White matter changes on MRI during treatment in children with acute lymphoblastic leukemia: correlation with neuropsychological findings

Med Pediatr Oncol. 2000 Nov;35(5):456-61. doi: 10.1002/1096-911x(20001101)35:5<456::aid-mpo3>3.0.co;2-1.

Abstract

Background: Treatment of childhood acute lymphoblastic leukemia (ALL) may cause structural and functional brain damage. To find out the incidence of white matter changes during therapy, a prospective MRI study was designed, and the findings were correlated with neuropsychological evaluation.

Procedure: Thirty-three children with ALL underwent serial cranial MRI before, during, and after therapy. Twenty-eight of these children underwent also neuropsychological assessment at the end of treatment. They all received intravenous and intrathecal methotrexate for central nervous system (CNS) therapy, 15 patients received cranial irradiation in addition.

Results: Transient high-intensity white matter changes were observed by MRI in three children 9% (95% CI, 2-24%) who received chemotherapy only. The high-intensity changes were most prominent in the frontal lobes in two of these children. The children with white matter changes were significantly younger than those with normal MRI (2.8 vs. 7.4 years; mean). There was no correlation between neuropsychological tests and white matter changes, except in attention and in tests referring to the frontal areas in general.

Conclusions: White matter changes are occasionally observed during therapy with the current Nordic protocols. Young children may be more susceptible to developing white matter changes after repeated intravenous methotrexate injections. There is no systematic correlation between neuropsychological deficits and MRI findings.

MeSH terms

  • Adolescent
  • Antimetabolites, Antineoplastic / adverse effects*
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Brain Injuries / chemically induced*
  • Child
  • Child, Preschool
  • Cytarabine / adverse effects
  • Demyelinating Diseases / chemically induced*
  • Female
  • Humans
  • Injections, Spinal
  • Magnetic Resonance Imaging
  • Male
  • Methotrexate / adverse effects*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Prospective Studies
  • Radiotherapy, Adjuvant
  • Statistics, Nonparametric

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Hormonal
  • Cytarabine
  • Methotrexate