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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. [ABSTRACT FROM AUTHOR]

Paraneoplastic neurological syndromes (PNS) are defined as remote effects on the central and peripheral nervous system that are not caused directly by the tumor, its metastases and treatment, or metabolic disorders. The most probable cause is a falsely initiated immune reaction. Well-defined classical PNSs are associated with distinct tumors and occur with onconeural antibodies directed against intracellular neuronal antigens. However, response to therapy is limited. Recently, new antibodies directed against neuronal surface antigens were described in encephalitic syndromes of autoimmune origin. These probably antibody-mediated disorders are more frequent than classical PNS, occur with or without tumor association and often show a good response to immunosuppressive treatment. [ABSTRACT FROM AUTHOR]

Autoantibodies to neuronal tissue are becoming increasingly more important in the evaluation and classification of several neurological diseases, e.g. neuromyelitis optica, paraneoplastic syndromes of the central nervous system (CNS), stiff person syndrome or autoimmune epilepsy. As these disorders are rare, no evidence-based recommendations for therapy are available. Currently, immunomodulating or immunosuppressive drugs are administered in most cases. In paraneoplastic syndromes treatment of the underlying cancer is of considerable importance. This overview summarizes current experiences and recommendations in the treatment of autoimmune neurological disorders. [ABSTRACT FROM AUTHOR]

Antibody-associated limbic encephalitis was usually seen as a paraneoplastic syndrome where the antibodies would target intracellular proteins. However, recent reports challenged this idea and described antibodies that target synaptic proteins expressed on the cell surface. These antibodies are not necessarily linked to tumors and should be regarded as a distinct entity of different autoimmune diseases. They are of direct clinical relevance since their binding to their target antigen is likely the cause of the clinical symptoms and, therefore, immune treatment often results in a beneficial outcome. Tests which differentiate these antibodies are now available in specialized laboratories. [ABSTRACT FROM AUTHOR]

Malignancy-associated musculiskeletal syndromes can present in a variety of ways which are not distinguishable from idiopathic rheumatic diseases. Furthermore, there are some rare, but typical syndromes with a high association with neoplasms. To perform a quick and exact diagnosis while avoiding useless invasive and expensive diagnostic procedures is a major challenge for the clinician. This article focuses on the clinical features of paraneoplastic musculoskeletal syndromes and theories about the underlying pathogenesis. We try to highlight those clinical to hidden malignancies. Paraneoplastic rheumatic syndromes are rare conditions, but timely recognition can save lives. [ABSTRACT FROM AUTHOR]