Blood–Brain Barrier Permeability and Long-Term Clinical and Imaging Outcomes in Cerebral Small Vessel Disease

Abstract

Background and Purpose Increased blood-brain barrier (BBB) permeability occurs in cerebral small vessel disease (SVD). It is not known if BBB changes predate progression of SVD. Methods We followed up patients with non-disabling lacunar or cortical stroke and BBB permeability MR imaging following their original stroke. About three years later, we assessed functional outcome (Oxford Handicap Score, OHS, poor outcome defined as 3-6), recurrent neurological events and white matter hyperintensity (WMH) progression on MRI. Results Amongst 70 patients, mean age 68 (SD±11) years, median time to clinical follow up was 39 months (IQR 30-45), median OHS was 2 (IQR 1-3); poor functional outcome was associated with higher baseline WMH score (p<0.001) and increased basal ganglia BBB permeability (p=0.046). Amongst 48 patients with follow-up MRI, WMH progression at follow-up was associated with baseline WMH (ANCOVA p<0.0001) and age (ANCOVA p=0.032). Conclusions Further long term studies to evaluate the role of BBB dysfunction in progression of SVD are required in studies that are large enough to account for key prognostic influences such as baseline WMH and age.

Perfusion Deficits and Mismatch in Patients with Acute Lacunar Infarcts Studied with Whole-Brain CT Perfusion

“…In experimental models, these lesions are accompanied by activation of inflammatory cells, 30 and extensive increases in vascular permeability have been described in patients with small-vessel disease and in particular LI. 31 Although we have seen patients in whom the final infarct was greater than the initial hypoperfused area, we were not able to accurately measure the initial ischemic volume, and therefore lesion expansion, because the segmentation of the perfusion abnormalities was focused on delineating the hypoperfusion within the DWI lesion.…”

Emerging Evidence for Pathogenesis of Sporadic Cerebral Small Vessel Disease

“…The magnetic resonance imaging mean diffusivity discriminates WMH from normal-appearing WM even within the mild range of WMH severity, suggesting that BBB leak is an early predictor of WM damage. 79,80 There are accumulating lines of evidence in support of a pivotal role of the BBB leakage in SVD stroke [81][82][83] and in VCI. 84 Therefore, endothelial damage and subsequent BBB breakdown seem to be pivotal factors contributing to the pathogenesis of SVD.…”

“…Средний коэффициент диффузии при магнитно-резонансной томографии позволяет отли-чить ГБВГМ от нормального БВГМ даже при умерен-ной тяжести ГБВГМ, подтверждая, что повышение проницаемости ГЭБ является ранним предиктором повреждения БВГМ [79,80]. Растет число доказа-тельств в поддержку ключевой роли разрушения ГЭБ при инсульте на фоне БМЦС [81][82][83] и при СКН [84]. Таким образом, повреждение эндотелия и последую-щее разрушение ГЭБ являются основополагающими факторами в патогенезе БМЦС.…”

Cerebral Small Vessel Disease Is Associated with Dysregulation in the Ubiquitin Proteasome System and Other Major Cellular Pathways in Specific Brain Regions

“…Some investigators have hypothesized that BBB dysfunction is associated with SVD [21]. However, this concept is not generally accepted, as studies in patients do not support this association [22,23].…”