Acute ischaemic stroke is a major cause of death and disability worldwide. Once diagnosed, treatment is generally limited to intravenous thrombolysis (IVT), endovascular thrombectomy, or both. Intravenous thrombolysis has theoretical benefits (enhancing reperfusion, dissolving smaller thrombi) and harms (delaying time to endovascular intervention, allergic reaction, increased bleeding risk).

To assess the effects of endovascular thrombectomy with IVT versus without IVT on functional independence (defined as a modified Rankin Scale score (mRS) < 3) within 90 days in people with acute ischaemic stroke.

We searched CENTRAL, MEDLINE, Embase, Scopus, LILACS, Google Scholar, the International HTA database, and two trial registries to November 2023.

We included randomised controlled trials of adults with acute ischaemic stroke who received endovascular therapy and were randomised to either intravenous thrombolysis within 4.5 hours or a control.

Outcomes were: functional independence (mRS score < 3), excellent functional outcome (mRS score < 2), mortality, asymptomatic intracranial haemorrhage, symptomatic intracranial haemorrhage, successful revascularisation (thrombolysis in cerebral infarction (TICI) grades 2b to 3), and complete revascularisation (TICI grade 3 only), within 90 days.

We used the Cochrane RoB 2 tool to assess the following potential sources of bias for each outcome: bias arising from the randomisation process; bias due to deviations from intended interventions; bias due to missing outcome data; bias in measurement of the outcome; and bias in selection of the reported result.

We pooled outcome data using the random-effects model and performed meta-analyses using the Mantel-Haenszel method. We assessed the statistical heterogeneity of pooled data by visually inspecting forest plots to consider the direction and magnitude of effects, and used the Chi2 test and I2 statistic to quantify the heterogeneity. We used GRADE to assess the certainty of evidence.

We included six studies, with a total of 2336 participants (1166 control and 1170 intervention). The mean age was 71 years. There were 1034 women and 1302 men. Four studies used alteplase 0.9 mg/kg, one study used alteplase 0.6 mg/kg, and one study used either alteplase 0.9 mg/kg or tenecteplase 0.25 mg/kg. There were no important variations in the outcomes reported across studies.

All six studies were at overall low risk of bias for each outcome. There was probably little to no difference in functional independence between the IVT and control groups (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.92 to 1.14; P = 0.62; 6 studies, 2336 participants; moderate-certainty evidence). There was no evidence of a difference in excellent functional outcome between the IVT and control groups (RR 0.99, 95% CI 0.92 to 1.05; P = 0.67; 6 studies, 2336 participants; high-certainty evidence). There was no evidence of a difference in mortality between the IVT and control groups (RR 0.94, 95% CI 0.78 to 1.14; P = 0.54; 6 studies, 2336 participants; high-certainty evidence). There was no evidence of a difference in asymptomatic intracranial haemorrhage between the IVT and control groups (RR 1.13, 95% CI 1.00 to 1.29; P = 0.06; 6 studies, 2334 participants; high-certainty evidence). There was probably little to no difference in symptomatic intracranial haemorrhage between the IVT and control groups (RR 1.20, 95% CI 0.84 to 1.70; P = 0.31; 6 studies, 2336 participants; moderate-certainty evidence). There was a higher rate of successful revascularisation with IVT over control (RR 1.04, 95% CI 1.01 to 1.08; P = 0.008; 6 studies, 2326 participants; high-certainty evidence). There was a higher rate of complete revascularisation with IVT over control (RR 1.14, 95% CI 1.02 to 1.28; P = 0.02; 5 studies, 2037 participants; high-certainty evidence). Limitations included: differences in inclusion and exclusion criteria between studies (e.g. age thresholds, pre-existing comorbidities or baseline functional status, time periods, diagnostic imaging, specific vessels); specific endovascular device used; thrombolysis medication and dose; and potential conflict of interest, as multiple study authors reported receiving funding or fees from pharmaceutical companies. For functional independence, assessed as an mRS score < 3 within 90 days, we downgraded the certainty of evidence by one level due to a high I2 value, indicating that heterogeneity may be substantial for this outcome. For symptomatic intracranial haemorrhage within 90 days, we downgraded the certainty of evidence by one level because the 95% CI included both important benefits and important harms.

The evidence does not currently support a clear benefit or harm for routine intravenous thrombolysis amongst people receiving endovascular thrombectomy. Amongst participants receiving endovascular thrombectomy, IVT did not demonstrate evidence of a difference in functional independence, excellent functional outcome, mortality, and asymptomatic intracranial haemorrhage, or symptomatic intracranial haemorrhage, when compared with no IVT. However, IVT did result in a higher rate of successful and complete revascularisation when compared with no IVT. Future research should include more high-quality trials to further evaluate the role of intravenous thrombolysis in people receiving endovascular thrombectomy to provide more robust data and further narrow the confidence intervals. Future research should also identify whether time- and person-specific factors influence the effect of IVT amongst those receiving endovascular thrombectomy.

