FSAP aggravated endothelial dysfunction and neurological deficits in acute ischemic stroke due to large vessel occlusion.
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ABSTRACT:
SUBMITTER: Tian DS
PROVIDER: S-EPMC8738761 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Acute ischemic stroke (AIS) due to large vessel occlusion (LVO) is a devastating cerebrovascular disorder, which could benefit from collateral circulation. Proteins associated with acute LVO pathogenesis and endothelial function may appear in blood samples of AIS patients due to LVO, thus permitting development of blood-based biomarkers for its diagnosis and prognosis. METHODS:This study is a single-center, retrospective, observational case-control trial. Consecutive patients who presented at the Department of Neurology of Tongji Hospital were recruited from July 2016 to April 2018. In the discovery phase, a proteomic approach with iTRAQ-based LC-MS/MS was used to investigate the altered proteomic pattern in plasma from patients with AIS due to LVO. In the validation study, Western blots was used to identify biomarkers associated with stroke diagnosis as well as their prognostic value associated with different collateral statuses. RESULTS:For this exploratory study, the proteomic analysis of plasma from 40 patients with AIS due to LVO and 20 healthy controls revealed seven differentially expressed proteins with a 1.2/0.83-fold or greater difference between groups. The four elevated proteins, PPBP (1.58 ± 0.78 vs 0.98 ± 0.37; P < 0.001), THBS1 (1.13 ± 0.88 vs 0.43 ± 0.26; P < 0.001), LYVE1 (1.61 ± 0.55 vs 0.97 ± 0.50; P < 0.001), and IGF2 (1.19 ± 0.42 vs 0.86 ± 0.24; P < 0.001), were verified by Western blots analysis in an independent cohort including 33 patients and 33 controls. A strong interaction was observed between the four-protein panel and the diagnosis of AIS due to LVO (AUC 0.947; P < 0.001). Furthermore, IGF2, LYVE1, and THBS1 were closely associated with collateral status (IGF2 0.115, 95% CI 0.016-0.841, P = 0.033; LYVE1 0.183, 95% CI 0.036-0.918, P = 0.039; THBS1 4.257, 95% CI 1.273-14.228, P = 0.019), and proved to be independent predictors of good outcome (IGF2 0.115, 95% CI 0.015-0.866, P = 0.036; LYVE1 0.028, 95% CI 0.002-0.334, P = 0.005; THBS1 3.294, 95% CI 1.158-9.372, P = 0.025) at a 3-month follow-up. CONCLUSIONS:The identified 4-biomarker panel could provide diagnostic aid to the existing imaging modalities for AIS due to LVO, and the prognostic value of IGF2, LYVE1, and THBS1 was proved in predicting functional outcomes related to collateral status. Trial registration ClinicalTrials.gov NCT03122002. Retrospectively registered April 20, 2017. URL of trial registry record: https://www.clinicaltrials.gov/ct2/show/NCT03122002?term=NCT+03122002&rank=1.
