Association of follow-up infarct volume with functional outcome in acute ischemic stroke: a pooled analysis of seven randomized trials

BackgroundFollow-up infarct volume (FIV) has been recommended as an early indicator of treatment efficacy in patients with acute ischemic stroke. Questions remain about the optimal imaging approach for FIV measurement.ObjectiveTo examine the association of FIV with 90-day modified Rankin Scale (mRS) score and investigate its dependency on acquisition time and modality.MethodsData of seven trials were pooled. FIV was assessed on follow-up (12 hours to 2 weeks) CT or MRI. Infarct location was defined as laterality and involvement of the Alberta Stroke Program Early CT Score regions. Relative quality and strength of multivariable regression models of the association between FIV and functional outcome were assessed. Dependency of imaging modality and acquisition time (≤48 hours vs >48 hours) was evaluated.ResultsOf 1665 included patients, 83% were imaged with CT. Median FIV was 41 mL (IQR 14–120). A large FIV was associated with worse functional outcome (OR=0.88(95% CI 0.87 to 0.89) per 10 mL) in adjusted analysis. A model including FIV, location, and hemorrhage type best predicted mRS score. FIV of ≥133 mL was highly specific for unfavorable outcome. FIV was equally strongly associated with mRS score for assessment on CT and MRI, even though large differences in volume were present (48 mL (IQR 15–131) vs 22 mL (IQR 8–71), respectively). Associations of both early and late FIV assessments with outcome were similar in strength (ρ=0.60(95% CI 0.56 to 0.64) and ρ=0.55(95% CI 0.50 to 0.60), respectively).ConclusionsIn patients with an acute ischemic stroke due to a proximal intracranial occlusion of the anterior circulation, FIV is a strong independent predictor of functional outcome and can be assessed before 48 hours, oneither CT or MRI.

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Endovascular Treatment Effect Diminishes With Increasing Thrombus Perviousness

Stroke ◽

10.1161/strokeaha.120.033124 ◽

2021 ◽

Author(s):

Manon Kappelhof ◽

Manon L. Tolhuisen ◽

Kilian M. Treurniet ◽

Bruna G. Dutra ◽

Heitor Alves ◽

...

Keyword(s):

Computed Tomography ◽

Ischemic Stroke ◽

Endovascular Treatment ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Odds Ratio ◽

Infarct Volume ◽

Treatment Allocation ◽

Common Odds Ratio

Background and Purpose: Thrombus perviousness estimates residual flow along a thrombus in acute ischemic stroke, based on radiological images, and may influence the benefit of endovascular treatment for acute ischemic stroke. We aimed to investigate potential endovascular treatment (EVT) effect modification by thrombus perviousness. Methods: We included 443 patients with thin-slice imaging available, out of 1766 patients from the pooled HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke trials) data set of 7 randomized trials on EVT in the early window (most within 8 hours). Control arm patients (n=233) received intravenous alteplase if eligible (212/233; 91%). Intervention arm patients (n=210) received additional EVT (prior alteplase in 178/210; 85%). Perviousness was quantified by thrombus attenuation increase on admission computed tomography angiography compared with noncontrast computed tomography. Multivariable regression analyses were performed including multiplicative interaction terms between thrombus attenuation increase and treatment allocation. In case of significant interaction, subgroup analyses by treatment arm were performed. Our primary outcome was 90-day functional outcome (modified Rankin Scale score), resulting in an adjusted common odds ratio for a one-step shift towards improved outcome. Secondary outcomes were mortality, successful reperfusion (extended Thrombolysis in Cerebral Infarction score, 2B–3), and follow-up infarct volume (in mL). Results: Increased perviousness was associated with improved functional outcome. After adding a multiplicative term of thrombus attenuation increase and treatment allocation, model fit improved significantly ( P =0.03), indicating interaction between perviousness and EVT benefit. Control arm patients showed significantly better outcomes with increased perviousness (adjusted common odds ratio, 1.2 [95% CI, 1.1–1.3]). In the EVT arm, no significant association was found (adjusted common odds ratio, 1.0 [95% CI, 0.9–1.1]), and perviousness was not significantly associated with successful reperfusion. Follow-up infarct volume (12% [95% CI, 7.0–17] per 5 Hounsfield units) and chance of mortality (adjusted odds ratio, 0.83 [95% CI, 0.70–0.97]) decreased with higher thrombus attenuation increase in the overall population, without significant treatment interaction. Conclusions: Our study suggests that the benefit of best medical care including alteplase, compared with additional EVT, increases in patients with more pervious thrombi.

