Neuroimmunologie: Neues zur limbischen Enzephalitis

Zusammenfassung

Die limbische Enzephalitis beschreibt ein heterogenes Krankheitsbild mit subakutem Beginn von progredienten mnestischen Störungen, neuropsychiatrischen Veränderungen und epileptischen Anfällen. Ursächlich sind entweder eine Hirnentzündung auf dem Boden einer Tumorerkrankung (paraneoplastisches Syndrom), zumeist mit Antikörpern gegen intrazelluläre Proteine (Hu, Ma2, CV2), oder eine Enzephalitis mit pathogenen Autoantikörpern gegen neuro­nale Oberflächenstrukturen, vor allem gegen Rezeptoren. Die Entdeckung dieser Neuropil-Antikörper hat zu einem Paradigmenwechsel geführt, denn damit wird die Mehrzahl der limbischen Enzephalitiden klar diagnostizierbar, sie sprechen im Vergleich zu paraneoplastischen Formen besser auf eine Immuntherapie an und haben eine günstigere Prognose. Prototypische Vertreter und zugleich am häufigsten sind Autoimmun-Enzephalitiden mit Antikörpern gegen NMDA-Rezeptoren oder Proteine des VGKC-Komplexes. Neben der klinischen Untersuchung, Lumbalpunktion und MRT-Bildgebung steht die Bestimmung onkoneuronaler und Oberflächen-Antikörper im Vordergrund differenzialdiagnostischer und therapeutischer Entscheidungen. Neuropil-Antikörper werden vor allem mit Zell-basierten Testverfahren bestimmt und müssen immer im klinischen Kontext interpretiert werden. Die Tumorsuche und -entfernung sowie eine rasch eingeleitete Immuntherapie sind maßgeblich für die Prognose. Die derzeitige rasante Erweiterung des klinischen Spektrums durch immer neue pathogene Autoantikörper wird sich fortsetzen. Es ist zu erwarten, dass dadurch in den kommenden Monaten und Jahren neue Syndrome abgrenzbar werden, dass aber auch schon bekannte Antikörper und deren Isotypen für Krankheiten verantwortlich sind, die bisher anderen Ätiologien zugeordnet wurden, beispielsweise neuropsychiatrischen Störungen, Epilepsien oder Demenzen. Die Kenntnis spezifischer Antikörper führt zu einem enorm wachsenden Verständnis der Pathomechanismen neurologischer Krankheiten und zu verbesserten Therapien bei Patienten aller Altersgruppen.

Abstract

Limbic encephalitis refers to a heterogeneous spectrum of neurological disorders with subacute onset of progressive mnestic deficits, neuropsychiatric disturbances and epileptic seizures. Traditionally limbic encephalitis was considered in the context of a tumour (paraneoplastic disease) with onconeuronal antibodies against intracellular proteins (Hu, Ma2, CV2) and a poor prognosis. Recently, distinct pathogenic autoantibodies were discovered against neuronal surface proteins, in particular receptors, causing limbic encephalitis primarily in the absence of malignancies, responding much better to immunotherapy and usually showing a favourable outcome. Autoimmune encephalitides with antibodies against the NMDA receptor or VGKC complex are prototypical and the most frequent forms. Together with clinical examination, cerebrospinal fluid analysis and MR imaging, detection of onconeuronal and neuronal surface antibodies have become the diagnostic mainstay, guiding differential diagnoses and therapeutic decisions. Surface antibodies are detected in cell-based assays, antibody levels must be interpreted in the overall context of clinical symptoms and disease course. The outcome largely depends on early tumour detection and removal as well as rapid initiation of immunotherapy. Currently there is a rapid ­expansion of the clinical spectrum related to further novel pathogenic antibodies. Without doubt, the coming months and years will reveal new syndromes, but also already known antibodies and their isotypes will be detected in diseases for which different aetiologies have been considered so far, for example, in neuropsychiatric disorders, epilepsy, or dementia. The knowledge of specific antibodies results in a swiftly growing understanding of neurological disease mechanisms and in improved therapies for patients of all ages.

Schlüsselwörter

limbische Enzephalitis - Neuropil-Antikörper - NMDA-Rezeptor - Paraneoplasie - Immuntherapie

Keywords

limbic encephalitis - neuropil antibodies - NMDA receptor - paraneoplastic lesions - immunotherapy

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