| S-EPMC6604304 | biostudies-literature
Project description:BackgroundThe efficacy and safety of mechanical thrombectomy (MT) in acute large vessel occlusion (LVO) patients with minor stroke (NIHSS ≤ 5) remains undetermined. We aimed to compare the efficacy and safety of intra-arterial thrombolysis (IAT) alone vs. MT for LVO patients with minor stroke.MethodsPatients were selected from the Acute Ischemic Stroke Cooperation Group of Endovascular Treatment (ANGEL) registry, a prospective multicenter registry study, and divided into MT and IAT alone groups. We compared the outcome measures between the two groups, including 90-day functional outcome evaluated by the modified Rankin Scale (mRS), the final recanalization level, intracranial hemorrhage, and mortality within 90-days by logistic regression models with adjustment. Besides the conventional multivariable analysis, we performed a sensitivity analysis by adjusting the propensity score to confirm our results. The propensity score was derived using a logistic regression model.ResultsOf the 120 patients, 63 received IAT alone and 57 received MT as the first-line treatment strategy. As compared to MT group, patients in the IAT alone group were associated with a higher chance of 90-day mRS 0-2 [93.7% vs. 71.9%, odds ratio (OR) = 4.75, 95% confidence interval (CI): 1.20-18.80, P = 0.027], a high chance of 90-day mRS 0-3 (96.8% vs. 86.7%, OR = 11.35, 95% CI: 1.93-66.86, P = 0.007), a shorter median time from puncture to recanalization (PTR) (60 min vs. 100 min, β = -63.70, 95% CI: -81.79- -45.61, P < 0.001), a lower chance of any intracranial hemorrhage (ICH) within 48 h (3.2% vs. 19.3%, OR = 0.15, 95% CI: 0.03-0.79, P = 0.025), and a lower chance of mortablity within 90 days (1.6% vs. 9.2%, OR = 0.05, 95% CI: 0.01-0.57, P = 0.016). Similarly, the sensitivity analysis showed the robustness of the primary analysis.ConclusionsCompared with MT, IAT may improve 90-day clinical outcomes with decreased ICH rate and mortality in LVO patients with minor stroke.
| S-EPMC9315389 | biostudies-literature
Project description:Intravenous recombinant tissue plasminogen activator (iv-rtPA) has been routinely used to treat ischemic stroke for 25 years, following large clinical trials. However, there are few prospective studies on the efficacy and safety of this therapy in strokes attributed to cerebral small vessel disease (SVD). We evaluated functional outcome (modified Rankin scale, mRS) and symptomatic intracerebral hemorrhage (sICH) using all available data on the effects of iv-rtPA in SVD-related ischemic stroke (defined either using neuroimaging, clinical features, or both). Using fixed-effect and random-effects models, we calculated the pooled effect estimates with regard to excellent and favorable outcomes (mRS=0-1 and 0-2 respectively, at 3 months), and the rate of sICH. Twenty-three studies fulfilled the eligibility criteria, 11 of which were comparative, and there were only 3 randomized clinical trials. In adjusted analyses, there was an increased odds of excellent outcome (adjusted OR=1.53, 95% CI: 1.29-1.82, I2: 0%) or favorable outcome (adjusted OR=1.68, 95% CI: 1.31-2.15,I2: 0%) in patients who received iv-rtPA compared with placebo. Across the six studies which reported it, the incidence of sICH was higher in the treatment group (M-H RR = 8.83, 95% CI: 2.76-28.27). The pooled rate of sICH in patients with SVD administered iv-rtPA was only 0.72% (95% CI: 0.12%-1.64%). We conclude that when ischemic stroke attributed to SVD is considered separately, available data on the effects of iv-rtPA therapy are insufficient for the highest level of recommendation, but it seems to be safe. Although further therapeutic trials in SVD-related ischemic stroke appear to be justified, our findings should not prevent its continued use for this group of patients in clinical practice.
