Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of structural alteration in brains of leukemic children have been attributed to intrathecal administration of methotrexate and radiation therapy. We report an instance of asymptomatic encephalopathy in an adult who received thio-TEPA (by subarachnoid injection) as treatment for leukemic meningitis. The lesions were microscopic, confined to cerebral white matter and included: vacuolation, myelin destruction, axonal swelling, gliosis, deposition of mineral salts and aggregates of large foamy cells. The etiology of this condition remains undetermined.
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PMID:Multifocal leukoencephalopathy in adult leukemia: histologic features and etiologic considerations. 41 9

The Central Nervous System has often been classified as a "drug sanctuary" as most anticancer drugs do not achieve effective penetration of the blood-brain barrier. With more effective systemic chemotherapy programs (especially in acute leukemia in children), the incidence of meningeal tumor involvement has increased. Even though a number of systemically administered agents might be used in treating the CNS, only three have been used intrathecally with good clinical results: the antimetabolites methotrexate (MTX) and cytosine arabinoside (Ara-C) and the alkylating derivative thiophosphoramide (thio-TEPA). Drug distribution in the CSF which is injected by lumbar puncture does not generally allow for delivery of effective quantities of drug to the cisternae nor the ventricles. Thus direct intraventricular injection via a subcutaneously implanted (Ommaya) reservoir is necessary to achieve adequate drug levels in the higher CNS cavities. The peak ventricular concentration of MTX, which was administered by Ommaya reservoir, at a dose of 15mg/m2, was 2.5 +/- 0.9 X 10(-4)M, and remained as a level of 10(-6)M for 72 hours with a half-life of 10.5 hours. During an intravenous 6 hour-infusion at a dose of 750-3,000mg/m2, MTX concentration in CSF reached 8.2 X 10(-7)M to 2.7 X 10(-6)M. The drug content in CSF had a linear concentration related to the drug level in plasma. Intrathecal MTX and Ara-C frequently cause symptoms of meningeal irritation. Occasionally cases of weakness and paralysis and rare instances of severe encephalopathy may occur. The best established causes of these symptoms is high concentration of these drugs in the CSF, or prolonged exposure of the brain to low CSF concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Pharmacokinetics of intrathecal chemotherapy and clinical problems]. 643 96