None REGISTRATION: Gottlieb M, Carlson JN, Westrick J, Peksa GD. Endovascular thrombectomy with versus without intravascular thrombolysis for acute ischaemic stroke. Cochrane Database of Systematic Reviews. 2024;2:1465-1858.

The comparative efficacy of tenecteplase versus alteplase in achieving early recanalization (ER) before mechanical thrombectomy (MT) for large-vessel occlusion (LVO) remains uncertain.

This study was a retrospective analysis of prospectively collected data of consecutive patients with LVO underwent intravenous thrombolysis (IVT) and brain angiography between January 2022 and December 2023. ER was defined as ≥ 50% reperfusion or absence of retrievable thrombus on initial angiography.

146 patients received tenecteplase and 307 received alteplase. Tenecteplase shortened door-to-IVT time (33 vs. 39 min, P < 0.001) and door-to-puncture time (97 vs. 109 min, P = 0.039) compared to alteplase. Overall ER rates did not differ significantly (17.1% vs. 12.1%, P = 0.223). However, a significant interaction was observed between thrombolytic agent and IVT-to-puncture time (Pinteraction = 0.034): tenecteplase achieved higher ER rates when IVT-to-puncture time was < 60 min (17.2% vs. 5.0%, aOR, 4.13 [95% CI 1.24-13.74]). With IVT-to-puncture time ≥ 60 min, ER rates were similar (17.2% vs. 16.8%, aOR 0.91 [95% CI 0.43-1.91]). No ER differences were noted across occlusion sites, clot burden, NIHSS, sex, and age. At 3 months, tenecteplase reduced disability rates (mRS 0-3: 73.5% vs. 65.7%, P = 0.041). Functional independence (mRS 0-2) was 57.4% with tenecteplase and 53.1% with alteplase (P = 0.301).

Real-world observations reveal tenecteplase has increased ER rates compared to alteplase within 1 h of IVT and reduced disability in LVO patients. Further randomized trials are warranted to evaluate the effect of tenecteplase rapid bridging mechanical thrombectomy.

For patients with large vessel occlusion and carotid tandem lesions, the best treatment approach is not clear. Intravenous thrombolysis in addition to endovascular treatment might increase the risk of intracranial haemorrhage and decrease effectiveness in this cohort, particularly for patients receiving acute carotid stenting. In an individual participant data meta-analysis of six randomised controlled trials (RCTs), no clear benefit was seen of intravenous thrombolysis in patients with large-vessel occlusion stroke who were eligible for direct endovascular treatment. We aimed to assess whether the presence of carotid tandem lesions would modify the safety and efficacy of intravenous thrombolysis in patients who could directly undergo endovascular treatment, in a prespecified secondary subgroup analysis of this individual participant data meta-analysis.

We previously did a systematic review and individual participant data meta-analysis of six RCTs comparing intravenous thrombolysis plus endovascular treatment with endovascular treatment alone in patients with anterior circulation stroke presenting directly at centres capable of endovascular treatment. The principal investigators of the six identified trials provided individual participant data for 2313 patients, which we pooled. The primary outcome was functional outcome, as measured by 90-day modified Rankin Scale score. Heterogeneity of treatment effect was assessed in the intention-to-treat population using ordinal regression models, with interaction terms for treatment and carotid tandem lesions, followed by a mixed-effects meta-analysis. A sensitivity analysis included only patients who received acute carotid stenting. The study is registered with PROSPERO, CRD42023411986.

Of the 2313 patients who were included in the individual patient data meta-analysis, 2267 (98%) had data for carotid tandem lesions, of whom 1136 were assigned intravenous thrombolysis plus endovascular treatment and 1131 were assigned endovascular treatment alone. 340 patients had carotid tandem lesions (161 intravenous thrombolysis plus endovascular treatment, 179 endovascular treatment alone) and 1927 did not have tandem lesions (975 intravenous thrombolysis plus endovascular treatment, 952 endovascular treatment alone). The median age of patients was 71 years (IQR 62-78); 1003 (44·2%) patients were female and 1264 (55·8%) were male. Compared with endovascular treatment alone, the addition of intravenous thrombolysis did not improve functional outcome in patients with tandem lesions (adjusted common odds ratio [acOR] 1·00, 95% CI 0·62-1·62) or in those without tandem lesions (1·17, 0·99-1·37). No significant heterogeneity of treatment effect was observed between patients with tandem lesions and those without (ratio of odds ratios 0·81, 95% CI 0·48-1·37; pinteraction=0·44). Intracranial haemorrhage rates in patients with tandem lesions were similar for those receiving intravenous thrombolysis plus endovascular treatment (58 [37%] of 155) and for those receiving endovascular treatment alone (65 [38%] of 172; acOR 0·95, 95% CI 0·59-1·54). Rates of symptomatic haemorrhage in patients with tandem lesions were also similar (six [4%] of 159 for those receiving intravenous thrombolysis plus endovascular treatment vs ten [6%] of 179 for those receiving endovascular treatment alone; 0·81, 0·28-2·30). The sensitivity analysis including only patients who received acute carotid stenting showed similar results to the primary analysis.

