Cerebral hemodynamics and white matter hyperintensities in CADASIL

J Cereb Blood Flow Metab. 2003 May;23(5):599-604. doi: 10.1097/01.WCB.0000062341.61367.D3.


Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small-vessel disease caused by mutations in the NOTCH3 gene on chromosome 19. On magnetic resonance imaging (MRI), subcortical white matter hyperintensities and lacunar infarcts are visualized. It is unknown whether a decrease in cerebral blood flow or cerebrovascular reactivity is primarily responsible for the development of white matter hyperintensities and lacunar infarcts. The authors used phase-contrast MRI in 40 NOTCH3 mutation carriers (mean age 45 +/- 10 years) and 22 nonmutated family members (mean age 39 +/- 12 years), to assess baseline total cerebral blood flow (TCBF) and cerebrovascular reactivity after acetazolamide. Mean baseline TCBF was significantly decreased in NOTCH3 mutation carriers. In young subjects, baseline TCBF was significantly lower than in nonmutation carriers (mean difference 124 mL/min). Furthermore, baseline TCBF did not differ significantly between mutation carriers with minimal and mutation carriers with moderate or severe white matter hyperintensities. No significant difference in mean cerebrovascular reactivity was found between mutation carriers and nonmutation carriers. This study suggests that a decrease in baseline TCBF in NOTCH3 mutation carriers precedes the development of white matter hyperintensities.

MeSH terms

  • Adult
  • Brain Infarction / genetics
  • Brain Infarction / pathology
  • Brain Infarction / physiopathology
  • Cerebrovascular Circulation / physiology*
  • Dementia, Multi-Infarct / genetics
  • Dementia, Multi-Infarct / pathology*
  • Dementia, Multi-Infarct / physiopathology*
  • Family
  • Female
  • Heterozygote
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Fibers / pathology
  • Proto-Oncogene Proteins / genetics
  • Receptor, Notch3
  • Receptors, Cell Surface*
  • Receptors, Notch
  • Severity of Illness Index


  • NOTCH3 protein, human
  • Proto-Oncogene Proteins
  • Receptor, Notch3
  • Receptors, Cell Surface
  • Receptors, Notch