Methotrexate-induced central nervous system toxicity in children treated for acute lymphoblastic leukemia: analysis of seven consecutive cases

Résumé 0

Methotrexate (MTX), a folate analogue, is widely used in the treatment of patients with autoimmune disease or certain types of cancer such as acute lymphoblastic leukaemia (ALL), lymphoma and osteosarcoma. Depending on disease type, MTX can be administered intravenously (iv), by intrathecal (it) injection or as a high dose (HD) perfusion. One of the major MTX toxicities is neurotoxicity that can be classified in three groups depending on the timing: acute, subacute and late neurotoxicity. In acute neurotoxicity, symptoms like seizures, confusion, somnolence and chemical arachnoïditis with headache, nausea, vomiting and fever arise within hours of MTX administration. In the subacute form, stroke-like symptoms like hemiparesis, ataxia, speech disorder, or myelopathy like sensory changes, leg pain and paraplegia can appear after days or weeks of MTX administration. The recovery is often spontaneous after 48 to 72h (1). Finally, patients can develop a chronic form of neurotoxicity after months or years, characterized by learning disabilities, neurocognitive impairment and other leukoencephalopathic symptoms such as quadriparesia, dementia, coma, even death (2).