The findings of this prespecified secondary analysis of an individual patient data meta-analysis show that, in patients with carotid tandem lesions, the addition of intravenous thrombolysis to endovascular treatment was not associated with an increase in the risk of bleeding or with modification of functional outcome. These data suggest that the presence of tandem lesions should not solely influence the decision to administer intravenous thrombolysis to patients who can directly undergo endovascular treatment.

Stryker, Boehringer Ingelheim, and Amsterdam University Medical Centers, University of Amsterdam.

Interactions of particles with unsteady non-linear viscous flows has widespread implications in physiological and biomedical systems. One key application where this plays a fundamental role is in the mechanism and etiology of embolic strokes. Specifically, there is a need to better understand how large occlusive emboli traverse complex vascular geometries, and block a vessel disrupting blood supply. Existing modeling approaches resort to key simplifications in terms of embolic particle shape, size, and their coupling to fluid flow. Here, we devise a novel computational model for resolving embolus-hemodynamics interactions for large non-spherical emboli approaching near occlusive regimes in anatomically real vascular segment. The formulation relies on extending an immersed finite element approach, coupled with a six degree-of-freedom particle dynamics model. The geometric complexities and their manifestation in embolus-flow and embolus-wall interactions are handles using a parametric shape representation, and projection of vessel signed distance fields on the particle boundaries. We illustrate our methodology and algorithmic details, as well as present examples of benchmark cases and convergence of our technique. Thereafter, we demonstrate a parametric study of large emboli for LVO strokes, showing that our methodology can capture the non-linear tumbling dynamics of emboli originating form their interactions with the flow and vessel walls; and resolve near-occlusive scenarios involving lubrication effects around the embolus and flow re-routing to non-occludes branches. This is a key methodological advancement in stroke modeling, as to the best of our knowledge this is the first modeling framework for LVO stroke and occlusion biofluid mechanics. Finally, even though we present our framework from the perspective of LVO strokes, the methodology as developed is broadly generalizable to two-way coupled fluid-particle interaction in unsteady viscous flows for a wide range of applications.

In this study, we aimed to investigate the risk factors and impact of poststroke pneumonia (PSP) on mortality and functional outcome in patients with acute ischemic stroke (AIS) after endovascular thrombectomy (EVT).

This was a post hoc analysis of a prospective randomized trial (Direct intraarterial thrombectomy in order to revascularize AIS patients with large-vessel occlusion efficiently in Chinese tertiary hospitals: a multicenter randomized clinical trial). Patients with AIS who completed EVT were evaluated for the occurrence of PSP during the hospitalization period and their modified Rankin Scale (mRS) scores at 90 days after AIS. Logistic regression analysis was conducted to investigate the independent predictors of PSP. Propensity score matching was conducted for the PSP and non-PSP groups by using the covariates resulting from the logistic regression analysis. The associations between PSP and outcomes were analyzed. The outcomes included 90-day poor functional outcome (mRS scores > 2), 90-day mortality, and early 2-week mortality.

A total of 639 patients were enrolled, of whom 29.58% (189) developed PSP. Logistic regression analysis revealed that history of chronic heart failure (unadjusted odds ratio [OR] 2.011, 95% confidence interval [CI] 1.026-3.941; P = 0.042), prethrombectomy reperfusion on initial digital subtraction angiography (OR 0.394, 95% CI 0.161-0.964; P = 0.041), creatinine levels at admission (OR 1.008, 95% CI 1.000-1.016; P = 0.049), and National Institutes of Health Stroke Scale at 24 h (OR 1.023, 95% CI 1.007-1.039; P = 0.004) were independent risk factors for PSP. With propensity scoring matching, poor functional outcome (mRS > 2) was more common in patients with PSP than in patients without PSP (81.03% vs. 71.83%, P = 0.043) at 90 days after EVT. The early 2-week mortality of patients with PSP was lower (5.74% vs. 12.07%, P = 0.038). But there was no statistically significant difference in 90-day mortality between the PSP group and non-PSP group (22.41% vs. 14.94%, P = 0.074). The survivorship curve also shows no statistical significance (P = 0.088) between the two groups.

Nearly one third of patients with AIS and EVT developed PSP. Heart failure, higher creatinine levels, prethrombectomy reperfusion, and National Institutes of Health Stroke Scale at 24 h were associated with PSP in these patients. PSP was associated with poor 90-day functional outcomes in patients with AIS treated with EVT.

When treating acute ischemic stroke due to large-vessel occlusion, both mechanical thrombectomy and intravenous (IV) thrombolysis carry the risk of intracerebral hemorrhage.

This study aimed to delve deeper into the risk of intracerebral hemorrhage and its subtypes associated with mechanical thrombectomy with or without IV thrombolysis to contribute to better decision-making in the treatment of acute ischemic stroke due to large-vessel occlusion.

