Stroke outcomes are worse with larger leukoaraiosis volumes

Abstract

Leukoaraiosis or white matter hyperintensities are frequently observed on magnetic resonance imaging of stroke patients. We investigated how white matter hyperintensity volumes affect stroke outcomes, generally and by subtype. In total, 5035 acute ischaemic stroke patients were enrolled. Strokes were classified as large artery atherosclerosis, small vessel occlusion, or cardioembolism. White matter hyperintensity volumes were stratified into quintiles. Mean age (± standard deviation) was 66.3 ± 12.8, 59.6% male. Median (interquartile range) modified Rankin Scale score was 2 (1-3) at discharge and 1 (0-3) at 3 months; 16.5% experienced early neurological deterioration, and 3.3% recurrent stroke. The Cochran-Mantel-Haenszel test with adjustment for age, stroke severity, sex, and thrombolysis status showed that the distributions of 3-month modified Rankin Scale scores differed across white matter hyperintensity quintiles (P < 0.001). Multiple ordinal logistic regression analysis showed that higher white matter hyperintensity quintiles were independently associated with worse 3-month modified Rankin Scale scores; adjusted odds ratios (95% confidence interval) for the second to fifth quintiles versus the first quintile were 1.29 (1.10-1.52), 1.40 (1.18-1.66), 1.69 (1.42-2.02) and 2.03 (1.69-2.43), respectively. For large artery atherosclerosis (39.0%), outcomes varied by white matter hyperintensity volume (P = 0.01, Cochran-Mantel-Haenszel test), and the upper three white matter hyperintensity quintiles (versus the first quintile) had worse 3-month modified Rankin Scale scores; adjusted odds ratios were 1.45 (1.10-1.90), 1.86 (1.41-2.47), and 1.89 (1.41-2.54), respectively. Patients with large artery atherosclerosis were vulnerable to early neurological deterioration (19.4%), and the top two white matter hyperintensity quintiles were more vulnerable still: 23.5% and 22.3%. Moreover, higher white matter hyperintensities were associated with poor modified Rankin Scale improvement: adjusted odds ratios for the upper two quintiles versus the first quintile were 0.66 (0.47-0.94) and 0.62 (0.43-0.89), respectively. For small vessel occlusion (17.8%), outcomes tended to vary by white matter hyperintensitiy volume (P = 0.10, Cochran-Mantel-Haenszel test), and the highest quintile was associated with worse 3-month modified Rankin Scale scores: adjusted odds ratio for the fifth quintile versus first quintile, 1.98 (1.23-3.18). In this subtype, worse white matter hyperintensities were associated with worse National Institute of Health Stroke Scale scores at presentation. For cardioembolism (20.6%), outcomes did not vary significantly by white matter hyperintensity volume (P = 0.19, Cochran-Mantel-Haenszel test); however, the adjusted odds ratio for the highest versus lowest quintiles was 1.62 (1.09-2.40). Regardless of stroke subtype, white matter hyperintensities were not associated with stroke recurrence within 3 months of follow-up. In conclusion, white matter hyperintensity volume independently correlates with stroke outcomes in acute ischaemic stroke. There are some suggestions that stroke outcomes may be affected by leukoaraiosis differentially depending on stroke subtypes, to be confirmed in future investigations.

Keywords: ischaemic stroke; magnetic resonance image; outcome; white matter hyperintensities.

Figure 1

Graphical summary of the major results of this study. Predicted prevalence of early neurological deterioration/post-discharge improvement of modified Rankin Scale score and relative risk of increased modified Rankin Scale score at 3 months: the impact of WMH volume, generally and by stroke subtype. Top left: Topographical frequency-volume maps that were generated by using the quantitative magnetic resonance data of the 5035 patients of this study, as previously reported in our study (n = 2699 patients with first-ever acute ischaemic stroke) using the Kim statistical WMH scoring system: a graphical reference system allowing the quantitative estimation of the severity of WMHs as a percentile rank score (Ryu et al., 2014). First to fifth (WMH volume quintile) images correspond to 10, 30, 50, 70 and 90 percentile maps, respectively. Predicted prevalence of early neurological deterioration and improvement of modified Rankin Scale score (from discharge to 3 months) were derived from multiple logistic regression analysis with adjustment for age, NIHSS score, sex, body mass index, hypertension, diabetes, hyperlipidemia, smoking, coronary artery disease, atrial fibrillation, prior use of statin, haemoglobin, total cholesterol, fasting glucose, and log-transformed infarct volume on diffusion-weighted image. Black or grey bars represent predicted prevalence with 95% CI (left y-axis). Red dots and lines indicate adjusted ORs with 95% CI for the relative risk of increased modified Rankin Scale score at 3 months by ordinal logistic regression analysis. *P < 0.05 and **P < 0.01 compared with the first quintile of WMHs.