To report a rare case of methotrexate-induced encephalopathy.

Methotrexate (MTX) is an immunosuppressant used for therapy of a variety of inflammatory, rheumatologic, and cancerous conditions. Neurotoxicity is a rare complication of methotrexate therapy mostly presenting as transient neurological dysfunction but rarely posing severe or life-threatening consequences for the patient. There is limited literature demonstrating MTX toxicity with a chronic low-dose regimen, we aim to investigate and define another similar case.

We present a case of a 44 y/o M with a past medical history of relapsing polychondritis who was brought to our hospital by family due to an acute onset of impaired anterograde memory, a confusional state, and insomnia three weeks after discontinuing methotrexate therapy for polychondritis. Patient had a history of weekly methotrexate injection for 5 years until three weeks prior to presenting to our hospital. Brain MRI demonstrated hyperintensities adjacent to the hippocampi, posterior ventricles, and external capsules. EEG and CSF analyses demonstrated no abnormalities. As other infectious, inflammatory, and epileptic etiologies were excluded, the patient was found to have methotrexate-induced encephalopathy. The patient was started on steroid treatment with prednisone and followed up as an outpatient. With continued treatment and serial MRIs, it was found that the patient’s original hyperintensities resolved, his memory deficits and behavior improved, and he was able to eventually return to work and drive. As the patient’s cognitive deficits improved, he was tapered off of prednisone and continued steroid treatment for polychondritis.

This case illustrates a presentation of methotrexate-induced encephalopathy, even after medication discontinuation. Clinicians should remain aware of this side effect of medication use and its clinical presentation when prescribing methotrexate to patients.