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Klinische Neurophysiologie 2014; 45(04): 193-200
DOI: 10.1055/s-0034-1395554
Originalia
© Georg Thieme Verlag KG Stuttgart · New York

Erworbene neuromuskuläre Überleitungsstörungen: Myasthenien und Lambert-Eaton Syndrom

Acquired Neuromuscular Transmission Disorders: Myasthenias and Lambert-Eaton Syndrome
L. Kirzinger
1   Neurologische Klinik der Universität im Bezirksklinikum Regensburg
,
B. Schalke
1   Neurologische Klinik der Universität im Bezirksklinikum Regensburg
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
22. Dezember 2014 (online)

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Zusammenfassung

Die Gruppe der erworbenen myasthenen Syndrome gliedert sich in die postsynaptischen Myasthenien (MG) und das präsynaptische Lambert-Eaton-Syndrom (LEMS). Durch Verbesserung der Diagnostik (Rezeptor-Auto-Antikörper Diagnostik, Elektrophysiologie, Bildgebung, pharmakologische Testung) ist es möglich die spezifischen Erkrankungen nach pathophysiologischen Gesichtspunkten definierten Untergruppen zuzuordnen. Dies ermöglicht eine bessere und speziellere Therapie z. B. Indikation für die Thymektomie oder Vermeidung von Thymektomie, unterschiedliche Immunsuppression oder differenzierter Einsatz der Cholinesteraseinhibitoren im Rahmen der symptomatischen Therapie. Durch die gezieltere Diagnostik aufgrund des besseren pathophysiologischen Verständnisses, ist es möglich Therapien gezielter einzusetzen, Fehlbehandlungen zu vermeiden und zu einer größeren Patientenzufriedenheit zu gelangen.

Abstract

The group of acquired myasthenic syndromes can be divided into the postsynaptic myasthenias (MG) and the presynaptic Lambert-Eaton syndrome (LEMS). By improvement of diagnostic procedures (receptor-auto-antibody testing, electrophysiology, imaging, pharmacological testing) it is possible to refer the specific diseases to pathophysiologically defined subgroups. This enables a better and more specific therapy, e. g., indication for thymectomy or no thymectomy, different or more specific use of cholinesterase inhibitors for symptomatic treatment. Having more selective diagnostic as a consequence of the better pathophysiological understanding of the underlying processes at the neuromuscular synapsis, it is possible to use therapies more selectively, to avoid medical malpractice and to provide a better satisfaction for the patient.

Schlüsselwörter

Myasthenia gravis - neuromuskuläre Erkrankungen - Myasthenien - Lambert-Eaton Syndrom

Key words

Myasthenia gravis - neuromuscular diseases - Myasthenias - Lambert-Eaton Syndrome
 

