Large-vessel Ischemic Stroke Research Articles

The Non-Targeted Lipidomic-Based Classifier Reveals Two Candidate Biomarkers for Ischemic Stroke in Hypertensive Individuals.

Traditional clinical risk factors are insufficient to estimate the residual risk of large-vessel ischemic stroke. Non-targeted lipidomic techniques provide an opportunity to evaluate these risks. Plasma samples were collected from 113 hypertensive individuals, including 55 individuals at high risk of ischemic stroke and 58 matched individuals, in a prospective nested case-control cohort. To identify dysregulated lipid metabolites, we conducted multivariate and univariate analyses. A classifier based on a cross-validated procedure was employed to select the optimal combination of lipid species and their ratios. We identified 23 dysregulated lipid species in patients with and without ischemic stroke, including 16 (69.6%) up-regulated and 7 (30.4%) down-regulated lipid species. Through internal cross-validation, the optimal combination of two lipid features (phosphatidylcholine 34:2 and triglyceride 18:1/18:1/22:1 / phosphatidylcholine 34:2, referred to as ischemic stroke-related 2 lipid features - IS2LP) was selected, leading to a more precise prediction probability for ischemic stroke within 3.9 years. In the comparison of different risk factors, the traditional risk score, the IS2LP risk score, and the combination of the traditional risk score with IS2LP yield AUC values of 0.613(95% CI:0.509-0.717), 0.833(95% CI:0.755-0.911), and 0.843(95% CI:0.777-0.916), respectively. The combination of the traditional risk score and IS2LP exhibited significantly improved discriminative performance, with an integrated discrimination improvement (IDI) of 0.31 (p<0.001) and a continuous net reclassification improvement (NRI) of 1.06 (p < 0.001) compared to the traditional risk score. We identified new lipidomic biomarkers associated with the futural event of large-vessel ischemic stroke. These lipid species could serve as potential blood biomarkers for assessing the residual risk of ischemic stroke in hypertensive individuals.

MMP-9 release into collateral blood vessels before endovascular thrombectomy to assess the risk of major intracerebral haemorrhages and poor outcome for acute ischaemic stroke: a proof-of-concept study

Matrix metalloproteinases (MMPs) are implied in blood-brain barrier degradation and haemorrhagic transformation following ischaemic stroke, but their local relevance in the hyperacute disease phase is unknown. We aimed to examine ultra-early MMP-9 and MMP-2 release into collateral blood vessels, and to assess its prognostic value before therapeutic recanalisation by endovascular thrombectomy (EVT). We report a cross-sectional proof-of-concept study including patients undergoing EVT for large-vessel ischaemic stroke at the University Hospital Würzburg, Germany. We obtained liquid biopsies from the collateral circulation before recanalisation, and systemic control samples. Laboratory workup included quantification of MMP-9 and MMP-2 plasma concentrations by cytometric bead array, immunohistochemical analyses of cellular MMP-9 and MMP-2 expression, and detection of proteolytic activity by gelatine zymography. The clinical impact of MMP concentrations was assessed by stratification according to intracranial haemorrhagic lesions on postinterventional computed tomography (Heidelberg Bleeding Classification, HBC) and early functional outcome (modified Rankin Scale, mRS). We used multivariable logistic regression, receiver-operating-characteristic (ROC) curves, and fixed-level estimates of test accuracy measures to study the prognostic value of MMP-9 concentrations. Between August 3, 2018, and September 16, 2021, 264 matched samples from 132 patients (86 [65.2%] women, 46 [34.8%] men, aged 40-94 years) were obtained. Median (interquartile range, IQR) MMP-9 (279.7 [IQR 126.4-569.6] vs 441 [IQR 223.4-731.5] ng/ml, p<0.0001) but not MMP-2 concentrations were increased within collateral blood vessels. The median MMP-9 expression level of invading neutrophils was elevated (fluorescence intensity, arbitrary unit: 2276 [IQR 1007-5086] vs 3078 [IQR 1108-7963], p=0.0018). Gelatine zymography experiments indicated the locally confined proteolytic activity of MMP-9 but not of MMP-2. Pretherapeutic MMP-9 release into stroke-affected brain regions predicted the degree of intracerebral haemorrhages and clinical stroke severity after recanalisation, and independently increased the odds of space-occupying parenchymal haematomas (HBC1c-3a) by 1.54 times, and the odds of severe disability or death (mRS ≥5at hospital discharge) by 2.33 times per 1000ng/ml increase. Excessive concentrations of MMP-9 indicated impending parenchymal haematomas and severe disability or death with high specificity. Measurement of MMP-9 within collateral blood vessels is feasible and identifies patients with stroke at risk of major intracerebral haemorrhages and poor outcome before therapeutic recanalisation by EVT, thereby providing evidence of the concept validity of ultra-early local stroke biomarkers. This work was funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) and the Interdisciplinary Centre for Clinical Research (IZKF) at the University of Würzburg.

