Clinical and radiological characteristics of methotrexate-induced acute encephalopathy in pediatric patients with cancer.
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.
Inaba
H
H
Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
Khan
R B
RB
Laningham
F H
FH
Crews
K R
KR
Pui
C-H
CH
Daw
N C
NC
D000208:Acute Disease; D000293:Adolescent; D000628:Aminophylline / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D002648:Child; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D051677:Histiocytoma, Malignant Fibrous / Q000188:drug therapy; D006801:Humans; D007275:Injections, Intravenous; D007278:Injections, Spinal; D007938:Leukemia / Q000188:drug therapy; D008297:Male; D008657:Metabolic Clearance Rate; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D020258:Neurotoxicity Syndromes / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D012516:Osteosarcoma / Q000188:drug therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D012189:Retrospective Studies
D000964:Antimetabolites, Antineoplastic; D000628:Aminophylline; D008727:Methotrexate