| S-EPMC8055574 | biostudies-literature
Project description:BackgroundThe drug 3-n-butylphthalide (NBP) was developed and approved in China, where it has been used to treat ischemic cerebrovascular diseases. It is also considered to have a neuroprotective effect. This study aimed to evaluate whether NBP combined with endovascular treatment (EVT) can improve the clinical outcome and safety in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO).MethodsData from three studies of patients treated with EVT for AIS due to LVO were combined in this study. Patients of LVO undergoing EVT were dichotomized into NBP and non-NBP subgroups. The primary efficacy outcome was the shift of the modified Rankin Scale (mRS) score at 90 days. The secondary efficacy outcome included favorable functional outcomes, functional independence, and excellent outcome (defined as an mRS score of 3 or less) at 90 days. Safety outcomes included mortality within 90 days and symptomatic intracranial hemorrhage (sICH) within 48 h.ResultsA total of 1820 patients undergoing EVT were included in this study; 628 (37.5%) patients received NBP treatment, whereas 1138 (62.5%) did not. After adjusting for multiple factors, NBP was associated with the improvement of functional outcomes at 90 days (adjusted common odds ratio [OR]: 1.503; 95% confidence interval (CI): 1.254-1.801; p < 0.001). NBP was associated with a higher rate of 90-day favorable outcomes (adjusted OR: 1.589; 95% CI: 1.251-2.020; p < 0.001) and a lower rate of 90-day mortality (adjusted OR: 0.486 [95% CI: 0.372-0.635]; p < 0.001). sICH occurred in 74 of 682 (10.9%) patients in the NBP group and 155 of 1126 (13.8%) patients in the non-NBP group; no statistical difference was detected (adjusted OR: 0.787 [95% CI: 0.567-1.092]; p = 0.152).ConclusionAmong patients with AIS due to LVO, NBP combined with EVT is associated with better functional outcomes and reduced mortality risk without increasing the risk of sICH.
| S-EPMC9627349 | biostudies-literature
Project description:The recent advances of endovascular procedures to treat stroke due to large cerebral vessel occlusion have made it possible to analyze the retrieved thrombus material. Analysis of cerebral thrombi is emerging as a relevant opportunity to complement the diagnostic workup of etiology, to develop new lytic approaches and to optimize the acute treatment of stroke due to large vessel occlusion. Nonetheless, retrieved thrombi are frequently discarded since their informative potential is often neglected and standards are missing. This review provides an overview of the current knowledge and expanding research relating to thrombus composition analysis in large vessel occlusions. We first discuss the heterogeneity of thrombogenic factors that underlie the thrombotic formation in stroke and its implications to identify stroke etiology and thrombus age. Further, we show that understanding structural characteristics of thrombus is pivotal for the development of new-targeted lytic therapies as well as to improve, through thrombus modeling, the development of thrombectomy devices. Finally, we discuss the on-going attempts to identify a signature of thrombus composition indirectly through imaging and peripheral blood biomarkers, which might in future assist treatment decision-making as well as secondary prevention. Thrombus analysis might contribute to the advancement and optimization of personalized stroke treatments.
| S-EPMC6681524 | biostudies-literature
Project description:ObjectivesWe aim to investigate whether cerebral small vessel disease (cSVD) imaging markers correlate with deep medullary vein (DMV) damage in small vessel occlusion acute ischemic stroke (SVO-AIS) patients.MethodsThe DMV was divided into six segments according to the regional anatomy. The total DMV score (0-18) was calculated based on segmental continuity and visibility. The damage of DMV was grouped according to the quartiles of the total DMV score. Neuroimaging biomarkers of cSVD including white matter hyperintensity (WMH), cerebral microbleed (CMB), perivascular space (PVS), and lacune were identified. The cSVD score were further analyzed.ResultsWe included 229 SVO-AIS patients, the mean age was 63.7 ± 23.1 years, the median NIHSS score was 3 (IQR, 2-6). In the severe DMV burden group (the 4th quartile), the NIHSS score grade (6 (3-9)) was significantly higher than other groups (p < 0.01). The grade scores for basal ganglia PVS (BG-PVS) were positively correlated with the degree of DMV (R = 0.67, p < 0.01), rather than centrum semivole PVS (CS-PVS) (R = 0.17, p = 0.1). In multivariate analysis, high CMB burden (adjusted odds ratio [aOR], 25.38; 95% confidence interval [CI], 1.87-345.23) was associated with severe DMV scores. In addition, BG-PVS was related to severe DMV burden in a dose-dependent manner: when BG-PVS score was 3 and 4, the aORs of severe DMV burden were 18.5 and 12.19, respectively.ConclusionThe DMV impairment was associated with the severity of cSVD, which suggests that DMV burden may be used for risk stratification in SVO-AIS patients.Clinical relevance statementThe DMV damage score, based on the association between small vessel disease and the deep medullary veins impairment, is a potential new imaging biomarker for the prognosis of small vessel occlusion acute ischemic stroke, with clinical management implications.Key points• The damage to the deep medullary vein may be one mechanism of cerebral small vessel disease. • Severe burden of the basal ganglia perivascular space and cerebral microbleed is closely associated with significant impairment to the deep medullary vein. • The deep medullary vein damage score may reflect a risk of added vascular damage in small vessel occlusion acute ischemic stroke patients.