Cerebral microbleeds and risk of symptomatic hemorrhagic transformation following mechanical thrombectomy for large vessel ischemic stroke.

In patients with acute ischemic stroke (AIS) treated with endovascular therapy (EVT), the association of pre-existing cerebral small vessel disease (cSVD) with symptomatic intracerebral hemorrhage (sICH) remains controversial. We tested the hypothesis that the presence of cerebral microbleeds (CMBs) and their burden would be associated with sICH after EVT of AIS. We conducted a retrospective study combining cohorts of patients that underwent EVT between January 1st 2015 and January 1st 2020. CMB presence, burden, and other cSVD markers were assessed on a pre-treatment MRI, evaluated independently by two observers. Primary outcome was the occurrence of sICH. 445 patients with pretreatment MRI were included, of which 70 (15.7%) demonstrated CMBs on baseline MRI. sICH occurred in 36 (7.6%) of all patients. Univariate analysis did not demonstrate an association between CMB and the occurrence of sICH (7.5% in CMB+ group vs 8.6% in CMB group, p = 0.805). In multivariable models, CMBs' presence was not significantly associated with increased odds for sICH (-aOR- 1.19; 95% CI [0.43-3.27], p = 0.73). Only ASPECTs (aOR 0.71 per point increase; 95% CI [0.60-0.85], p < 0.001) and collaterals status (aOR 0.22 for adequate versus poor collaterals; 95% CI [0.06-0.93], p 0.019) were independently associated with sICH. CMB presence and burden is not associated with increased occurrence of sICH after EVT. This result incites not to exclude patients with CMBs from EVT. The risk of sICH after EVT in patients with more than10 CMBs will require further investigation. Registration-URL: http://www. gov ; Unique identifier: NCT01062698.

Abstract WP7: Utilization and Outcomes Associated With DAPT and ASA Monotherapy Amongst Hospitalizations With Large Vessel Occlusion: A Nationwide Cross-Sectional Analysis

Background: In clinical trials like SPS3, MATCH, CHANCE, and POINT, dual antiplatelet treatment (DAPT) has been compared to aspirin (ASA) alone for preventing symptomatic large vessel occlusion (LVO) and ischemic strokes. Based on the effect size in the aforementioned studies, nationwide research may provide a more complete assessment of outcomes and relationships and help fill knowledge gaps. We used a nationwide inpatient sample to evaluate the outcomes of symptomatic LVO among patients using DAPT versus ASA monotherapy. Methods: We performed a cross-sectional study of a nationwide inpatient sample (2003-2014) in adult LVO hospitalizations. The patients taking DAPT and ASA on admission were identified using ICD-9-CM code. The univariate analysis (chi-square test) and multivariable survey logistic regression analyses were performed to compare mortality, morbidity, discharge (home vs transfer to short-term hospital, skilled nursing facility, and home health care), and disability to calculate odds ratio with 95% CI using SAS 9.4. Results: Of 4,224,924 hospitalizations, 1.24% and 7.38% were on DAPT and ASA, respectively. In comparison to ASA monotherapy, DAPT users were associated with lower prevalence of mortality (2.2% vs 3.1%) and morbidity (3.8% vs 3.9%) with similar prevalence of discharge to the non-home (58.8% vs 58.8%), (p&lt;0.0001). On weighted analysis, use of DAPT vs. ASA was associated with lower odds of mortality (DAPT: OR 0.45; 95%CI 0.39-0.51; ASA: 0.61, 0.58-0.64), morbidity (DAPT: 0.54, 0.49-0.61, ASA: 0.56, 0.54-0.59), discharge to non-home (DAPT: 0.78, 0.75-0.82, ASA: 0.80, 0.79-0.82), and disability (DAPT: 0.76, 0.73-0.80, ASA: 0.80, 0.78-0.82) compared to non-users. Conclusion: This comprehensive national investigation revealed that DAPT resulted in more favorable outcomes for individuals with symptomatic large vessel occlusion. There is a need for additional prospective studies to validate the findings and ascertain the most suitable population at risk for primary prevention of stroke.

