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. It is not known if BBB changes predate progression of small vessel disease.

Methods: We followed-up patients with nondisabling lacunar or cortical stroke and BBB permeability magnetic resonance imaging after their original stroke. Approximately 3 years later, we assessed functional outcome (Oxford Handicap Score, poor outcome defined as 3-6), recurrent neurological events, and white matter hyperintensity (WMH) progression on magnetic resonance imaging.

Results: Among 70 patients with mean age of 68 (SD ± 11) years, median time to clinical follow-up was 39 months (interquartile range, 30-45) and median Oxford Handicap Score was 2 (interquartile range, 1-3); poor functional outcome was associated with higher baseline WMH score (P<0.001) and increased basal ganglia BBB permeability (P=0.046). Among 48 patients with follow-up magnetic resonance imaging, 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 small vessel disease are required in studies that are large enough to account for key prognostic influences such as baseline WMH and age.

Figure 1

72-year-old patient with right hemisphere lacunar stroke. (a) two days after stroke MR DWI shows the acute right centrum semiovale lacunar infarct, T2* shows a few microbleeds, FLAIR shows numerous WMHs. BBB imaging six weeks later: FLAIR 30 minutes after iv Gadolinium (Gd) shows Gadolinium in cortical sulci and perivascular spaces (arrows). (b) FLAIR and T2* images two years later show increased WMHs and microbleeds (baseline FLAIR and T2* shown for comparison).

Figure 1

72-year-old patient with right hemisphere lacunar stroke. (a) two days after stroke MR DWI shows the acute right centrum semiovale lacunar infarct, T2* shows a few microbleeds, FLAIR shows numerous WMHs. BBB imaging six weeks later: FLAIR 30 minutes after iv Gadolinium (Gd) shows Gadolinium in cortical sulci and perivascular spaces (arrows). (b) FLAIR and T2* images two years later show increased WMHs and microbleeds (baseline FLAIR and T2* shown for comparison).