  • Literatur

  • 1 Berrih-Aknin S, Frenkian-Cuvelier M, Eymard B. Diagnostic and clinical classification of autoimmune myasthenia gravis. J Autoimmun 2014; 48-49: 143-148 DOI: 10.1016/j.jaut.2014.01.003. . [Epub 2014 Feb 13]
    CrossrefPubMedGoogle Scholar
  • 2 Osserman KE, Genkins G. Studies in myasthenia gravis: review of a twenty-year experience in over 1 200 patients. Mt Sinai J Med 1971; 38: 497-537
    PubMedGoogle Scholar
  • 3 Benatar M, Sanders DB, Burns TM et al. Recommendations for myasthenia gravis clinical trials. Task Force on MG Study Design of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Muscle Nerve 2012; 45: 909-917
    CrossrefPubMedGoogle Scholar
  • 4 Compston DAS, Vincent A, Newsomdavis J et al. Clinical pathological, HLA-antigen and immunological evidence for disease heterogeneity in myasthenia gravis. Brain 1980; 103: 579-601
    CrossrefPubMedGoogle Scholar
  • 5 Meriggioli MN, Sanders DB. Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol 2009; 8: 475-490
    CrossrefPubMedGoogle Scholar
  • 6 Benatar M, Kaminski HJ. Evidence report: The medical treatment of ocular myasthenia (an evidence-based review) – Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2007; 68: 2144-2214
    CrossrefPubMedGoogle Scholar
  • 7 Luchanok U, Kaminski HJ. Ocular myasthenia: diagnostic and treatment recommendations and the evidence base. Curr Opin Neurol 2008; 21: 8-15
    CrossrefPubMedGoogle Scholar
  • 8 Mehndiratta MM, Pandey S, Kuntzer T. Acetylcholinesterase inhibitor treatment for myasthenia gravis. Cochrane Database Syst Rev 2011; 2 CD006986
    PubMedGoogle Scholar
  • 9 Seybold ME, Drachman DB. Gradually increasing doses of prednisone in myasthenia gravis – reducing hazards of treatment. N Engl J Med 1974; 290: 81-84
    CrossrefPubMedGoogle Scholar
  • 10 Schneider-Gold C, Gajdos P, Toyka KV et al. Corticosteroids for myasthenia gravis. Cochrane Database Syst Rev 2005; 2 CD002828
    PubMedGoogle Scholar
  • 11 Mertens HG, Balzerei F, Leipert M. Treatment of severe myasthenia gravis with immunosuppressive agents. Eur Neurol 1969; 2: 321-326
    CrossrefPubMedGoogle Scholar
  • 12 Bromberg MB, Wald JJ, Forshew DA et al. Randomized trial of azathioprine or prednisone for initial immunosuppressive treatment of myasthenia gravis. J Neurol Sci 1997; 150: 59-62
    CrossrefPubMedGoogle Scholar
  • 13 Mantegazza R, Antozzi C, Peluchetti D et al. Azathioprine as a single drug or in combination with steroids in the treatment of myasthenia gravis. J Neurology 1988; 235: 449-453
    CrossrefPubMedGoogle Scholar
  • 14 Sanders DB, Hart IK, Mantegazza R et al. An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis. Neurology 2008; 71: 400-406
    CrossrefPubMedGoogle Scholar
  • 15 Henze T, Janzen RWC, Schumm F et al. für den Ärztlichen Beirat der Deutschen Myasthenie-Gesellschaft (DMG), Weber Schondorfer C . Immuntherapie bei Myasthenia gravis und Lambert-Eaton-Syndrom. Teil 1: Medikamentöse Immunsuppression. Akt Neurol 2010; 37: 505-517
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 16 Henze T, Janzen RWC, Schumm F et al. für den Ärztlichen Beirat der Deutschen Myasthenie-Gesellschaft (DMG), Weber Schondorfer C . Immuntherapie bei Myasthenia gravis und Lambert-Eaton-Syndrom. Teil 2: Intravenöse Immunglobuline und Plasmaaustauschverfahren. Akt Neurol 2010; 37: 518-523
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 17 Dau PC, Lindstrom JM, Cassel CK et al. Plasmapheresis and immunosuppressive drug therapy in myasthenia gravis. N Engl J Med 1977; 297: 1134-1140
    CrossrefPubMedGoogle Scholar
  • 18 Achiron A, Barak Y, Miron S et al. Immunoglobulin treatment in refractory myasthenia gravis. Muscle Nerve 2000; 23: 551-555
    CrossrefPubMedGoogle Scholar
  • 19 Gajdos P, Tranchant C, Clair B et al. Treatment of myasthenia gravis exacerbation with intravenous immunoglobulin – a randomized double-blind clinical trial. Arch Neurol 2005; 62: 1689-1693
    CrossrefPubMedGoogle Scholar
  • 20 Michels M, Hohlfeld R, Hartung HP et al. Myasthenia gravis – discontinuation of long-term azathioprine. Ann Neurol 1988; 24: 798
    CrossrefPubMedGoogle Scholar
  • 21 Hoch W, McConville J, Helms S et al. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med 2001; 7: 365-368
    CrossrefPubMedGoogle Scholar
  • 22 Bartoccioni E, Scuderi F, Minicuci GM et al. Anti-MuSK antibodies: correlation with myasthenia gravis severity. Neurology 2006; 67: 505-507
    CrossrefPubMedGoogle Scholar
  • 23 Deymeer F, Gungor-Tuncer O, Yilmaz V et al. Clinical comparison of anti-MuSK- vs. anti-AChR-positive and seronegative myasthenia gravis. Neurology 2007; 68: 609-611
    CrossrefPubMedGoogle Scholar
  • 24 Pevzner A, Schoser B, Peters K et al. Anti-LPR autoantibodies in AChR- and MuSK-seronegative myasthenia gravis. J Neurol 2012; 259: 427-435
