A Novel Combination of Blood Biomarkers and Clinical Stroke Scales Facilitates Detection of Large Vessel Occlusion Ischemic Strokes.
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SUBMITTER: Gaude E
PROVIDER: S-EPMC8306880 | 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:IntroductionPrehospital stroke scales have been proposed to identify stroke patients with a large vessel occlusion to allow direct transport to an intervention centre capable of endovascular treatment (EVT). It is unclear whether these scales are able to detect not only proximal, but also more distal treatable occlusions. Our aim was to assess the sensitivity of prehospital stroke scales for different EVT-eligible occlusion locations in the anterior circulation.Patients and methodsThe MR CLEAN Registry is a prospective, observational study in all centres that perform EVT in the Netherlands. We included adult patients with an anterior circulation stroke treated between March 2014 and November 2017. We used National Institutes of Health Stroke Scale scores at admission to reconstruct previously published prehospital stroke scales. We compared the sensitivity of each scale for different occlusion locations. Occlusions were assessed with CT angiography by an imaging core laboratory blinded to clinical findings.ResultsWe included 3021 patients for the analysis of 14 scales. All scales had the highest sensitivity to detect internal carotid artery terminus occlusions (ranging from 0.21 to 0.97) and lowest for occlusions of the M2 segment (0.08 to 0.84, p-values < 0.001).Discussion and conclusion: Although prehospital stroke scales are generally sensitive for proximal large vessel occlusions, they are less sensitive to detect more distal occlusions.
| S-EPMC8370085 | 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: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: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
Project description:ObjectiveStroke severity screens typically include cortical signs, such as field cut, aphasia, neglect, gaze preference, and dense hemiparesis (FANG-D). The accuracy and reliability of these signs, when assessed by emergency physicians, to identify patients with anterior circulation large vessel occlusion (ACLVO) acute ischemic stroke (AIS) is unknown. We hypothesized that the FANG-D screen applied by emergency physicians would be sensitive and reliable for identifying ACLVO AIS.MethodsWe conducted a prospective cohort study enrolling consecutive patients with suspected AIS presenting within 4.5 hours of last known well to the emergency department (ED). Emergency physicians performed the FANG-D screen prior to, and blinded to the results of, imaging. The imaging standard was defined as a non-contrast computed tomography (CT) for identifying hemorrhage and CT angiography for identifying large vessel occlusion. ACLVO was defined as an occlusion of the internal carotid artery, the middle cerebral artery, or its first branch. A convenience sample of patients had a duplicate FANG-D screen performed by a second emergency physician to assess interobserver agreement.ResultsWe performed 608 FANG-D assessments on 491 patients presenting to the ED, of whom 64 (10%) had an ACLVO. FANG-D had a sensitivity of 91% (confidence interval [CI] = 81%-96%) and a specificity of 35% (CI = 31%-39%) for identifying ACLVO. Interobserver agreement was tested on 133 patients and was found to be substantial, with a Fleiss' kappa of 0.77 (CI = 0.64-0.88).ConclusionsThe FANG-D screen is a sensitive test for identifying ACLVO when performed by emergency physicians and demonstrates substantial interrater reliability.
| S-EPMC7593424 | biostudies-literature
Project description:Ischemic lesion net water uptake (NWU) represents a quantitative imaging biomarker for cerebral edema in acute ischemic stroke. Data on NWU for distinct occlusion locations remain scarce, but might help to improve the prognostic value of NWU. In this retrospective multicenter cohort study, we compared NWU between patients with proximal large vessel occlusion (pLVO; ICA or proximal M1) and distal large vessel occlusion (dLVO; distal M1 or M2). NWU was quantified by densitometric measurements of the early ischemic region. Arterial collateral status was assessed using the Maas scale. Regression analysis was used to investigate the relationship between occlusion location, NWU and ischemic lesion growth. A total of 685 patients met inclusion criteria. Early ischemic lesion NWU was higher in patients with pLVO compared with dLVO (7.7% vs 3.9%, P < .001). The relationship between occlusion location and NWU was partially mediated by arterial collateral status. NWU was associated with absolute ischemic lesion growth between admission and follow-up imaging (β estimate, 5.50, 95% CI, 3.81-7.19, P < .001). This study establishes a framework for the relationship between occlusion location, arterial collateral status, early ischemic lesion NWU and ischemic lesion growth. Future prognostic thresholds for NWU might be optimized by adjusting for the occlusion location.