PubMed, EMBASE, and Scopus databases were searched for relevant studies from inception to September 6, 2023.

The eligibility criteria included randomized clinical trials or post hoc analysis of randomized controlled trials that focused on patients with acute ischemic stroke in the anterior circulation. After screening 4870 retrieved records, we included 9 studies (6 randomized controlled trials and 3 post hoc analyses of randomized controlled trials) with 3241 patients.

The interventions compared were mechanical thrombectomy + IV thrombolysis versus mechanical thrombectomy alone, with the outcome of interest being any form of intracerebral hemorrhage and symptomatic intracerebral hemorrhage after intervention. A common definition for symptomatic intracerebral hemorrhage was pooled from various classification systems, and subgroup analyses were performed on the basis of different definitions and anatomic descriptions of hemorrhage. The quality of the studies was assessed using the revised version of Cochrane Risk of Bias 2 assessment tool. Meta-analysis was performed using the random effects model.

Eight studies had some concerns, and 1 study was considered high risk. Overall, the risk of symptomatic intracerebral hemorrhage was comparable between mechanical thrombectomy + IV thrombolysis and mechanical thrombectomy alone (risk ratio, 1.24 [95% CI, 0.89-1.72]; P = .20), with no heterogeneity across studies. Subgroup analysis of symptomatic intracerebral hemorrhage showed a non-significant difference between 2 groups based on the National Institute of Neurological Disorders and Stroke (P = .3), the Heidelberg Bleeding Classification (P = .5), the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (P = .4), and the European Cooperative Acute Stroke Study III (P = .7) criteria. Subgroup analysis of different anatomic descriptions of intracerebral hemorrhage showed no difference between the 2 groups. Also, we found no difference in the risk of any intracerebral hemorrhage between two groups (risk ratio, 1.10 [95% CI, 1.00-1.21]; P = .052) with no heterogeneity across studies.

There was a potential for performance bias in most studies.

In this systematic review and meta-analysis, the risk of any intracerebral hemorrhage and symptomatic intracerebral hemorrhage, including its various classifications and anatomic descriptions, was comparable between mechanical thrombectomy + IV thrombolysis and mechanical thrombectomy alone.

Mechanical thrombectomy (MT) is the gold standard treatment for large vessel occlusion (LVO). A vital factor that might influence MT outcomes is the use of intravenous thrombolysis (IVT). A few clinical trials in this domain thus far have not yielded consistent outcomes. We conducted this meta-analysis to synthesize collective evidence in this regard.

The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines were followed, and we performed a comprehensive literature search of four databases (PubMed, Scopus, Web of Science, Cochrane CENTRAL). For outcomes constituting continuous data, the mean difference (MD) and its standard deviation (SD) were pooled. For outcomes constituting dichotomous data, the frequency of events and the total number of patients were pooled as the risk ratio (RR).

Seven clinical trials with a total of 2317 patients are included in this meta-analysis. Six trials are randomized, and one trial was nonrandomized. No significant differences were found between MT plus IVT and MT alone in successful recanalization (RR 1.04, 95% Confidence Interval (CI) [0.92 to 1.17], P = 0.53), 90-day functional independence (RR 1.03, 95% CI [0.90 to 1.19], P = 0.65), symptomatic intracranial hemorrhage (sICH) (RR 1.22, 95% CI [0.84 to 1.75], P = 0.30), or mortality (RR 0.94, 95% CI [0.76 to 1.18], P = 0.61).

The current evidence does not favor either MT plus IVT or MT alone for LVO except for the procedural time. More trials are needed in this regard, and certain factors should be considered when comparing the two approaches.

This meta-analysis aimed to evaluate the safety and efficacy of direct endovascular therapy (EVT) and bridging therapy (EVT with preceding intravenous thrombolysis i.e. IVT), in acute anterior circulation, large vessel occlusion stroke.

Following the PRISMA guidelines, a systematic literature review of the English language literature was conducted using PubMed, Cochrane CENTRAL, SCOPUS and ClinicalTrials.gov. Outcomes of interest were measured by the modified Rankin Scale (mRS), and included: no disability (mRS0), no significant disability despite some symptoms (mRS1), slight disability (mRS2), moderate disability (mRS3), moderately severe disability (mRS4), severe disability (mRS5), mortality (mRS6). Additionally, we inspected patients having excellent outcome, functional independence outcome, and poor outcome, along with successful reperfusion and intracranial hemorrhage. We calculated pooled risk ratios (RRs) and their corresponding 95% confidence intervals (CI).

A total of seven RCTs involving 2,392 patients were finally included. The chances of achieving successful reperfusion were significantly more with IVT+EVT as compared to EVT alone (RR: 0.97; 95% CI: 0.94, 1.00; P=0.03) (I2=0%). There was no significant difference in the number of patients having outcomes ranging from mRS0 to mRS6, excellent outcome, functional independence, poor outcome or incidence of intracranial hemorrhage, who underwent either EVT alone or IVT+EVT.

