Effects of Chemotherapeutic Agents

      Many of the cancer chemotherapeutic drugs are neurotoxic. The blood-brain barrier (BBB) limits the direct entry of these substances into the brain, but the BBB may be damaged by the disease process or by the therapeutic agent itself. Also, in the case of CNS disease, agents may be given to open the BBB to allow greater access of the anticancer drug to the tumor. Lipid solubility and intrathecal administration are other factors that increase delivery to the brain. The chemotherapeutic agents commonly associated with leukoencephalopathy include methotrexate, cis-platin, cytosine arabinoside (ARA-C), carmustine (BCNU), and thiotepa.

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      Both acute and delayed effects are observed with chemotherapy. The acute changes develop during therapy, often within the first few days of initiating treatment. High-dose intravenous methotrexate is the most common cause. The bilateral diffuse white matter hyperintensity is transient in nature, and patients may be entirely asymptomatic.

      The delayed effects of chemotherapy range from asymptomatic white matter hyperintensities to a severe necrotizing leukoencephalopathy. The onset of clinical and imaging findings is earlier than that observed with radiation, usually a few weeks or months following therapy. The reported incidence of necrotizing leukoencephalopathy varies widely, but is much higher with CNS leukemia, or when combinations of intravenous and intrathecal chemotherapy and radiation is employed. Endnote

      MR imaging initially reveals patchy involvement of the periventricular white matter and centrum semiovale, which over time evolves to a confluent pattern. The process tends to spare the deep white matter tracts, brain stem, and cerebellum. Enhancement or mass effect are seen only in the most severe cases. Long term follow-up often shows some brain atrophy, and in children treated for cancer, cerebral calcification is commonly found. 

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