scholarly journals Platelet Activation and Chemokine Release Are Related to Local Neutrophil-Dominant Inflammation During Hyperacute Human Stroke

Author(s):  
Alexander M. Kollikowski ◽  
Mirko Pham ◽  
Alexander G. März ◽  
Lena Papp ◽  
Bernhard Nieswandt ◽  
...  

AbstractExperimental evidence has emerged that local platelet activation contributes to inflammation and infarct formation in acute ischemic stroke (AIS) which awaits confirmation in human studies. We conducted a prospective observational study on 258 consecutive patients undergoing mechanical thrombectomy (MT) due to large-vessel-occlusion stroke of the anterior circulation (08/2018–05/2020). Intraprocedural microcatheter aspiration of 1 ml of local (occlusion condition) and systemic arterial blood samples (self-control) was performed according to a prespecified protocol. The samples were analyzed for differential leukocyte counts, platelet counts, and plasma levels of the platelet-derived neutrophil-activating chemokine C-X-C-motif ligand (CXCL) 4 (PF-4), the neutrophil attractant CXCL7 (NAP-2), and myeloperoxidase (MPO). The clinical-biological relevance of these variables was corroborated by specific associations with molecular-cellular, structural-radiological, hemodynamic, and clinical-functional parameters. Seventy consecutive patients fulfilling all predefined criteria entered analysis. Mean local CXCL4 (+ 39%: 571 vs 410 ng/ml, P = .0095) and CXCL7 (+ 9%: 693 vs 636 ng/ml, P = .013) concentrations were higher compared with self-controls. Local platelet counts were lower (− 10%: 347,582 vs 383,284/µl, P = .0052), whereas neutrophil counts were elevated (+ 10%: 6022 vs 5485/µl, P = 0.0027). Correlation analyses revealed associations between local platelet and neutrophil counts (r = 0.27, P = .034), and between CXCL7 and MPO (r = 0.24, P = .048). Local CXCL4 was associated with the angiographic degree of reperfusion following recanalization (r =  − 0.2523, P = .0479). Functional outcome at discharge correlated with local MPO concentrations (r = 0.3832, P = .0014) and platelet counts (r = 0.288, P = .0181). This study provides human evidence of cerebral platelet activation and platelet-neutrophil interactions during AIS and points to the relevance of per-ischemic thrombo-inflammatory mechanisms to impaired reperfusion and worse functional outcome following recanalization.

2021 ◽  
Vol 22 (17) ◽  
pp. 9161
Author(s):  
Marc Strinitz ◽  
Mirko Pham ◽  
Alexander G. März ◽  
Jörn Feick ◽  
Franziska Weidner ◽  
...  

It remains unclear if principal components of the local cerebral stroke immune response can be reliably and reproducibly observed in patients with acute large-vessel-occlusion (LVO) stroke. We prospectively studied a large independent cohort of n = 318 consecutive LVO stroke patients undergoing mechanical thrombectomy during which cerebral blood samples from within the occluded anterior circulation and systemic control samples from the ipsilateral cervical internal carotid artery were obtained. An extensive protocol was applied to homogenize the patient cohort and to standardize the procedural steps of endovascular sample collection, sample processing, and laboratory analyses. N = 58 patients met all inclusion criteria. (1) Mean total leukocyte counts were significantly higher within the occluded ischemic cerebral vasculature (I) vs. intraindividual systemic controls (S): +9.6%, I: 8114/µL ± 529 vs. S: 7406/µL ± 468, p = 0.0125. (2) This increase was driven by neutrophils: +12.1%, I: 7197/µL ± 510 vs. S: 6420/µL ± 438, p = 0.0022. Leukocyte influx was associated with (3) reduced retrograde collateral flow (R2 = 0.09696, p = 0.0373) and (4) greater infarct extent (R2 = 0.08382, p = 0.032). Despite LVO, leukocytes invade the occluded territory via retrograde collateral pathways early during ischemia, likely compromising cerebral hemodynamics and tissue integrity. This inflammatory response can be reliably observed in human stroke by harvesting immune cells from the occluded cerebral vascular compartment.


