The Role of Edema in Subacute Lesion Progression After Treatment of Acute Ischemic Stroke

Background: Ischemic lesions commonly continue to progress even days after treatment, and this lesion growth is associated with unfavorable functional outcome in acute ischemic stroke patients. The aim of this study is to elucidate the role of edema in subacute lesion progression and its influence on unfavorable functional outcome by quantifying net water uptake.Methods: We included all 187 patients from the MR CLEAN trial who had high quality follow-up non-contrast CT at 24 h and 1 week. Using a CT densitometry-based method to calculate the net water uptake, we differentiated total ischemic lesion volume (TILV) into edema volume (EV) and edema-corrected infarct volume (ecIV). We calculated these volumes at 24 h and 1 week after stroke and determined their progression in the subacute period. We assessed the effect of 24-h lesion characteristics on EV and ecIV progression. We evaluated the influence of edema and edema-corrected infarct progression on favorable functional outcome after 90 days (modified Rankin Scale: 0–2) after correcting for potential confounders. Lastly, we compared these volumes between subgroups of patients with and without successful recanalization using the Mann–Whitney U-test.Results: Median TILV increased from 37 (IQR: 18–81) ml to 68 (IQR: 30–130) ml between 24 h and 1 week after stroke, while the net water uptake increased from 22 (IQR: 16–26)% to 27 (IQR: 22–32)%. The TILV progression of 20 (8.8–40) ml was mostly caused by ecIV with a median increase of 12 (2.4–21) ml vs. 6.5 (2.7–15) ml of EV progression. Larger TILV, EV, and ecIV volumes at 24 h were all associated with more edema and lesion progression. Edema progression was associated with unfavorable functional outcome [aOR: 0.53 (0.28–0.94) per 10 ml; p-value: 0.05], while edema-corrected infarct progression showed a similar, non-significant association [aOR: 0.80 (0.62–0.99); p-value: 0.06]. Lastly, edema progression was larger in patients without successful recanalization, whereas ecIV progression was comparable between the subgroups.Conclusion: EV increases in evolving ischemic lesions in the period between 1 day and 1 week after acute ischemic stroke. This progression is larger in patients without successful recanalization and is associated with unfavorable functional outcome. However, the extent of edema cannot explain the total expansion of ischemic lesions since edema-corrected infarct progression is larger than the edema progression.

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Associations of Ischemic Lesion Volume With Functional Outcome in Patients With Acute Ischemic Stroke

Stroke ◽

10.1161/strokeaha.116.015156 ◽

2017 ◽

Vol 48 (5) ◽

pp. 1233-1240 ◽

Cited By ~ 20

Author(s):

Amber Bucker ◽

Anna M. Boers ◽

Joseph C.J. Bot ◽

Olvert A. Berkhemer ◽

Hester F. Lingsma ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Lesion Volume ◽

Ischemic Lesion

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Radiological predictors of hemorrhagic transformation after acute ischemic stroke: An evidence-based analysis

The Neuroradiology Journal ◽

10.1177/1971400919900275 ◽

2020 ◽

Vol 33 (2) ◽

pp. 118-133 ◽

Cited By ~ 1

Author(s):

Nada Elsaid ◽

Wessam Mustafa ◽

Ahmed Saied

Keyword(s):

Blood Flow ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Ct Perfusion ◽

Treatment Plan ◽

Hemorrhagic Transformation ◽

Lesion Volume ◽

Ischemic Lesion ◽

Blood Brain Barrier Disruption

Hemorrhagic transformation (HT) is one of the most common adverse events related to acute ischemic stroke (AIS) that affects the treatment plan and clinical outcome. Identification of a sensitive radiological marker may influence the controversial thrombolytic decision in the setting of AIS and may at a minimum indicate more intensive monitoring or further prophylactic interventions. In this article we summarize possible radiological biomarkers and the role of different radiological modalities including computed tomography (CT), magnetic resonance imaging, angiography, and ultrasound in predicting HT. Different radiological indices of early ischemic changes, large ischemic lesion volume, severe blood flow restriction, blood-brain barrier disruption, poor collaterals and high blood flow velocities have been reported to be associated with higher risk of HT. The current levels of evidence of the available studies highlight the role of the different CT perfusion parameters in predicting HT. Further large standardized studies are recommended to compare the sensitivity and specificity of the different radiological markers combined and delineate the most reliable predictor.

