Grundlagen autoimmuner und paraneoplastischer Enzephalitiden

Für den Kliniker

Zusammenfassung

Die paraneoplastischen und autoimmunen Enzephalitiden sind inzwischen gut etablierte Entitäten. Der Nachweis neuraler Autoantikörper ermöglicht spezifische Diagnosen, gibt Informationen über die zugrunde liegende Pathophysiologie, die immunologische Behandelbarkeit und die Wahrscheinlichkeit, dass ein Tumor ursächlich ist. Dies gilt für die „hochwertigen“ neuralen Antikörper, die im Kontext umschriebener klinischer Bilder und unter Berücksichtigung großer Kontrollkollektive etabliert, von anderen Labors in gleicher Weise gefunden wurden und auf Immuntherapie ansprechen. Die Triggerung der Immunreaktion kann durch Tumoren und Virusenzephalitiden (NMDA-Rezeptor-Antikörper) erfolgen; z. T. wurde eine genetische Prädisposition nachgewiesen. Manche Antikörper werden peripher gebildet, andere (auch) intrathekal. Der Weg der Antikörper ins Gehirn kann über die Blut-Hirn-Schranke oder aus dem Liquor erfolgen. Im Gehirn selbst führen die Antikörper zur Internalisierung antigener Rezeptoren (NMDA-, AMPA-Rezeptor) oder zur nervenzellzerstörenden Aktivierung der klassischen Komplementkaskade. Bei manchen Enzephalitiden stehen zytotoxische T‑Zellen im Zentrum der Pathogenese. Für die Diagnostik ist die Testung von Liquor-Serum-Paaren mit breiten Antigenpanels empfehlenswert. Therapeutisch strebt man die Unterdrückung der Produktion pathogener Antikörper, z. T. ihre direkte Beseitigung an. Hierfür hat sich eine Sequenz aus First-line-Therapien (Steroide, intravenöse Immunglobuline und/oder Apheresen) und Second-line-Behandlungen (Rituximab und/oder Cyclophosphamid) etabliert.

Schlüsselwörter

Paraneoplastische Syndrome Neurale Antikörper Pathophysiologie First-line-Therapie Second-line-Therapie 

Principles of autoimmune and paraneoplastic encephalitis

Abstract

The paraneoplastic and autoimmune encephalitides are now well-established entities. Detection of neural autoantibodies enables specific diagnoses, provides information on the underlying disease pathophysiology, immunological treatability and the likelihood of a tumor being the underlying cause. This is true for the “high ranking” neural antibodies that have been established in the context of circumscribed clinical images and in consideration of large control groups, have been found in the same way by other laboratories and they respond to immunotherapy. The immune reaction can be triggered by tumors and virus encephalitides, e.g. N‑methyl-D-aspartate (NMDA) receptor antibodies. In some cases a genetic predisposition has been shown. Some antibodies are formed peripherally, others intrathecally. The route of the antibodies into the brain can be via the blood-brain barrier or cerebrospinal fluid (CSF). In the brain itself, the antibodies lead to an internalization of antigenic receptors, such as NMDA and α‑amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, or to nerve-destroying activation of the classical complement cascade. In other conditions, cytotoxic T cells are at the core of the pathophysiology. For diagnostic purposes, the testing of CSF-serum pairs with broad spectrum antigen panels is recommended. Therapeutically, the aim is to suppress the production of pathogenic antibodies or even to eliminate them directly. A sequence of first-line treatment (steroids, intravenous immunoglobulins and/or apheresis) and second-line treatment (rituximab and/or cyclophosphamide) has been established.

Keywords

Paraneoplastic syndromes Neural antibodies Pathophysiology First-line therapy Second-line therapy 

Notes

Danksagung

Der Verfasser dankt Frau Dr. Corinna Bien für die Durchsicht und kritische Diskussion des Manuskripts.

Einhaltung ethischer Richtlinien

Interessenkonflikt

C. G. Bien wirkte in Advisory Boards von Eisai (Frankfurt) und UCB (Monheim) mit, erhielt Honorare für Fortbildungsvorträge von Eisai (Frankfurt), UCB (Monheim), Desitin (Hamburg), Diamed (Köln), Fresenius Medical Care (Bad Homburg), Biogen (Ismaning) und Euroimmun (Lübeck). Er erhält oder erhielt Forschungsunterstützung von der Deutschen Forschungsgemeinschaft (Bonn), der Gerd-Altenhof-Stiftung im Deutschen Stiftungszentrum (Essen), Diamed (Köln) und Fresenius Medical Care (Bad Homburg). Er ist Berater des Labor Krone (Bad Salzuflen) für die Diagnostik von neuralen Antikörpern und Antiepileptika-Blutspiegelbestimmungen.

Dieser Beitrag beinhaltet keine vom Autor durchgeführten Studien an Menschen oder Tieren.

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Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2018

Authors and Affiliations

  1. 1.Epilepsie-Zentrum BethelKrankenhaus MaraBielefeldDeutschland

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