Cerebral Computed Tomography-Graded White Matter Lesions Are Associated With Worse Outcome After Thrombolysis in Patients With Stroke

Abstract

Background and Purpose— Compared with other stroke causes, small-vessel disease is associated with better 3-month outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis. Another question is the impact of coexisting cerebral white matter lesions (WMLs; a surrogate marker of small-vessel disease) on outcome, which was addressed in the current study. Methods— We analyzed 2485 consecutive intravenous thrombolysis–treated patients at the Helsinki University Central Hospital, 2001 to 2014. WMLs were scored according to 4 previously published computed tomographic visual rating scales from all baseline head scans. The inter-rater agreement was calculated. The primary outcome measure was shift analysis, and the secondary examined all possible binary cutoffs in the modified Rankin Scale at 3 months. The associations of modified Rankin Scale with nominal, ordinal, and continuous variables were analyzed in univariate and adjusted in multivariate binary and ordinal regression (shift analysis) models. Results— In univariate and multivariate regression analyses, all 4 tested visual WML rating scales (as continuous variables, or dichotomized at different cutoff points) were associated with worse outcome at all binary levels and in shift analyses of the modified Rankin Scale. After adjusting for confounders, the statistically strongest association in shift analyses remained for the Blennow scale dichotomized at >3 points, reflecting at least moderate WMLs (odds ratio, 1.90; 95% confidence interval, 1.48–2.44). Conclusions— WMLs on admission computed tomographic scan are independently associated with worse outcome in intravenous thrombolysis–treated patients with stroke.

Leukoaraiosis, Cerebral Hemorrhage, and Outcome After Intravenous Thrombolysis for Acute Ischemic Stroke

“…Five studies (n=3688 patients, accounting for 66% of the included population with outcome data) provided adjusted effect sizes describing the independent association between leukoaraiosis and poor outcome at 3–6 month post-stroke in multivariable analyses (adjusted for different co-variates depending on each study’s results, see Supplemental Table I). 5, 14, 18, 19 In a pooled sensitivity analysis of these studies, leukoaraiosis remained an independent predictor of poor outcome, with an adjusted OR of 1.61 (95%CI: 1.44–1.79; p<0.0001), but high degree of statistical heterogeneity (Figure 3B). Leukoaraiosis was also a predictor or poor outcome defined as mRS>1, in a sensitivity univariable analysis of four studies which had extractable data (OR: 1.76; 95%CI: 1.23–2.51; p=0.002, I 2 =69.2%, p=0.021, see Supplementary figure 1).…”

White Matter Lesions Double the Risk of Post-Thrombolytic Intracerebral Hemorrhage

“…19 The interclass correlation of raters (50 patients were rated by all 8 raters independently) indicated at least substantial agreement (defined as 0.61-0.80) for all 4 CT visual rating scales for WMLs as previously described. 12 Almost perfect agreement was reached for the van Swieten and the Blennow scores. In addition, the Wahlund score reached almost perfect agreement at frontal and parieto-occipital sites, but only fair agreement (defined as 0.21-0.40) for the other sites 12 ; therefore, the score was truncated to frontal and parietooccipital scores.…”

“…12 Almost perfect agreement was reached for the van Swieten and the Blennow scores. In addition, the Wahlund score reached almost perfect agreement at frontal and parieto-occipital sites, but only fair agreement (defined as 0.21-0.40) for the other sites 12 ; therefore, the score was truncated to frontal and parietooccipital scores.…”

“…12 Six previously used CT visual rating scales had been identified. We found that the rating scale of Rezek with scores from 0 to 180 was inappropriate for use in acute settings of IVT candidates.…”

“…The modified van Swieten scale was initially calculated for this publication but was omitted because the results were redundant to the original van Swieten scale. 12,14,15 The 4 previously published CT visual rating scales for WMLs were scored by 8 experienced stroke neurologists from all baseline CT head scans in a blinded fashion without knowledge of patients' clinical data or outcome as previously described 12 : the Gorter scale, 16 the van Swieten scale, 17 the Blennow rating scale, 18 and the Wahlund rating scale. 19 The interclass correlation of raters (50 patients were rated by all 8 raters independently) indicated at least substantial agreement (defined as 0.61-0.80) for all 4 CT visual rating scales for WMLs as previously described.…”