemiological studies in Myasthenia Gravis. BMC Neurol 2010; 10: 46
  • 3 Chen J, Tian DC, Zhang C. et al. Incidence, mortality, and economic burden of myasthenia gravis in China: A nationwide population-based study. Lancet Reg Health West Pac 2020; 5: 100063
  • 4 Deenen JC, Horlings CG, Verschuuren JJ. et al. The Epidemiology of Neuromuscular Disorders: A Comprehensive Overview of the Literature. J Neuromuscul Dis 2015; 2: 73-85
  • 5 Bundesministerium für Gesundheit. Seltene Erkrankungen. Stand: 23. Juni 2022. 10.1007/s00103-022-03597-w.
  • 6 Chamberlain-Banoub J, Neal JW, Mizuno M. et al. Complement membrane attack is required for endplate damage and clinical disease in passive experimental myasthenia gravis in Lewis rats. Clin Exp Immunol 2006; 146: 278-286
  • 7 Engel AG, Lambert EH, Howard FM. Immune complexes (IgG and C3) at the motor end-plate in myasthenia gravis: ultrastructural and light microscopic localization and electrophysiologic correlations. Mayo Clin Proc 1977; 52: 267-280
  • 8 Almon RR, Andrew CG, Appel SH. Serum globulin in myasthenia gravis: inhibition of alpha-bungarotoxin binding to acetylcholine receptors. Science 1974; 186: 55-57
  • 9 Drachman DB, Angus CW, Adams RN. et al. Myasthenic antibodies cross-link acetylcholine receptors to accelerate degradation. N Engl J Med 1978; 298: 1116-1122
  • 10 Szczudlik P, Szyluk B, Lipowska M. et al. Antititin antibody in early- and late-onset myasthenia gravis. Acta Neurol Scand 2014; 130: 229-233
  • 11 Jaretzki A, Barohn 3rd RJ, Ernstoff RM. et al. Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology 2000; 55: 16-23
  • 12 Ruiter AM, Verschuuren J, Tannemaat MR. Fatigue in patients with myasthenia gravis. A systematic review of the literature. Neuromuscul Disord 2020; 30: 631-639
  • 13 Putman MT, Wise RA. Myasthenia gravis and upper airway obstruction. Chest 1996; 109: 400-404
  • 14 Grob D, Brunner N, Namba T. et al. Lifetime course of myasthenia gravis. Muscle Nerve 2008; 37: 141-149
  • 15 Maddison P, Ambrose PA, Sadalage G. et al. A Prospective Study of the Incidence of Myasthenia Gravis in the East Midlands of England. Neuroepidemiology 2019; 53: 93-99
  • 16 Rivner MH, Pasnoor M, Dimachkie MM. et al. Muscle-Specific Tyrosine Kinase and Myasthenia Gravis Owing to Other Antibodies. Neurol Clin 2018; 36: 293-310
  • 17 Gilhus NE, Skeie GO, Romi F. et al. Myasthenia gravis - autoantibody characteristics and their implications for therapy. Nat Rev Neurol 2016; 12: 259-268
  • 18 O'Connell K, Ramdas S, Palace J. Management of juvenile myasthenia gravis. Front Neurol 2020; 11: 743
  • 19 Marx A, Pfister F, Schalke B. et al. The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes. Autoimmun Rev 2013; 12: 875-884
  • 20 Cron MA, Maillard S, Villegas J. et al. Thymus involvement in early-onset myasthenia gravis. Ann N Y Acad Sci 2018; 1412: 137-145
  • 21 Wendell LC, Levine JM. Myasthenic crisis. Neurohospitalist 2011; 1: 16-22
  • 22 Nelke C, Stascheit F, Eckert C. et al. Independent risk factors for myasthenic crisis and disease exacerbation in a retrospective cohort of myasthenia gravis patients. J Neuroinflammation 2022; 19: 89
  • 23 Blum S, Lee D, Gillis D. et al. Clinical features and impact of myasthenia gravis disease in Australian patients. J Clin Neurosci 2015; 22: 1164-1169
  • 24 Gummi RR, Kukulka NA, Deroche CB. et al. Factors associated with acute exacerbations of myasthenia gravis. Muscle Nerve 2019; 60: 693-699
  • 25 Wiendl H, Meisel A. et al. Diagnostik und Therapie myasthener Syndrome, S2k-Leitlinie. DGN 2022; in: Deutsche Gesellschaft für Neurologie (Hrsg.).