Abstract WP153: Factors Affecting Length of ICU Stay After Endovascular Thrombectomy for Acute Large Vessel Ischemic Stroke

Introduction: The advent of endovascular thrombectomy (EVT) for acute large vessel occlusion (LVO) ischemic stroke has reduced the overall ICU length of stay (LoS), especially for patients undergoing successful reperfusion. Prolonged ICU LoS is reported to be associated with worse clinical outcomes, but factors associated with prolonged LoS after MT are not established. Methods: A retrospective analysis of 499 patients undergoing EVT at a single large comprehensive stroke center from January 2015 to May 2020 was performed. Demographics, procedure variables, ICU LoS, ICU complications, and modified Rankin scale at discharge were collected. Multiple regression was used to identify independent variables affecting the ICU LoS. Additional analysis using t-test assuming unequal variances was performed for select variables. Results: The median age was 72 [61-82], 254 (51%) male &amp; median NIHSS was 16 [10-20]. The average door-to-puncture time was 104 ±28 mins and the average procedure time 43.9 ±28.7. General anesthesia (GA) was administered in 257 (51%) patients. Successful reperfusion (TICI 2c-3) was achieved in 334 (67%) patients. Median ICU LoS was 3 days [1-5]. Patients with mRS 0-2 at discharge (33%) had shorter ICU LoS (2.8 vs 5.7, P&lt;0.001). ASPECTS &lt; 7 (6.9 vs 4.6, P=0.03), use of GA (6.2 vs 3.3 days, P&lt;0.001) and ICU complications such as pulmonary embolism (PE) and pneumonia (10 vs 4 days; p &lt;0.001) significantly increased the ICU LoS. Successful reperfusion significantly reduced ICU LoS (4.2 vs 5.8 days, p=0.015). After adjusting for age, sex, baseline NIHSS and ASPECTS, both the procedure time (b= 0.03, P=0.02) and final TICI score (b= -0.76, P=0.001) were independently associated with prolonged ICU LoS (R2=0.1, F=4, P&lt;0.001). Conclusion: Pre-procedural factors such as poor ASPECTS (&lt; 7), procedural factors such as the use of GA, prolonged procedure time, and TICI 0-2b reperfusion, and ICU complications such as pneumonia and PE are associated with prolonged ICU LoS.

Clinical Uncertainty in Large Vessel Occlusion ischemic stroke (CULVO): Does automated perfusion scanning make a difference? Protocol of an intrarater and interrater agreement study.

Guidelines recommend the use of perfusion computed tomography (CT) to identify emergent large vessel ischemic stroke (ELVIS) patients who are likely to benefit from endovascular thrombectomy (EVT) if they present within 6-24 hour (late window) of stroke onset. We aim to determine if the interrater and intrarater reliability among physicians when recommending EVT is significantly different when perfusion CT or non-perfusion CT is reviewed. A total of 30 non-consecutive patients will be selected from our institutional database comprising 3144 cranial CT scans performed for acute stroke symptoms January 2018 to August 2022. The clinical and radiologic data of the 30 patients will be presented in random order to a group of 29 physicians in two separate sessions at least three weeks apart. In each session, the physicians will evaluate each patient once with automated perfusion images and once without. We will use non-overlapping 95% confidence intervals and difference in agreement classification as criteria to suggest a difference between the Gwet AC1 statistics (κG). The results obtained from this study, combined with the clinical outcomes data of patients categorized through the two imaging techniques and a cost-effectiveness analysis, will offer a comprehensive evaluation of the clinical utility of perfusion CT neuroimaging. Should there be no significant disparity in the reliability of decisions made by clinicians using the two neuroimaging protocols, it may be necessary to revise existing recommendations regarding neuroimaging in the later time window to align with these findings.

Perfusion vs non-perfusion computed tomography imaging in the late window of emergent large vessel ischemic stroke: A systematic review and meta-analysis.

Guidelines recommend the treatment of emergent large vessel ischemic stroke (ELVIS) patients presenting beyond 6 hours of last known well time with endovascular thrombectomy (EVT) based on perfusion computed tomography (CT) neuroimaging. We compared the outcomes (long-term good clinical outcomes, symptomatic intracranial hemorrhage (sICH), and mortality) of ELVIS patients according to the type of CT neuroimaging they underwent. We searched the following databases: Medline, Embase, CENTRAL, and Scopus from January 1, 2015, to June 14, 2023. We included studies of late-presenting ELVIS patients undergoing EVT that had with data for non-perfusion and perfusion CT neuroimaging. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Data were pooled using a random effects model. We found 7 observational cohorts. Non-perfusion versus perfusion CT was not statistically significantly different for both long-term clinical (n = 3,224; RR: 0.96; 95% CI 0.86 to 1.06; I2 = 18%) and sICH (n = 3,724; RR: 1.08 95% CI 0.60 to 1.94; I2 = 76%). Perfusion CT had less mortality (n = 3874; RR: 1.22; 95% CI 1.07 to 1.40; I2 = 0%). The certainty of these findings is very low because of limitations in the risk of bias, indirectness, and imprecision domains of the Grading of Recommendations, Assessment, Development and Evaluations. The use of either non-perfusion or perfusion CT neuroimaging may have little to no effect on long-term clinical outcomes and sICH for late-presenting EVT patients. Perfusion CT neuroimaging may be associated with a reduced the risk of mortality. Evidence uncertainty warrants randomized trial data.

