Blood brain barrier leakage is not a consistent feature of white matter lesions in CADASIL.
Level 4 - case-series / case-control
Post-mortem case-control tissue analysis combined with animal research
PubMed 31753008 · doi:10.1186/s40478-019-0844-x
What was done
Researchers examined post-mortem brain tissue from 12 CADASIL patients and 10 age-matched controls, alongside a transgenic mouse model of CADASIL, to assess blood-brain barrier (BBB) integrity and pericyte coverage across different white matter lesion (WML) subtypes. They measured fibrinogen extravasation in pure WMLs versus WMLs associated with enlarged perivascular spaces (ePVS) or lacunes, quantified pericyte coverage, and evaluated the extravasation of endogenous fibrinogen and injected tracers in mice.
What was found
The abstract reports no numerical values, effect sizes, or test statistics. Fibrinogen extravasation was significantly elevated only in WMLs surrounding ePVS and lacunes; levels in pure WMLs were comparable to normal-appearing white matter in both CADASIL patients and controls. CADASIL mice demonstrated no extravasation of endogenous fibrinogen or injected small/large tracers. Pericyte coverage was unmodified across all WML types in both human tissue and mice.
Why it matters
This study challenges the consensus that BBB leakage and pericyte loss are primary initiators of all white matter damage in CADASIL. It demonstrates that BBB breakdown is heterogeneous and restricted to specific lesion sub-types, suggesting that in vivo neuroimaging of BBB permeability cannot be generalized to all white matter hyperintensities.
Limits
The human study is cross-sectional, post-mortem, and limited to a small sample size (12 CADASIL cases, 10 controls). The abstract provides directional findings without exact quantitative measurements or confidence intervals. The mouse model incompletely phenocopies human disease, as it does not develop lacunar infarcts or ePVS.
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