  • 26 Meriggioli MN, Sanders DB. Advances in the diagnosis of neuromuscular junction disorders. Am J Phys Med Rehabil 2005; 84: 627-638
  • 27 Benatar M. A systematic review of diagnostic studies in myasthenia gravis. Neuromuscul Disord 2006; 16: 459-467
  • 28 Sanders DB, Cao L, Massey JM. et al. Is the decremental pattern in Lambert-Eaton syndrome different from that in myasthenia gravis?. Clin Neurophysiol 2014; 125: 1274-1277
  • 29 Lennon VA, Kryzer TJ, Griesmann GE. et al. Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes. N Engl J Med 1995; 332: 1467-1474
  • 30 Motomura M, Lang B, Johnston I. et al. Incidence of serum anti-P/O-type and anti-N-type calcium channel autoantibodies in the Lambert-Eaton myasthenic syndrome. J Neurol Sci 1997; 147: 35-42
  • 31 Titulaer MJ, Maddison P, Sont JK. et al. Clinical Dutch-English Lambert-Eaton Myasthenic syndrome (LEMS) tumor association prediction score accurately predicts small-cell lung cancer in the LEMS. J Clin Oncol 2011; 29: 902-908
  • 32 Oh SJ, Jeong D, Lee I. et al. Repetitive nerve stimulation test in myasthenic crisis. Muscle Nerve 2019; 59: 544-548
  • 33 Priola AM, Priola SM. Imaging of thymus in myasthenia gravis: from thymic hyperplasia to thymic tumor. Clin Radiol 2014; 69: e230-245
  • 34 Klimiec E, Quirke M, Leite MI. et al. Thymus imaging in myasthenia gravis: The relevance in clinical practice. Muscle Nerve 2018;
  • 35 Christensen PB, Jensen TS, Tsiropoulos I. et al. Associated autoimmune diseases in myasthenia gravis. A population-based study. Acta Neurol Scand 1995; 91: 192-195
  • 36 Fang F, Sveinsson O, Thormar G. et al. The autoimmune spectrum of myasthenia gravis: a Swedish population-based study. J Intern Med 2015; 277: 594-604
  • 37 Maggi L, Mantegazza R. Treatment of myasthenia gravis: focus on pyridostigmine. Clin Drug Investig 2011; 31: 691-701
  • 38 Pascuzzi RM, Coslett HB, Johns TR. Long-term corticosteroid treatment of myasthenia gravis: report of 116 patients. Ann Neurol 1984; 15: 291-298
  • 39 Palace J, Newsom-Davis J, Lecky B. A randomized double-blind trial of prednisolone alone or with azathioprine in myasthenia gravis. Myasthenia Gravis Study Group. Neurology 1998; 50: 1778-1783
  • 40 Blum S, Gillis D, Brown H. et al. Use and monitoring of low dose rituximab in myasthenia gravis. J Neurol Neurosurg Psychiatry 2011; 82: 659-663
  • 41 Maddison P, McConville J, Farrugia ME. et al. The use of rituximab in myasthenia gravis and Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry 2011; 82: 671-673
  • 42 Diaz-Manera J, Martinez-Hernandez E, Querol L. et al. Long-lasting treatment effect of rituximab in MuSK myasthenia. Neurology 2012; 78: 189-193
  • 43 Evoli A, Bianchi MR, Riso R. et al. Response to therapy in myasthenia gravis with anti-MuSK antibodies. Ann N Y Acad Sci 2008; 1132: 76-83
  • 44 Piehl F, Eriksson-Dufva A, Budzianowska A. et al. Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis: The RINOMAX Randomized Clinical Trial. JAMA Neurol 2022; 79: 1105-1112
  • 45 Meisel A, Annane D, Vu T. et al. Long-term efficacy and safety of ravulizumab in adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis: results from the phase 3 CHAMPION MG open-label extension. J Neurol 2023;
  • 46 Muppidi S, Utsugisawa K, Benatar M. et al. Long-term safety and efficacy of eculizumab in generalized myasthenia gravis. Muscle Nerve 2019; 60: 14-24
  • 47 Ulrichts P, Guglietta A, Dreier T. et al. Neonatal Fc receptor antagonist efgartigimod safely and sustainably reduces IgGs in humans. J Clin Invest 2018; 128: 4372-4386
