Purpose or Case Report: Encephalopathy is a well-recognised complication of intrathecal methotrexate in paediatric acute lymphoblastic leukaemia (ALL), often presenting with seizures, altered consciousness, and motor deficits that typically resolve spontaneously within 24–48 hours. In contrast, methotrexate-induced myelopathy is a far rarer and under-recognised entity, with the potential for lasting neurological sequelae if not diagnosed and treated promptly.
We present an unusual case of methotrexate-induced myelopathy in a child with ALL, featuring an atypical clinical presentation and novel MRI findings that expand the recognised radiological phenotype.

A 4-year-old boy in remission from low-risk B-cell ALL (without CNS involvement) received intrathecal and intravenous methotrexate via an atraumatic lumbar puncture. Within hours, he developed left-sided hemiparesis, progressing to quadriparesis, with predominant weakness on the left and brief truncal involvement. He remained afebrile and haemodynamically stable, and laboratory tests, CSF analysis, and methotrexate clearance were all unremarkable. Brain imaging (CT, MRI, MRA) was normal. However, spinal MRI revealed extensive T2 hyperintensity throughout the cervical, thoracic, and lumbar spinal cord, involving both grey and white matter — a pattern more reminiscent of transverse myelitis than classic methotrexate myelopathy. CSF cytology was negative for malignant cells, and autoimmune and infectious screens, including MOG and AQP4 antibodies, were negative. Treatment with high-dose corticosteroids, folinic acid rescue, and IVIG was initiated within 12 hours of symptom onset. The patient showed marked improvement and was discharged ambulant after six weeks, with only mild residual left-sided weakness.

Classic methotrexate myelopathy typically affects the dorsal columns in a caudal-to-rostral progression. In contrast, this case demonstrated diffuse longitudinal cord involvement with mixed grey and white matter changes. Such imaging findings are not widely reported. Histopathological studies in similar cases support a mechanism of superficial demyelination from CSF-contact toxicity, aligning with this radiological presentation.

This case expands the radiological spectrum of methotrexate-induced myelopathy. Recognition of atypical spinal imaging findings is critical for timely diagnosis and early immunomodulatory treatment, which can significantly improve neurological outcomes.
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