Download PDF
Nervenheilkunde 2004; 23(03): 127-131
DOI: 10.1055/s-0038-1626299
Arbeiten zum Schwerpunkt - Theme Articles
Schattauer GmbH

Neues zur Myasthenia gravis

Advances in myasthenia gravis
A. Berthele
1   Neurologische Klinik der TU München (Direktor: Prof. Dr. med. Bastian Conrad)
,
B. Conrad
1   Neurologische Klinik der TU München (Direktor: Prof. Dr. med. Bastian Conrad)
› Author Affiliations
Further Information

Publication History

Publication Date:
19 January 2018 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Die Myasthenia gravis ist die klassische neurologische Autoimmunerkrankung. Bei dieser Erkrankung kommt es durch pathologische Autoantikörper zu einer Störung der neuromuskulären Übertragung. Bei der überwiegenden Zahl der Betroffenen lassen sich ursächlich Antikörper gegen den Acetylcholinrezeptor (AChR) nachweisen. Fortschritte wurden in den letzten Jahren insbesondere durch die Identifikation eines weiteren pathogenen Auto-Antikörpers bei der so genannten AChR-Antikörper-negativen Myasthenie gemacht. Außerdem liegen Untersuchungen vor, anhand derer der diagnostische Stellenwert der Antikörper gegen quergestreifte Muskulatur, insbesondere der Titin-Antikörper, besser beurteilt werden kann. In dieser Übersicht werden darüber hinaus die Datenlage zum Nutzen der Thymektomie und neue Entwicklungen in der Pharmakotherapie zusammengefasst.

Summary

Myasthenia gravis is an antibody-mediated autoimmune disease. Classically, antibodies against the acetylcholine receptor (AChR) cause inactivation and loss of acetylcholine receptors at the neuromuscular junction. Progress has been made not only in the identification of alternate autoantibodies in so called AChR-antibody negative patients but also concerning the diagnostic value of antibodies against striated muscle proteins. In this review, these advances in myasthenia gravis are summarized. Moreover, concerning therapy, the value of thymectomy is discussed and recent developments in immunotherapy are reported.

Schlüsselwörter

Antikörper-negative Myasthenie - MuSK-Antikörper - Titin-Antikörper - Thymektomie - Mycophenolat Mofetil

Keywords

Antibody-negative myasthenia - MuSK-antibody - Titin-antibody - thymectomy - mycophenolate mofetil
 