Additional trials are needed to determine if the absence of significant differences is due to insufficient sample size or if the combination therapy is truly not beneficial.

The use of alteplase (ALT) bridging to endovascular mechanical thrombectomy (MT) has become the standard approach in treating patients with large vessel occlusion (LVO) stroke. Tenecteplase (TNK) has emerged as an equivalent fibrinolytic agent in treating ischemic stroke due to its remarkable pharmacological characteristics. This study aimed to compare the use of intravenous TNK to ALT bridging to MT in patients with LVO.

We included observational and randomized controlled trials of patients with LVO who received bridging TNK versus ALT before undergoing MT. Efficacy outcomes included functional independence which is indicated by a modified Rankin Scale [mRS] score of 0-2 at 90 days. Radiological outcomes included the rate of successful recanalization post-MT (Modified Treatment in Cerebral Ischemia [mTICI] score of 2b/3) and the rate of pre-MT recanalization, indicated by an mTICI of 2b/3 at the first angiographic assessment. The all-cause mortality at 90 days (mRS of 6) was considered the primary safety outcome, while the symptomatic intracranial hemorrhage rate was reported as an adverse event.

We identified 5 comparative observational studies and 1 randomized controlled trial, totaling 4,186 patients with LVO. The crude odds ratio (OR) for post-MT recanalization in patients with LVO who received TNK was comparable to those who received ALT (OR = 1.14; 95% CI: 0.57-2.27, I2 = 54%). The rate of pre-MT recanalization was significantly higher in those given TNK as a bridging therapy to MT compared to those who received ALT (OR = 2.66; 95% CI: 1.60-4.41, I2 = 0%; p <0.001). Functional independence at 90 days was not significantly different between patients with stroke who received TNK and those who were given ALT before MT (OR = 1.41; 95% CI: 0.84-2.35; I2 = 45%). The 90-day mortality was similar between patients with LVO who received TNK and those who were given ALT prior to undergoing MT (OR = 0.74; 95% CI: 0.46-1.21; I2 = 0%).

Patients with LVO who received TNK as the primary fibrinolytic agent bridging to MT demonstrated higher rates of pre-MT recanalization, similar rates in post-MT recanalization and equivalent functional independence outcomes at 90 days compared to those who received ALT. The administration of TNK before MT showed comparable results in the 90-day all-cause mortality rate compared to those who received ALT. These results warrant further trials for TNK to be used as a superior fibrinolytic agent to ALT in LVO-MT candidates.

Strokes rank as the second most common cause of mortality and disability in the human population across the world. Currently, available methods of treating or preventing strokes have significant limitations, primarily the need to use high doses of drugs due to the presence of the blood-brain barrier. In the last decade, increasing attention has been paid to the capabilities of nanotechnology. However, the vast majority of research in this area is focused on the mechanisms of anticancer and antiviral effects of nanoparticles. In our opinion, not enough attention is paid to the neuroprotective mechanisms of nanomaterials. In this review, we attempted to summarize the key molecular mechanisms of brain cell damage during ischemia. We discussed the current literature regarding the use of various nanomaterials for the treatment of strokes. In this review, we examined the features of all known nanomaterials, the possibility of which are currently being studied for the treatment of strokes. In this regard, the positive and negative properties of nanomaterials for the treatment of strokes have been identified. Particular attention in the review was paid to nanoselenium since selenium is a vital microelement and is part of very important and little-studied proteins, e.g., selenoproteins and selenium-containing proteins. An analysis of modern studies of the cytoprotective effects of nanoselenium made it possible to establish the mechanisms of acute and chronic protective effects of selenium nanoparticles. In this review, we aimed to combine all the available information regarding the neuroprotective properties and mechanisms of action of nanoparticles in neurodegenerative processes, especially in cerebral ischemia.

To this date, whether to administer intravenous thrombolysis (IVT) prior to endovascular thrombectomy (EVT) for stroke patients still stirs some debate. We aimed to systematically update the evidence from randomized trials comparing EVT alone vs EVT with bridging IVT.

We searched MEDLINE, EMBASE, and the Cochrane Library to identify randomized controlled trials (RCTs) comparing EVT with or without IVT in patients presenting with stroke secondary to a large vessel occlusion. We conducted meta-analyses using random-effects models to compare functional independence, mortality, and symptomatic intracranial hemorrhage (sICH), between EVT and EVT with IVT. We assessed risk of bias using the Cochrane risk-of-bias tool and certainty of evidence for each outcome using the GRADE approach.

Of 11,111 citations, we included 6 studies with a total of 2336 participants. We found low-certainty evidence of possibly a small decrease in the proportion of patients with functional independence (risk difference [RD] -2.0%, 95% CI -5.9% to 2.0%), low-certainty evidence that there is possibly a small increase in mortality (RD 1.0%, 95% CI -2.2% to 4.7%), and moderate-certainty evidence that there is probably a decrease in sICH (RD -1.0%, 95% CI -1.6% to .7%) for patients with EVT alone compared to EVT plus IVT, respectively.