| S-EPMC11364723 | biostudies-literature
Project description:Background: The clinical benefit from endovascular therapy (EVT) for patients with acute ischemic stroke is time-dependent. We tested the hypothesis that team prenotification results in faster procedure times prior to initiation of EVT. Methods: We analyzed data from our prospective database (01/2016-02/2018) including all patients with acute ischemic stroke who were evaluated for EVT at our comprehensive stroke center. We established a standardized algorithm (EVT-Call) in 06/2017 to prenotify team members (interventional neuroradiologist, neurologist, anesthesiologist, CT and angiography technicians) about patient transfer from remote hospitals for evaluation of EVT, and team members were present in the emergency department at the expected patient arrival time. We calculated door-to-image, image-to-groin and door-to-groin times for patients who were transferred to our center for evaluation of EVT, and analyzed changes before (-EVT-Call) and after (+EVT-Call) implementation of the EVT-Call. Results: Among 494 patients in our database, 328 patients were transferred from remote hospitals for evaluation of EVT (208 -EVT-Call and 120 +EVT-Call, median [IQR] age 75 years [65-81], NIHSS score 17 [12-22], 49.1% female). Of these, 177 patients (54%) underwent EVT after repeated imaging at our center (111/208 [53%) -EVT-Call, 66/120 [55%] +EVT-Call). Median (IQR) door-to-image time (18 min [14-22] vs. 10 min [7-13]; p < 0.001), image-to-groin time (54 min [43.5-69.25] vs. 47 min [38.3-58.75]; p = 0.042) and door-to-groin time (74 min [58-86.5] vs. 60 min [49.3-71]; p < 0.001) were reduced after implementation of the EVT-Call. Conclusions: Team prenotification results in faster patient assessment and initiation of EVT in patients with acute ischemic stroke. Its impact on functional outcome needs to be determined.
| S-EPMC8761669 | biostudies-literature
Project description:The mechanisms and phenotype of ischemic stroke associated with coronavirus disease 2019 (COVID-19) remain uncertain. A retrospective study was conducted in patients with COVID-19 presenting with ischemic stroke from March 1 to May 25, 2020, and cases with large-vessel occlusion were identified. To provide baseline institutional stroke data within and outside the COVID-19 pandemic, all consecutive ischemic stroke and TIA admissions (COVID and non-COVID) to the hospital during a 10-week period from March 1 to May 10, 2020, were collected and compared with data from the same time period in 2019. Among 20 patients with COVID-19 and acute ischemic stroke, 15 (75%) had large-vessel occlusion. These patients were young (mean age, 46.5 years), male (93%), without major burden of traditional cardiovascular risk factors, and had a severe stroke presentation. Large-vessel occlusions were observed in multiple vessels (40%), uncommonly affected vessels, and atypical locations with a large thrombus burden. Systemic thrombosis separate from large-vessel occlusion was not uncommon (26%). At short-term follow-up, stroke etiology remained undetermined in 46% of patients and functional outcome was poor. The above findings raise the possibility of stroke related to mechanisms induced by the COVID-19 infection itself, including a hypercoagulable state and/or endothelial damage. In addition, they document the severe presentation and poor outcomes of large-vessel occlusion in COVID-19 ischemic stroke.