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Posttreatment Ischemic Lesion Evolution Is Associated With Reduced Favorable Functional Outcome in Patients With Stroke

Stroke ◽

10.1161/strokeaha.120.032331 ◽

2021 ◽

Author(s):

Praneeta Konduri ◽

Henk van Voorst ◽

Amber Bucker ◽

Katinka van Kranendonk ◽

Anna Boers ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Odds Ratio ◽

Interaction Analysis ◽

Univariate Analysis ◽

Arterial Occlusion ◽

Lesion Volume ◽

Ischemic Lesion ◽

Favorable Functional Outcome

Background and Purpose: Ischemic lesion volume can increase even 24 hours after onset of an acute ischemic stroke. In this study, we investigated the association of lesion evolution with functional outcome and the influence of successful recanalization on this association. Methods: We included patients from the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) who received good quality noncontrast CT images 24 hours and 1 week after stroke onset. The ischemic lesion delineations included infarct, edema, and hemorrhagic transformation. Lesion evolution was defined as the difference between the volumes measured on the 1-week and 24-hour noncontrast CTs. The association of lesion evolution with functional outcome was evaluated using unadjusted and adjusted logistic regression. Adjustments were made for baseline, clinical, and imaging parameters that were associated P <0.10) in univariate analysis with favorable functional outcome, defined as modified Rankin Scale score of ≤2. Interaction analysis was performed to evaluate the influence of successful recanalization, defined as modified Arterial Occlusion Lesion score of 3 points, on this association. Results: Of the 226 patients who were included, 69 (31%) patients achieved the favorable functional outcome. Median lesion evolution was 22 (interquartile range, 10–45) mL. Lesion evolution was significantly inversely correlated with favourable functional outcome: unadjusted odds ratio, 0.76 (95% CI, 0.66–0.86; per 10 mL of lesion evolution; P <0.01) and adjusted odds ratio: 0.85 (95% CI, 0.72–0.97; per 10 mL of lesion evolution; P =0.03). There was no significant interaction of successful recanalization on the association of lesion evolution and favorable functional outcome (odds ratio, 1.01 [95% CI, 0.77–1.36]; P =0.94). Conclusions: In our population, subacute ischemic lesion evolution is associated with unfavorable functional outcome. This study suggests that even 24 hours after onset of stroke, deterioration of the brain continues, which has a negative effect on functional outcome. This finding may warrant additional treatment in the subacute phase.

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Perfusion imaging-based tissue-level collaterals predict ischemic lesion net water uptake in patients with acute ischemic stroke and large vessel occlusion

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x21992200 ◽

2021 ◽

pp. 0271678X2199220

Author(s):

Tobias D Faizy ◽

Reza Kabiri ◽

Soren Christensen ◽

Michael Mlynash ◽

Gabriella Kuraitis ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Water Uptake ◽

Tissue Level ◽

Large Vessel ◽

Large Vessel Occlusion ◽

Vessel Occlusion ◽

Ischemic Lesion ◽

Good Functional Outcome

Ischemic lesion Net Water Uptake (NWU) quantifies cerebral edema formation and likely correlates with the microvascular perfusion status of patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). We hypothesized that favorable tissue-level collaterals (TLC) predict less NWU and good functional outcomes. We performed a retrospective multicenter analysis of AIS-LVO patients who underwent thrombectomy triage. TLC were measured on cerebral perfusion studies using the hypoperfusion intensity ratio (HIR; volume ratio of brain tissue with [Tmax > 10 sec/Tmax > 6 sec]); favorable TLC were regarded as HIR [Formula: see text] 0.4. NWU was determined using a quantitative densitometry approach on follow-up CT. Primary outcome was NWU. Secondary outcome was a good functional outcome (modified Rankin Scale [mRS] 0–2). 580 patients met inclusion criteria. Favorable TLC ( β: 4.23, SE: 0.65; p < 0.001) predicted smaller NWU after treatment. Favorable TLC (OR: 2.35, [95% CI: 1.31–4.21]; p < 0.001), and decreased NWU (OR: 0.75, [95% CI: 0.70–0.79]; p < 0.001) predicted good functional outcome, while controlling for age, glucose, CTA collaterals, baseline NIHSS and good vessel reperfusion status. We conclude that favorable TLC predict less ischemic lesion NWU after treatment in AIS-LVO patients. Favorable TLC and decreased NWU were independent predictors of good functional outcome.

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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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Abstract WMP15: Automated Volumetric Assessment of Infarct Core in Non-Contrast Computed Tomography in Patients With Acute Ischemic Stroke Secondary to Large Vessel Occlusion

Stroke ◽

10.1161/str.51.suppl_1.wmp15 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Alvaro Garcia-Tornel ◽

Matias Deck ◽

Marc Ribo ◽

David Rodriguez-Luna ◽

Jorge Pagola ◽

...