2022 ◽  
pp. neurintsurg-2021-018292
Author(s):  
Dapeng Sun ◽  
Baixue Jia ◽  
Xu Tong ◽  
Peter Kan ◽  
Xiaochuan Huo ◽  
...  

BackgroundParenchymal hemorrhage (PH) is a troublesome complication after endovascular treatment (EVT).ObjectiveTo investigate the incidence, independent predictors, and clinical impact of PH after EVT in patients with acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO).MethodsSubjects were selected from the ANGEL-ACT Registry. PH was diagnosed according to the European Collaborative Acute Stroke Study classification. Logistic regression analyses were performed to determine the independent predictors of PH, as well as the association between PH and 90-day functional outcome assessed by modified Rankin Scale (mRS) score.ResultsOf the 1227 enrolled patients, 147 (12.0%) were diagnosed with PH within 12–36 hours after EVT. On multivariable analysis, low admission Alberta Stroke Program Early CT score (ASPECTS)(adjusted OR (aOR)=1.13, 95% CI 1.02 to 1.26, p=0.020), serum glucose >7 mmol/L (aOR=1.82, 95% CI 1.16 to 2.84, p=0.009), and neutrophil-to-lymphocyte ratio (NLR; aOR=1.05, 95% CI 1.02 to 1.09, p=0.005) were associated with a high risk of PH, while underlying intracranial atherosclerotic stenosis (ICAS; aOR=0.42, 95% CI 0.22 to 0.81, p=0.009) and intracranial angioplasty/stenting (aOR=0.37, 95% CI 0.15 to 0.93, p=0.035) were associated with a low risk of PH. Furthermore, patients with PH were associated with a shift towards to worse functional outcome (mRS score 4 vs 3, adjusted common OR (acOR)=2.27, 95% CI 1.53 to 3.38, p<0.001).ConclusionsIn Chinese patients with AIS caused by anterior circulation LVO, the risk of PH was positively associated with low admission ASPECTS, serum glucose >7 mmol/L, and NLR, but negatively related to underlying ICAS and intracranial angioplasty/stenting.Trial registration numberNCT03370939.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Pedro Cardona ◽  
Helena Quesada ◽  
Luis Cano ◽  
Lucia Aja ◽  
De Miquel MA. ◽  
...  

In our comprehensive stroke center we analyze correct selection criteria to use self-expandable retrievable intracranial stents for acute stroke treatment. The criteria for intervention were the onset of neurological symptoms, a National Institute of Health Stroke Scale Score (NIHSS) ≥9 at presentation, large vessel occlusion stroke demonstrated by angio-CT, and failure of intravenous thrombolysis or exclusion criteria to administrate it. METHODS: We performed an retrospective analysis of 512 consecutive patients with acute ischemic stroke candidates for thrombectomy, from April of 2010 to June of 2012, that met inclusion criteria for intervention. Experienced vascular neurologists selected 171 patients to undergoing endovascular therapy using retrievable stents (Solitaire,Trevo). Successful recanalization results were assessed by follow-up angiography immediately after the procedure (TIMI 2-3/TICI 2b-3 score), and good functional outcome was considered when ≤2 mRankin score (mRS) was achieved at 90 days. RESULTS: A total of 171 patients were treated, 87% with anterior circulation stroke. The mean age was 67.5 years (range 32-87); 58% men. The median NIHSS at presentation was 17 (range 6-26). Recanalization (TICI 2b-3) was achieved in 73% of patients. Symptomatic hemorrhage occurred in 8%. Ninety-day mortality was 19, 5% and good 90-day functional outcome (mRS ≤2) was achieved by 45%. Unsuccessful recanalization (TICI 0-2a) was a significant predictor of poor outcome (mRS≤2: 9%). When we analyzed these patients according to inclusion criteria of IMS trial, 101 patients who met strict criteria achieved good neurological outcome more frequently (51% versus 34%) and significant lower mortality rates (17% vs 28%) compared with the group of 70 patients with IMS exclusion criteria. CONCLUSIONS: Efficacy in recanalization, safety of thrombectomy and its consequent good clinical outcome is sufficiently established. It is important an experienced vascular neurologist to select possible candidates (proportion of evaluated/treated patients 3:1). Inclusion criteria for acute stroke trials do not always represent real population of stroke patients as well as their clinical results.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Joseph F Carrera ◽  
Joseph H Donahue ◽  
Prem P Batchala ◽  
Andrew M Southerland ◽  
Bradford B Worrall

