Diffusion-weighted MRI correlates of subacute methotrexate-related neurotoxicity

Objectives: A delayed stroke-like leukoencephalopathy has been observed in patients receiving methotrexate (MTX) for childhood leukemia. Diffusion-weighted MRI (DWI) may help to distinguish between ischemic stroke and chemotherapy-related leukoencephalopathy. Although conventional MRI correlates have been described for this stroke-like syndrome, DWI data are largely unavailable. Our objective is to present a retrospective analysis of the DWI findings in four patients who suffered subacute neurotoxicity after intrathecal MTX. Design: We reviewed the medical records of four patients, who were seen by us between July 2000 and February 2004 for sudden onset of a central neurological syndrome within days of intrathecal MTX. Patients underwent standardized MRI within 48 h of symptom onset; MRI included DWI and apparent diffusion coefficient (ADC) maps. Results: DWI of all patients revealed well-demarcated hyperintense lesions within the subcortical white matter corresponding to areas of restricted proton diffusion on ADC maps. Lesions exceeded the confines of adjacent vascular territories. Complete resolution of symptoms within 1-4 days was accompanied by normalization of ADC abnormalities. Conclusions: DWI findings in this cohort seem to reflect cytotoxic edema within cerebral white matter suggesting a reversible metabolic derangement, rather than ischemia, as the basis for this syndrome.