Methotrexate-induced leukoencephalopathy presenting as acute-onset limb weakness in a child: a case report

Methotrexate is an essential medicine used to treat childhood malignancies including acute lymphoblastic leukemia. Neurotoxicity manifesting as leukoencephalopathy is an important adverse effect of methotrexate. Methotrexate-induced leukoencephalopathy classically demonstrates sub-acute-onset neurological manifestations that include learning disability, progressive dementia, drowsiness, seizures, ataxia, and hemiparesis. These are rare in children and are generally reported following intrathecal or intravenous use of methotrexate. In contrast, acute onset neurotoxicity with oral use of methotrexate is very rare. We report a 10-year-old boy presenting with acute onset limb weakness and neurological signs due to methotrexate-induced leukoencephalopathy following oral methotrexate.

A 10-year-old Sri Lankan boy presented with fever and headache for 5 days and difficulty in walking for 2 days. He was unable to stand unaided on admission, and his parents complained of repetitive, involuntary extension movements involving the right upper limb. He is a child diagnosed with acute lymphoblastic leukemia who was on treatment for a relapse with daily oral dexamethasone and mercaptopurine, weekly oral methotrexate and folinic acid, and once every two weeks intrathecal vincristine. On examination, he had dystonic movements of the right upper limb and hypotonia and reduced muscle power (grade 3/5) of the left upper and lower limbs proximally and distally. The muscle power of the right side was grade 4 (out of 5). Tendon reflexes were diminished in all four limbs, and the plantar response was flexor bilaterally. The child had dysmetria and intension tremors on both sides. T2-weighted magnetic resonance imaging of the brain revealed symmetrical high signal intensities with diffusion restriction involving bilateral putamen, subcortical areas, and deep white matter, suggesting treatment-related neurotoxicity due to methotrexate-induced leukoencephalopathy. Oral methotrexate was discontinued. He showed gradual improvement in limb weakness and other neurological signs following treatment with intravenous folinic acid, aminophylline, dexamethasone, and oral dextromethorphan.

This case report describes a patient with rapidly progressing methotrexate-induced leukoencephalopathy following oral methotrexate. It highlights that the risk of neurotoxicity persists even with the oral use of methotrexate; therefore, the prescribers should be vigilant of this uncommon side effect.