Proton magnetic resonance spectroscopy ((1)H-MRS) of the brain following high-dose methotrexate treatment for childhood cancer

Med Pediatr Oncol. 2000 Jul;35(1):28-34. doi: 10.1002/1096-911x(200007)35:1<28::aid-mpo5>;2-v.


Background: To avoid the late sequelae associated with cranial radiation therapy in childhood, intermediate- or high-dose intravenous methotrexate (HDMTX) has found increasing application as a means of preventing the development of overt central nervous system disease in childhood acute leukaemia. However, acute and chronic neurotoxicity has been described following HDMTX therapy, and the long-term intellectual outcome in children treated in this way is inadequately documented. Proton magnetic resonance spectroscopy ((1)H-MRS) of the brain is a noninvasive, quantitative way of assessing aspects of cerebral metabolism, which has not previously been applied to the study of children undergoing central nervous system directed therapy.

Procedure: To evaluate the potential role of (1)H-MRS in the investigation of related neurotoxicity, 11 children who had received HDMTX (cumulative dose 6-96 g/m(2)) underwent localised (1)H-MRS, magnetic resonance imaging. Neuropsychological assessments were performed on the children who had more than 1 year of follow-up time since last methotrexate treatment. Control (1)H-MRS studies on 11 adult and 6 young volunteers were undertaken. Eight patients had spectra of adequate quality. Comparisons between (1)H-MRS metabolite ratios and normal controls were made.

Results: Patients had a low choline/water ratio compared to controls (P < 0.01). No differences between patient and control NAA/water, Cr/water, Naa/Cr, and Cho/Cr ratios were seen. Overall, 3 patients had abnormal white matter changes on MRI. The mean IQ of the patients (104.1) was in the normal range.

Conclusions: It is postulated that choline depletion in the brains of these patients may reflect subclinical disturbances of myelin metabolism as a result of methotrexate therapy and may represent a possible avenue of treatment in patients with clinical chronic methotrexate-related neurotoxicity.

MeSH terms

  • Adolescent
  • Adult
  • Antimetabolites, Antineoplastic / adverse effects*
  • Brain / drug effects*
  • Brain / pathology
  • Case-Control Studies
  • Central Nervous System Diseases / etiology*
  • Central Nervous System Diseases / pathology*
  • Central Nervous System Diseases / prevention & control
  • Child
  • Female
  • Humans
  • Leukemia / drug therapy*
  • Leukemia / radiotherapy
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Methotrexate / adverse effects*


  • Antimetabolites, Antineoplastic
  • Methotrexate