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

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 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.

Keywords: Cerebral hemorrhage; Cerebral small vessel diseases; Leukoaraiosis; Leukoencephalopathies; Prognosis; Stroke.

Conflict of interest statement

The other authors report no conflicts.

Figures

Figure 1.

Patient selection diagram. CLEAR III Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage phase III, dCT diagnostic CT scan, EVD external ventricular drainage, h hours, ICES Intraoperative Stereotactic Computed Tomography-Guided Endoscopic Surgery, ICH intracerebral hemorrhage, IVH intraventricular hemorrhage, MIS minimally invasive surgery, MISTIE II Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase II, rt-PA recombinant tissue plasminogen activator, mRS modified Rankin Scale.

Figure 2.

Distribution of modified Rankin Scale (mRS) scores between van Swieten Scale (vSS) grades