Thrombectomy improves functional outcome in large core stroke partly by preventing severe cerebral edema: a real-world mediation analysis
10 affiliations
- 1Stroke Department, Da Nang Hospital
- 2Department of Cerebrovascular Disease, 115 People's Hospital
- 3University of Medicine and Pharmacy at Ho Chi Minh City
- 4Department of Neurosurgery, Washington University School of Medicine, St. Louis
- 5Oxford Neurovascular and Neuroradiology Unit, Nuffield Department of Surgical Sciences, Medical Sciences Division, University of Oxford
- 6Neuroendovascular Program, Massachusetts General Hospital & Brigham and Women's Hospital, Harvard Medical School, Boston
- 7Neurointerventional and Neuroanalytics Consortium (NAN-C), School of Medicine, Toronto Metropolitan University, Toronto
- 8Radiology Department, Neurointervention Unit, Da Nang Hospital
- 9Department of Intensive Care and Poisoning Control, Da Nang Hospital
- 10The University of Danang - School of Medicine and Pharmacy
Abstract
Objective: Endovascular thrombectomy (EVT) is effective in large infarct core (LIC) stroke, but mortality and severe disability remain high when cerebral edema (CED) develops. We assessed the effect of EVT on CED and outcomes in LIC patients within 24 h of stroke onset.
Methods: In a prospective observational cohort study, we enrolled patients with large-vessel occlusion in the anterior circulation, National Institutes of Health Stroke Scale (NIHSS) score ≥ 6, Alberta Stroke Program Early CT Score (ASPECTS) ≤ 5, and admission within 24 h of onset. The primary outcome was mass effect (ME) due to severe cerebral edema, defined as a maximum midline shift (MLS) ≥ 5 mm on follow-up imaging within 72 h. The secondary outcome was favorable outcome, defined as modified Rankin Scale (mRS) score of 0–3 at 90 days. Safety outcomes were determined by death at 90 days, symptomatic intracranial hemorrhage (sICH) according to SITS-MOST criteria. Treatment effects were estimated using inverse probability of treatment weighting (IPTW) with doubly robust adjustment. Mediation analysis assessed whether ME contributed to the association between EVT and favorable outcome.
Results: Of 202 patients (EVT group: 119; medical management group: 83), after IPTW adjustment, EVT was associated with lower odds of ME [31.1% vs. 51.8%; IPTW-adjusted odds ratio (aOR), 0.28; 95% CI, 0.12–0.67], higher odds of favorable outcome (aOR, 2.32; 95% CI, 1.01–5.31), and lower mortality (aOR 0.45; 95% CI, 0.21–0.97) with no excess sICH. ME independently predicted poor outcome (aOR for mRS 4–6, 7.7; 95% CI, 3.01–19.69), and approximately 29.5% of the association between EVT and favorable outcome was statistically mediated by ME attenuation. Two admission variables—lower baseline ASPECTS and higher admission glucose—independently predicted ME (optimism-corrected AUC 0.82).
Conclusion: In large-core stroke, EVT was associated with better functional outcome and lower odds of mass effect. Approximately one-third of EVT's functional benefit was statistically mediated by attenuation of severe CED. ME independently predicted poor outcome, whereas lower ASPECTS and higher admission glucose identified patients at greater risk of severe swelling, supporting bedside risk stratification to guide intensified monitoring and edema-targeted management.
Trial registration: ClinicalTrials.gov , Identifier [NCT06016348].
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BibTeX
@article{le2026thrombectomy,
title = {{Thrombectomy improves functional outcome in large core stroke partly by preventing severe cerebral edema: a real-world mediation analysis}},
author = {Thien Quang Le and Son Van Dang Nguyen and Tuan Phuoc Pham and Tao Van Tran and Trung Quoc Nguyen and Alexander T. Yahanda and Adam A. Dmytriw and Vu Thanh Huynh and Hai Quang Duong and Trung Thanh Nguyen and Nhan Duc Le},
journal = {Frontiers in Neurology},
year = {2026},
month = oct,
doi = {10.3389/fneur.2026.1936247},
url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1936247/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Thrombectomy improves functional outcome in large core stroke partly by preventing severe cerebral edema: a real-world mediation analysis
AU - Thien Quang Le
AU - Son Van Dang Nguyen
AU - Tuan Phuoc Pham
AU - Tao Van Tran
AU - Trung Quoc Nguyen
AU - Alexander T. Yahanda
AU - Adam A. Dmytriw
AU - Vu Thanh Huynh
AU - Hai Quang Duong
AU - Trung Thanh Nguyen
AU - Nhan Duc Le
PY - 2026
DA - 2026/10/16
JO - Frontiers in Neurology
DO - 10.3389/fneur.2026.1936247
UR - https://www.frontiersin.org/articles/10.3389/fneur.2026.1936247/full
AB - Objective: Endovascular thrombectomy (EVT) is effective in large infarct core (LIC) stroke, but mortality and severe disability remain high when cerebral edema (CED) develops. We assessed the effect of EVT on CED and outcomes in LIC patients within 24 h of stroke onset. Methods: In a prospective observational cohort study, we enrolled patients with large-vessel occlusion in the anterior circulation, National Institutes of Health Stroke Scale (NIHSS) score ≥ 6, Alberta Stroke Program Early CT Score (ASPECTS) ≤ 5, and admission within 24 h of onset. The primary outcome was mass effect (ME) due to severe cerebral edema, defined as a maximum midline shift (MLS) ≥ 5 mm on follow-up imaging within 72 h. The secondary outcome was favorable outcome, defined as modified Rankin Scale (mRS) score of 0–3 at 90 days. Safety outcomes were determined by death at 90 days, symptomatic intracranial hemorrhage (sICH) according to SITS-MOST criteria. Treatment effects were estimated using inverse probability of treatment weighting (IPTW) with doubly robust adjustment. Mediation analysis assessed whether ME contributed to the association between EVT and favorable outcome. Results: Of 202 patients (EVT group: 119; medical management group: 83), after IPTW adjustment, EVT was associated with lower odds of ME [31.1% vs. 51.8%; IPTW-adjusted odds ratio (aOR), 0.28; 95% CI, 0.12–0.67], higher odds of favorable outcome (aOR, 2.32; 95% CI, 1.01–5.31), and lower mortality (aOR 0.45; 95% CI, 0.21–0.97) with no excess sICH. ME independently predicted poor outcome (aOR for mRS 4–6, 7.7; 95% CI, 3.01–19.69), and approximately 29.5% of the association between EVT and favorable outcome was statistically mediated by ME attenuation. Two admission variables—lower baseline ASPECTS and higher admission glucose—independently predicted ME (optimism-corrected AUC 0.82). Conclusion: In large-core stroke, EVT was associated with better functional outcome and lower odds of mass effect. Approximately one-third of EVT's functional benefit was statistically mediated by attenuation of severe CED. ME independently predicted poor outcome, whereas lower ASPECTS and higher admission glucose identified patients at greater risk of severe swelling, supporting bedside risk stratification to guide intensified monitoring and edema-targeted management. Trial registration: ClinicalTrials.gov , Identifier [NCT06016348].
SN - 1664-2295
ER -