Occupation and the risk of chronic toxic leukoencephalopathy

Among the hundreds of environmental insults capable of inducing nervous system injury, a small number can produce clinically significant damage to the brain white matter. The use of magnetic resonance imaging (MRI) in affected individuals has greatly illuminated this previously obscure area of neurotoxicology. Toxic leukoencephalopathy has acute and chronic forms, in both of which cognitive dysfunction is the major clinical manifestation. Chronic toxic leukoencephalopathy (CTL) has been most thoroughly described in individuals with intense and prolonged exposure to leukotoxins, but the consequences of lesser degrees of exposure are not well understood. Rare cases of CTL have been reported in workers exposed to culpable leukotoxins, but study of this syndrome is hindered by many confounds such as uncertain level of toxin exposure, the presence of multiple toxins, vague dose-response relationship, comorbid medical or neurologic disorders, psychiatric illness, and legal issues. The risk of CTL in workers is low, although it is not possible to determine quantitative risk estimates. More knowledge can be expected with the application of advanced MRI techniques to the assessment of workers who may have been exposed to known or potential leukotoxins. Preventive measures for avoiding workplace CTL will be informed by clinical assessment involving the use of advanced neuroimaging and neuropsychologic evaluation in combination with accurate measurement of leukotoxin exposure.