Leukoencephalopathy Associated with 5-Fluorouraeil and Cisplatin Therapy

ABSTRACT

Increasing vigorous chemotherapy for cancers including primary and matastatic tumors has resulted in prolonged survival. However, there has been an associated increase in neurotoxicity as a result of it. All classes of chemotherapeutic agents contain drugs that are potentially neurotoxic. The authors has studied three cases of leukoencephalopthies developed during adjunctive therapy with 5-flurouracil and cisplatin for adenocarcinoma of the stomach. None of the patients had evidence of metastasis or any previous neurologic diseases. The duration of chemotherapy before onset of neurological symptoms ranged from 8 to 12 weeks. Two of the 3 patients presented progressive decline in mental status and ataxia after 2~3 weeks, while the third one had two unexplained episodes of loss of consciousness. In all of these patients, magnetic resonance imagings demonstrated prominent periventricular white matter lesions. Cerebral biopsies were performed stereotaxically in 2 patients. The morphological features were active demyelinating disease and edema. All three patients had improved after the cessation of chemotherapy and a short course of corticosteroid therapy, suggesting that these alarming events such as nausea, vomiting dizziness, dysarthria, and mental change were a toxic reversible side effects from these chemotherapeutic agents. This syndrome may represent the pathological basis for 5-fluorouracil neurotoxicity, however we cannot completely exclude the role of cisplatin in the occurences of the above syndromes.