[Leukoencephalopathy caused by antineoplastic drugs]

Leucoencephalopathy caused by antineoplastic drugs was reviewed. This leucoencephalopathy primarily involved the cerebral white matter, caused by various anti-neoplastic drugs such as carmofur, fluorouracil, cytarabine, cisplatin, tegafur, methotrexate, tacrolimus, and interferon alfa. The interval between the time of drug administration and the onset of leucoencephalopathy varies among the drugs, depending on the kind of the drugs, their daily dosage, duration of the administration, and presence or absence of other combined treatments. This review primarily focused on carmofur-induced leucoencephaloathy, since this drug is developed and widely used in Japan against the carcinomas of the gastrointestinal tract and breast, and has caused leucoencephalopathy at the estimated incidence of 0.026% since 1982. The common symptoms of carmofur leucoencephalopaty were gait disturbance followed by dysarthria and dementia in that order of frequency, leading to coma in the advanced stage of the encephalopathy. EEG is the most sensitive test, but cranial CT and MRI tests are more specific, and MRI T2-weighted imaging is the most useful test, revealing symmetrical bilateral diffuse high intensity areas in the cerebral white matter. Intravenous high dose MTX has a strong tendency to cause leucoencephalopathy when combined with cranial radiation therapy. Reversible posterior leucoencephalopathy proposed by Hinchey et al. in 1996 has also been caused by some antineoplastic drugs. The most important treatment of the leucoencephalopathy caused by antineoplastic drugs is the immediate cessation of the causative drugs, followed by supportive therapy which included treatment to various complications and prevention of the decubitus and contractures of the joints.