Zytostatikainduzierte Polyneuropathien

Zusammenfassung

Im Rahmen maligner Erkrankungen kommt es häufig zu einer Schädigung neuromuskulärer Strukturen. Die ursächlichen pathophysiologischen Mechanismen sind jedoch vielschichtig. Neben der direkten Infiltration durch neoplastische Zellen kann das Nervengewebe paraneoplastisch geschädigt werden. Zusammengenommen führt dies bei ca. 2,5 % der Patienten mit Karzinomen oder Lymphomen zu einer klinisch manifesten sensomotorischen Polyneuropathie. Weitaus häufiger tritt die Neuropathie als Nebenwirkung einer zytostatischen Therapie mit Taxoiden, Vinca-Alkaloiden oder platinhaltigen Substanzen (Cisplatin) auf. Pathophysiologisch liegt der Neurotoxizität eine Behinderung des axonalen Transportes mit nachfolgender Gewebsschädigung zugrunde. In Abhängigkeit des verwendeten Pharmakons ergeben sich unterschiedlich starke Schädigungen der einzelnen Faserqualitäten. Unter einer Therapie mit Cisplatin entwickelt sich eine rein sensible Polyneuropathie mit einem frühzeitigen Verlust des Vibrationsempfindens. Elektrophysiologische und somatosensorische Untersuchungen wiesen eine Schädigung der myelinisierten und unmyelinisierten Afferenzen nach. Neben der Schädigung sensibler Fasern tritt unter Taxol, insbesondere nach hohen Kumulativdosen, eine Schädigung der motorischen Fasern auf. Klinisch stehen jedoch Parästhesien und Störungen der Mechanorezeption sowie Propriozeption im Vordergrund. Durch Vinca-Alkaloide induzierte Polyneuropathien manifestieren sich häufig in schmerzhaften Parästhesien. Zusätzlich können sensible Störungen sowie Paresen insbesondere der distalen Muskulatur bestehen. Elektrophysiologische Daten bestätigen das klinische Bild. Das Ausmaß der Nervenschädigung wird durch die verabreichte Gesamtdosis des jeweiligen Zytostatikums beeinflusst. Bei schweren Verläufen können die neurotoxischen Nebenwirkungen einen Abbruch der Chemotherapie notwendig machen. Versuche, durch den Einsatz neuroprotektiver Substanzen eine Reduktion der Nebenwirkungen zu erreichen, waren bis jetzt nur eingeschränkt erfolgreich.

Chemotherapy Induced Neuropathy

An underlying carcinoma is an important differential diagnosis in peripheral neuropathy, but the pathophysiological mechanisms are different. In addition to direct infiltration of nerve tissue paraneoplastic processes are posssible. The prevalence of a clinically detectable peripheral neuropathy in cancer patients is approximately 2.5 %. More frequently peripheral neuropathy occurs as a side effect of zytostatic treatment with taxoides, vinca-alcaloides or cisplatin. Pathophysiologically these drugs interact with neurotubules and microtubules which results in a block of fast axoplasmic transport followed by axonal nerve degeneration. The extent and the clinical manifestation of these drug-induced neuropathies depend on the substance and the total dosage. Cisplatin-induced neuropathy is restricted to sensory fibres. The earliest clinical sign is the loss of vibration sensation. Hypaesthesia, the loss of vibration sensation and sense of position are also side effects of taxoid therapy. In addition, involvement of motor fibres can be observed especially after administration of high doses. The occurrence of sensory deficits, painful paraesthesias and weakness is characteristic for a vinca alkaloid-induced neuropathy. The early detection of peripheral neuropathy due to cancer chemotherapy is important, because it is a potentially dose-limiting complication. Until now attemps to reduce neurotoxicity by administration of neuroprotective substances had only limited success.

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