Vascular changes of methotrexate-related disseminated necrotizing leukoencephalopathy.

We investigated cerebral lesions of methotrexate (MTX)-related disseminated necrotizing leukoencephalopathy (DNL) in two autopsy cases of leukemia by the reconstruction technique of the serial sections and thick sections (700-800 microns) stained with silver impregnation to detect the topographic relation between the vascular changes and parenchymal lesions. We revealed the vascular changes, such as fibrinoid degeneration, hyalinized thickening of the vascular wall, dilatation of lumen and stenosis due to swelling of the endothelial cells and exsudation in the wall, particularly prominent in venules and capillaries of venous side in the territory of the superficial medullary veins. There were no remarkable changes in the arteries, except for the moderate endothelial swelling of arteriolar capillaries. The parenchymal lesions were topographically associated with these vascular changes, and the small necrotic foci confluented each other and formed large irregular necrotic foci. We considered that the DNL may be ascribed to dyshoric damage of the veins and capillaries of the venous side and that the mechanism of vascular injury was probably due to the prolonged direct action of intrathecal MTX on the vessels.