Introduction: CTP and MRI are increasingly used to assess endovascular thrombectomy (EVT) candidacy in large vessel occlusion stroke. Unfortunately, availability of these advanced neuroimaging techniques is not widespread and this can lead to over-triage to EVT-capable centers. Hypothesis: ASPECTS scoring applied to computed tomography angiography source images (CTA-SI) will be predictive of final infarct volume (FIV) and functional outcome. Methods: We reviewed data from consecutive patients undergoing EVT at our institution for anterior circulation occlusion between 01/14 - 01/19. We recorded demographics, comorbidities, NIHSS, treatment time parameters, and outcomes as defined by mRS (0-2 = good outcome). Cerebrovascular images were assessed by outcome-blinded raters and collateral score, TICI score, FIV, and both CT and CTA-SI ASPECTS scores were noted. Patients were grouped by ASPECTS score into low (0-4), intermediate (5-7), and high (8-10) for some analyses. FIV was predicted using a linear regression with NIHSS, good reperfusion (TICI 2b/3), collateral score, CT to groin puncture, CT and CTA-SI ASPECTS as independent variables. After excluding those with baseline mRS≥2, a binary logistic regression was performed including covariates of age, NIHSS, good reperfusion, and diabetes (factors significant at p<0.05 on univariate analysis) to assess the impact of CTA-SI ASPECTS group on outcome. Results: Analysis included 137 patients for FIV and 102 for outcome analysis (35 excluded for baseline mRS≥ 2). Linear regression found CTA-SI ASPECTS (Beta -10.8, p=0.002), collateral score (Beta -42.9, p=0.001) and good reperfusion (Beta 72.605, p=0.000) were independent predictors of FIV. Relative to the low CTA-SI ASPECTS group, the high CTA-SI ASPECTS group was more likely to have good outcome (OR 3.75 [95% CI 1.05-13.3]; p=0.41). CT ASPECTS was not predictive of FIV or good outcome. Outcomes: In those undergoing EVT for anterior circulation occlusion, CTA-SI ASPECTS is predictive of both FIV and functional outcome, while CT ASPECTS predicts neither. CTA-SI ASPECTS holds promise as a lower-cost, more widely available option for triage of patients with large vessel occlusion. Further study is needed comparing CTA-SI ASPECTS to CTP parameters.


Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Natalia Perez de la Ossa ◽  
Srikant Rangaraju ◽  
Tudor Jovin ◽  
Anoni Dávalos ◽  

Introduction: Various scales have been developed to predict long-term clinical outcome after endovascular therapy (EVT) in stroke patients. The objective of this study was to validate and compare five well-validated scales in terms of predictive accuracy for functional independence in a recent endovascular stroke trial (REVASCAT). Hypothesis: We hypothesize that predictive scales (PRE, THRIVE, HIAT2, SPAN-100, FAR) have good-excellent (AUC>0.7) predictive accuracy for good functional outcome and can predict the beneficial effect of EVT demonstrated in randomized clinical trials. Methods: REVASCAT (Randomized Trial of Revascularization with Solitaire-FR Device versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting within Eight Hours of Symptom Onset) enrolled 206 patients who were randomized to receive EVT or best medical treatment. Five scores (PRE-score, THRIVE, HIAT2, SPAN-100 and FAR-score) were retrospectively calculated on patients who received EVT. Receiver-operator characteristics (ROC) for good outcome (mRS 0-2 at 90 days) for each scale were compared. Using the highest predictive scales, the proportion of patients with good outcome by the score categorized in quartiles was analyzed. Results: 103 patients received EVT in the REVASCAT trial (mean age 65.7, median NIHSS 17). Baseline NIHSS, baseline CT-ASPECTS, age and atrial fibrillation, but not previous iv tPA or DM, were associated with good outcome in multivariable analysis. AUC for good outcome was ≥0.70 for FAR (0.74) and PRE (0.70) scores while SPAN-100 (0.67), HIAT2 (0.65) and THRIVE (0.64) had lower AUCs although differences were not statistically significant. The higher the score on the PRE and FAR scores, the lower the proportion of patients with good outcome (PRE-score: 1QT 44.4%, 2QT 24.4%, 3QT 22.2%, 4 QT 8.9%; FAR-score: 1QT 57.8%, 2QT 22.2%, 3QT 6.7%, 4QT 3.3%). Benefit of EVT accordingly to the score on the different scales will be also presented. Conclusions: Of the 5 stroke scales, FAR and PRE had better predictive accuracy for functional independence after EVT. These tools may facilitate decision making for EVT in anterior circulation large vessel occlusion stroke.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Christian Hartmann ◽  
Simon Winzer ◽  
Timo Siepmann ◽  
Lars-Peder Pallesen ◽  
Alexandra Prakapenia ◽  
...  

