Arterial, Venous, and Cerebrospinal Fluid Flow and Pulsatility in Stroke-Related Cerebral Small Vessel Disease: A...

Cerebral small vessel disease (SVD) causes up to 45% of dementias and 25% of ischemic strokes, but the understanding of vascular pathophysiology is limited. We aimed to investigate the contribution of pulsatility of intracranial arteries, veins, and cerebrospinal fluid (CSF) and cerebral blood flow to long-term imaging and clinical outcomes in SVD.

We prospectively recruited participants in Edinburgh/Lothian, Scotland, with lacunar or nonlacunar ischemic stroke (modified Rankin Scale score ≤2, as controls) and assessed medical and brain magnetic resonance imaging characteristics at baseline and 1 year (2018-2022). We used phase-contrast magnetic resonance imaging to measure flow and pulsatility in major cerebral vessels and CSF to investigate independent associations with baseline white matter hyperintensity (WMH) and perivascular space (PVS) volumes and their progression, as well as with recurrent stroke, functional, and cognitive outcomes at 1 year. We applied linear, logistic, and ordinal regression models in our analysis.

We recruited 210 participants; 205 (66.8% male; aged 66.4±11.1 years) had useable data. In covariate-adjusted analyses, higher baseline arterial pulsatility was associated with larger volumes of baseline WMH (B=0.26 [95% CI, 0.08-0.44]; P=0.01) and basal ganglia PVS (B=0.12 [95% CI, 0.04-0.20]; P<0.01) but not with their change at 1 year (WMH: B=0.01 [95% CI, -0.05 to 0.06]; P=0.78; basal ganglia PVS: B=0.02 [95% CI, -0.04 to -0.07]; P=0.62) or cognition, dependency, or recurrent stroke at 1 year. Neither cerebral blood flow nor CSF pulsatility was related to baseline SVD severity, WMH/PVS progression, or clinical outcomes at 1 year.

Associations between vascular/CSF pulsatility, cerebral blood flow, WMH/PVS, and clinical SVD features are complex. The lack of association between intracranial arterial, venous, or CSF pulsatility, cerebral blood flow, and WMH or PVS longitudinal change in this large, covariate-adjusted analysis questions the presumption that high intracranial vascular pulsatility causes SVD and its progression, consistent with other recent longitudinal studies. Intracranial pulsatility may differ from systemic vascular measures in their cause-pathogenic role(s) in SVD and should be considered separately.