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Toxic Leukoencephalopathy Christopher M. Filley, M.D. B.K. Kleinschmidt-DeMasters, M.D. Douglas K. Novins, M.D. Spero M. Manson, Ph.D. Departments of Neurology, Psychiatry, and Pathology University of Colorado School of Medicine Background • Leukoencephalopathy is a structural alteration of brain white matter • Toxic causes include drugs of abuse, cranial irradiation, therapeutic drugs, and environmental toxins • Affected individuals may develop white matter dementia Cranial Irradiation • Radiation for brain tumors can reduce the tumor size but also can produce unwanted leukoencephalopathy • The left MRI scan shows a malignant brain tumor before radiation; after radiation (right), the tumor is smaller but the white matter is damaged Other Toxins that Can Damage Brain White Matter • Alcohol (ethanol) • Cocaine • Intravenous heroin • Hallucinogenic drugs (psilocybin) • Probably Ecstacy • Even anticancer drugs doctors use for treatment of the tumor may have the unwanted (but currently unpreventable) side effect of leukoencephalopathy Pathogenesis • In toxic leukoencephalopathy, white matter damage can result from injury to any important part of the white matter including myelin, oligodendrocytes, axons, astrocytes, or blood vessels Toluene Abuse • Toluene is an organic solvent commonly used in many household products, including spray paint, and in industry • Heavy “glue/paint/ or gasoline sniffing”, a form of inhalant drug abuse often used by American Indian and urban youth, results in leukoencephalopathy Future Aim • Study brain damage due to toluene abuse in American Indian and urban youth, in whom the prevalence of this problem is high, by performing detailed neurological, neuropsychological, & psychiatric evaluations, in conjunction with advanced brain imaging (MRI) techniques, to clarify the impact of this toxin on brain function • This population has NEVER been adequately studied, nor has the impact of the problem been fully appreciated The American Indian and Alaska Native Program: Mission To promote the health and well-being of American Indians and Alaska Natives, of all ages, by pursuing research, training, continuing education, technical assistance, and information dissemination within a biopsychosocial framework that recognizes the unique cultural contexts of this special population.
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