Introduction: Hypothermia may be neuroprotective in acute ischemic stroke. Stroke patients with anterior circulation large vessel occlusion (acLVO) who receive endovascular therapy (EVT) are frequently hypothermic after the procedure. We sought to analyze whether this unintended hypothermia was associated with improved functional outcome. Methods: We extracted data of consecutive patients (01/2016-04/2019) from our prospective EVT database that includes all patients screened for EVT at our center. We included patients with acLVO who received EVT and analyzed recanalization (mTICI 2b-3) and complications (i.e., pneumonia, bradyarrhythmia, venous thromboembolism) during the hospital course. We assessed functional outcome at 3 months and analyzed risk ratios (RR) for good outcome (mRS scores 0-2) and mortality of patients who were hypothermic (<36°C) compared to patients who were normothermic ( > 36°C) after EVT. We compared the frequency of complications and calculated RRs for good outcome and mortality in the subgroup with recanalization. Results: Among 674 patients with anterior circulation ischemic stroke, 372 patients received EVT for acLVO (178 [47%] male, age 77 years [65-82], NIHSS score 16 [12 - 20]). Of these, 186 patients (50%) were hypothermic (median [IQR] temperature 35.2°C [34.7-35.6]) and 186 patients were normothermic (media temperature 36.4 [36.2-36.8]) after EVT. At 3 months, 54 of 186 (29.0%) hypothermic patients compared with 65 of 186 (35.0%) normothermic patients had a good outcome (RR, 0.83; 95%CI 0.62-1.12) and 52 of 186 (27.9%) hypothermic patients compared with 46 of 186 (24.7%) normothermic patients had died (RR, 1.13; 95%CI 0.8-1.59). This relation was consistent in 307 patients (82.5% of all EVTs) with successful recanalization (good outcome: RR, 0.85; 95%CI 0.63-1.14.; mortality: RR, 1.05; 95%CI 0.7-1.57). More hypothermic patients suffered pneumonia (37.8% vs. 24.7%; p=0.003) or bradyarrhythmia (55.6% vs. 18.3%; p<0.001). Venous thromboembolism was distributed similarly (5.4% vs. 6.5%; p=0.42). Conclusion: Unintended hypothermia following EVT for acLVO was not associated with improved functional outcome or reduced mortality but an increased complication rate in patients with acute ischemic stroke.


Stroke ◽  
2019 ◽  
Vol 50 (10) ◽  
pp. 2842-2850 ◽  
Author(s):  
Wouter H. Hinsenveld ◽  
Inger R. de Ridder ◽  
Robert J. van Oostenbrugge ◽  
Jan A. Vos ◽  
Adrien E. Groot ◽  
...  

