Pathophysiologie und Prognosefaktoren der Autoimmunenzephalitiden

Zusammenfassung

Die rasante Entdeckung immer neuer Autoimmunenzephalitiden umfasst vielgestaltige Krankheitsbilder von Epilepsien über Bewegungsstörungen bis zu Psychosen. Aufgrund des wachsenden Verständnisses der klinischen Symptomatik rücken zunehmend Fragen nach den pathophysiologischen Mechanismen und Prognosefaktoren in den Vordergrund. Wesentliche neue Erkenntnisse zur Ätiologie belegen die Triggerung von Autoimmunenzephalitiden durch verschiedene Tumoren, aber auch durch Infektionen des Nervensystems, wie die Herpes-Enzephalitis. Die Antikörper gegen neuronale Oberflächenstrukturen sind in aller Regel direkt pathogen und entfalten ihre Wirkung über die Internalisierung der Zielproteine, über Rezeptorblockade oder Komplementaktivierung. Für die Prognose maßgeblich sind Art und Titer des Antikörpers (z. B. gegen NMDA-, GABA-, AMPA-Rezeptoren oder spannungsgesteuerte Kaliumkanal-Komplexe), ein assoziierter Tumor, eine forcierte Immuntherapie sowie bildgebende und Liquor-Biomarker.

Abstract

More and more forms of autoimmune encephalitis are being identified with the clinical spectrum ranging from epilepsy over movement disorders to psychosis. The increasing appreciation of clinical symptoms raises questions about the underlying pathophysiological mechanisms and prognostic factors. Numerous novel findings on the aetiology demonstrate that diverse tumours, but also infections of the central nervous system such as Herpes encephalitis can trigger autoimmune encephalitis. Antibodies against neuronal surface epitopes are directly pathogenic in the majority of cases. They act via binding and internalization of target proteins, receptor blockage, or activation of complement. Most relevant for the patients’ prognosis are the type and titer of antibodies (e. g. against NMDA, GABA, AMPA receptors or voltage-gated potassium channel complexes), associated tumours, sufficiently aggressive immunotherapies, and imaging as well as cerebrospinal fluid biomarkers.

Schlüsselwörter

Enzephalitis - NMDA-Rezeptor - Autoantikörper - Pathogenese - Immuntherapie

Key words

encephalitis - NMDA receptor - autoantibodies - pathogenesis - immunotherapy

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