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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J. Schattschneider
Klinik für Neurologie
Christian-Albrechts-Universität
Niemannsweg 147
24105 Kiel
Email: j.schattschneider@neurologie.uni-kiel.de