Mendelian randomization of stroke risk after total hip and knee replacements.

Previous epidemiological studies have indicated an increased risk of neurovascular diseases in patients following total hip and knee replacements. However, definitive conclusions regarding the increased risk of stroke post-replacement remain elusive. Therefore, we conducted a two-sample Mendelian randomization study to investigate the causal relationship between total hip and knee replacements and stroke. We utilized summary data from publicly available genome-wide association studies (GWAS). Data concerning total hip replacements (THR, N = 319,037) and total knee replacements (TKR, N = 252,041) were sourced from the Genetics of Osteoarthritis (GO) Consortium. Stroke-related data were obtained from the International Stroke Genetics Consortium, encompassing any stroke (AS), any ischemic stroke (AIS), large vessel ischemic stroke (LV-IS), cardioembolic ischemic stroke (CE-IS), and small vessel ischemic stroke (SV-IS). Our primary causal inference method was the inverse variance weighted (IVW) approach, supplemented by weighted median and MR-Egger regression as secondary inference methods. We utilized the MR-PRESSO global test for outlier detection, Cochran's Q statistic to assess heterogeneity, and assessed the multiplicity and stability of our findings using p-values from MR-PRESSO and MR-Egger regressions, and the leave-one-out method, respectively. We identified significant genetic associations between THR and both AS (IVW p = 0.0001, OR = 1.08, 95% CI = 1.04-1.12) and AIS (IVW p = 0.0016, OR = 1.07, 95% CI = 1.03-1.12). Significant associations were also observed between TKR and AS (IVW p = 0.0002, OR = 1.08, 95% CI = 1.04-1.12), as well as AIS (IVW p = 0.0005, OR = 1.15, 95% CI = 1.06-1.24). Our findings genetically support an increased risk of stroke following total hip and knee replacements. However, further studies are necessary to elucidate the specific mechanisms underlying stroke episodes post-replacement.

Abstract 204: On Old Dogs and New Tricks: Connecticut Perfusion Predicts Hemorrhagic Transformation After Thrombectomy

Introduction Hemorrhagic transformation is a major complication of large vessel occlusion (LVO) recanalization after mechanical thrombectomy in acute ischemic stroke. We investigated whether computed tomography perfusion (CTP) derived hypoperfusion index ratio correlates with the rate of hemorrhagic transformation. Methods We conducted a retrospective cohort analysis of a prospectively maintained patient database. Included patients underwent mechanical thrombectomy for large vessel ischemic stroke from January 2019 to December 2022. Patients were separated into 2 groups depending on whether or not hemorrhagic transformation developed. Hypoperfusion index ratio on admission CTP was determined using VizAI software. Data were analyzed using Chi‐square and Mann‐Whitney U tests. Results Among the 289 patients included (median age, 72.5; 41.5% female), 55 (19%) had hemorrhagic transformation. Patients with hemorrhagic transformation had a significantly higher hypoperfusion index ratio (median, 0 vs 0.2; P= 0.004) compared with those with no hemorrhagic transformation. Multivariable analysis showed that for every 0.1 increase in the hypoperfusion index ratio, there was a significant 4.64‐fold increase in hemorrhagic transformation (OR 4.64; 95% CI 1.40 to 15.18; p=0.011). Conclusion In patients with LVO who underwent mechanical thrombectomy, a higher hypoperfusion index ratio on admission CTP was associated with an increased rate of hemorrhagic transformation. This suggests that the hypoperfusion index ratio could be used as a predictor for hemorrhagic transformation after mechanical thrombectomy.

AutoML accurately predicts endovascular mechanical thrombectomy in acute large vessel ischemic stroke.

Automated machine learning or autoML has been widely deployed in various industries. However, their adoption in healthcare, especially in clinical settings is constrained due to a lack of clear understanding and explainability. The aim of this study is to utilize autoML for the prediction of functional outcomes in patients who underwent mechanical thrombectomy and compare it with traditional ML models with a focus on the explainability of the trained models. A total of 156 patients of acute ischemic stroke with Large Vessel Occlusion (LVO) who underwent mechanical thrombectomy within 24 h of stroke onset were included in the study. A total of 34 treatment variables including clinical, demographic, imaging, and procedure-related data were extracted. Various conventional machine learning models such as decision tree classifier, logistic regression, random forest, kNN, and SVM as well as various autoML models such as AutoGluon, MLJAR, Auto-Sklearn, TPOT, and H2O were used to predict the modified Rankin score (mRS) at the time of patient discharge and 3 months follow-up. The sensitivity, specificity, accuracy, and AUC for traditional ML and autoML models were compared. The autoML models outperformed the traditional ML models. For the prediction of mRS at discharge, the highest testing accuracy obtained by traditional ML models for the decision tree classifier was 74.11%, whereas for autoML which was obtained through AutoGluon, it showed an accuracy of 88.23%. Similarly, for mRS at 3 months, the highest testing accuracy of traditional ML was that of the SVM classifier at 76.5%, whereas that of autoML was 85.18% obtained through MLJAR. The 24-h ASPECTS score was the most important predictor for mRS at discharge whereas for prediction of mRS at 3 months, the most important factor was mRS at discharge. Automated machine learning models based on multiple treatment variables can predict the functional outcome in patients more accurately than traditional ML models. The ease of clinical coding and deployment can assist clinicians in the critical decision-making process. We have developed a demo application which can be accessed at https://mrs-score-calculator.onrender.com/.

