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Updated: Aug 20, 2026
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Acute methotrexate neurotoxicity: findings on diffusion-weighted imaging and correlation with clinical outcome
Nancy Rollins1, Naomi Winick, Robert Bash
1Department of Pediatric Radiology, University of Texas Southwestern Medical Center and Children's Medical Center of Dallas, 1935 Motor St., Dallas, TX 75235, USA.
Background And Purpose:
Acute lymphocytic leukemia (ALL) is a common malignancy of childhood treated with methotrexate (MTX), which is associated with acute neurotoxicity. We evaluated diffusion-weighted (DW) and conventional MR images in children with ALL and acute MTX-induced neurotoxicity, with clinical correlation.
Methods:
Five patients aged 12-15 years underwent fluid-attenuated inversion recovery (FLAIR), T2-weighted fast spin-echo and gradient-echo, T1-weighted gadolinium-enhanced spin-echo, and DW imaging within 24 hours of symptom onset. Records were reviewed for the temporal relationship to MTX administration, strokelike symptoms, and neurologic outcome.
Results:
Six strokelike events were temporally related to intrathecal MTX given 6-11 days before symptom onset. FLAIR images showed abnormal hyperintensity in the callosal splenium in one patient but were otherwise normal. Diffusion abnormalities were frontoparietal in three events and frontal in one; nonfluent aphasia was seen in all. Bilateral frontoparietal diffusion abnormalities were associated with bilateral upper-extremity weakness, right-sided hemiparesis, or left-sided hemiparesis (one patient each); one patient had mild facial droop. Unilateral precentral subcortical diffusion abnormality was associated with contralateral motor deficit and ipsilateral upper-extremity sensory loss. Strokelike symptoms resolved rapidly and were not associated with other signs of encephalopathy. Subsequent intrathecal MTX administration was not associated with recurrence in four patients.
Conclusion:
Diffusion abnormalities in acute MTX neurotoxicity indicated cerebral dysfunction but not necessarily overt structural injury to the cerebrum. Subsequent demyelination or gliosis could not be predicted on the basis of diffusion abnormalities. A single strokelike episode with diffusion abnormalities should not necessarily prompt modification of potentially curative chemotherapeutic regimens.
Insights
Diffusion MRI can detect acute neurotoxicity from methotrexate (MTX) in children with acute lymphocytic leukemia (ALL). These diffusion abnormalities indicate cerebral dysfunction, not necessarily permanent structural injury, guiding treatment decisions.
Area of Science:
- Pediatric Oncology
- Neuroradiology
- Neuroscience
Background:
- Acute lymphocytic leukemia (ALL) is a common childhood cancer.
- Methotrexate (MTX) is a standard ALL treatment but can cause neurotoxicity.
- Understanding MTX neurotoxicity is crucial for managing pediatric cancer patients.
Purpose of the Study:
- To evaluate diffusion-weighted (DW) and conventional MRI findings in children with ALL experiencing acute MTX-induced neurotoxicity.
- To correlate imaging findings with clinical presentation and neurological outcomes.
- To assess the implications of imaging findings for ongoing chemotherapy.
Main Methods:
- Five pediatric patients (aged 12-15) with ALL and suspected MTX neurotoxicity underwent MRI, including DW imaging, within 24 hours of symptom onset.
- Conventional MRI sequences (FLAIR, T2, T1-gadolinium) were also performed.
- Clinical data, including MTX administration timing, symptoms, and outcomes, were reviewed.
Main Results:
- Six strokelike events were linked to intrathecal MTX administration.
- Diffusion abnormalities were observed in the frontoparietal or frontal lobes, correlating with neurological deficits like aphasia and hemiparesis.
- FLAIR imaging showed limited abnormalities; diffusion abnormalities indicated cerebral dysfunction without overt structural damage.
Conclusions:
- Diffusion abnormalities on MRI are sensitive indicators of acute MTX neurotoxicity in children with ALL.
- These findings suggest cerebral dysfunction rather than irreversible structural injury.
- A single episode of neurotoxicity with diffusion abnormalities may not necessitate altering curative chemotherapy regimens.
