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Cerebral hemodynamics and white matter hyperintensities in CADASIL
Rivka van den Boom1, Saskia A Lesnik Oberstein, Aart Spilt
1Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands. t.van_den_boom@lumc.nl
Summary
Reduced cerebral blood flow precedes white matter changes in CADASIL. This hereditary small-vessel disease, caused by NOTCH3 gene mutations, shows decreased baseline total cerebral blood flow (TCBF) in carriers, even before MRI-visible lesions appear.
Area of Science:
- Neurology
- Genetics
- Vascular Biology
Background:
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic small-vessel disease linked to NOTCH3 gene mutations.
- MRI reveals white matter hyperintensities and lacunar infarcts in CADASIL patients.
- The primary cause of these MRI findings—reduced cerebral blood flow or impaired cerebrovascular reactivity—remains unclear.
Purpose of the Study:
- To investigate whether decreased baseline cerebral blood flow or impaired cerebrovascular reactivity is the primary factor in CADASIL pathogenesis.
- To assess total cerebral blood flow (TCBF) and cerebrovascular reactivity in NOTCH3 mutation carriers versus non-carriers.
Main Methods:
- Phase-contrast MRI was employed to measure baseline TCBF and cerebrovascular reactivity post-acetazolamide administration.
- The study included 40 NOTCH3 mutation carriers and 22 non-carriers from affected families.
- Participants' ages ranged from young adults to older individuals.
Main Results:
- NOTCH3 mutation carriers exhibited significantly lower baseline TCBF compared to non-carriers, particularly noticeable in younger subjects.
- Baseline TCBF was reduced even in mutation carriers with minimal white matter hyperintensities, suggesting an early disease process.
- No significant differences in cerebrovascular reactivity were observed between mutation carriers and non-carriers.
Conclusions:
- A decrease in baseline cerebral blood flow appears to be an early event in CADASIL, preceding the development of white matter hyperintensities.
- These findings suggest that reduced TCBF is a primary factor in the pathogenesis of CADASIL.
- Targeting cerebral blood flow may offer a therapeutic strategy for CADASIL.