Endovascular thrombectomy with or without intravenous thrombolysis in large-vessel ischemic stroke: A non-inferiority meta-analysis of 6 randomised controlled trials

BackgroundIt is unclear whether thrombectomy alone is non-inferior to thrombectomy with intravenous thrombolysis in patients with acute ischemic stroke due to large-vessel occlusion. PurposeTo perform a comprehensive, trial-level data, non-inferiority meta-analysis of randomised controlled trials comparing endovascular thrombectomy with and without intravenous thrombolysis in patients with ischemic stroke due to large-vessel occlusion of anterior circulation. MethodsThe prespecified primary efficacy outcome was functional independence, defined as a modified Rankin scale (mRS)score of 0 to 2 at 90 days. The two prespecified non-inferiority margins were risk differences of −10% and − 5%. The study was registered in PROSPERO (CRD42022361110) and conducted according to PRISMA guidelines. ResultsSix trials were included in this analysis (DIRECT-MT, DEVT, SKIP, MR CLEAN-NO IV, DIRECT-SAFE and SWIFT DIRECT) comprising a total of 2334 patients. Functional independence at 90 days was achieved by 570 (49·0%) of 1164 patients in the thrombectomy alone group and 595 (50·9%) of 1170 patients in the thrombectomy with thrombolysis group (pooled risk difference − 0·02, [95% CI -0·06–0·02]). Combined thrombectomy and thrombolysis were associated with significantly higher rates of successful reperfusion (pooled risk ratio 0·96 [95% CI, 0·93–0·99], p = 0·006) but at the expense of a significantly increased risk of overall - but not symptomatic - intracranial haemorrhage (pooled risk ratio 0·87 [95% CI, 0·77–0·98], p = 0·02). ConclusionsCompared with a combined treatment approach, thrombectomy alone was non-inferior at −10% non-inferiority margin, but not at a − 5% inferiority margin for functional independence. Current evidence cannot exclude clinically important differences between the two treatment approaches.

Predictors for large vessel recanalization before stroke thrombectomy: the HALT score

BackgroundLarge vessel recanalization (LVR) before endovascular therapy (EVT) for acute large vessel ischemic strokes is a poorly understood phenomenon. Better understanding of predictors for LVR is important for optimizing stroke...

Osteoarthritis is associated with lower likelihood of receiving stroke thrombectomy despite similar post-thrombectomy outcomes: a national study (P8-5.023)

<h3>Objective:</h3> To investigate whether osteoarthritis (OA) impacts stroke thrombectomy treatment rates or post-thrombectomy outcomes. <h3>Background:</h3> Osteoarthritis (OA) is a common condition affecting as many as 30 million Americans. While OA is not a direct risk factor for acute ischemic stroke, it can be associated with pre-stroke disability and influence patient selection for endovascular thrombectomy (EVT). Whether OA impacts post-EVT outcomes is currently unknown. <h3>Design/Methods:</h3> This was a retrospective study of the 2016–2019 National Inpatient Sample database. Adult patients with large vessel acute ischemic stroke were included. Patients with osteoarthritis were identified. Primary outcome was rate of EVT treatment in OA patients versus non-OA patients. Secondary outcomes include rates of discharge to home and in-hospital mortality after EVT treatment. Propensity score-matching (PSM) and multivariable logistic regression models were used to account for possible confounders. <h3>Results:</h3> 252,505 large vessel ischemic stroke patients were identified, of whom 21,500 patients (8.5% of study population) were diagnosed with OA. After PSM for 27 clinical variables, OA patients were 21.3% less likely to receive EVT than non-OA patients (14.4% vs. 18.3%, respectively; p&lt;0.001). In multivariable logistic regression analysis, OA was associated with 31% lower odds of receiving EVT (OR 0.69 [95%CI 0.63 to 0.76], p&lt;0.001), an effect size second only to dementia and larger than that of any other comorbidity captured in this study. Among patients who received EVT, multivariable logistic regression models showed that OA was not associated with different odds of being discharged home (OR 1.01 [95%CI 0.83 to 1.23], p=0.92); however, OA was associated with lower odds of in-hospital mortality compared to non-OA patients (OR 0.74 [95%CI 0.55 to 0.99], p=0.044). <h3>Conclusions:</h3> Large vessel ischemic stroke patients with OA were significantly less likely to receive EVT therapy despite similar post-EVT outcomes. These results warrant further investigation and prompt a critical review of current patient selection practices for EVT. <b>Disclosure:</b> Mr. Chen has received research support from National Institues of Health. Mr. Khunte has nothing to disclose. Dr. Colasurdo has nothing to disclose. Gaurav Jindal has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Penumbra. Ajay Malhotra, 9122 has nothing to disclose. Dheeraj Gandhi has nothing to disclose. Dr. Chaturvedi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astra Zeneca. Dr. Chaturvedi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for University of Calgary. Dr. Chaturvedi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Heart Association. Dr. Chaturvedi has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Ramar &amp; Paradiso. Dr. Chaturvedi has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Cole, Scott, Kissane. The institution of Dr. Chaturvedi has received research support from NINDS.

