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Reversible acute methotrexate leukoencephalopathy: atypical brain MR imaging features
France Ziereisen1, Bernard Dan, Nadira Azzi
1Department of Radiology, Queen Fabiola Children's University Hospital, Avenue J J Crocq 15, 1020 Brussels, Belgium. france.ziereisen@huderf.be
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.
Materials And 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.
Insights
Methotrexate (MTX) can cause unusual, reversible brain changes in children, sometimes leading to acute neurological symptoms. Recognizing these atypical signs on MRI is crucial for diagnosis and treatment.
Area of Science:
- Pediatric Oncology
- Neuroimaging
- Toxicology
Background:
- Methotrexate (MTX) is known to induce acute, reversible leukoencephalopathy.
- Atypical presentations of MTX neurotoxicity are less understood.
Purpose of the Study:
- To determine the incidence of atypical MTX neurotoxicity in pediatric patients.
- To characterize the magnetic resonance (MR) imaging findings of this condition.
Main Methods:
- Retrospective review of clinical data and brain MRIs in 90 children treated with MTX.
- Patients received MTX for acute lymphoblastic leukemia or non-Hodgkin lymphoma.
- Brain imaging was assessed post-treatment, post-relapse, or upon neurological symptom onset.
Main Results:
- 16.7% of patients showed MTX neurotoxicity on MRI; 10% were asymptomatic with typical findings.
- 6.7% of patients exhibited acute leukoencephalopathy with atypical MR findings.
- Symptomatic patients showed T2 hyperintensities in cortical, subcortical, and cerebellar regions, differing from typical periventricular findings.
Conclusions:
- MTX can cause both typical, often asymptomatic, and unusual, severe but reversible leukoencephalopathy.
- Atypical MTX-induced leukoencephalopathy requires recognition in the differential diagnosis of acute neurological issues in pediatric patients.
- MR imaging plays a key role in identifying and characterizing MTX neurotoxicity.
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