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Intravenous fibrinolysis plus endovascular thrombectomy versus direct endovascular thrombectomy for anterior circulation acute ischemic stroke: clinical and infarct volume results.

10.21203/rs.2.482/v1 ◽

2019 ◽

Author(s):

Massimo Gamba ◽

Nicola Gilberti ◽

Enrico Premi ◽

Angelo Costa ◽

Michele Frigerio ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Safety Profile ◽

Infarct Volume ◽

Intravenous Thrombolysis ◽

Functional Independence ◽

Anterior Circulation ◽

Endovascular Thrombectomy ◽

Symptomatic Intracerebral Hemorrhage

Abstract Background and Purpose endovascular therapy (ET) is the standard of care for anterior circulation acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). The role of adjunctive intravenous thrombolysis (IVT) in these patients is still unclear. The present study aims to test whether IVT plus ET (CoT, combined therapy) provides additional benefits over direct ET for anterior circulation AIS by LVO. Methods we performed a single center retrospective observational study of patients with AIS caused by anterior circulation LVO, referred to our center between January 2014 and January 2017 and treated with ET. The patients were divided in 2 groups based on the treatment they received: CoT and, if IVT contraindicated, direct ET. We compared functional recovery (modified Rankin at 3-months follow-up), recanalization rate (thrombolysis in cerebral infarction [TICI] score) and time, early follow-up infarct volume (EFIV) (for recanalized patients only) as well as safety profile, defined as symptomatic intracerebral hemorrhage (sICH) and 3-month mortality, between groups. Results 145 subjects were included in the study, 70 in direct ET group and 75 in CoT group. Patients who received CoT presented more frequently a functional independence at 3-months follow-up compared to patients who received direct ET (mRS score 0-1: 48.5% vs 18.6%; P<0.001. mRS score 0-2: 67.1% vs 37.3%; P<0.001), higher first-pass success rate (62.7% vs 38.6%, P<0.05), higher recanalization rate (84.3% vs 65.3%; P=0.009) and, in recanalized subjects, smaller EFIV (16.4ml vs 62.3ml; P=0.003). The safety profile was similar for the 2 groups. In multivariable regression analysis, low baseline NIHSS score (P<0.05), vessel recanalization (P=0.05) and CoT (P=0.03) were indipendent predictors of 3-month favorable outcome. Conclusions CoT appears more effective than ET alone for anterior circulation AIS with LVO, with similar safety profile.

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Mediation of the Relationship Between Endovascular Therapy and Functional Outcome by Follow-up Infarct Volume in Patients With Acute Ischemic Stroke

JAMA Neurology ◽

10.1001/jamaneurol.2018.3661 ◽

2019 ◽

Vol 76 (2) ◽

pp. 194 ◽

Cited By ~ 16

Author(s):

Anna M. M. Boers ◽

Ivo G. H. Jansen ◽

Scott Brown ◽

Hester F. Lingsma ◽

Ludo F. M. Beenen ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Endovascular Therapy ◽

Infarct Volume ◽

The Relationship

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Abstract W P17: Factors Associated With DWI Lesion Growth After Endovascular Therapy for Acute Ischemic Stroke

Stroke ◽

10.1161/str.45.suppl_1.wp17 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Shumei Man ◽

M. Shazam Hussain ◽

Dolora Wisco ◽

Esteban Cheng-ching ◽

Toshiya Osanai ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Infarct Volume ◽

