Transient encephalopathy following a single exposure of high-dose methotrexate in a child with acute lymphoblastic...

An episode of transient encephalopathy after the first course of intravenous high-dose methotrexate (HD-MTX; 1000 mg/m2) was observed in a 4-year-old girl with acute lymphoblastic leukemia. The neurological abnormalities took place 5 days after HD-MTX therapy. She experienced complex partial seizure and left hemiparesis, which resolved spontaneously in 5 days. Cranial computed tomographic scan and magnetic resonance imaging showed multiple low-density lesions in bilateral hemispheres. It is well appreciated that neurotoxicity from MTX follows prolonged exposures, often accompanying or following radiation therapy. To our knowledge, however, there have been no reports that such neurological complications developed following a single exposure of HD-MTX in patients with ALL. Follow-up electroencephalograms showed that she had periodic lateralized epileptiform discharges (PLEDS), suggesting functional deafferentation of cortical neurons following HD-MTX. Moreover, the serum and CSF MTX levels following a second low-dose course and her clinical course suggested that she had presumably central nervous system leukemia at the time of HD-MTX therapy, which might have been related to neurological complications. The pathogenesis of MTX-induced neurotoxicity is discussed.