Poor Outcomes Related to Anterior Extension of Large Hemispheric Infarction: Topographic Analysis of GAMES-RP Trial MRI Scans

Abstract

Background: We aimed to assess the correlation of lesion location and clinical outcome in patients with large hemispheric infarction (LHI).

Methods: We analyzed admission MRI data from the GAMES-RP trial, which enrolled patients with anterior circulation infarct volumes of 82-300 cm3 within 10 hours of onset. Infarct lesions were segmented and co-registered onto MNI-152 brain space. Voxel-wise general linear models were applied to assess location-outcome correlations after correction for infarct volume as a co-variate.

Results: We included 83 patients with known 3-month modified Rankin scale (mRS). In voxel-wise analysis, there was significant correlation between admission infarct lesions involving the anterior cerebral artery (ACA) territory and its middle cerebral artery (MCA) border zone with both higher 3-month mRS and post-stroke day 3 and 7 National Institutes of Health Stroke Scale (NIHSS) total score and arm/leg subscores. Higher NIHSS total scores from admission through poststroke day 2 correlated with left MCA infarcts. In multivariate analysis, ACA territory infarct volume (P = .001) and admission NIHSS (P = .005) were independent predictors of 3-month mRS. Moreover, in a subgroup of 36 patients with infarct lesions involving right MCA-ACA border zone, intravenous (IV) glibenclamide (BIIB093; glyburide) treatment was the only independent predictor of 3-month mRS in multivariate regression analysis (P = .016).

Conclusions: Anterior extension of LHI with involvement of ACA territory and ACA-MCA border zone is an independent predictor of poor functional outcome, likely due to impairment of arm/leg motor function. If confirmed in larger cohorts, infarct topology may potentially help triage LHI patients who may benefit from IV glibenclamide.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01794182.

Keywords: Ischemic stroke; glibenclamide; glyburide; infarct location; lesion topography; malignant infarction.

Copyright © 2019. Published by Elsevier Inc.

Figures

Figure 1.

Voxel-wise analysis correlating the admission MRI infarct location with 3-month mRS and NIHSS scores, after correction for infarct lesion volume as a covariate. The color coding represents the p values (

Figure 2.

Voxel-wise analysis correlating the admission MRI infarct location with NIHSS arm (a-b) and leg (c-d) subscores on post-stroke days 3 and 7, after correcting for infarct lesion volume as a covariate. The color coding represents the p values (

Figure 3.

There was a trend toward statistically significant interaction of intravenous (IV) glibenclamide treatment and 3-month mRS with regards to topographic distribution of admission infarct (the lowest voxel-wise p value reaching 0.070). The green-colored voxels represent regions, with p value