Cleveland Clinic ◽

Antiplatelet Agents ◽

Lesion Size ◽

Anterior Circulation ◽

Ischemic Lesion ◽

Large Growth

Background: The factors impacting infarct evolution after intra-arterial(IA) intervention for acute ischemic stroke remain uncertain. We studied the infarct evolution on MRI DWI among acute stroke patients who underwent IA therapy. Methods: We reviewed the early ischemic stroke imaging database at Cleveland Clinic Cerebrovascular Center for those undergoing IA therapy in anterior circulation from 2009 to 2012. Patients with both pre-treatment and follow-up MRI were included. Infarct volume was measured on initial and follow-up DWI by region of interest demarcation. Patients were grouped into quartiles by infarct growth from initial to follow-up. Outcome were defined as modified Rankin Score 0-2 at 30 days. Results: Among the 76 patients, the median (range) infarct growth of four quartiles were 0.5 cc (-19.1-4.2), 13.8 cc (4.8-25.8), 38.8 cc (28.0-77.6), and 166.3 cc (78.0-314.5). Baseline characteristics of age, gender, race, diabetes, and hypertension were similar among groups except more smokers (p=0.017) and fewer patients on anticoagulation or antiplatelet agents in large-growth group (p=0.049). Compared to No-growth group (Quartile 1), large-growth group (Quartile 4) had more Hyperdense M1 MCA sign ( 26.3% vs 73.7%, p=0.004), larger initial ischemic lesion measured by CT ASPECT (p=0.002) and DWI volume (p=0.012), and absence of full collaterals on CTA ( 36.8% vs 0, p=0.004). There was a trend of lower recanalization rate in large-growth group (73.7% vs 47.4%, p=0.097). With the increment of infarct growth, there is a decrement in favorable outcomes (mRS 0-2) at 30 days: 42%, 37%, 26% and 10.5% (p=0.027). Conclusion: Infarct growth after IA therapy determines outcome. Initial ischemic lesion size, collaterals, and hyperdense vessel sign are associated with infarct growth.

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Abstract 75: Hemorrhagic Transformation After Acute Ischemic Stroke Due to a Large Vessel Occlusion is Associated With Less Treatment Benefit

Stroke ◽

10.1161/str.51.suppl_1.75 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Katinka R van Kranendonk ◽

Manon Kappelhof ◽

Vicky Chalos ◽

Kilian M Treurniet ◽

Wim van Zwam ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Infarct Volume ◽

Hemorrhagic Transformation ◽

Vessel Occlusion ◽

Treatment Benefit ◽

Natural Progression ◽

Before And After

Introduction: Intracranial hemorrhage after acute ischemic stroke patients manifests as natural progression or as a complication of treatment with potential subsequent neurological deterioration. Currently it is unclear whether these hemorrhagic transformations (HT) contribute to the poorer functional outcomes observed in patients with large infarcts. The purpose of this study is to assess the association of HT with follow-up infarct volume (FIV) and functional outcome at 90 days after AIS. Additionally, we determined whether the development of HT was associated with a diminished endovascular therapy (EVT) effect. Methods: All patients from the HERMES collaboration with follow-up imaging were included. HERMES is pooled data from seven randomized controlled trials that assessed the efficacy and safety of EVT compared to usual care. Patients with HT were identified according to the ECASS classification and FIV was assessed on CT or MRI. Infarct and hemorrhage were included in the FIV. We assessed functional outcome using the modified Rankin Scale 90 days after stroke onset. Ordinal logistic regression with adjustment for potential confounders was used to determine the association of HT and FIV with functional outcome. Results: Of all included patients with follow-up imaging (n=1665), 42% had HT (n=698). Before and after adjustment for confounders HT and FIV were associated with a shift in the direction of poorer functional outcome (aOR:0.71,95%CI:0.58-0.86 and aOR:0.99,95%CI:0.99-0.99). EVT was beneficial in patients with and without HT, but effect was greater in patients without (aOR:1.70,95%CI:1.27-2.28 vs. aOR:2.51,95%CI:1.97-3.20)(figure 1.) Conclusions: In this analysis, patients with HT after AIS were less likely to have good functional outcome compared to those without HT, independent of the FIV. While the EVT effect was slightly diminished in patients who developed HT, EVT was always of significant benefit.

