Effects of intraventricular methotrexate on folate, adenosine, and homocysteine metabolism in cerebrospinal fluid

Methotrexate (MTX) is an antifolate that affects many metabolic pathways. MTX may cause neurologic toxicity, but the biochemical effects of MTX on the central nervous system (CNS) are poorly characterized. The authors studied serial cerebrospinal fluid (CSF) samples from a child during two courses of intraventricular MTX and found a rapid and reproducible depletion in CSF of reduced folates and S-adenosylmethionine that was accompanied by marked increases in homocysteine and adenosine. No sulfur-containing excitatory amino acids were detected. This study demonstrates multiple profound effects of MTX on CNS metabolism and provides insight to the pathogenesis of MTX neurotoxicity.