Prevalence of leukoencephalopathy and its potential cognitive sequelae in cancer patients

J Chemother. 2020 Nov;32(7):327-343. doi: 10.1080/1120009X.2020.1805239. Epub 2020 Aug 17.


Due to the rising use of chemotherapy treatment in cancer patients and growing survival rates, therapy-induced neurotoxic side effects are increasingly reported. Given the ambiguity about the prevalence and severity of leukoencephalopathy, one of such toxic side effects, in non-central nervous system (CNS) cancer patients, we performed a systematic literature search using the PubMed/Medline database to summarize existing literature regarding leukoencephalopathy epidemiology in non-CNS cancer patients and its potential cognitive sequelae. The search was based on the following terms: ('MRI' OR 'T2-weighted MRI' OR 'FLAIR') AND ('cancer' OR 'tumour' OR 'leukaemia' OR 'neoplasms') AND ('chemotherapy' OR 'radiotherapy') AND ('posterior reversible encephalopathy' OR 'leukoencephalopathy' OR 'cerebral ischaemia' OR 'stroke'). Thirty-two studies discussing the occurrence of leukoencephalopathy in cancer patients were included, of which the majority investigated Acute Lymphoblastic Leukaemia (ALL) patients (n = 22).Regularly scanned ALL patients showed a prevalence of leukoencephalopathy between 17 - 87%, and 15 - 83% of patients presented with leukoencephalopathy when only scanned after a CNS event. When diagnosed with posterior reversible encephalopathy syndrome, 100% of patients showed leukoencephalopathy because its diagnosis is based in part on observable lesions. An increased prevalence was observed in ALL patients treated with higher doses of methotrexate (5 g/m2 MTX, 42 - 87%) when compared to lower doses (< 5 g/m2, 32 - 67%). By contrast, in breast cancer patients, white matter lesions were mainly detected in case of neurological symptoms, but not (yet) clearly associated with chemotherapy administration. However, chemotherapy treatment was associated with more infratentorial microbleeds in breast cancer patients . Up to 50% of other (neurologically asymptomatic) solid tumour patients presented white matter lesions, even years after treatment. When cognitive data were investigated, lesioned patients showed lower scores on neurocognitive tests in 50% of studies, years after ending therapy.In conclusion, leukoencephalopathy is well-documented for ALL patients (with a focus on methotrexate), but there is a lack of knowledge for other intravenous chemotherapeutics, other oncological populations, wider age ranges and possible risk factors (e.g. history of CNS event). Furthermore, the long-term neuropsychological impact and potential risk for neurodegenerative processes due to leukoencephalopathy remains inconclusive. Hence, large international databanks, epidemiological and prospective case-control studies are necessary to stratify risk groups for CNS-related side effects.

Keywords: cancer; chemotherapy; imaging; leukoencephalopathy; review; structural.

Publication types

  • Systematic Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms / drug therapy
  • Case-Control Studies
  • Cognition / drug effects*
  • Dose-Response Relationship, Drug
  • Humans
  • Leukoencephalopathies / chemically induced*
  • Leukoencephalopathies / physiopathology*
  • Methotrexate
  • Posterior Leukoencephalopathy Syndrome / chemically induced
  • Posterior Leukoencephalopathy Syndrome / physiopathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Prevalence
  • Prospective Studies
  • Severity of Illness Index


  • Methotrexate