Cerebrovascular Manifestations of SARS-CoV-2: A Comprehensive Review.

The risks of cerebrovascular manifestations due to SARS-CoV-2 infection are significantly increased within the first 6 months of the infection. Our work aims to give an update on current clinical aspects of diagnosis and treatment of cerebrovascular manifestations during acute and long-term SARS-CoV-2 infection. The incidence of acute ischemic stroke and haemorrhagic stroke during acute SARS-CoV-2 patients is estimated at 0.9 to 4.6% and 0.5-0.9%, respectively, and were associated with increased mortality. The majority presented with hemiparesis, dysarthria, sensory deficits, and a NIHSS score within 5-15. In addition, beyond the first 30 days of infection people with COVID-19 exhibited increased risk of stroke. During acute phase, age, hypertension, diabetes, and medical history of vascular disease were increased in patients with COVID-19 with new onset of cerebrovascular manifestations, while during long-COVID-19, the risk of cerebrovascular manifestations were found increased regardless of these factors. The management of patients with large-vessel ischemic stroke fulfilling the intravenous thrombolysis criteria are successfully treated according to the guidelines, while hyperosmolar therapy is typically administered in 4- to 6-h intervals. In addition, prophylaxis of anticoagulation therapy is associated with a better prognosis and low mortality during acute and post hospital discharge of patients with COVID-19. In this work, we provide a comprehensive review of the current literature on acute and post-acute COVID-19 cerebrovascular sequelae, symptomatology, and its pathophysiology mechanisms. Moreover, we discuss therapeutic strategies for these patients during acute and long-term care and point populations at risk. Our findings suggest that older patients with risk factors such as hypertension, diabetes, and medical history of vascular disease are more likely to develop cerebrovascular complications.

Initial Experience Using the New pHLO 0.072-inch Large-Bore Catheter for Direct Aspiration Thrombectomy in Acute Ischemic Stroke.

A direct aspiration, first pass technique (ADAPT) has been introduced as a rapid and safe thrombectomy strategy in patients with intracranial large vessel occlusion (LVO). The aim of the study is to determine the technical feasibility, safety, and functional outcome of ADAPT using the newly released large bore pHLO 0.072-inch aspiration catheter (AC; Phenox). We performed a retrospective analysis of data collected prospectively (October 2019-November 2021) from 2 comprehensive stroke centers. Accessibility of the thrombus, vascular recanalization, time to recanalization, and procedure-related complications were evaluated. National Institutes of Health stroke scale scores at presentation and discharge and the modified Rankin scale (mRS) score at 90 days post-procedure were recorded. Twenty-five patients (14 female, 11 male) with occlusions of the anterior circulation were treated. In 84% of cases, ADAPT led to successful recanalization with a median procedure time of 28 minutes. In the remaining cases, successful recanalization required (to a total of 96%; modified thrombolysis in cerebral infarction score 2b/3) the use of stent retrievers. No AC-related complications were reported. Other complications included distal migration of the thrombus, requiring a stent-retriever, and symptomatic PH2 hemorrhage in 16% and 4%, respectively. After 3 months, 52% of the patients had mRS scores of 0-2 with an overall mortality rate of 20%. Results from our retrospective case series revealed that thrombectomy of LVOs with pHLO AC is safe and effective in cases of large-vessel ischemic stroke. Rates of complete or near-complete recanalization after the first pass with this method might be used as a new benchmark in future trials.

Prehospital technologies for early stroke detection - A review.