Low-certainty evidence shows that there is possibly a small decrease in functional independence, low-certainty evidence shows that there is possibly a small increase in mortality, and moderate-certainty evidence that there is probably a decrease in sICH for patients with EVT alone compared to EVT plus IVT.

Although Endovascular Thrombectomy (EVT) significantly improves the prognosis of Acute Ischemic Stroke (AIS) patients with large vessel occlusion, the mortality rate remains higher. This study aimed to construct and validate a nomogram for predicting 90-day all-cause mortality in AIS patients with large vessel occlusion and who have undergone EVT.

AIS patients with large vessel occlusion in the anterior circulation who underwent EVT from May 2017 to December 2022 were included. 430 patients were randomly split into a training group (N=302) and a test group (N=128) for the construction and validation of our nomogram. In the training group, multivariate logistic regression analysis was performed to determine the predictors of 90-day all-cause mortality. The C-index, calibration plots, and decision curve analysis were applied to evaluate the nomogram performance.

Multivariate logistic regression analysis revealed neurological deterioration during hospitalization, age, baseline National Institutes of Health Stroke Scale (NIHSS) score, occlusive vessel location, malignant brain edema, and Neutrophil-to-lymphocyte Ratio (NLR) as the independent predictors of 90-day all-cause mortality (all p ≤ 0.039). The C-index of the training and test groups was 0.891 (95%CI 0.848-0.934) and 0.916 (95% CI: 0.865-0.937), respectively, showing the nomogram to be well distinguished. The Hosmer-Lemeshow goodness-of-fit test revealed the p-values for both the internal and external verification datasets to be greater than 0.5.

Our nomogram has incorporated relevant clinical and imaging features, including neurological deterioration, age, baseline NIHSS score, occlusive vessel location, malignant brain edema, and NLR ratio, to provide an accurate and reliable prediction of 90-day all-cause mortality in AIS patients undergoing EVT.

Approximately 20-30% of patients with acute ischemic stroke, caused by large intracranial vessel occlusion, have a tandem lesion, defined as simultaneous presence of high-grade stenosis or occlusion of the cervical internal carotid artery and thromboembolic occlusion of the intracranial terminal internal carotid artery or its branches, usually the middle cerebral artery. Patients with tandem lesions have usually worse outcomes than patients with single intracranial occlusions, and intravenous thrombolysis is less effective in these patients. Although endovascular thrombectomy is currently a cornerstone therapy in the management of acute ischemic stroke due to large vessel occlusion, the optimal management of extracranial carotid lesions in tandem occlusion remains controversial. Acute placement of a stent in the cervical carotid artery lesion is the most used therapeutic strategy compared with stented balloon angioplasty and thrombectomy alone without carotid artery revascularization; however, treatment strategies in these patients are often more complex than with single occlusion, so treatment decisions can change based on clinical and technical considerations. The aim of this review is to analyze the results of different studies and trials, investigating the periprocedural neurointerventional management of patients with tandem lesions and the safety, efficacy of the different technical strategies available as well as their impact on the clinical outcome in these patients, to strengthen current recommendations and thus optimize patient care.

The major concern for bridging intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) is the potentially increased risk of symptomatic intracerebral hemorrhage (sICH). Thus we conducted this study to clarify whether evaluation of individual bleeding risk could assist in the decision to perform IVT before EVT.

The study was a subgroup analysis of a randomized trial evaluating the safety and efficacy of IVT before EVT. The SEDAN (blood Sugar, Early infarct signs and (hyper) Dense cerebral artery sign, Age, and National Institutes of Health Stroke Score) score, GRASPS (Glucose, Race, Age, Sex, systolic blood Pressure, and Severity of stroke) score, and SITS-SICH (Safe Implementation of Thrombolysis in Stroke-Symptomatic Intracerebral Hemorrhage) score were used to evaluate individual bleeding risk. The primary outcome was functional independence, defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days. Binary logistic regression with an interaction term was used to estimate treatment effect modification to clarify whether direct EVT was more beneficial in patients with a higher sICH risk, while adjunctive IVT before EVT was more beneficial in patients with a lower sICH risk.

Among 658 randomized patients, 639 (361 men, 56.5%; median age 69 (IQR 61-76) years) were included in the study. With the SITS-SICH score as an example, adjusted OR for functional independence with EVT alone was 1.12 (95% CI 0.68 to 1.82) in patients with a lower sICH risk (SITS-SICH score 0-4) and 0.92 (0.53 to 1.60) in those with a higher sICH risk (SITS-SICH score 5-15). There were no treatment-by-bleeding-risk interactions for all dichotomized mRS outcomes based on the three scores (all p>0.05).

We found no evidence that clinicians can decide whether to omit IVT before EVT based on an individualized assessment of bleeding risk.