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Intravenous fibrinolysis plus endovascular thrombectomy versus direct endovascular thrombectomy for anterior circulation acute ischemic stroke: clinical and infarct volume results.

10.21203/rs.2.482/v2 ◽

2019 ◽

Author(s):

Massimo Gamba ◽

Nicola Gilberti ◽

Enrico Premi ◽

Angelo Costa ◽

Michele Frigerio ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Safety Profile ◽

Infarct Volume ◽

Intravenous Thrombolysis ◽

Functional Independence ◽

Anterior Circulation ◽

Endovascular Thrombectomy ◽

Symptomatic Intracerebral Hemorrhage

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Abstract P538: A Detailed Analysis of Intracranial Hemorrhage After Endovascular Treatment in Acute Ischemic Stroke Due to Large Vessel Occlusion in the Escape-NA1 Trial

Stroke ◽

10.1161/str.52.suppl_1.p538 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Johanna Ospel ◽

Michael D Hill ◽

Nima Kashani ◽

Arnuv Mayank ◽

Nishita Singh ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Intracranial Hemorrhage ◽

Intraventricular Hemorrhage ◽

Infarct Volume ◽

Prognostic Impact ◽

Vessel Occlusion ◽

Good Outcome

Purpose: We investigated the prevalence and prognostic impact on outcome of any intracranial hemorrhage, hemorrhage morphology, type and volume in acute ischemic stroke patients undergoing mechanical thrombectomy. Methods: Prevalence of intracranial hemorrhage, hemorrhage type, morphology and volume was determined on 24h follow-up imaging (non contrast head CT or gradient-echo/susceptibility-weighted MRI). Proportions of good outcome (mRS 0-2 at 90 days) were reported for patients with vs. without any intracranial hemorrhage. Multivariable logistic regression with adjustment for key minimization variables and total infarct volume was performed to obtain adjusted effect size estimates for hemorrhage type and volume on good outcome. Results: Hemorrhage on follow up-imaging was seen in 372/1097 (33.9%) patients, among them 126 (33.9%) with hemorrhagic infarction (HI) type 1, 108 (29.0%) with HI-2, 72 /19.4%) with parenchymal hematoma (PH) type 1, 37 (10.0) with PH2, 8 (2.2%) with remote PH and 21 (5.7%) with extra-parenchymal/intraventricular hemorrhage. Good outcomes were less often achieved by patients with hemorrhage on follow-up imaging (164/369 [44.4%] vs. 500/720 [69.4%]). Any type of intracranial hemorrhage was strongly associated with decreased chances of good outcome ( adj OR 0.62 [CI 95 0.44 - 0.87]). The effect of hemorrhage was driven by both PH hemorrhage sub-type [PH-1 ( adj OR 0.39 [CI 95 0.21 - 0.72]), PH-2 ( adj OR 0.15 [CI 95 0.05 - 0.50])] and extra-parenchymal/intraventricular hemorrhage ( adj OR 0.60 (0.20-1.78) Petechial hemorrhages (HI-1 and HI-2) were not associated with poorer outcomes. Hemorrhage volume ( adj OR 0.97 [CI 95 0.05 - 0.99] per ml increase) was significantly associated with decreased chances of good outcome. Conclusion: Presence of any hemorrhage on follow-up imaging was seen in one third of patients and strongly associated with decreased chances of good outcome.

