Methotrexate-related multifocal axonopathy. Report of an autopsy case.

A case of multifocal axonopathy associated with intrathecal methotrexate (IT MTX) and radiation therapy is presented. A 33-year-old woman suffering from meningeal carcinomatosis of breast cancer origin had developed prominent multifocal axonal degeneration in the cerebral white matter after treatment with IT MTX therapy and cranial irradiation. The principal features of this axonal degeneration were segmental hydropic swellings, macrophage infiltration of swollen axons, and scattered spheroid formation associated with reactive astrocytosis. These features were similar to those observed in our previous experimental study using cats treated with IT MTX alone. This "multifocal axonopathy" without necrotizing lesions seems to be different from disseminated necrotizing leukoencephalopathy, and, therefore, may be another form of MTX-related leukoencephalopathy. IT MTX and cranial irradiation seem to have exerted synergistic effects in producing the "multifocal axonopathy" in this case.