Carotid revascularization and hemispheric white matter disease progression

Carotid revascularization prevents ipsilateral ischemic stroke in high-grade stenosis, but its effect on hemispheric white matter disease (WMD) progression is not known.

We conducted a longitudinal study of patients ≥40 years with carotid stenosis (moderate50-69%, high-grade 70-99% or occluded) seen at Mayo Clinic (Florida, Rochester, Arizona) between 2011 and 2015 with serial brain MRIs ≥1 year apart and clinical follow-up through 2020. Hemispheric WMD volumes were quantified from axial T2-FLAIR using automated segmentation. Patients were stratified by revascularization status. The primary outcome was annual change in WMD volume ipsilateral or contralateral to the index carotid. Hemispheric differences in the annual rate of WMD progression (cm³/yr) were compared between revascularized vs not revascularized using multivariable linear regression adjusted for demographic and vascular risk factors, with additional adjustment for baseline imbalances between groups. Because three outcomes were evaluated, a Bonferroni-corrected significance threshold of p < 0.0167 was applied.

Among 150 patients (mean age 71 ± 10 years, 36.7% female), 37.3% had moderate stenosis, 42% high-grade, and 20.7% occlusion. Seventy-three (48.7%) underwent carotid revascularization; median follow-up was 5.1 years. Baseline WMD volume was 4.86 cm³ ipsilateral and 4.39 cm³ contralateral. Revascularized patients had a numerically slower ipsilateral WMD progression than non-revascularized patients (0.32 vs. 0.63 cm³/year, p = 0.34), with no contralateral difference. In fully adjusted models, revascularization was associated with attenuation of hemispheric difference in WMD progression (β = -0.46; 95% CI -0.84 to -0.08; p = 0.019). Although this association did not meet the Bonferroni-adjusted threshold, the effect estimate remained directionally consistent.

Carotid revascularization was associated with numerically slower ipsilateral WMD progression (∼50% relative difference) and attenuation of hemispheric asymmetry over a median 5-year follow-up. Given the modest statistical signal and correction for multiple comparisons, these findings should be interpreted as observational and hypothesis-generating. Prospective studies should evaluate whether modulation of WMD progression translates into meaningful cognitive benefit.