Cerebrovascular reactivity in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

J Cereb Blood Flow Metab. 2021 Apr;41(4):831-840. doi: 10.1177/0271678X20929430. Epub 2020 Jun 17.


Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S) is a small vessel disease caused by TREX1 mutations. RVCL-S is characterized by retinal vasculopathy and brain white matter lesions with and without contrast enhancement. We aimed to investigate cerebrovascular reactivity (CVR) in RVCL-S. In this cross-sectional observational study, 21 RVCL-S patients, 23 mutation-negative family members, and 31 healthy unrelated controls were included. CVR to a hypercapnic challenge was measured using dual-echo arterial spin labeling magnetic resonance imaging. Stratified analyses based on age were performed. We found that CVR was decreased in gray and white matter of RVCL-S patients compared with family members and healthy controls (ANCOVA; P < 0.05 for all comparisons). This was most noticeable in RVCL-S patients aged ≥40 years (ANCOVA, P < 0.05 for all comparisons). In RVCL-S patients aged < 40 years, only CVR in white matter was lower when compared to healthy controls (P < 0.05). Gray matter CVR was associated with white matter lesion volume in RVCL-S patients (r = -0.527, P = 0.01). In conclusion, impaired cerebrovascular reactivity may play an important role in the pathophysiology of RVCL-S and may be an useful early biomarker of cerebrovascular disease severity.

Keywords: Cerebrovascular circulation; cerebrovascular disorders; leukoencephalopathies; magnetic resonance imaging; mutation.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging / pathology
  • Anatomy, Cross-Sectional
  • Biomarkers
  • Cerebrovascular Circulation*
  • Exodeoxyribonucleases / genetics
  • Female
  • Humans
  • Hypercapnia / diagnostic imaging
  • Hypercapnia / physiopathology
  • Leukoencephalopathies / diagnostic imaging
  • Leukoencephalopathies / physiopathology*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mutation
  • Netherlands
  • Phosphoproteins / genetics
  • Retinal Vasculitis / diagnostic imaging
  • Retinal Vasculitis / physiopathology*
  • Syndrome
  • White Matter / diagnostic imaging
  • White Matter / pathology


  • Biomarkers
  • Phosphoproteins
  • Exodeoxyribonucleases
  • three prime repair exonuclease 1