Neurosarkoidose

 

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Zusammenfassung

Neurosarkoidose ist die seltene Manifestation der granulomatösen Multisystemerkrankung Sarkoidose im zentralen oder peripheren Nervensystem. Die Ätiologie ist ungeklärt, vermutete Auslöser sind infektiösen Agentien und Umwelttoxine. Das histopathologische Korrelat besteht aus nicht-verkäsenden epitheloidzelligen Granulomen mit geordneten Riesenzellen vom Langhans-Typ und einem peripheren Lymphozytenwall. Die klinische Präsentation ist variabel und manifestiert sich im zentralen und peripheren Nervensystem. Ausfällen der kranialen Hirnnerven, aseptischen Meningitiden, raumfordernden Parenchymläsionen im ZNS mit Störung des neuroendokrinologischen Systems oder Krampfanfällen sind bekannt. Periphere Neuropathien, insbesondere Small-Fiber-Neuropathien und Myopathien kommen vor. 1/3 zeigt mehr als eine neurologische Manifestation. Die Diagnose ist eine Herausforderung und Sicherheit ist nur mittels positiver Biopsie des Nervensystems möglich. Da eine Biopsie nicht immer durchführbar ist, kann der Verdacht auf Neurosarkoidose bei suggestiven klinischen/paraklinischen Befunden gestellt werden. Neurosarkoidose kann nur dann diagnostiziert wird, wenn mögliche Differenzialdiagnosen ausgeschlossen wurden. Jede symptomatische Neurosarkoidose sollte immunsupprimierend therapiert werden – für asymptomatische Krankheitsverläufe liegen keine Empfehlungen vor. Therapiestudien liegen nicht vor, dennoch besteht Konsens darüber, primär Kortikosteroide anzuwenden. Bei unzureichendem Ansprechen oder schwerwiegenden Symptomen ist eine Eskalation auf Immunsuppressiva empfohlen. Neuerdings können auch Therapieempfehlungen für neutralisierende Antikörper gegen TNF-α bei therapierefraktären Verläufen abgeleitet werden. Diese Therapien werden empfohlen und werden aufgrund guter Wirksamkeit bei günstigen Nebenwirkungsprofilen zunehmend an Bedeutung gewinnen. Die Prognose hängt vom Manifestationsort ab, ein isolierter Hirnnervenbefall ist günstig, Parenchymläsionen können komplizierte Verläufe nehmen. Bei 2/3 verläuft die Neurosarkoidose monophasisch mit Remission. Bei dem Rest sind schubförmige oder progrediente Verläufe möglich, mit einer Letalität von ca. 10%.

Abstract

Neurosarcoidosis is a rare manifestation of the granulomatous multisystem disease, sarcoidosis, in the central/peripheral nervous systems. Its aetiology is not clear, possible triggers are infectious agents and environmental toxins. The histopathologogical correlate is non-caseating epitheliod-cell granuloma with ordered giant cells of Langhans type and peripheral lymophocyte wall. The clinical presentation is variable. Defects of cranial nerves, aseptic meningitis, space-filling parenchymal lesions in the CNS with disorders of the neuroendocrine system or seizures are common. Peripheral neuropathies, especially small-fibre neuropathies, and myopathies can occur. 1/3 exhibit more than one manifestation. The diagnosis is a challenge and a clear result requires a positive biopsy of the nervous system. Since biopsies are not always possible the suspicion of neurosarcoidosis is based on suggestive clinical/paraclinical findings. The diagnosis is only made when all possible differential diagnoses have been excluded. Symptomatic neurosarcoidosis calls for immunosuppressive therapy – there are no clear recommendations for asymptomatic courses. Studies are not available but there is consensus for the primary use of corticosteroids. In cases of inadequate response or severe symptoms escalation to immunosuppressants is recommended. Recent cases recommend neutralising antibodies against TNF-α for therapy-resistant courses. These new therapies are important due to their good efficacy and favourable side effect profiles. The prognosis depends on the site of manifestation with an isolated cranial nerve attack being more favourable while parenchymal lesions take a complicated course. In 2/3 neurosarcoidosis is monophasic with complete remission. In the rest, episodic or progressive courses occur with a lethality of approx. 10%.

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