White matter hyperintensity reduction and outcomes after minor stroke

Abstract

Objective: To assess factors associated with white matter hyperintensity (WMH) change in a large cohort after observing obvious WMH shrinkage 1 year after minor stroke in several participants in a longitudinal study.

Methods: We recruited participants with minor ischemic stroke and performed clinical assessments and brain MRI. At 1 year, we assessed recurrent cerebrovascular events and dependency and repeated the MRI. We assessed change in WMH volume from baseline to 1 year (normalized to percent intracranial volume [ICV]) and associations with baseline variables, clinical outcomes, and imaging parameters using multivariable analysis of covariance, model of changes, and multinomial logistic regression.

Results: Among 190 participants (mean age 65.3 years, range 34.3-96.9 years, 112 [59%] male), WMH decreased in 71 participants by 1 year. At baseline, participants whose WMH decreased had similar WMH volumes but higher blood pressure (p = 0.0064) compared with participants whose WMH increased. At 1 year, participants with WMH decrease (expressed as percent ICV) had larger reductions in blood pressure (β = 0.0053, 95% confidence interval [CI] 0.00099-0.0097 fewer WMH per 1-mm Hg decrease, p = 0.017) and in mean diffusivity in normal-appearing white matter (β = 0.075, 95% CI 0.0025-0.15 fewer WMH per 1-unit mean diffusivity decrease, p = 0.043) than participants with WMH increase; those with WMH increase experienced more recurrent cerebrovascular events (32%, vs 16% with WMH decrease, β = 0.27, 95% CI 0.047-0.50 more WMH per event, p = 0.018).

Conclusions: Some WMH may regress after minor stroke, with potentially better clinical and brain tissue outcomes. The role of risk factor control requires verification. Interstitial fluid alterations may account for some WMH reversibility, offering potential intervention targets.

Figure 1. Examples of WMH reduction in 2 participants

MRIs from patients (A, top and B, bottom) who showed definite visible reduction in WMH on MRIs between presentation with minor stroke (left, baseline; inset, the acute index infarct [arrow] on MRI diffusion tensor imaging) and 1 year (right). Note also the increase in visibility of sulci at 1 year (arrowheads, B, bottom right), indicating a reduction in brain volume accompanying the reduction in WMH volume. FLAIR = fluid-attenuated inversion recovery; WMH = white matter hyperintensities.

Figure 2. Individual participants' changes in WMH volume between baseline and 1 year by quintile of WMH volume change

Each line represents an individual patient, linking baseline WMH volume (left) to follow-up WMH volume (right) of each quintile column. WMH = white matter hyperintensities.

Figure 3. WMH change according to (A) WMH volume at 1 year, (B) WMH volume at baseline, (C) patient age, and (D) mean arterial blood pressure at baseline

Participants in Q1 had the most WMH shrinkage and those in Q5 had the most WMH growth between baseline and 1 year. In the box and whiskers, the central line is median, box lower margin is 25th percentile, upper margin is 75th percentile, lower whisker is 5th percentile, and upper whisker is 95th percentile. WMH vol = white matter hyperintensity volume.