In recent decades the organic solvent toluene (methylbenzene) has emerged as one of the best-studied neurotoxins. Long-term and intense exposure to toluene vapors in humans who abuse spray paint and related substances has led to the recognition that toluene has a severe impact on central nervous system myelin. Chronic toluene abuse produces a devastating neurological disorder, of which dementia is the most disabling component. The clinical syndrome, toluene leukoencephalopathy, can be detected by a combination of characteristic symptoms and signs, detailed neurobehavioral evaluation, and brain magnetic resonance imaging. In this paper, we consider the impact of toluene abuse on our society, describe the specific neurobehavioral deficits in toluene leukoencephalopathy, review the spectrum of neuroimaging findings in patients with this disorder, summarize the teratogenic effects of toluene in both humans and animal models, and offer possible explanations for the range of neuropathological damage seen in brains of individuals who chronically abuse toluene.

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We describe the findings of magnetic resonance imaging (MRI) of the brain in 6 chronic toluene vapor abusers and the neuropathological findings in 1 abuser not studied by MRI. MRI in 6 chronic toluene abusers revealed the following abnormalities: (1) diffuse cerebral, cerebellar, and brainstem atrophy; (2) loss of differentiation between the gray and white matter throughout the central nervous system; and (3) increased periventricular white matter signal intensity on T2-weighted images. Another chronic toluene abuser (MRI not performed) died as a result of acute toluene overdose. The brain displayed diffuse, ill-defined myelin pallor, maximal in cerebellar, periventricular, and deep cerebral white matter. Neurons were preserved throughout, axonal swelling or beading was not seen, gliosis was minimal, and occasional, scant perivascular macrophage collections were seen. Taken in concert, these findings suggest that the pathological and MRI abnormalities are due to either increased water content of the white matter or subtle toluene-induced metabolic changes in myelin.

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Clinical, pathologic, immunologic and virologic features of simian varicella virus (SVV) infection in primates closely resemble varicella-zoster virus (VZV) infection in humans. Such similarities provide a rationale to analyze SVV infection in primates as a model of varicella pathogenesis and latency. Thus, we constructed an SVV-expressing green¯uorescent protein (SVV ± GFP) by inserting the GFP gene into the unique short segment of the virus genome by homologous recombination. Analysis of recombinant viral DNA and the expressed proteins of plaque-puri®ed SVV ± GFP con®rmed the location of the GFP insert and that the recombinant SVV expressed the 27 kDa GFP. Infection of monkey kidney cells in tissue culture with SVV ± GFP revealed bright green¯uorescence associated with the characteristic focal cytopathic effect produced by SVV infection. Microscopic examination of lung from a 3-month-old African green monkey 10 days after infection with SVV ± GFP revealed bright green¯uorescence in areas of acute necrotizing pneumonitis. SVV ± GFP allows ready identi®cation of cells infected with SVV both in vitro and in vivo, and will be useful for further analysis of varicella pathogenesis and latency in experimentally infected animals ± studies not possible in humans.