title: Reversible acute methotrexate leukoencephalopathy: atypical brain MR imaging features.
abstract: BACKGROUND
  Unusual acute symptomatic and reversible early-delayed leukoencephalopathy has been reported to be induced by methotrexate (MTX).
  
  
  OBJECTIVE
  We aimed to identify the occurrence of such atypical MTX neurotoxicity in children and document its MR presentation.
  
  
  METHODS
  We retrospectively reviewed the clinical findings and brain MRI obtained in 90 children treated with MTX for acute lymphoblastic leukaemia or non-B malignant non-Hodgkin lymphoma. All 90 patients had normal brain imaging before treatment. In these patients, brain imaging was performed after treatment completion and/or relapse and/or occurrence of neurological symptoms.
  
  
  RESULTS
  Of the 90 patients, 15 (16.7%) showed signs of MTX neurotoxicity on brain MRI, 9 (10%) were asymptomatic, and 6 (6.7%) showed signs of acute leukoencephalopathy. On the routine brain MRI performed at the end of treatment, all asymptomatic patients had classical MR findings of reversible MTX neurotoxicity, such as abnormal high-intensity areas localized in the deep periventricular white matter on T2-weighted images. In contrast, the six symptomatic patients had atypical brain MRI characterized by T2 high-intensity areas in the supratentorial cortex and subcortical white matter (n=6), cerebellar cortex and white matter (n=4), deep periventricular white matter (n=2) and thalamus (n=1). MR normalization occurred later than clinical recovery in these six patients.
  
  
  CONCLUSIONS
  In addition to mostly asymptomatic classical MTX neurotoxicity, MTX may induce severe but reversible unusual leukoencephalopathy. It is important to recognize this clinicoradiological presentation in the differential diagnosis of acute neurological deterioration in children treated with MTX.
authors.affiliation: Department of Radiology, Queen Fabiola Children's University Hospital, Avenue J J Crocq 15, 1020 Brussels, Belgium. france.ziereisen@huderf.be
authors.forename: France
authors.initials: F
authors.lastname: Ziereisen
authors.forename: Bernard
authors.initials: B
authors.lastname: Dan
authors.forename: Nadira
authors.initials: N
authors.lastname: Azzi
authors.forename: Alina
authors.initials: A
authors.lastname: Ferster
authors.forename: Nash
authors.initials: N
authors.lastname: Damry
authors.forename: Catherine
authors.initials: C
authors.lastname: Christophe
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001927:Brain Diseases / Q000139:chemically induced* / Q000175:diagnosis; D002648:Child; D002675:Child, Preschool; D003287:Contrast Media; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012189:Retrospective Studies
chemical_list: D003287:Contrast Media; D008727:Methotrexate