Cognitive performance and magnetic resonance imaging findings after high-dose systemic and intraventricular chemotherapy for primary central nervous system lymphoma

Arch Neurol. 2003 Apr;60(4):563-8. doi: 10.1001/archneur.60.4.563.


Background: Long-term neurotoxicity is a frequent complication of combined radiotherapy and chemotherapy in patients with primary central nervous system lymphoma. Treatment protocols without radiotherapy have been implemented to avoid this; however, little detailed neuropsychologic and neuroradiologic data exist to assess the frequency of long-term treatment sequelae in this patient group.

Objective: To determine whether a polychemotherapy regimen based on high-dose methotrexate results in cognitive impairment and/or changes detectable by magnetic resonance imaging of the brain during long-term follow-up.

Patients and methods: Twenty patients with histologically proven primary central nervous system lymphoma were treated with a novel chemotherapy protocol that included systemic and intraventricular administration of methotrexate and cytarabine (ara-C). Standardized neuropsychologic testing and magnetic resonance imaging investigations were performed prior to therapy and prospectively during a median follow-up period of 36 months (range, 21-69 months).

Results: Ten patients achieved durable remissions without relapse for more than 1 year after completion of chemotherapy. There was no gross cognitive decline in any of these patients during the follow-up period. In contrast, magnetic resonance imaging revealed therapy-induced white matter changes in 5 of these patients.

Conclusions: We conclude that chemotherapy alone is associated with a low risk of long-term neurotoxicity in primary central nervous system lymphoma. Methotrexate-induced white matter lesions detectable on magnetic resonance imaging are not inevitably associated with significant cognitive decline.

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Brain / drug effects*
  • Brain / pathology*
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / pathology
  • Brain Neoplasms* / psychology
  • Cognition / drug effects*
  • Cognition Disorders / chemically induced
  • Cognition Disorders / pathology
  • Female
  • Humans
  • Infusions, Intravenous
  • Injections, Intraventricular
  • Lymphoma* / drug therapy
  • Lymphoma* / pathology
  • Lymphoma* / psychology
  • Magnetic Resonance Imaging
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Middle Aged
  • Neuropsychological Tests


  • Antimetabolites, Antineoplastic
  • Methotrexate