Abstract Objective Lacunar stroke is common (25% of ischemic strokes) and mostly because of an intrinsic cerebral microvascular disease of unknown cause. Although considered primarily to be an ischemic process, the vessel and tissue damage could also be explained by dysfunctional endothelium or blood–brain barrier (BBB) leak, not just ischemia. We tested for subtle generalized BBB leakiness in patients with lacunar stroke and control patients with cortical ischemic stroke. Methods We recruited patients with lacunar and mild cortical stroke. We assessed BBB leak in gray matter, white matter, and cerebrospinal fluid, at least 1 month after stroke, using magnetic resonance imaging before and after intravenous gadolinium. We measured tissue enhancement for 30 minutes after intravenous gadolinium by two image analysis approaches (regions of interest and tissue segmentation). We compared the enhancement (leak) between lacunar and cortical patients, and associations with key variables, using general linear modeling. Results We recruited 51 lacunar and 46 cortical stroke patients. Signal enhancement after gadolinium was higher in lacunar than cortical stroke patients in white matter ( p &lt; 0.001) and cerebrospinal fluid ( p &lt; 0.003) by both analysis methods, independent of other variables. Signal enhancement after gadolinium was also associated with increasing age and enlarged perivascular spaces, but these did not explain the lacunar‐cortical difference. Interpretation Patients with lacunar stroke have subtle, diffuse BBB dysfunction in white matter. Further studies are required to determine the relative contributions of BBB dysfunction and/or ischemia to the microvascular and brain abnormalities in lacunar stroke. Ann Neurol 2009;65:194–202

Lacunar stroke is associated with diffuse blood–brain barrier dysfunction