"Aseptic Meningoencephalopathy" or "Neurotoxicity" in Leukemia?

The "aseptic meningoencephalopathy" following CNS prophylaxis in childhood lymphoblastic leukemia reported by McIntosh and Aspnes would seem to be explained by the findings of Bleyer et al. They found markedly elevated CSF levels of methotrexate in five patients manifesting "neurotoxicity" following intrathecal injection in the dose range normally used for this form of therapy. Speculation regarding "geographical differences in virus infection or other factors" will now need to center on the reason(s) for the marked elevation (up to 100 times) of CSF methotrexate levels in these patients.