1. 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

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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.