Therapie der immunvermittelten paraneoplastischen neurologischen Erkrankungen

Zusammenfassung

Die paraneoplastischen neurologischen Erkrankungen sind insgesamt selten und zeichnen sich durch eine mannigfaltige klinische Präsentation aus. Sie können sowohl das zentrale und periphere Nervensystem als auch den neuromuskulären Übergang und die Muskulatur betreffen. In zweidrittel der Fälle ist der Tumor zum Zeitpunkt des Auftretens der neurologischen Symptome noch nicht bekannt. Für die Diagnosestellung sind eine Testung der antineuronalen Antikörper und eine gezielte Tumorsuche notwendig. Eine schnellstmögliche adäquate Tumortherapie in Kombination mit einer Immuntherapie sind die Grundpfeiler der Behandlung von paraneoplastischen Erkrankungen. Aufgrund des Fehlens von kontrollierten Studien basieren die Therapieempfehlungen auf Fallserien und Expertenmeinungen. Im Akutstadium werden meist eine Steroidstoßtherapie, intravenöse Immunglobuline oder die therapeutische Apherese angewendet. Angesichts des potenziell irreversiblen Schadens muss diese Therapie früh, ggf. bereits während der Tumordiagnostik, begonnen werden. Für die Langzeittherapie werden je nach Krankheitsbild unterschiedliche Immunsuppressiva empfohlen.

Neben der Tumorprognose hängt der Krankheitsverlauf weitgehend davon ab, ob die Antikörper gegen intrazelluläre Antigene oder gegen Oberflächenantigene gerichtet sind. Letztere Erkrankungen sprechen auf B-Zell gerichtete Therapien gut an und sind mit einer deutlich besseren Prognose assoziiert. Diese Übersichtsarbeit fasst die aktuellen Therapieempfehlungen zusammen und gibt einen Ausblick auf einige noch nicht validierte, aber perspektivisch interessante Ansätze.

Abstract

Paraneoplastic neurological disorders are rare and clinically heterogeneous diseases. They can affect both the central and peripheral nervous system as well as the neuromuscular junction and muscle. The neurological deficits develop in 2 /3 of cases prior to cancer diagnosis. The diagnostic approach includes screening for antineural antibodies and a search for the underlying tumor. A prompt tumor therapy in combination with immunotherapy is the cornerstone in the management of these diseases. Due to lack of clinical trials, treatment recommendations are based on case series and expert opinions. High-dose corticosteroids, intravenous immunoglobulins and apheresis therapies are often used in the acute stage of the disease. These therapies should be started as early as possible, e. g. during the tumor screening, in order to prevent irreversible damage. Long-term treatment is mostly immunosuppressive and depends on the specific paraneoplastic syndrome. Outcomes vary depending upon the prognosis of the underlying cancer and the nature of antineuronal antibodies. Antibodies directed against antigens on the neuronal cell surface are highly sensitive to B cell-directed therapies and mostly associated with a favorable outcome. A thorough review of published data on actual treatment recommendations is provided along with discussion of currently not validated, but potentially highly effective new therapies.

Schlüsselwörter

paraneoplastisch - Autoantikörper - Enzephalitis - Polyneuropathie

Keywords

paraneoplastic - autoantibody - encephalitis - polyneuropathy

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