Pathology of toxic leucoencephalopathy in drug abuse supports hypoxic-ischemic pathophysiology/etiology.

The histopathological features of leucoencephalopathy caused by illicit drugs (such as opioids and cocaine) are well documented in acute cases but not in long-survival cases. There are several hypotheses about the pathogenesis of this disorder, including hypoperfusion, direct drug toxicity resulting from the neurotoxic effects of the drug itself or contaminants in the illicit drug vehicle. We reviewed the post mortem findings in five males (aged 24 to 56 years, with survival intervals ranging from 7 days to 5 months) with a history of illicit drug use and concomitant fatal white matter changes. The histological characteristics of leucoencephalopathy vary with survival period. Prominent axonal injury and axonal spheroids were observed with shorter survival and spongiform changes becoming apparent with longer survival (acute and chronic incomplete infarct pattern). Necrosis was present in all cases and its appearance changed with longer survival (acute and chronic complete infarct pattern). Significant primary demyelination was not observed. These observations suggest that the primary defect in this leucoencephalopathy is hypoxic-ischemic injury, predominantly in the white matter. Spongiform leucoencephalopathy likely represents the longer-survival incomplete infarct pattern and is observed with polydrug abuse.