Background and Purpose— Endovascular treatment (EVT) of patients with acute ischemic stroke because of large vessel occlusion involves complicated logistics, which may cause a delay in treatment initiation during off-hours. This might lead to a worse functional outcome. We compared workflow intervals between endovascular treatment–treated patients presenting during off- and on-hours. Methods— We retrospectively analyzed data from the MR CLEAN Registry, a prospective, multicenter, observational study in the Netherlands and included patients with an anterior circulation large vessel occlusion who presented between March 2014 and June 2016. Off-hours were defined as presentation on Monday to Friday between 17:00 and 08:00 hours, weekends (Friday 17:00 to Monday 8:00) and national holidays. Primary end point was first door to groin time. Secondary end points were functional outcome at 90 days (modified Rankin Scale) and workflow time intervals. We stratified for transfer status, adjusted for prognostic factors, and used linear and ordinal regression models. Results— We included 1488 patients of which 936 (62.9%) presented during off-hours. Median first door to groin time was 140 minutes (95% CI, 110–182) during off-hours and 121 minutes (95% CI, 85–157) during on-hours. Adjusted first door to groin time was 14.6 minutes (95% CI, 9.3–20.0) longer during off-hours. Door to needle times for intravenous therapy were slightly longer (3.5 minutes, 95% CI, 0.7–6.3) during off-hours. Groin puncture to reperfusion times did not differ between groups. For transferred patients, the delay within the intervention center was 5.0 minutes (95% CI, 0.5–9.6) longer. There was no significant difference in functional outcome between patients presenting during off- and on-hours (adjusted odds ratio, 0.92; 95% CI, 0.74–1.14). Reperfusion rates and complication rates were similar. Conclusions— Presentation during off-hours is associated with a slight delay in start of endovascular treatment in patients with acute ischemic stroke. This treatment delay did not translate into worse functional outcome or increased complication rates.


Neurosurgery ◽  
2019 ◽  
Vol 86 (2) ◽  
pp. E156-E163 ◽  
Author(s):  
James E Siegler ◽  
Steven R Messé ◽  
Heidi Sucharew ◽  
Scott E Kasner ◽  
Tapan Mehta ◽  
...  

Abstract BACKGROUND Because of the overwhelming benefit of thrombectomy for highly selected trial patients with large vessel occlusion (LVO), some trial-ineligible patients are being treated in practice. OBJECTIVE To determine the safety and efficacy of thrombectomy in DAWN/DEFUSE-3-ineligible patients. METHODS Using a multicenter prospective observational study of consecutive patients with anterior circulation LVO who underwent late thrombectomy, we compared symptomatic intracerebral hemorrhage (sICH) and good outcome (90-d mRS 0-2) among DAWN/DEFUSE-3-ineligible patients to trial-eligible patients and to untreated DAWN/DEFUSE-3 controls. RESULTS Ninety-eight patients had perfusion imaging and underwent thrombectomy &gt;6 h; 46 (47%) were trial ineligible (41% M2 occlusions, 39% mild deficits, 28% ASPECTS &lt;6). In multivariable regression, the odds of a good outcome (aOR 0.76, 95% CI 0.49-1.19) and sICH (aOR 3.33, 95% CI 0.42-26.12) were not different among trial-ineligible vs eligible patients. Patients with mild deficits were more likely to achieve a good outcome (aOR 3.62, 95% CI 1.48-8.86) and less sICH (0% vs 10%, P = .16), whereas patients with ASPECTS &lt;6 had poorer outcomes (aOR 0.14, 95% CI 0.05-0.44) and more sICH (aOR 24, 95% CI 5.7-103). Compared to untreated DAWN/DEFUSE-3 controls, trial-ineligible patients had more sICH (13%BEST vs 3%DAWN [P = .02] vs 4%DEFUSE [P = .05]), but were more likely to achieve a good outcome at 90 d (36%BEST vs 13%DAWN [P &lt; .01] vs 17%DEFUSE [P = .01]). CONCLUSION Thrombectomy is used in practice for some patients ineligible for the DAWN/DEFUSE-3 trials with potentially favorable outcomes. Additional trials are needed to confirm the safety and efficacy of thrombectomy in broader populations, such as large core infarction and M2 occlusions.


2018 ◽  
Vol 45 (5-6) ◽  
pp. 221-227 ◽  
Author(s):  
Zhenhui Duan ◽  
Huaiming Wang ◽  
Zhen Wang ◽  
Yonggang Hao ◽  
Wenjie Zi ◽  
...  

