Relationship of White Matter Lesions with Intracerebral Hemorrhage Expansion and Functional Outcome: MISTIE II and CLEAR III

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 post-stroke 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, ' 24 h after ictus) was assessed using the van Swieten scale (vSS, range 0–4). The primary outcome for HE was ' 33% or ' 6 mL ICH volume increase from dCT to the last pre-randomization CT (' 72 h of dCT). Secondary HE outcomes were: absolute ICH expansion, ' 10.4 mL total clot volume increase, and a subgroup analysis including patients with dCT ' 6 h after ictus using the primary HE definition of ' 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 ' 0.001) which persisted in multivariable analyses after adjustment for HE and other outcome risk factors. Conclusions: Concomitant WML does not increase the odds for HE in patients with ICH but increases the odds for poor functional outcome. Clinical Trial Registration: http://www.clinicaltrials.gov trial-identifiers: NCT00224770 and NCT00784134.