| S-EPMC7963240 | biostudies-literature
Project description:Background and Purpose- Accurate prediction of acute ischemic stroke (AIS) caused by anterior large vessel occlusion (LVO) that is amendable to mechanical thrombectomy remains a challenge. We developed and validated a prediction model for anterior circulation LVO stroke using past medical history elements present on admission and neurological examination. Methods- We retrospectively reviewed AIS patients admitted between 2009 and 2017 to 3 hospitals within a large healthcare system in the United States. Patients with occlusions of the internal carotid artery or M1 or M2 segments of the middle cerebral artery were randomly split into 2/3 derivation and 1/3 validation cohorts for development of an anterior circulation LVO prediction model and score that was further curtailed for potential use in the prehospital setting. Results- A total of 1654 AIS were reviewed, including 248 (15%) with proximal anterior circulation LVO AIS. In the derivation cohort, National Institutes of Health Stroke Scale score at the time of cerebrovascular imaging, current smoking status, type 2 diabetes mellitus, extracranial carotid, and intracranial atherosclerotic stenosis was significantly associated with anterior circulation LVO stroke. The prehospital score was curtailed to National Institutes of Health Stroke Scale score, current smoking status, and type 2 diabetes mellitus. The areas under the curve for the prediction model, prehospital score, and National Institutes of Health Stroke Scale score alone were 0.796, 0.757, and 0.725 for the derivation cohort and 0.770, 0.689, and 0.665 for the validation cohort, respectively. The Youden index J was 0.46 for a score of >6 with 84.7% sensitivity and 62.0% specificity for the prediction model. Conclusions- Previously reported LVO stroke prediction scores focus solely on elements of the neurological examination. In addition to stroke severity, smoking, diabetes mellitus, extracranial carotid, and intracranial atherosclerotic stenosis were associated with anterior circulation LVO AIS. Although atherosclerotic stenosis may not be known until imaging is obtained, smoking and diabetes mellitus history can be readily obtained in the field and represent important elements of the prehospital score supplementing National Institutes of Health Stroke Scale score.
| S-EPMC6509557 | biostudies-literature
Project description:BackgroundNeuroinflammation plays an important role in the pathogenesis of acute ischemic stroke (AIS) and peripheral leukocyte counts have proved to be independent predictors of stroke severity and outcomes. Clinical significance of large vessel occlusion (LVO) in AIS is increasing, as these patients are potential candidates for endovascular thrombectomy and likely to have worse outcomes if not treated urgently. The aim of our study was to assess the relationship between on admission leukocyte counts and the presence of LVO in the early phase of AIS.MethodsWe have conducted a cross-sectional, observational study based on a registry of consecutive AIS patients admitted up to 4.5 h after stroke onset. Blood samples were taken at admission and leukocyte counts were measured immediately. The presence of LVO was verified based on the computed tomography angiography scan on admission.ResultsTotal white blood cell (WBC) and neutrophil counts were significantly higher in patients with LVO than those without LVO (P < 0.001 respectively). After adjustment for potential confounders total WBC counts (adjusted OR: 1.405 per 1 × 109/L increase, 95% CI: 1.209 to 1.632) and neutrophil counts (adjusted OR: 1.344 per 1 × 109/L increase, 95% CI: 1.155 to 1.564) were found to have the strongest associations with the presence of LVO. Total WBC and neutrophil counts had moderate ability to discriminate an LVO in AIS (AUC: 0.667 and 0.655 respectively). No differences were recorded in leukocyte counts according to the size of the occluded vessel and the status of collateral circulation in the anterior vascular territory. However, total WBC and neutrophil counts tended to be higher in patients with LVO in the posterior circulation (p = 0.005 and 0.010 respectively).ConclusionHigher admission total WBC and neutrophil counts are strongly associated with the presence of LVO and has moderate ability to discriminate an LVO in AIS. Detailed evaluation of stroke-evoked inflammatory mechanisms and changes according to the presence of LVO demands further investigation.
| S-EPMC7716438 | biostudies-literature