| S-EPMC11342730 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Prehospital stroke scales may help identify patients likely to have large-vessel occlusion to facilitate rapid triage to thrombectomy-capable stroke centers. Scale misclassification may result in inaccurate decisions and possible harm. Pre-existing leukoaraiosis has been shown to attenuate the association between deficit type and stroke severity. We sought to determine whether leukoaraiosis affects the predictive ability of 5 commonly used large-vessel occlusion scales. MATERIALS AND METHODS:We retrospectively analyzed 274 consecutive patients with stroke with available brain MR imaging and vessel imaging. We used the following large-vessel occlusion scales: the 3-Item Stroke Scale; Field Assessment Stroke Triage for Emergency Destination; Rapid Arterial Occlusion Evaluation; Vision, Aphasia, Neglect score; and Cincinnati Prehospital Stroke Severity Scale. For diagnostic scale accuracy, we assessed sensitivity, specificity, positive predictive value, negative predictive value, and ?. Multivariable logistic regression was used to determine the predictive ability of the scales after adjustment for leukoaraiosis and potential confounders. RESULTS:In unadjusted analyses, all scales predicted the presence of large-vessel occlusion (n = 46, P < .01 each), though diagnostic accuracy was attenuated among patients with moderate-to-severe leukoaraiosis. After adjustment, the Field Assessment Stroke Triage for Emergency Destination (OR = 3.2; 95% CI, 1.1-9.5; P = .033) and Rapid Arterial Occlusion Evaluation (OR = 3.7; 95% CI, 1.3-10.8; P = .015), but not the 3-Item Stroke Scale (OR = 5.4; 95% CI, 0.86-33.9; P = .073), Vision, Aphasia, Neglect score (OR = 2.5; 95% CI, 0.8-7.2), and Cincinnati Prehospital Stroke Severity Scale (OR = 2.8; 95% CI, 1.0-8.0), predicted large-vessel occlusion. CONCLUSIONS:The diagnostic accuracy of the tested large-vessel occlusion scales was attenuated in the presence of moderate-to-severe leukoaraiosis. This information that may aid the design of future studies that require large-vessel occlusion scale screening of patients who are likely to have concomitant leukoaraiosis.
| S-EPMC5812815 | biostudies-literature
Project description:High revascularization rates in large-vessel occlusion strokes treated by mechanical thrombectomy are not always associated with good clinical outcomes. We evaluated predictors of functional dependence despite successful revascularization among patients with acute ischemic stroke treated with thrombectomy.We analyzed the pooled data from the Multi Mechanical Embolus Removal in Cerebral Ischemia (MERCI), Thrombectomy Revascularization of Large Vessel Occlusions in Acute Ischemic Stroke (TREVO), and TREVO 2 trials. Successful revascularization was defined as thrombolysis in cerebral infarction score 2b or 3. Functional dependence was defined as a score of 3 to 6 on the modified Rankin Scale at 3 months. We assessed relationship of demographic, clinical, angiographic characteristics, and hemorrhage with functional dependence despite successful revascularization.Two hundred and twenty-eight patients with successful revascularization had clinical outcome follow-up. The rates of functional dependence with endovascular success were 48.6% for Trevo thrombectomy and 58.0% for Merci thrombectomy. Age (odds ratio, 1.04; 95% confidence interval, 1.02-1.06 per 1-year increase), National Institutes of Health Stroke Scale score (odds ratio, 1.08; 95% confidence interval, 1.02-1.15 per 1-point increase), and symptom onset to endovascular treatment time (odds ratio, 1.11; 95% confidence interval, 1.01-1.22 per 30-minute delay) were predictors of functional dependence despite successful revascularization. Symptom onset to reperfusion time beyond 5 hours was associated with functional dependence. All subjects with symptomatic intracranial hemorrhage had functional dependence.One half of patients with successful mechanical thrombectomy do not have good outcomes. Age, severe neurological deficits, and delayed endovascular treatment were associated with functional dependence despite successful revascularization. Our data support efforts to minimize delays to endovascular therapy in patients with acute ischemic stroke to improve outcomes.http://www.clinicaltrials.gov. Unique identifier: NCT00318071, NCT01088672, and NCT01270867.
| S-EPMC4160889 | biostudies-literature
Project description:BackgroundSince large-vessel occlusion (LVO)-related acute ischemic strokes (AIS) are associated with more severe deficits, we hypothesize that the endovascular thrombectomy (ET) may disproportionately benefit stroke-related dependence and death.MethodsTo delineate LVO-AIS impact, systematic search identified studies measuring dependence or death [modified Rankin Scale (mRS) 3-6] or mortality following ischemic stroke among consecutive patients presenting with both LVO and non-LVO events within 24?h of symptom onset.ResultsAmong 197 articles reviewed, 2 met inclusion criteria, collectively enrolling 1,467 patients. Rates of dependence or death (mRS 3-6) within 3-6?months were higher after LVO than non-LVO ischemic stroke, 64 vs. 24%, odds ratio (OR) 4.46 (CI: 3.53-5.63, p?<?0.0001). Mortality within 3-6?months was higher after LVO than non-LVO ischemic stroke, 26.2 vs. 1.3%, OR 4.09 (CI: 2.5-6.68), p?<?0.0001. Consequently, while LVO ischemic events accounted for 38.7% (CI: 21.8-55.7%) of all acutely presenting ischemic strokes, they accounted for 61.6% (CI: 41.8-81.3%) of poststroke dependence or death and 95.6% (CI: 89.0-98.8%) of poststroke mortality. Using literature-based projections of LVO cerebral ischemia patients treatable within 8?h of onset, ET can be used in 21.4% of acutely presenting patients with ischemic stroke, and these events account for 34% of poststroke dependence and death and 52.8% of poststroke mortality.ConclusionLVOs cause a little more than one-third of acutely presenting AIS, but are responsible for three-fifths of dependency and more than nine-tenths of mortality after AIS. At the population level, ET has a disproportionate benefit in reducing severe stroke outcomes.
| S-EPMC5715197 | biostudies-literature