Poor Outcomes Related to Anterior Extension of Large Hemispheric Infarction: Topographic Analysis of GAMES-RP Trial MRI Scans
Seyedmehdi Payabvash, Guido J Falcone, Gordon K Sze, Abhi Jain, Lauren A Beslow, Nils H Petersen, Kevin N Sheth, W Taylor Kimberly, Seyedmehdi Payabvash, Guido J Falcone, Gordon K Sze, Abhi Jain, Lauren A Beslow, Nils H Petersen, Kevin N Sheth, W Taylor Kimberly
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.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/8820410/bin/nihms-1774072-f0001.jpg)
Figure 2.
Voxel-wise analysis correlating the admission…
Figure 2.
Voxel-wise analysis correlating the admission MRI infarct location with NIHSS arm (a-b) and…
Figure 3.
There was a trend toward…
Figure 3.
There was a trend toward statistically significant interaction of intravenous (IV) glibenclamide treatment…
- Bihemisphere Ischemia Due to a Unilateral Lesion: A Case Report.Wadi LC, Nnodim S, Pack J, Fisher MJ. Wadi LC, et al. J Stroke Cerebrovasc Dis. 2020 Apr;29(4):104590. doi: 10.1016/j.jstrokecerebrovasdis.2019.104590. Epub 2019 Dec 26. J Stroke Cerebrovasc Dis. 2020. PMID: 31883780
- Long-Term Outcomes in Patients Aged ≤70 Years With Intravenous Glyburide From the Phase II GAMES-RP Study of Large Hemispheric Infarction: An Exploratory Analysis.Sheth KN, Petersen NH, Cheung K, Elm JJ, Hinson HE, Molyneaux BJ, Beslow LA, Sze GK, Simard JM, Kimberly WT. Sheth KN, et al. Stroke. 2018 Jun;49(6):1457-1463. doi: 10.1161/STROKEAHA.117.020365. Epub 2018 May 22. Stroke. 2018. PMID: 29789393 Free PMC article. Clinical Trial.
- Large Vessel Occlusion in Acute Ischemic Stroke Patients: A Dual-Center Estimate Based on a Broad Definition of Occlusion Site.Waqas M, Mokin M, Primiani CT, Gong AD, Rai HH, Chin F, Rai AT, Levy EI, Siddiqui AH. Waqas M, et al. J Stroke Cerebrovasc Dis. 2020 Feb;29(2):104504. doi: 10.1016/j.jstrokecerebrovasdis.2019.104504. Epub 2019 Nov 21. J Stroke Cerebrovasc Dis. 2020. PMID: 31761735
- The hyperdense anterior cerebral artery sign (HACAS) as a computed tomography marker for acute ischemia in the anterior cerebral artery territory.Jensen UR, Weiss M, Zimmermann P, Jansen O, Riedel C. Jensen UR, et al. Cerebrovasc Dis. 2010;29(1):62-7. doi: 10.1159/000256648. Epub 2009 Nov 10. Cerebrovasc Dis. 2010. PMID: 19907164
- Spontaneous dissecting aneurysms of anterior and middle cerebral artery associated with brain infarction: a case report and review of the literature.Kurino M, Yoshioka S, Ushio Y. Kurino M, et al. Surg Neurol. 2002 Jun;57(6):428-36; discussion 436-8. doi: 10.1016/s0090-3019(02)00725-5. Surg Neurol. 2002. PMID: 12176212 Review.
- Comparative Study
- Multicenter Study
- 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
- ClinicalTrials.gov/NCT01794182
- Full Text Sources
- Medical
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![Figure 2.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/8820410/bin/nihms-1774072-f0002.jpg)
Figure 3.
There was a trend toward…
Figure 3.
There was a trend toward statistically significant interaction of intravenous (IV) glibenclamide treatment…
- Bihemisphere Ischemia Due to a Unilateral Lesion: A Case Report.Wadi LC, Nnodim S, Pack J, Fisher MJ. Wadi LC, et al. J Stroke Cerebrovasc Dis. 2020 Apr;29(4):104590. doi: 10.1016/j.jstrokecerebrovasdis.2019.104590. Epub 2019 Dec 26. J Stroke Cerebrovasc Dis. 2020. PMID: 31883780
- Long-Term Outcomes in Patients Aged ≤70 Years With Intravenous Glyburide From the Phase II GAMES-RP Study of Large Hemispheric Infarction: An Exploratory Analysis.Sheth KN, Petersen NH, Cheung K, Elm JJ, Hinson HE, Molyneaux BJ, Beslow LA, Sze GK, Simard JM, Kimberly WT. Sheth KN, et al. Stroke. 2018 Jun;49(6):1457-1463. doi: 10.1161/STROKEAHA.117.020365. Epub 2018 May 22. Stroke. 2018. PMID: 29789393 Free PMC article. Clinical Trial.
- Large Vessel Occlusion in Acute Ischemic Stroke Patients: A Dual-Center Estimate Based on a Broad Definition of Occlusion Site.Waqas M, Mokin M, Primiani CT, Gong AD, Rai HH, Chin F, Rai AT, Levy EI, Siddiqui AH. Waqas M, et al. J Stroke Cerebrovasc Dis. 2020 Feb;29(2):104504. doi: 10.1016/j.jstrokecerebrovasdis.2019.104504. Epub 2019 Nov 21. J Stroke Cerebrovasc Dis. 2020. PMID: 31761735
- The hyperdense anterior cerebral artery sign (HACAS) as a computed tomography marker for acute ischemia in the anterior cerebral artery territory.Jensen UR, Weiss M, Zimmermann P, Jansen O, Riedel C. Jensen UR, et al. Cerebrovasc Dis. 2010;29(1):62-7. doi: 10.1159/000256648. Epub 2009 Nov 10. Cerebrovasc Dis. 2010. PMID: 19907164
- Spontaneous dissecting aneurysms of anterior and middle cerebral artery associated with brain infarction: a case report and review of the literature.Kurino M, Yoshioka S, Ushio Y. Kurino M, et al. Surg Neurol. 2002 Jun;57(6):428-36; discussion 436-8. doi: 10.1016/s0090-3019(02)00725-5. Surg Neurol. 2002. PMID: 12176212 Review.
- Comparative Study
- Multicenter Study
- 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
- ClinicalTrials.gov/NCT01794182
- Full Text Sources
- Medical
![Figure 3.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/8820410/bin/nihms-1774072-f0003.jpg)
Source: PubMed