Light and electron microscopic observations on the cerebellum of guinea pigs following low-dose methotrexate.

The neurotoxicity of single and divided low-dose methotrexate (MTX) and the rescue effect of leucovorin (folic acid) were investigated by light and electron microscopic examination of the cerebellum of Guinea pigs. One group of animals received a single weekly intraperitoneal MTX in a dose of 10 mg/kg, a second received a similar dose divided into three equal fractions, and the third group received MTX rescued with an equal dose of leucovorin. The results showed degeneration of Purkinje cells indicated by shrinkage and distortion of perikarya, dissolution of mitochondrial cristae, and nuclear and nucleolar changes in all groups which received MTX. There was also astrocytic proliferation and perivascular edema. Lesser changes were found in the group which was rescued with leucovorin. The degenerative changes in the cerebellum particularly those of the Purkinje cells explain the neurological signs reported in cancer patients treated with MTX.