A potential benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is pre-interventional reperfusion. Currently, there are few data on the occurrence of pre-interventional reperfusion in patients randomized to IVT or no IVT before MT.

SWIFT DIRECT (Solitaire With the Intention For Thrombectomy Plus Intravenous t-PA vs DIRECT Solitaire Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke) was a randomized controlled trial including acute ischemic stroke IVT eligible patients being directly admitted to a comprehensive stroke center, with allocation to IVT with MT versus MT alone. The primary endpoint of this analysis was the occurrence of pre-interventional reperfusion, defined as a pre-interventional expanded Thrombolysis in Cerebral Infarction score of ≥2a. The effect of IVT and potential treatment effect heterogeneity were analyzed using logistic regression analyses.

Of 396 patients, pre-interventional reperfusion occurred in 20 (10.0%) patients randomized to IVT with MT, and in 7 (3.6%) patients randomized to MT alone. Receiving IVT favored the occurrence of pre-interventional reperfusion (adjusted OR 2.91, 95% CI 1.23 to 6.87). There was no IVT treatment effect heterogeneity on the occurrence of pre-interventional reperfusion with different strata of Randomization-to-Groin-Puncture time (p for interaction=0.33), although the effect tended to be stronger in patients with a Randomization-to-Groin-Puncture time >28 min (adjusted OR 4.65, 95% CI 1.16 to 18.68). There were no significant differences in rates of functional outcomes between patients with and without pre-interventional reperfusion.

Even for patients with proximal large vessel occlusions and direct access to MT, IVT resulted in an absolute increase of 6% in rates of pre-interventional reperfusion. The influence of time strata on the occurrence of pre-interventional reperfusion should be studied further in an individual patient data meta-analysis of comparable trials.

clinicaltrials.gov NCT03192332.

This study aimed to investigate the long-term functional outcome of patients with different degrees of thrombus perviousness (TP) undergoing mechanical thrombectomy alone and those undergoing combined intravenous thrombolysis (IVT) plus mechanical thrombectomy.

We conducted a retrospective analysis of consecutive patients with acute ischemic stroke due to large vessel occlusion who underwent mechanical thrombectomy alone or bridging therapy between January 2016 and October 2020. TP was quantified by thrombus attenuation increase (TAI) on admission computed tomography angiography compared with non-contrast computed tomography. After dichotomization of TAI as higher or lower perviousness, Fisher exact tests were performed to estimate the associations of different therapies with favorable functional outcomes [Modified Ranking Scale score at 90 days (90-day mRS) of 0 to 2].

A total of 73 patients were included in our study. 35 (47.9%) thrombi were classified as higher-perviousness clots with TAI of ≥ 24 HU, and the other 38 thrombi were lower-perviousness clots. A favorable outcome with a 90-day mRS of 0 to 2 was observed in 32 patients. In patients with thrombi of lower perviousness, favorable outcome was more common in the bridging therapy group than in the thrombectomy-alone group (p = 0.013), whereas in patients with thrombi of higher perviousness, the long-term neurological outcome did not significantly differ between two therapy groups (p = 0.094).

Patients with thrombi of lower perviousness were recommended to undergo intravenous alteplase followed by endovascular thrombectomy, and those with thrombi of higher perviousness could undergo thrombectomy alone.

Despite the high incidence of acute ischemic stroke (AIS) in cancer patients, there is still no consensus about the safety of recanalization therapies in this cohort.

In this observational study, our aim was to investigate the bleeding risk after acute recanalization therapy in AIS patients with active malignancy.

We retrospectively analyzed observational data of 1016 AIS patients who received intravenous thrombolysis with rtPA (IVT) and/or endovascular therapy (EVT) between January 2017 and December 2020 with a focus on patients with active malignancy. The primary safety endpoint was the occurrence of stroke treatment-related major bleeding events, that is, symptomatic intracranial hemorrhage (SICH) and/or relevant systemic bleeding. The primary efficacy endpoint was neurological improvement during hospital stay (NI).

None of the 79 AIS patients with active malignancy suffered from stroke treatment-related systemic bleeding. The increased rate (7.6% versus 4.7%) of SICH after therapy compared to the control group was explained by confounding factors. A total of nine patients with cerebral tumor manifestation received acute stroke therapy, two of them suffered from stroke treatment-related intracranial hemorrhage remote from the tumor, both asymptomatic. The group of patients with active malignancy and the control group showed comparable rates of NI.

Recanalization therapy in AIS patients with active malignancy was not associated with a higher risk for stroke treatment-related systemic or intracranial bleeding. IVT and/or EVT can be regarded as a safe therapy option for AIS patients with active malignancy.

Intravenous thrombolysis (IVT) with alteplase or tenecteplase before mechanical thrombectomy is the recommended treatment for large-vessel occlusion acute ischemic stroke. There are divergent data on whether these agents differ in terms of early recanalization (ER) rates before mechanical thrombectomy, and little data on their potential differences stratified by ER predictors such as IVT to ER evaluation (IVT-to-EReval) time, occlusion site and thrombus length.