  • 48 Kuo TT, Baker K, Yoshida M. et al. Neonatal Fc receptor: from immunity to therapeutics. J Clin Immunol 2010; 30: 777-789
  • 49 Howard JF, Bril V, Vu T. et al. Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet Neurol 2021; 20: 526-536
  • 50 Kohler W, Bucka C, Klingel R. A randomized and controlled study comparing immunoadsorption and plasma exchange in myasthenic crisis. J Clin Apher 2011; 26: 347-355
  • 51 Gajdos P, Chevret S, Toyka KV. Intravenous immunoglobulin for myasthenia gravis. Cochrane Database Syst Rev 2012; 12: CD002277
  • 52 Ried M, Marx A, Gotz A. et al. State of the art: diagnostic tools and innovative therapies for treatment of advanced thymoma and thymic carcinoma. Eur J Cardiothorac Surg 2016; 49: 1545-1552
  • 53 Kurup A, Loehrer Sr PJ. Thymoma and thymic carcinoma: therapeutic approaches. Clin Lung Cancer 2004; 6: 28-32
  • 54 Wolfe GI, Kaminski HJ, Aban IB. et al. Randomized Trial of Thymectomy in Myasthenia Gravis. N Engl J Med 2016; 375: 511-522
  • 55 Wolfe GI, Kaminski HJ, Aban IB. et al. Long-term effect of thymectomy plus prednisone versus prednisone alone in patients with non-thymomatous myasthenia gravis: 2-year extension of the MGTX randomised trial. Lancet Neurol 2019; 18: 259-268
  • 56 Li F, Takahashi R, Bauer G. et al. Results of Robotic Thymectomy Performed in Myasthenia Gravis Patients Older Than 60 Years at Onset. Ann Thorac Surg 2019; 108: 912-919
  • 57 Clifford KM, Hobson-Webb LD, Benatar M. et al. Thymectomy may not be associated with clinical improvement in MuSK myasthenia gravis. Muscle Nerve 2019; 59: 404-410
  • 58 Schneider-Gold C, Hagenacker T, Melzer N. et al. Understanding the burden of refractory myasthenia gravis. Ther Adv Neurol Disord 2019; 12: 1756286419832242
  • 59 Neumann B, Angstwurm K, Mergenthaler P. et al. Myasthenic crisis demanding mechanical ventilation: A multicenter analysis of 250 cases. Neurology 2020; 94: e299-e313
  • 60 Mantegazza R, Antozzi C. When myasthenia gravis is deemed refractory: clinical signposts and treatment strategies. Ther Adv Neurol Disord 2018; 11: 1756285617749134
  • 61 Wolfe GI, Herbelin L, Nations SP. et al. Myasthenia gravis activities of daily living profile. Neurology 1999; 52: 1487-1489
  • 62 Stetefeld H, Schroeter M. SOP myasthenic crisis. Neurol Res Pract 2019; 1: 19
  • 63 Stetefeld HR, Schroeter M. Myasthenic Crisis. Fortschr Neurol Psychiatr 2018; 86: 301-307
  • 64 Fakiri MO, Tavy DL, Hama-Amin AD. et al. Accuracy of the ice test in the diagnosis of myasthenia gravis in patients with ptosis. Muscle Nerve 2013; 48: 902-904
  • 65 Bedlack RS, Simel DL, Bosworth H. et al. Quantitative myasthenia gravis score: assessment of responsiveness and longitudinal validity. Neurology 2005; 64: 1968-1970
  • 66 Damato V, Spagni G, Monte G. et al. Clinical value of cell-based assays in the characterisation of seronegative myasthenia gravis. J Neurol Neurosurg Psychiatry 2022; 93: 995-1000
  • 67 Ing EB, Ing SY, Ing T. et al. The complication rate of edrophonium testing for suspected myasthenia gravis. Can J Ophthalmol 2000; 35: 141-144 discussion 145
  • 68 Beekman R, Kuks JB, Oosterhuis HJ. Myasthenia gravis: diagnosis and follow-up of 100 consecutive patients. J Neurol 1997; 244: 112-118
  • 69 Jack KL, Koopman WJ, Hulley D. et al. A Review of Azathioprine-Associated Hepatotoxicity and Myelosuppression in Myasthenia Gravis. J Clin Neuromuscul Dis 2016; 18: 12-20