Relationship of White Matter Lesions with Intracerebral Hemorrhage Expansion and Functional Outcome: MISTIE II and CLEAR
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ORIGINAL WORK
Relationship of White Matter Lesions with Intracerebral Hemorrhage Expansion and Functional Outcome: MISTIE II and CLEAR III Björn M. Hansen1†, Natalie Ullman2*† , John Muschelli3, Bo Norrving1, Rachel Dlugash4, Radhika Avadhani4, Issam Awad5, Mario Zuccarello6, Wendy C. Ziai4, Daniel F. Hanley4, Richard E. Thompson3†, Arne Lindgren1† and for the MISTIE and CLEAR Investigators © 2020 Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society
Abstract Background/Objective: Intracerebral hemorrhage (ICH) patients commonly have concomitant white matter lesions (WML) which may be associated with poor outcome. We studied if WML affects hematoma expansion (HE) and poststroke functional outcome in a post hoc analysis of patients from randomized controlled trials. Methods: In ICH patients from the clinical trials MISTIE II and CLEAR III, WML grade on diagnostic computed tomography (dCT) scan (dCT, 33% or > 6 mL ICH volume increase from dCT to the last pre-randomization CT ( 10.4 mL total clot volume increase, and a subgroup analysis including patients with dCT 33% or > 6 mL ICH volume increase. Poor functional outcome was assessed at 180 days and defined as modified Rankin Scale (mRS) ≥ 4, with ordinal mRS as a secondary endpoint. Results: Of 635 patients, 55% had WML grade 1–4 at dCT (median 2.2 h from ictus) and 13% had subsequent HE. WML at dCT did not increase the odds for primary or secondary HE endpoints (P ≥ 0.05) after adjustment for ICH volume, intraventricular hemorrhage volume, warfarin/INR > 1.5, ictus to dCT time in hours, age, diabetes mellitus, and thalamic ICH location. WML increased the odds for having poor functional outcome (mRS ≥ 4) in univariate analyses (vSS 4; OR 4.16; 95% CI 2.54–6.83; P 1.5 at baseline was combined into a dichotomous variable in our study. Baseline platelet count was dichotomized at 33% or > 6 mL, a combination of frequently used cutoffs for ICH expansion [7, 29]. Secondary HE outcomes were: the abovementioned analysis of HE defined as > 33% or > 6 mL ICH volume increase including only patients with dCT 10.4 mL, a recently suggested limit to minimize impact of measurement error [30]. Poor functional outcome was assessed 180 days after ICH and primarily defined as modified Rankin Scale [31] (mRS) 4–5 or death; and secondarily defined as mRS as an ordinal scale, and lower severe disability, vegetative state, or death on the extended Glasgow Outcome Scale (eGOS) [32]. Statistics
Univariate and multivariable logistic regression tests were used to analyze the dichotomized primary and secondary HE endpoints and the pre-defined covariates: vSS, age, ICH volume, IVH volume, warfarin/INR > 1.5 at baseline, time between ictus and dCT, diabetes mellitus, and thalamic ICH location. Linear regression with and without adjustment for the previously mentioned risk factors was used to analyze the relationship between vSS grades and continuous HE. We performed logistic regression for binary poor functional outcome. In addition to the prev
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