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

J Stroke Cerebrovasc Dis. 2020 Feb;29(2):104488. doi: 10.1016/j.jstrokecerebrovasdis.2019.104488. Epub 2019 Nov 29.


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.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Administration, Intravenous
  • Aged
  • Anterior Cerebral Artery / diagnostic imaging*
  • Anterior Cerebral Artery / physiopathology
  • Cerebrovascular Circulation
  • Cerebrum / blood supply*
  • Clinical Trials as Topic
  • Clinical Trials, Phase II as Topic
  • Diffusion Magnetic Resonance Imaging*
  • Disability Evaluation
  • Extremities / innervation*
  • Female
  • Glyburide / administration & dosage
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Infarction, Anterior Cerebral Artery / diagnostic imaging*
  • Infarction, Anterior Cerebral Artery / physiopathology
  • Infarction, Anterior Cerebral Artery / therapy
  • Infarction, Middle Cerebral Artery / diagnostic imaging*
  • Infarction, Middle Cerebral Artery / physiopathology
  • Infarction, Middle Cerebral Artery / therapy
  • Male
  • Middle Aged
  • Middle Cerebral Artery / diagnostic imaging*
  • Middle Cerebral Artery / physiopathology
  • Patient Admission
  • Predictive Value of Tests
  • Recovery of Function
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • United States


  • Hypoglycemic Agents
  • Glyburide

Associated data

  • ClinicalTrials.gov/NCT01794182