The observed lesions likely represent direct toxic effects of methanol and its metabolites, as well as injury secondary to anoxia and acidosis.
Methanol is metabolized to formaldehyde and formic acid by hepatic alcohol dehydrogenase.
High levels of formaldehyde do not appear in the blood, and toxic effects appear to be related to high levels of formic acid. In experimental animals, formic acid toxicity ensues despite correction of metabolic acidosis. The basis for the anatomic specificity of methanol poisoning is unknown. Injury to the putamen likely represents a selective toxic effect, possibly potentiated by poor venous drainage. The pathogenesis of the white matter hemorrhagic necrosis remains unexplained.