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.
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 cancerpatients 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 MTXtoxicity often manifests as fluctuating neurologic symptoms with alternating hemispheric involvement. Restricted diffusion on DWI is a reliable early sign of acute MTXencephalopathy and resolves as clinical status improves, despite the persistence of subtle abnormalities on MRI.
Authors: Chelsea C Pinnix; Linda Chi; Elias J Jabbour; Sarah A Milgrom; Grace L Smith; Naval Daver; Naveen Garg; Matthew D Cykowski; Greg Fuller; David Cachia; Carlos Kamiya-Matsuoka; Karin Woodman; Courtney Dinardo; Nitin Jain; Tapan M Kadia; Naveen Pemmaraju; Maro Ohanian; Marina Konopleva; Hagop M Kantarjian; Bouthaina S Dabaja Journal: Am J Hematol Date: 2017-02 Impact factor: 10.047
Authors: Deepa Bhojwani; Noah D Sabin; Deqing Pei; Jun J Yang; Raja B Khan; John C Panetta; Kevin R Krull; Hiroto Inaba; Jeffrey E Rubnitz; Monika L Metzger; Scott C Howard; Raul C Ribeiro; Cheng Cheng; Wilburn E Reddick; Sima Jeha; John T Sandlund; William E Evans; Ching-Hon Pui; Mary V Relling Journal: J Clin Oncol Date: 2014-02-18 Impact factor: 44.544