The neurotoxicology of illicit drugs is not well understood in general. Drug abusers often abuse more than one agent, and it is difficult to determine the effects of one drug in isolation. There are examples, however, of relatively pure syndromes of impairment, and certain drugs have a known or putative effect on the cerebral white matter.
a. Toluene This drug, methylbenzene, is an organic compound widely used in industry and is the major solvent found in spray paints. Occupational
exposure to toluene occurs in painters and other workers, but it is debated whether low-level toluene exposure has any deleterious effects. In contrast, toluene abuse may have dramatic sequelae. Intentional inhalation of toluene vapors from products such as spray paint leads to euphoria, and abuse of toluene over extended periods may produce severe leukoence-phalopathy. Clinical studies of individuals who inhaled toluene fumes on a regular basis for months to years have documented dementia, ataxia, and various other neurologic deficits. Cognitive dysfunction is particularly devastating, and the severity of the neurobehavioral deficits approximately correlates with the duration of exposure to toluene. MRI scans reveal diffuse white matter change in the cerebrum (Fig. 6) and cerebellum, and autopsy studies disclose diffuse myelin loss without damage to cortical or subcortical gray matter. Abstinence arrests the neuro-pathologic process, but there may be little recovery of function if enough white matter damage has occurred. Toluene leukoencephalopathy offers one of the best examples of a major neurologic and neurobehavioral disorder caused by selective white matter involvement.
b. Ethanol The neurology of alcohol has received much attention, and many classic neurologic syndro mes—including acute intoxication, withdrawal states, cerebellar ataxia, and peripheral neuropathy—are well recognized in alcohol abusers. However, the pathophysiology of alcohol's effects on the brain are not as well understood. A nutritional deficiency of thiamine (vitamin B1) is known to cause the Wernicke-Korsakoff syndrome, in which acute confusion, ophthalmoplegia, and a gait disorder can herald the onset of severe amnesia; however, other mechanisms may also contribute to neurobehavioral dysfunction. Substantial evidence, both in humans and in laboratory animals, has been gathered for a direct toxic effect of alcohol on cerebral white matter. Thus, in contrast to the isolated amnesia of the Korsakoff's syndrome, it may be appropriate to consider the syndrome of alcoholic dementia, in which more widespread intellectual deterioration occurs in the setting of toxic white matter damage.
c. Heroin This narcotic drug does not cause leukoencephalopathy when abused by the usual routes of inhalation or injection, but the syndrome has been reported to appear after the inhalation of heroin pyrolysate, a form of the drug resulting from the heating of heroin on tin foil. Memory loss, dementia, akinetic mutism, cerebellar signs, and impaired gait may ensue. Neuroimaging and neuropathologic studies demonstrate white matter degeneration, but the specific toxic agent remains unknown.
d. Methylenedioxymethamphetamine Methylene-dioxymethamphetamine (MDMA), also known as ecstacy, has recently become widely popular. Leu-koencephalopathy has been reported in individuals exposed to MDMA, possibly related to its effects on serotonergic neurons.
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