  • Literatur

  • 1 Aarli JA, Skeie GO, Mygland A, Gilhus NE. Muscle striation antibodies in myasthenia gravis: diagnostic and functional significance. Ann New York Acad Sci 1998; 841: 505-15.
    CrossrefPubMedSearch in Google Scholar
  • 2 Beghi E, Antozzi C, Batocchi AP, Cornelio F, Cosi V, Evoli A, Lombardi M, Mantegazza R, Monticelli ML, Piccolo G. et al. Prognosis of myasthenia gravis: a multicenter follow-up study of 844 patients. J Neurol Sci 1991; 106: 213-20.
    CrossrefPubMedSearch in Google Scholar
  • 3 Blattner R, Köhler W, Janzen RWC. Umfrage zur Praxis der Thymektomie bei Myasthenia gravis. Akt Neurol 1998; 25: S77-80.
    Thieme ConnectSearch in Google Scholar
  • 4 Chaudhry V, Cornblath DR, Griffin JW, O’Brien R, Drachman DB. Mycophenolate mofetil: a safe and promising immunosuppressant in neuromuscular diseases. Neurology 2001; 56: 94-6.
    CrossrefPubMedSearch in Google Scholar
  • 5 Ciafaloni E, Massey JM, Tucker-Lipscomb B, Sanders DB. Mycophenolate mofetil for myasthenia gravis: An open-label pilot study. Neurology 2001; 56: 97-9.
    CrossrefPubMedSearch in Google Scholar
  • 6 De Baets M, Stassen MHW. The role of antibodies in myasthenia gravis. J Neurol Sci 2002; 202: 5-11.
    CrossrefPubMedSearch in Google Scholar
  • 7 Diener HC. Off-label use in der Neurologie. Akt Neurol 2003; 29: 379-81.
    Thieme ConnectSearch in Google Scholar
  • 8 Engel AG, Ohno K, Sine SM. Sleuthing molecular targets for neurological diseases at the neuromuscular junction. Nature Rev 2003; 04: 339-52.
    Search in Google Scholar
  • 9 Evoli A, Di Schino C, Marsili F, Punzi C. Successful treatment of myasthenia gravis with tacrolimus. Muscle Nerve 2002; 25: 111-4.
    CrossrefPubMedSearch in Google Scholar
  • 10 Evoli A, Minisci C, Di Schino C, Marsili F, Punzi C, Batocchi AP, Tonali PA, Doglietto GB, Granone P, Trodella L, Cassano A, Lauriola L. Thymoma in patients with MG: characteristics and long-term outcome. Neurology 2002; 59: 1844-50.
    CrossrefPubMedSearch in Google Scholar
  • 11 Evoli A, Tonali PA, Padua L, Monaco ML, Scuderi F, Batocchi AP, Marino M, Bartoccioni E. Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis. Brain 2003; 126: 2304-11.
    CrossrefPubMedSearch in Google Scholar
  • 12 Gronseth GS, Barohn RJ. Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence-based review). Report of the quality standards subcommittee of the American Academy of Neurology. Neurology 2000; 55: 7-15.
    CrossrefPubMedSearch in Google Scholar
  • 13 Hoch W, McConville J, Helms S, Newsom-Davis J, Melms A, Vincent A. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nature Medicine 2001; 07: 365-8.
    CrossrefPubMedSearch in Google Scholar
  • 14 Hohlfeld R, Toyka KV, Besinger UA, Gerhold B, Heininger K. Myasthenia gravis: reactivation of clinical disease and of autoimmune factors after discontinuation of long-term azathioprine. Ann Neurol 1985; 17: 238-42.
    CrossrefPubMedSearch in Google Scholar
  • 15 Johnson SB, Eng TY, Giaccone G, Thomas Jr CR. Thymoma – update for the new millenium. Oncologist 2001; 06: 239-46.
    CrossrefPubMedSearch in Google Scholar
  • 16 Labeit S, Kolmerer B. Titins: giant proteins in charge of muscle ultrastructure and elasticity. Science 1995; 270: 293-6.
    CrossrefPubMedSearch in Google Scholar
  • 17 Liyanage Y, Hoch W, Beeson D, Vincent A. The agrin/muscle-specific kinase pathway: new targets for autoimmune and genetic disorders at the neuromuscular junction. Muscle Nerve 2002; 25: 4-16.
    CrossrefPubMedSearch in Google Scholar
  • 18 Marienhagen J, Schalke B, Aebert H, Held P, Eilles C, Bogdahn U. Somatostatin receptor scintigraphy in thymoma imaging: method and clinical application. Pathol Res Pract 1999; 195: 575-81.
    CrossrefPubMedSearch in Google Scholar
  • 19 Marx A, Wilisch A, Schultz A, Gattenlöhner S, Nenninger R, Müller-Hermelink HK. Pathogenesis of myasthenia gravis. Virchows Arch 1997; 430: 355-64.
