Jay Shah, MD

Traylor M, Rutten-Jacobs LCA,Thijs V, Holliday EG, Levi C, Bevan S, et al. Genetic Associations With White Matter Hyperintensities Confer Risk of Lacunar Stroke. Stroke. 2016

Small vessel disease (SVD) can lead to various pathologies including lacunar infarcts, hemorrhage and microbleeds but the underlying pathophysiological mechanism remains unknown. White matter hyperintensities (WMH) are increased in lacunar stroke suggesting a shared pathological mechanism. Furthermore, WMH and lacunar infarcts co-exist in patients with inherited forms of SVD such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Genome-wide association studies (GWAS) have identified multiple genetic variants associated with WMH. In this study, the authors evaluated the impact of common genetic variants associated with WMH on the risk of lacunar stroke in patients with lacunar strokes and controls.
The authors used a genetic risk score approach to determine if SNPs associated with WMH were associated with lacunar strokes along with cardioembolic and large vessel infarcts. Each subgroup included approximately 1300 patients and 9000 controls. Secondly, lacunar strokes were separated into WMH (n = 568) and without WMH (n=787) to test for association. WMH genetic risk score was associated with lacunar stroke in patients regardless of WMH status but not with cardioembolic or large vessel strokes. However, none of the WMH-associated SNPs met significance for association with lacunar stroke.

This study supports the known belief that features of cerebral SVD share pathophysiology. Interestingly, the risk of lacunar stroke remained in patients without significant WMH. This could potentially be to the effect of “time”, in that patients without WMH could possibly be younger and have not had accumulated SVD damage. Another possibility is that patients without WMH have an unknown protective mechanism that protects against WMH but not lacunar stroke. The latter would be interesting in that it would suggest differing pathological mechanism. The study had large number of patients and controls but a potential confounding variable is that control patients did not have MRI images raising the possibility that controls had lacunar strokes and/or WMH as such pathology can potentially be clinically “silent”. Nonetheless, this study highlights a shared pathophysiological process that underlies various manifestations of CVD.