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Abstract 3681: Early Anticoagulation Is Not Associated With Hemorrhagic Transformation Of Ischemic Stroke In Patients With Atrial Fibrillation

Stroke ◽

10.1161/str.43.suppl_1.a3681 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

H. B Brouwers ◽

Svetlana Lorenzano ◽

Lyndsey H Starks ◽

David M Greer ◽

Steven K Feske ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Clinical Data ◽

Infarct Volume ◽

Hemorrhagic Transformation ◽

P Value ◽

Long Term Outcome ◽

Nihss Score

Purpose: Hemorrhagic transformation (HT) is a common and potentially devastating complication of ischemic stroke, however its prevalence, predictors, and outcome remain unclear. Early anticoagulation is thought to be a risk factor for HT which raises the clinical question when to (re)start anticoagulation in ischemic stroke patients who have a compelling indication, such as atrial fibrillation. We conducted a prospective cohort study to address this question and to identify association of hemorrhagic transformation with outcome measures in patients with atrial fibrillation in the setting of acute ischemic stroke. Materials and Methods: We performed a prospective study which enrolled consecutive patients admitted with acute ischemic stroke presenting to a single center over a three-year period. As part of the observational study, baseline clinical data and stroke characteristics as well as 3 month functional outcome were collected. For this sub-study, we restricted the analysis to subjects diagnosed with atrial fibrillation. CT and MRI scans were reviewed by experienced readers, blinded to clinical data, to assess for hemorrhagic transformation (using ECASS 2 criteria), microbleeds and infarct volumes in both admission and follow-up scans. Clinical and outcome data were analyzed for association with hemorrhagic transformation. Results: Of 94 patients, 63 had a history of atrial fibrillation (67.0%) and 31 had newly discovered atrial fibrillation (33.0%). We identified HT in 3 of 94 baseline scans (3.2%) and 22 of 48 follow-up scans (45.8%) obtained a median of 3 days post-stroke. In-hospital initiation of either anti-platelet (n = 36; OR 0.34 [95% CI 0.10-1.16], p-value = 0.09) or anticoagulation with unfractionated intravenous heparin or low molecular weight heparin (n = 72; OR 0.25 [95% CI 0.06-1.15], p-value = 0.08) was not associated with HT. Initial NIH Stroke Scale (NIHSS) score (median 13.0 [IQR 15.0] vs. 7.0 [IQR 10.0], p-value = 0.029) and baseline infarct volume (median 17 [IQR 42.03] vs. 5 [IQR 10.95], p-value = 0.011) were significantly higher in patients with HT compared to those without. Hemorrhagic transformation was associated with a significantly higher 48-hour median NIHSS score (20 [IQR 3.0] vs. 2 [IQR 3.25], p-value = 0.007) and larger final infarct volume (81.40 [IQR 82.75] vs. 9.95 [IQR 19.73], p-value < 0.001). Finally, we found a trend towards poorer 3-month modified Rankin Scale scores in subjects with HT (OR 11.25 [95% CI 0.97-130.22], p-value = 0.05). Conclusion: In patients with atrial fibrillation, initial NIHSS score and baseline infarct volume are associated with hemorrhagic transformation in acute ischemic stroke. Early initiation of antithrombotic therapy was not associated with hemorrhagic transformation. Patients with hemorrhagic transformation were found to have a poorer short and long term outcome and larger final infarct volumes.

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Hypotension during endovascular treatment under general anesthesia for acute ischemic stroke

PLoS ONE ◽

10.1371/journal.pone.0249093 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0249093

Author(s):

Sabine L. Collette ◽

Maarten Uyttenboogaart ◽

Noor Samuels ◽

Irene C. van der Schaaf ◽

H. Bart van der Worp ◽

...

Keyword(s):

Ischemic Stroke ◽

Endovascular Treatment ◽

General Anesthesia ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Randomized Clinical Trials ◽