    CrossrefPubMedGoogle Scholar
  • 25 Gasperi C, Melms A, Schoser B et al. Anti-agrin autoantibodies in myasthenia gravis. Neurology 2014; 82: 1976-1983
    CrossrefPubMedGoogle Scholar
  • 26 Chen G, Marx A, Wen-Hu C et al. New WHO histologic classification predicts prognosis of thymic epithelial tumors: a clinicopathologic study of 200 thymoma cases from China. Cancer 2002; 95: 420-429
    CrossrefPubMedGoogle Scholar
  • 27 Detterbeck FC, Nicholson AG, Kondo K et al. The Masaoka-Koga stage classification for thymic malignancies: clarification and definition of terms. J Thorac Oncol 2011; 6 (Suppl. 03) S1710-S1716
    CrossrefPubMedGoogle Scholar
  • 28 Palmieri G, Montella L, Martignetti A et al. Somatostatin analogs and prednisone in advanced refractory thymic tumors. Cancer 2002; 94: 1414-1420
    CrossrefPubMedGoogle Scholar
  • 29 Ried M, Neu R, Schalke B et al. Radical pleurectomy and hyperthermic intrathoracic chemotherapy for treatment of thymoma with pleural spread. Zentralbl Chir 2013; 138 (Suppl. 01) S52-S57
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 30 Janzen RW, Lachenmayer L, Fischer K. Problems of postthymectomy-syndromes, e. g. myasthenia gravis (author’s transl). Med Klin. 1977 72. 1931-1937
    PubMedGoogle Scholar
  • 31 Brüggemann W, Herath H, Ferbert A. Follow-up and immunologic findings in drug-induced myasthenia. Med Klin (Munich) 1996; 91: 268-271
    PubMedGoogle Scholar
  • 32 Smith CI, Aarli JA, Biberfeld P et al. Myasthenia gravis after bone-marrow transplantation. Evidence for a donor origin. N Engl J Med 1983; 309: 1565-1568
    CrossrefPubMedGoogle Scholar
  • 33 Abicht A, Müller J, Lochmüller H. Congenital Myasthenic Syndromes. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong CT, Smith RJH, Stephens K. (ed.). GeneReviews® Internet. Seattle (WA): University of Washington, Seattle; 1993–2014 2003. [updated 2012 Jun 28]
    Google Scholar
  • 34 Van Dyk HJ, Florence L. The Tensilon test. A safe office procedure. Ophthalmology 1980; 87: 210-212
    CrossrefPubMedGoogle Scholar
  • 35 Juel VC, Massey JM. Myasthenia gravis. Orphanet J Rare Dis 2007; 2: 44
    CrossrefPubMedGoogle Scholar
  • 36 Marienhagen J, Schalke B, Aebert H et al. Somatostatin receptor scintigraphy in thymoma, imaging method and clinical application. Pathol Res Pract 1999; 195: 575-581
    CrossrefPubMedGoogle Scholar
  • 37 Gronseth GS, Barohn RJ. Practice parameter: Thymectomy for autoimmune myasthenia gravis (an evidencebasedreview) – report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000; 55: 7-15
    CrossrefPubMedGoogle Scholar
  • 38 https://www.embryotox.de/azathioprin.html
    PubMed
  • 39 Illa I, Diaz-Manera J, Rojas-Garcia R. Sustained response to Rituximab in anti-AChR and anti-MuSK positive Myasthenia Gravis patients. J Neuroimmunol 2008; 201–202: 90-94
    PubMedGoogle Scholar
  • 40 Lambert EH, Eaton LM, Rooke ED. Defect of neuromuscular conduction associated with malignant neoplasms. Am J Physiol 1956; 187: 612-613
    PubMedGoogle Scholar
  • 41 Wirtz PW, Sotodeh M, Nijnuis M et al. Difference in distribution of muscle weakness between myasthenia gravis and the Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry 2002; 73: 766-768
    CrossrefPubMedGoogle Scholar
  • 42 Sabater L, Titulaer M, Saiz A. SOX1 antibodies are markers of paraneoplastic Lambert-Eaton myasthenic syndrome. Neurology 2008; 70: 924-928
    CrossrefPubMedGoogle Scholar
  • 43 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
    CrossrefPubMedGoogle Scholar
  • 44 Sanders DB, Massey JM, Sanders LL et al. A randomized trial of 3,4-diaminopyridine in Lambert-Eaton myasthenic syndrome. Neurology 2000; 54: 603-607
    CrossrefPubMedGoogle Scholar
  • 45 Wirtz PW, Verschuuren JJ, van Dijk JG et al. Efficacy of 3,4-diaminopyridine and pyridostigmine in the treatment of Lambert-Eaton myasthenic syndrome: a randomized, double-blind, placebo-controlled, crossover study. Clin Pharmacol Ther 2009; 86: 44-48
    CrossrefPubMedGoogle Scholar
  • 46 Oh SJ, Claussen GG, Hatanaka Y et al. 3,4-Diaminopyridine is more effective than placebo in a randomized,double-blind, cross-over drug study in LEMS. Muscle Nerve 2009; 40: 795-800
    CrossrefPubMedGoogle Scholar
  • 47 Deutschen Arzneimittel Codex, Neues Rezeptur Formularium (22.3.)
    PubMed
  • 48 Newsom-Davis J, Murray NMF. Plasma-exchange and immunosuppressive drug-treatment in the Lambert-Eaton myasthenic syndrome. Neurology 1984; 34: 480-485
    CrossrefPubMedGoogle Scholar
  • 49 Keogh M, Sedehizadeh S, Maddison P. Treatment for Lambert-Eaton myasthenic syndrome. Cochrane Database Syst Rev 2011; 2 CD003279
    PubMedGoogle Scholar
  • 50 AWMF-Leitlinie Myasthenia gravis und Lambert-Eaton-Syndrom, Diagnostik und Therapie Registernummer 030-087, Klassifikation S1, Stand: 30.09.2012, gültig bis 31.12.2015
    PubMed