Keyword(s):

Computed Tomography ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Infarct Volume ◽

Large Vessel Occlusion ◽

Infarct Core ◽

Vessel Occlusion ◽

Good Functional Outcome ◽

Volumetric Assessment

Introduction: Perfusion imaging has emerged as an imaging tool to select patients with acute ischemic stroke (AIS) secondary to large vessel occlusion (LVO) for endovascular treatment (EVT). We aim to compare an automated method to assess the infarct ischemic core (IC) in Non-Contrast Computed Tomography (NCCT) with Computed Tomography Perfusion (CTP) imaging and its ability to predict functional outcome and final infarct volume (FIV). Methods: 494 patients with anterior circulation stroke treated with EVT were included. Volumetric assessment of IC in NCCT (eA-IC) was calculated using eASPECTS™ (Brainomix, Oxford). CTP was processed using availaible software considering CTP-IC as volume of Cerebral Blood Flow (CBF) <30% comparing with the contralateral hemisphere. FIV was calculated in patients with complete recanalization using a semiautomated method with a NCCT performed 48-72 hours after EVT. Complete recanalization was considered as modified Thrombolysis In Cerebral Ischemia (mTICI) ≥2B after EVT. Good functional outcome was defined as modified Rankin score (mRs) ≤2 at 90 days. Statistical analysis was performed to assess the correlation between EA-IC and CTP-IC and its ability to predict prognosis and FIV. Results: Median eA-IC and CTP-IC were 16 (IQR 7-31) and 8 (IQR 0-28), respectively. 419 patients (85%) achieved complete recanalization, and their median FIV was 17.5cc (IQR 5-52). Good functional outcome was achieved in 230 patients (47%). EA-IC and CTP-IC had moderate correlation between them (r=0.52, p<0.01) and similar correlation with FIV (r=0.52 and 0.51, respectively, p<0.01). Using ROC curves, both methods had similar performance in its ability to predict good functional outcome (EA-IC AUC 0.68 p<0.01, CTP-IC AUC 0.66 p<0.01). Multivariate analysis adjusted by confounding factors showed that eA-IC and CTP-IC predicted good functional outcome (for every 10cc and >40cc, OR 1.5, IC1.3-1.8, p<0.01 and OR 1.3, IC1.1-1.5, p<0.01, respectively). Conclusion: Automated volumetric assessment of infarct core in NCCT has similar performance predicting prognosis and final infarct volume than CTP. Prospective studies should evaluate a NCCT-core / vessel occlusion penumbra missmatch as an alternative method to select patients for EVT.

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Abstract 35: MR CLEAN Registry: A Post-trial Multicenter Registry of Intra-arterial Treatment for Acute Ischemic Stroke in the Netherlands

Stroke ◽

10.1161/str.48.suppl_1.35 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Ivo Jansen ◽

Maxim Mulder ◽

Robert-Jan Goldhoorn ◽

Aad van der Lugt ◽

Henk Marquering ◽

...

Keyword(s):

Ischemic Stroke ◽

The Netherlands ◽

Acute Ischemic Stroke ◽

Randomized Clinical Trials ◽

Infarct Volume ◽

Primary Study ◽

Anterior Circulation ◽

Serious Adverse Events ◽

Post Trial ◽

Mr Clean

Background & Purpose: Intra-arterial therapy (IAT) is being implemented worldwide as the main treatment option for acute ischemic stroke (AIS). We wondered whether effectiveness and safety results that have been reported in randomized clinical trials can be reproduced in everyday clinical practice. We will report results of the Dutch National post MR CLEAN IAT registry including work flow parameters, primary and secondary outcomes, as well as serious adverse events. Methods: The MR CLEAN Registry is a prospective registry of all patients undergoing IAT for AIS in the Netherlands, started after completion of the MR CLEAN trial in March 2014. Registration was required for reimbursement. A core set was defined, with inclusion criteria similar to those of the MR CLEAN trial, including a proven anterior circulation occlusion and treatment possible withing 6 hours from onset. The primary study outcome is the score on the modified Rankin Scale (mRS) at 90 days. The secondary clinical outcome is NIHSS after 24 to 48 hours. Secondary radiological outcomes include the mTICI score on DSA and final infarct volume and major bleeding on follow up NCCT. We used a propensity weighted and an unadjusted ordinal logistic regression model to compare outcomes in the MR CLEAN Registry core and total dataset with the treatment arm of MR CLEAN. Results: Between March 2014 and August 2016 the inclusion rate of the MR CLEAN Registry has been increasing steadily to an average of 79 (SD 22) per month for a cumulative inclusion of 1548 patients in July 2016 (Figure 1). Conclusions: The MR CLEAN registry data is now being analyzed. Results will be reported at the conference.

