Case of the Month
Section Editor: Nicholas Stence, MD
Children's Hospital Colorado, Aurora, CO
May 2023
Next Case of the Month Coming June 6...
Methotrexate Toxicity
- Background:
- Additional clinical history: Patient was undergoing therapy for ALL and had received intrathecal methotrexate 7 days prior; MRI was performed 24 hours after the onset of HA, RUE and RLE weakness, which had resolved at the time of imaging.
- Methotrexate (MTX) is in wide use for treatment of pediatric neoplasms.
- It can be administered orally, intravenously, or intrathecally.
- In high doses, it is used for the treatment of acute lymphoblastic leukemia and osteosarcoma.
- Acute encephalopathy is a known toxic effect of MTX administration, usually occurring 1–2 weeks after administration of either IT MTX or high-dose oral MTX in 3–15% of patients.
- Clinical Presentation:
- Symptoms can include nausea/vomiting, AMS, and headache. It can also present with focal neurologic findings such as hemiparesis, aphasia, and seizures.
- These symptoms may wax and wane in a similar fashion to migraines, which has been speculated to reflect cortical spreading depression as opposed to vascular occlusion.
- Hemiparesis can present over minutes to hours and appear strokelike, leading to emergent imaging. It can be unilateral, bilateral, or alternating.
- Key Diagnostic Features:
- CT imaging is typically normal.
- MRI classically demonstrates a well-defined area of restricted diffusion in the cerebral white matter that usually corresponds to symptoms. The area of restricted diffusion is often either normal or can be very mildly T2 hyperintense relative to the degree of restricted diffusion.
- The area of diffusion restriction may resolve completely or fade with mild residual T2 hyperintensity.
- The relative hyperperfusion on pCASL in the affected hemisphere in this case may reflect changes from the hyperperfusion stage of cortical spreading depression, which can occur anywhere from 11 hours to days after onset of symptoms in cases of migraine with aura.
- Differential Diagnoses:
- Chronic MTX toxicity: Usually distinguished by history and a lack of significant diffusion restriction
- Posterior reversible encephalopathy syndrome (PRES): Different patterns of involvement (classically watershed or posterior distribution of signal abnormality); most often increased or mixed diffusivity
- Arterial ischemic stroke: Should present with arterial stenosis or occlusion, occur in a more stereotypical arterial distribution, and generally have more significant T2 hyperintensity and swelling by the time MRI is obtained
- Treatment:
- Acute MTX encephalopathy can be treated with IV aminophylline, with or without leucovorin, and seizures can be managed acutely with phenytoin.
- Most patients can continue to receive further doses of MTX according to their treatment protocols after resolution of symptoms.
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