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 The American Indian and Indian and Alaska Native Alaska Native Program: Program: MissionMission

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.