Anesthetic Management ◽

Poor Functional Outcome ◽

Anterior Circulation ◽

Period Increase

Objective The effect of anesthetic management (general anesthesia [GA], conscious sedation, or local anesthesia) on functional outcome and the role of blood pressure management during endovascular treatment (EVT) for acute ischemic stroke is under debate. We aimed to determine whether hypotension during EVT under GA is associated with functional outcome at 90 days. Methods We retrospectively collected data from patients with a proximal intracranial occlusion of the anterior circulation treated with EVT under GA. The primary outcome was the distribution on the modified Rankin Scale at 90 days. Hypotension was defined using two thresholds: a mean arterial pressure (MAP) of 70 mm Hg and a MAP 30% below baseline MAP. To quantify the extent and duration of hypotension, the area under the threshold (AUT) was calculated using both thresholds. Results Of the 366 patients included, procedural hypotension was observed in approximately half of them. The occurrence of hypotension was associated with poor functional outcome (MAP <70 mm Hg: adjusted common odds ratio [acOR], 0.57; 95% confidence interval [CI], 0.35–0.94; MAP decrease ≥30%: acOR, 0.76; 95% CI, 0.48–1.21). In addition, an association was found between the number of hypotensive periods and poor functional outcome (MAP <70 mm Hg: acOR, 0.85 per period increase; 95% CI, 0.73–0.99; MAP decrease ≥30%: acOR, 0.90 per period; 95% CI, 0.78–1.04). No association existed between AUT and functional outcome (MAP <70 mm Hg: acOR, 1.000 per 10 mm Hg*min increase; 95% CI, 0.998–1.001; MAP decrease ≥30%: acOR, 1.000 per 10 mm Hg*min; 95% CI, 0.999–1.000). Conclusions Occurrence of procedural hypotension and an increase in number of procedural hypotensive periods were associated with poor functional outcome, whereas the extent and duration of hypotension were not. Randomized clinical trials are needed to confirm our hypothesis that hypotension during EVT under GA has detrimental effects.

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Abstract P343: Relationship of Infarct Volume to Inflammation and Prognostic Significance in Patients With Acute Ischemic Stroke

Stroke ◽

10.1161/str.52.suppl_1.p343 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Lingling Ding ◽

Zixiao Li ◽

Yongjun Wang

Keyword(s):

Ischemic Stroke ◽

Deep Learning ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Acute Inflammation ◽

Infarct Volume ◽

Prognostic Significance ◽

Stroke Recurrence ◽

Vascular Events ◽

Poor Functional Outcome

Background and Purpose: The diffusion weighted imaging (DWI) lesion volumes in acute ischemic stroke (AIS) can be automatically measured using deep learning-based segmentation algorithms. We aim to explore the prognostic significance of artificial intelligence-predicted infarct volume, and the association of markers of acute inflammation with the infarct volume. Methods: 12,598 AIS/TIA patients were included in this analysis. Intarct volume was automatically measured using a U-Net model for acute ischemic stroke lesion segmentation on DWI. Participants were divided into 5 subgroups according to infarct volume. Spearman’s correlations were employed to study the association between infarct volume and markers of acute inflammation. Multivariable logistic regression and Cox proportional hazards model were performed to explore the relationship between infarct volume and the incidence of poor functional outcome (modified Rankin scale score 3-6), stroke recurrence or combined vascular events at 3 months. Results: The U-Net model prediction correlated and agreed well with manual annotation ground truth for infarct volume (r=0.96; P<0.001). There were positive correlations between the infarct volume and markers of acute inflammation (neutrophil [r=0.175; P<0.001], hs-CRP [r=0.180; P<0.001], and IL-6 [r=0.225; P<0.001]). Compared with those without DWI lesions, patients with the largest infarct volume (4th Quartile) were nearly five times more likely to have poor functional outcome (mRS 3-6) (adjusted odds ratio, 4.70; 95% confidence intervals [CI], 3.29-6.72; P for trend<0.001) after adjustment for confounding factors and markers of acute inflammation. The infarct volume category was significantly associated with stroke recurrence (adjusted hazard ratios [HRs], 1.0, 1.43[0.95,2.17], 2.22[1.49,3.29], 2.06[1.40,3.05], 2.26[1.52,3.36]; P for trend<0.001) and combined vascular events(adjusted HRs, 1.0, 1.38[0.92,2.09], 2.25[1.53,3.32], 2.03[1.38,2.98], 2.28[1.54,3.36]; P for trend<0.001). Conclusions: Infarct volume measured automatically by deep learning-based tool was a strong predictor of poor functional outcome as well as stroke recurrence, with the potential for widespread adoption in both research and clinical settings.

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