Prevention of Neurotoxicity by High-dose Folinic Acid Rescue after High-dose Methotrexate and Intrathecal Methotrexate without Compromising Cure inspite of Previous Transient Leukoencephalopathy after Intrathecal Methotrexate

Methotrexate (MTX) is a frequently used chemotherapeutic agent in the treatment of childhood acute lymphoblastic leukaemia (ALL) and lymphoma.Besides oral and intravenous MTX, intrathecal MTX is an essential component of chemotherapy for ALL and is effective in preventing recurrences of central nervous system (CNS) leukaemia.Acute, subacute and chronic neurotoxicity have been observed after the administration of high-dose intravenous and/or intrathecal MTX. 1 The incidence varies with the route of administration, with less than 10% of those treated intravenously developing some neurotoxicity compared with up to 40% of patients treated intrathecally in combination with intravenous therapy. 2 Case ReportA 10-year-old boy was diagnosed with pre-B ALL.There was no CNS involvement at diagnosis.The leukaemia remitted after induction chemotherapy with prednisone, vincristine and L-asparaginase according to the MRC ALL97/revised 99 Protocol for standard risk ALL.During week 22 of treatment, delayed intensifi cation 1, he developed sudden onset quadriparesis (left more than right), numbness of upper limbs, slurred speech, and expressive dysphasia 3 days following his 8 th intrathecal MTX of 12 mg.Oral thioguanine and subcutaneous cytarabine were concomitantly given at that time.A physical examination revealed hypotonia, arefl exia and muscle power of three-fi fth of all limbs.A cerebrospinal fl uid (CSF) examination taken 6 days after the intrathecal MTX did not reveal any evidence of CNS leukaemia or infection (CSF: total protein -427 mg/L, glucose -2.8 mmol/L, cell count -0/cmm).MTX level was not performed on the CSF.His clinical condition improved spontaneously, and 6 days after admission the neurological defi cit had completely resolved.Magnetic resonance imaging (MRI) of the brain performed 16 days after the intrathecal MTX revealed bilateral white matter hyperdensity in the frontal lobes at the level of corona radiata extending to the centrum semiovale on T2-weighted images and fl uid-attenuated inversion recovery images (FLAIR) (Figs.1a and1b).These clinical and MRI fi ndings were in keeping with MTX-induced leukoencephalopathy.He received a further full dose of intrathecal MTX without any complications at week 32 and week 36 of treatment.However, he developed mild left-sided hand tremor at rest PhD(UK)