Clinical and radiological characteristics of methotrexate-induced acute encephalopathy in pediatric patients with cancer

H. Inaba, R. B. Khan, F. H. Laningham, K. R. Crews, C. H. Pui, Najat C. Daw

Research output: Contribution to journalArticle

103 Scopus citations


Background: Little information is available about the diagnosis and management of acute methotrexate (MTX)-induced encephalopathy. Methods: We reviewed clinical and magnetic resonance imaging (MRI) [including diffusion-weighted imaging (DWI)] characteristics of this complication in pediatric cancer patients treated from 2000 to 2006. Results: Six of 754 (0.8%) patients with leukemia or lymphoma and 2 of 44 (4.5%) with bone sarcoma experienced acute encephalopathy within 2 weeks (median, 7.5 days) after receiving high-dose i.v. and/or intrathecal MTX. The signs and symptoms varied at presentation and during episodes: hemiparesis (eight patients, alternating from side to side in four), dysphasia (six), confusion/emotionality (six), headache (three), choreoathetosis (two), and seizure (two). All patients recovered after 1-7 days (median, 5.5 days). DWI revealed restricted diffusion in anatomic brain regions associated with the symptoms; changes on T2-weighted and fluid-attenuated inversion recovery (FLAIR) imaging were consistently less marked. After recovery, DWI findings were normal but T2 and/or FLAIR imaging usually showed residual abnormalities. Conclusions: Acute MTX toxicity often manifests as fluctuating neurologic symptoms with alternating hemispheric involvement. Restricted diffusion on DWI is a reliable early sign of acute MTX encephalopathy and resolves as clinical status improves, despite the persistence of subtle abnormalities on MRI.

Original languageEnglish (US)
Pages (from-to)178-184
Number of pages7
JournalAnnals of Oncology
Issue number1
StatePublished - Jan 1 2008



  • Encephalopathy
  • Leukemia
  • Magnetic resonance imaging
  • Methotrexate
  • Neurotoxicity
  • Osteosarcoma

ASJC Scopus subject areas

  • Hematology
  • Oncology

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