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„Seronegative“ Myasthenie mit Antikörpern gegen die muskelspezifische Tyrosin-Kinase

Seronegative myasthenia with antibodies against muscle-specific tyrosine kinase

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Zusammenfassung

Etwa 10–20% der Patienten mit generalisierter Myasthenie weisen keine Azetylcholinrezeptor (AChR)-Antikörper auf und werden als „seronegativ“ bezeichnet. Kürzlich wurden bei der Hälfte dieser Patienten Antikörper gegen die muskelspezifische Tyrosin-Kinase (MuSK-AK) nachgewiesen, welche über Agrin die Aggregation der Azetylcholinrezeptoren vermittelt. Wir haben bei 6 „seronegativen“ Patienten MuSK-AK untersucht und 2 charakteristische MuSK-positive Fälle identifiziert. Eine 56-jährige Patientin entwickelte eine Ptosis und Doppelbilder gefolgt von ausgeprägter bulbärer Symptomatik und respiratorischer Insuffizienz. Auf Pyridostigmin-Therapie sprach sie nur gering an, auf Prednisolon, Azathioprin und Immunglobuline nicht. Mehrere Plasmapheresebehandlungen waren jedoch gut wirksam. Ein 46-jähriger Patient mit seit 9 Jahren bestehender belastungsabhängiger proximaler Schwäche der Arme und des Schultergürtels sowie leichter bulbärer und respiratorischer Symptomatik zeigte einen weniger schweren Krankheitsverlauf. Die Fälle illustrieren die klinischen Unterschiede der MuSK-AK-positiven Myasthenie untereinander sowie im Vergleich zur AChR-AK-positiven Form mit vorwiegend bulbärer Symptomatik und häufigerer schwerer, auch respiratorischer Symptomatik. Außerdem zeigen sie die therapeutischen Schwierigkeiten mit schlechterem Ansprechen auf Pyridostigmin und Immunsuppressiva.

Abstract

About 10–20% of patients with generalized myasthenia gravis do not have acetylcholin receptor (AChR) antibodies and are referred to as having “seronegative” myasthenia. Recently, antibodies to muscle-specific kinase (MuSK), which mediates aggregation of AChR, were detected in half of these patients. We investigated six patients with seronegative myasthenia and identified two characteristic cases with MuSK antibodies. A 56-year-old woman developed ptosis and double vision followed by bulbar symptoms and respiratory insufficiency. She showed moderate response to treatment with pyridostigmine and no response to prednisolone, azathioprine, or intravenous immunoglobulin but good response to several plasma exchanges. A 46-year-old man with exercise-induced weakness of the upper limbs and mild bulbar and respiratory symptoms had a milder course for 9 years. These cases highlight the clinical spectrum of MuSK-positive myasthenia and the differences to AChR-positive myasthenia with predominant bulbar symptoms and often severe symptoms with respiratory insufficiency. Finally, they illustrate the therapeutic difficulties with less response to pyridostigmine and immunosuppressive drugs.

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Danksagung

Frau Prof. A. Vincent, Oxford, danken wir für die Durchführung der MuSK-AK-Testung bei Patient 1(Abb. 2)

Abb. 2
figure 2

56-jährige Patientin mit leichter Ptosis bei MuSK-Antikörper-positiver Myasthenie

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Authors and Affiliations

  1. Klinik und Poliklinik für Neurologie, Martin-Luther-Universität Halle-Wittenberg, Halle/Saale, Deutschland

    B. Hain, F. Hanisch & M. Deschauer

  2. Klinik und Poliklinik für Neurologie, Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Straße 40, 06097, Halle/Saale, Deutschland

    B. Hain

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  1. B. Hain
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  2. F. Hanisch
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  3. M. Deschauer
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Correspondence to B. Hain.

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Hain, B., Hanisch, F. & Deschauer, M. „Seronegative“ Myasthenie mit Antikörpern gegen die muskelspezifische Tyrosin-Kinase . Nervenarzt 75, 362–367 (2004). https://doi.org/10.1007/s00115-003-1672-5

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