    CrossrefPubMedSearch in Google Scholar
  • 20 Moder KG. Mycophenolate mofetil: new applications for this immunosuppressant. Ann Allergy Asthma Immunol 2003; 90: 15-20.
    CrossrefPubMedSearch in Google Scholar
  • 21 Mowzoon N, Sussman A, Bradley WG. Mycofenolate (CellCept) treatment of myasthenia gravis, chronic inflammatory polyneuropathy and inclusion body myositis. J Neurol Sci 2001; 185: 119-22.
    CrossrefPubMedSearch in Google Scholar
  • 22 Müller-Hermelink HK, Marx A. Thymoma. Curr Opin Oncol 2000; 12: 426-33.
    CrossrefPubMedSearch in Google Scholar
  • 23 Myasthenia gravis clinical study group. A randomized clinical trial comparing prednisolone and azathioprine in myasthenia gravis. Results of the second interim analysis. J Neurol Neurosurg Psychiatry 1993; 56: 1157-63.
    CrossrefPubMedSearch in Google Scholar
  • 24 Palace J, Newsom-Davis J, Lecky B. A randomized double-blind trial of prednisolone alone or with azathioprine im myasthenia gravis. Myasthenia Gravis Study Group. Neurology 1998; 50: 1778-83.
    CrossrefPubMedSearch in Google Scholar
  • 25 Papanastasiou D, Poulas K, Kokla A, Tzartos SJ. Prevention of passively transferred experimental autoimmune myasthenia gravis by Fab fragments of monoclonal antibodies directed against the main immunogenic region of the acetylcholine receptor. J Neuroimmunol 2000; 104: 124-32.
    CrossrefPubMedSearch in Google Scholar
  • 26 Romi F, Skeie GO, Aarli JA, Gilhus NE. Muscle autoantibodies in subgroups of myasthenia gravis patients. J Neurol 2000; 247: 369-75.
    CrossrefPubMedSearch in Google Scholar
  • 27 Romi F, Skeie GO, Aarli JA, Gilhus NE. The severity of myasthenia gravis correlates with the serum concentration of titin and ryanodine receptors antibodies. Arch Neurol 2000; 57: 1596-600.
    PubMedSearch in Google Scholar
  • 28 Romi F, Gilhus NE, Varhaug JE, Myking A, Skeie GO, Aarli JA. Thymectomy and antimuscle autoantibodies in late-onset myasthenia gravis. Eur J Neurol 2002; 09: 55-61.
    Search in Google Scholar
  • 29 Sanders DB, Andrews I, Howard JF, Massey JM. Seronegative myasthenia gravis. Neurology 1997; 48: S40-5.
    CrossrefSearch in Google Scholar
  • 30 Schneider C, Gold R, Reiners K, Toyka KV. Mycophenolate mofetil in the therapy of severe myasthenia gravis. Eur Neurol 2001; 46: 79-82.
    CrossrefPubMedSearch in Google Scholar
  • 31 Sieb JP, Kraner S, Köhler W, Schalke B, Steinlein OK. Myasthenia gravis und myasthene Syndrome. Deutsches Ärzteblatt 2000; 97: A 3496-500.
    Search in Google Scholar
  • 32 Toyka KV. Therapeutischer Stellenwert von Azathioprin bei der Behandlung der Myasthenia gravis: Stellungnahme der Deutschen Gesellschaft für Neurologie. Akt Neurol 2003; 30: 1-2.
    Thieme ConnectSearch in Google Scholar
  • 33 Vincent A. Unravelling the pathogenesis of myasthenia gravis. Nature Rev Immunol 2002; 02: 797-804.
    CrossrefPubMedSearch in Google Scholar
  • 34 Voltz RD, Albrich WC, Nägele A, Schumm F, Wick M, Freiburg A, Gautel M, Thaler HT, Aarli JA, Kirchner T, Hohlfeld R. Paraneoplastic myasthenia gravis: detection of anti-MGT30 (titin) antibodies predicts thymic epithelial tumor. Neurology 1997; 49: 1454-7.
    CrossrefPubMedSearch in Google Scholar
  • 35 Voltz RD, Albrich WC, Hohlfeld R, Nagel D, Wick M, Kirchner T, Sommer N, Illa I, Kaminski H, Schumm F. Anti-titin antibodies are not associated with a specific thymoma histology. J Neurol Neurosurg Psychiatry 2003; 74: 282.
    CrossrefPubMedSearch in Google Scholar
  • 36 Yamamoto AM, Gajdos P, Eymard B, Tranchant C, Warter J-M, Gomez L, Bourquin C, Bach J-F, Garchon H-J. Anti-titin antibodies in myasthenia gravis. Arch Neurol 2001; 58: 885-90.
    CrossrefPubMedSearch in Google Scholar
  • 37 Yoshikawa H, Mabuchi K, Yasukawa Y, Takamori M, Yamada M. Low-dose tacrolimus for intractable myasthenia gravis. J Clin Neurosci 2002; 09: 627-8.
    CrossrefPubMedSearch in Google Scholar