Background and Objective: Endovascular treatment (EVT) is proven to be safe and effective for treating acute large vessel occlusion stroke (LVOS). The neutrophil-lymphocyte ratio (NLR) reflects systemic inflammation, which plays an important role in the process of treating ischemic stroke. This study aims to explore the relationship between NLR and the clinical outcomes of LVOS patients undergoing EVT. Methods: Patients were selected from the EVT for acUte Anterior circuLation (ACTUAL) ischemic stroke registry. The laboratory data (neutrophil count, lymphocyte count) before EVT were collected. Poor functional outcome was defined as modified Rankin Scale (mRS) of 3–6 at 3 months. Multivariable logistic regression analyses were performed to explore the relationship of NLR with functional outcome, symptomatic intracranial hemorrhage (sICH), and mortality. Results: We eventually included 616 patients (median of age, 66 years; 40.3% female). There were 350 (56.7%) patients achieving mRS of 3–6 at 3 months, 98 (15.9%) patients with sICH, and the mortality at 3 months was 24.8% (153/616). Baseline NLR was independently associated with poor functional outcome (OR 1.58; 95% CI 1.02–2.45; p = 0.039) and sICH (OR 1.84; 95% CI 1.09–3.11; p = 0.023) but showed a trend for predicting 3-month mortality (OR 1.57; 95% CI 0.94–2.65; p = 0.088). Conclusions: NLR independently predicts 3-month functional outcome and sICH but the existence of a trend association with mortality after EVT for acute anterior circulation LVOS patients.


2017 ◽  
Vol 7 (2) ◽  
pp. 95-102 ◽  
Author(s):  
Chee-Keong Wee ◽  
William McAuliffe ◽  
Constantine C. Phatouros ◽  
Timothy J. Phillips ◽  
David Blacker ◽  
...  

Background and Purpose: Endovascular thrombectomy (EVT) improves the functional outcome when added to best medical therapy, including alteplase, in patients with acute ischaemic stroke secondary to large vessel occlusion (LVO) in the anterior circulation. However, the evidence for EVT in alteplase-ineligible patients is less compelling. It is also uncertain whether alteplase is necessary in patients with successful recanalization by EVT, as the treatment effect of EVT may be so powerful that bridging alteplase may not add to efficacy and may compromise safety by increasing bleeding risks. We aimed to survey the proportion of patients suitable for EVT who are alteplase-ineligible and to compare the safety and effectiveness of standard care of acute large artery ischaemic stroke by EVT plus thrombolysis with that of EVT alone in a tertiary hospital clinical stroke service. Methods: We performed a retrospective analysis of acute ischaemic stroke patients treated with EVT at our centre between October 2013 and April 2016, based on a registry with prospective and consecutive patient collection. Individual patient records were retrieved for review. Significant early neurological improvement was defined as a NIHSS score of 0–1, or a decrease from baseline of ≤8, at 24 h after stroke onset. Results: Fifty patients with acute ischaemic stroke secondary to LVO in the anterior circulation received EVT in this period, of whom 21 (42%) received concurrent alteplase and 29 (58%) EVT alone. The 2 groups had similar baseline characteristics and similar outcomes. Significant neurological improvement at 24 h occurred in 47.6% of the patients with EVT and bridging alteplase and in 51.7% of the patients with EVT alone (p = 0.774). Mortality during acute hospitalization was 20% for the bridging alteplase group versus 7.1% for EVT alone (p = 0.184). Intracranial haemorrhage rates were 14.3% for bridging alteplase versus 20.7% for EVT alone (p = 0.716). Local complications, groin haematoma (23.8 vs. 10.3%) and groin pseudoaneurysms (4.8 vs. 0%) (p = 0.170), were not significantly different. Conclusion: Our study highlights the relatively large proportion of patients suitable for EVT who have a contraindication to alteplase and raises the hypothesis that adding alteplase to successful EVT may not be necessary to optimize functional outcome. The results are consistent with observational data from other endovascular centres and support a randomised controlled trial of EVT versus EVT with bridging alteplase.


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