The rate of neural circuitry loss in a typical large vessel occlusion well emphasizes that 'Time is Brain'. Every untreated minute in a large vessel ischaemic stroke results in loss of 1.9 million neurons and 13.8 billion synapses. As such, it is essential to optimize the flow-limiting steps in delivering the current standard of care. The current diagnostic model involves recognition of symptoms by patients, followed by access to Emergency Medical Services and subsequent physical examination and neuroimaging in the Emergency Department. With more than 50% of stroke patients using Emergency Medical Services as the first point of care contact, it can be deduced that the outcome of the 'stroke chain of survival' can be improved by addressing the bottleneck of prehospital stroke diagnosis. Here we present a review of the existing technologies.

Associations of Osteoarthritis With Thrombectomy Utilization and Outcomes for Large Vessel Acute Ischemic Stroke.

Osteoarthritis and other musculoskeletal disorders are the leading causes of disability in the United States. While osteoarthritis is not a direct risk factor for stroke, osteoarthritis may impact patient selection for endovascular thrombectomy (EVT) due to prestroke disability. This study investigates associations of osteoarthritis with EVT utilization and outcomes. This was a large-scale cross-sectional study of the 2016 to 2019 National Inpatient Sample database. Adult patients with anterior large vessel ischemic strokes were identified. Patient demographics, stroke risk factors, stroke etiology, presence of osteoarthritis, medical comorbidities, EVT, intravenous thrombolysis treatments, and discharge destinations were recorded. Primary outcome was the rate of EVT treatment. Secondary outcomes include rates of discharge to home and in-hospital mortality. Propensity score matching and multivariable logistic regression models were used to account for possible confounders. Two hundred fifty-two thousand five hundred five patients were identified, of whom 8.5% (21 500 patients) had osteoarthritis. After propensity score matching for 32 clinical variables, osteoarthritis patients were found to be 17.3% less likely to receive EVT than non-osteoarthritis patients (14.4% versus 17.3%, respectively; P<0.001). In multivariable logistic regression analysis, osteoarthritis was associated with 22.6% lower odds of receiving EVT (OR, 0.77 [95% CI, 0.70-0.86]; P<0.001), an effect size larger than any medical comorbidity captured in this study other than dementia and nonstroke neurological disease. Among those treated with EVT, multivariable logistic regression models showed that osteoarthritis was not associated with different odds of being discharged home (OR, 0.99 [95% CI, 0.81-1.21]; P=0.93); however, osteoarthritis was marginally associated with lower odds of in-hospital mortality (OR, 0.74 [95% CI, 0.54-1.01]; P=0.054). Large vessel ischemic stroke patients with osteoarthritis were significantly less likely to receive EVT therapy despite similar post-EVT outcomes. These results warrant further investigation and prompt a critical review of current patient selection practices for stroke EVT therapy, specifically for patients with baseline disability due to musculoskeletal conditions such as osteoarthritis.

Exploring the risk factors for ischemic cerebrovascular disease in systemic lupus erythematosus: A single-center case-control study.

ObjectivesIschemic cerebrovascular disease (ICVD) is one of the most common and severe complications in systemic lupus erythematosus (SLE). We aim to explore the risk factors for ICVD in SLE and to assess their associated clinical characteristics.MethodsIn this study, 44 lupus patients with ICVD (ICVD-SLE) and 80 age- and sex-matched lupus patients without ICVD (non-ICVD-SLE) who were hospitalized in our center between 2014 and 2021 were enrolled. A comprehensive set of clinical and socio-demographic data was recorded. In the ICVD-SLE group, the modified Rankin score (mRS) at 90 days after the occurrence of ICVD, the brain MRI, and arterial ultrasonography findings were collected. Group comparisons were made with continuous variables using an independent t-test or the Mann–Whitney test, and with categorical variables using the chi-square test or Fisher exact test. Multivariate logistic regression analysis was performed to identify the risk factors for ICVD in SLE. Patients with ICVD-SLE were divided into three subgroups according to the gradations of intracranial arterial stenosis (ICAS). The subgroup comparisons were performed by one-way ANOVA test or Kruskal–Wallis test.ResultsOf the 44 patients with ICVD, 45% had a large-vessel ischemic stroke, 50% had a symptomatic lacunar stroke, and 9% had a transient ischemic attack. 2 (4.5%) had both large-vessel ischemic stroke and symptomatic lacunar stroke. Multivariate logistic regression analysis showed that cutaneous vasculitis (OR=7.36, 95% CI=2.11–25.65), anticardiolipin antibody (aCL) (OR=4.38, 95% CI=1.435–13.350), and lupus anticoagulant (LA) (OR=7.543,95% CI=1.789–31.808) were the risk factors, and hydroxychloroquine (HCQ) therapy (OR=0.198, 95% CI=0.078–0.502) was the protective factor, after controlling for confounders. During the analysis of the subgroups, no significant difference was observed between the patients in the group without internal carotid arterial occlusion (ICAS) and those with severe ICAS except for diagnostic delay. However, patients in the moderate ICAS group were older when SLE occurred (P<0.01), had a longer diagnostic delay (P<0.01), a lower percentage of hypocomplementemia (P=0.05) and steroids and HCQ therapy (P=0.01, P=0.05, respectively), a trend toward lower mRS score, but a higher incidence of carotid atherosclerotic plaque (P<0.01), when compared with the other two subgroups.ConclusionCutaneous vasculitis and antiphospholipid antibodies (aPLs) are associated with an increased risk of ICVD, while HCQ therapy may provide protection against ICVD in SLE. The ICVD in younger lupus patients is associated with complement-mediated inflammation and poorer outcome, and require immunosuppressive therapy, whereas the ICVD in elderly patients are characterized by moderate ICAS and carotid atherosclerotic plaques.