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Abstract WMP17: Computerized Tomography Perfusion to Characterize Lack of Clinical Improvement After Recanalization in Acute Ischemic Stroke

Stroke ◽

10.1161/str.51.suppl_1.wmp17 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Alvaro Garcia-Tornel ◽

Marta Olive-Gadea ◽

Marc Ribo ◽

David Rodriguez-Luna ◽

Jorge Pagola ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Infarct Volume ◽

Significant Proportion ◽

Hemorrhagic Transformation ◽

Vessel Occlusion ◽

Clinical Recovery ◽

Good Functional Outcome ◽

Significant Difference

A significant proportion of patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) present poor functional outcome despite recanalization. We aim to investigate computed tomography perfusion (CTP) patterns after EVT and their association with outcome Methods: Prospective study of anterior large vessel occlusion AIS patients who achieved complete recanalization (defined as modified Thrombolysis in Cerebral Ischemia (TICI) 2b - 3) after EVT. CTP was performed within 30 minutes post-EVT recanalization (POST-CTP): hypoperfusion was defined as volume of time to maximal arrival of contrast (Tmax) delay ≥6 seconds in the affected territory. Hyperperfusion was defined as visual increase in cerebral blood flow (CBF) and volume (CBV) with advanced Tmax compared with the unaffected hemisphere. Dramatic clinical recovery (DCR) was defined as a decrease of ≥8 points in NIHSS score at 24h or NIHSS≤2 and good functional outcome by mRS ≤2 at 3 months. Results: One-hundred and forty-one patients were included. 49 (34.7%) patients did not have any perfusion abnormality on POST-CTP, 60 (42.5%) showed hypoperfusion (median volume Tmax≥6s 17.5cc, IQR 6-45cc) and 32 (22.8%) hyperperfusion. DCR appeared in 56% of patients and good functional outcome in 55.3%. Post-EVT hypoperfusion was related with worse final TICI, and associated worse early clinical evolution, larger final infarct volume (p<0.01 for all) and was an independent predictor of functional outcome (OR 0.98, CI 0.97-0.99, p=0.01). Furthermore, POST-CTP identified patients with delayed improvement: in patients without DCR (n=62, 44%), there was a significant difference in post-EVT hypoperfusion volume according to functional outcome (hypoperfusion volume of 2cc in good outcome vs 11cc in poor outcome, OR 0.97 CI 0.93-0.99, p=0.04), adjusted by confounding factors. Hyperperfusion was not associated with worse outcome (p=0.45) nor symptomatic hemorrhagic transformation (p=0.55). Conclusion: Hypoperfusion volume after EVT is an accurate predictor of functional outcome. In patients without dramatic clinical recovery, hypoperfusion predicts good functional outcome and defines a “stunned-brain” pattern. POST-CTP may help to select EVT patients for additional therapies.

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Role of plasma copeptin levels in assessing the functional outcome of patients with acute ischemic stroke

Journal of the Neurological Sciences ◽

10.1016/j.jns.2017.08.3689 ◽

2017 ◽

Vol 381 ◽

pp. 525

Author(s):

K. John ◽

N. Iqbal ◽

N. Nagarajan ◽

J. Arulneyam ◽

G. Abraham

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome

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Role of regulatory T-cells on ischemic stroke outcome: new clinical evidences

10.21203/rs.2.16371/v1 ◽

2019 ◽

Author(s):

María Santamaría-Cadavid ◽

Emilio Rodríguez-Castro ◽

Manuel Rodríguez-Yáñez ◽

Susana Arias-Rivas ◽

Iria López-Dequidt ◽

...

Keyword(s):

Ischemic Stroke ◽

Functional Outcome ◽

Infarct Volume ◽

Treg Cells ◽

Potential Therapeutic Target ◽

Control Subjects ◽

Good Functional Outcome ◽

Early Neurological Deterioration ◽

The Relationship

Abstract Background: Recent preclinical studies have shown that regulatory T (Treg) cells play a key role in the immune response after ischemic stroke (IS). However, the role of Treg-cells in human acute IS has been poorly investigated. Our aim was to study the relationship between circulating Treg-cells and outcome in human IS patients.Methods Methods: A total of 204 IS patients and 22 control subjects were recruited. The main study variable was good functional outcome at 3 months (modified Rankin scale ≤2) considering infarct volume, Early Neurological Deterioration (END) and risk of infections as secondary variables. The percentage of circulating Treg-cells was measured at admission, 48, 72h and at day 7 after stroke onset.Results Results: Circulating Treg-cell levels were higher in IS patients compared to control subjects. Treg-cells at 48h were independently associated with good functional outcome (OR, 3.5; CI: 1.9-7.8) after adjusting by confounding factors. Patients with lower Treg-cells at 48h showed higher frequency of END and risk of infections. In addition, a negative correlation was found between circulating Treg-cells at 48h (r=-0.414) and 72h (r=-0.418) and infarct volume. Conclusions: These findings suggest that Treg-cells may participate in the recovery of IS patients. Therefore, Treg-cells may be considered a potential therapeutic target in acute ischemic stroke.

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