Age and composition of the thrombus retrieved by mechanical thrombectomy from patients with acute ischemic stroke are associated with revascularization and clinical outcomes

IntroductionUnderstanding the composition of stroke thrombi retrieved by mechanical thrombectomy is essential to clarify the pathogenesis of stroke. However, it is difficult to evaluate thrombus composition precisely and objectively. Immunohistochemical staining was used to evaluate thrombus composition and age. Materials and methodsConsecutive thrombi (n = 108) retrieved from patients who underwent mechanical thrombectomy for acute large-vessel ischemic stroke were retrospectively analyzed. Lytic features of granulocytes and CD163 were estimated as indicators of the age of the cardioembolic (CE) thrombus. ResultsThe stroke subtypes were as follows: CE, 74 cases; large artery atherosclerosis, 11; undetermined etiology, 12; and other determined etiology, 11. There were no statistical differences in thrombi composition according to stroke subtypes. The fibrin area was positively correlated with the red blood cell (RBC) and platelet areas. The following analysis was performed using CE only. Regarding age, the thrombus was judged as fresh in 30.0 % and older in 70.0 % based on the lytic features. The RBC areas of older thrombi were smaller than those of fresh thrombi. The puncture-to-reperfusion time of older thrombi was longer than that of fresh thrombi. Platelet-rich thrombi were associated with a greater number of maneuvers, a smaller prevalence of TICI 3, and unfavorable functional outcomes compared to platelet-poor thrombi. The number of CD163 positive cells in thrombi with anticoagulants was higher than in those without anticoagulants. ConclusionThrombus composition correlated with revascularization and clinical outcomes. The composition of an acute ischemic thrombus may reflect the pathophysiology of stroke and influence treatment efficacy.

Intravenous thrombolysis before thrombectomy for acute ischaemic stroke

Before endovascular therapy, patients with ischaemic stroke due to occlusion of large arteries were treated with only intravenous thrombolysis, specifically alteplase. Intravenous thrombolysis recanalised about 25% of occluded large arteries, resulting in fewer than 30% of patients achieving functional independence (modified Rankin Score [mRS] 0–2) at 90 days. 1 Menon BK Al-Ajlan FS Najm M et al. Association of clinical, imaging, and thrombus characteristics with recanalization of visible intracranial occlusion in patients with acute ischemic stroke. JAMA. 2018; 320: 1017-1026 Crossref PubMed Scopus (117) Google Scholar In 2015, second-generation thrombectomy devices, in combination with intravenous thrombolysis, were proven to recanalise about 70–80% of arteries and improve rates of functional independence by 20–30% compared with intravenous thrombolysis alone. 2 Goyal M Menon BK van Zwam WH et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016; 387: 1723-1731 Summary Full Text Full Text PDF PubMed Scopus (3448) Google Scholar Some in the field began to ask if intravenous thrombolysis is even necessary for these patients. Intravenous thrombolysis can delay the more often definitive therapy of endovascular therapy. Moreover, intravenous thrombolysis could increase symptomatic intracerebral haemorrhage, or distal migration of thrombi, rendering them inaccessible to thrombectomy. Intravenous thrombolysis certainly incurs substantial cost. 3 de Souza AC Sebastian IA Zaidi WAW et al. Regional and national differences in stroke thrombolysis use and disparities in pricing, treatment availability, and coverage. Int J Stroke. 2022; (published online March 18.)https://doi.org/10.1177/17474930221082446 Crossref PubMed Scopus (2) Google Scholar Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trialThrombectomy alone was not shown to be non-inferior to intravenous alteplase plus thrombectomy and resulted in decreased reperfusion rates. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients. Full-Text PDF Endovascular thrombectomy versus standard bridging thrombolytic with endovascular thrombectomy within 4·5 h of stroke onset: an open-label, blinded-endpoint, randomised non-inferiority trialWe did not show non-inferiority of direct endovascular thrombectomy compared with bridging therapy. The additional information from our study should inform guidelines to recommend bridging therapy as standard treatment. Full-Text PDF