We retrospectively compared the likelihood of ER after IVT with tenecteplase or alteplase in anterior circulation large-vessel occlusion acute ischemic stroke patients from the PREDICT-RECANAL (alteplase) and Tenecteplase Treatment in Ischemic Stroke (tenecteplase) French multicenter registries. ER was defined as a modified Thrombolysis in Cerebral Infarction score 2b-3 on the first angiographic run, or noninvasive vascular imaging in patients with early neurological improvement. Analyses were based on propensity score overlap weighting (leading to exact balance in patient history, stroke characteristics, and initial management between groups) and confirmed with adjusted logistic regression (sensitivity analysis). A stratified analysis based on pre-established ER predictors (IVT-to-EReval time, occlusion site, and thrombus length) was conducted.

Overall, 1865 patients were included. ER occurred in 156/787 (19.8%) and 199/1078 (18.5%) patients treated with tenecteplase or alteplase, respectively (odds ratio, 1.09 [95% CI, 0.83-1.44]; P=0.52). A differential effect of tenecteplase versus alteplase on the probability of ER according to thrombus length was observed (Pinteraction=0.003), with tenecteplase being associated with higher odds of ER in thrombi >10 mm (odds ratio, 2.43 [95% CI, 1.02-5.81]; P=0.04). There was no differential effect of tenecteplase versus alteplase on the likelihood of ER according to the IVT-to-EReval time (Pinteraction=0.40) or occlusion site (Pinteraction=0.80).

Both thrombolytics achieved ER in one-fifth of patients with large-vessel occlusion acute ischemic stroke without significant interaction with IVT-to-EReval time and occlusion site. Compared with alteplase, tenecteplase was associated with a 2-fold higher likelihood of ER in larger thrombi.

We aimed to describe the safety and efficacy of mechanical thrombectomy (MT) with or without intravenous thrombolysis (IVT) for patients with tandem lesions and whether using intraprocedural antiplatelet therapy influences MT's safety with IVT treatment.

This is a subanalysis of a pooled, multicenter cohort of patients with acute anterior circulation tandem lesions treated with MT from 16 stroke centers between January 2015 and December 2020. Primary outcomes included symptomatic intracranial hemorrhage (sICH) and parenchymal hematoma type 2. Additional outcomes included hemorrhagic transformation, successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3), complete reperfusion (modified Thrombolysis in Cerebral Infarction score 3), favorable functional outcome (90-day modified Rankin Scale score 0-2), excellent functional outcome (90-day modified Rankin Scale score 0-1), in-hospital mortality, and 90-day mortality.

Of 691 patients, 512 were included (218 underwent IVT+MT and 294 MT alone). There was no difference in the risk of sICH (adjusted odds ratio [aOR], 1.22 [95% CI, 0.60-2.51]; P=0.583), parenchymal hematoma type 2 (aOR, 0.99 [95% CI, 0.47-2.08]; P=0.985), and hemorrhagic transformation (aOR, 0.95 [95% CI, 0.62-1.46]; P=0.817) between the IVT+MT and MT alone groups after adjusting for confounders. Administration of IVT was associated with an increased risk of sICH in patients who received intravenous antiplatelet therapy (aOR, 3.04 [95% CI, 0.99-9.37]; P=0.05). The IVT+MT group had higher odds of a 90-day modified Rankin Scale score 0 to 2 (aOR, 1.72 [95% CI, 1.01-2.91]; P=0.04). The odds of successful reperfusion, complete reperfusion, 90-day modified Rankin Scale score 0 to 1, in-hospital mortality, or 90-day mortality did not differ between the IVT+MT versus MT alone groups.

Our study showed that the combination of IVT with MT for tandem lesions did not increase the overall risk of sICH, parenchymal hematoma type 2, or overall hemorrhagic transformation independently of the cervical revascularization technique used. However, intraprocedural intravenous antiplatelet therapy during acute stent implantation might be associated with an increased risk of sICH in patients who received IVT before MT. Importantly, IVT+MT treatment was associated with a higher rate of favorable functional outcomes at 90 days.

Risk factors and functional outcome of hemorrhagic transformation (HT) after mechanical thrombectomy (MT) are to be elucidated in patients with acute large vessel occlusion stroke.

We retrospectively analyzed data from 88 patients who underwent MT treatment. Independent risk factors of hemorrhagic infarction (HI), parenchymal hematoma (PH) and symptomatic intracranial hemorrhage (sICH) were implemented to determine. Association between HI, PH, sICH and mortality at 90 days after treatment were analyzed.

Of 88 patients, 44.3%had HT (N.=39). 64.1% had HI (N.=25), 35.9% had PH (N.=14) and 12.5% had sICH (N.=11). Independent risk factors for HI were associated with higher NIHSS Score (OR 1.190; 95% CI 1.073~1.319, P=0.001, per 1 score increase), history of coronary heart disease (OR 4.645; 95% CI 1.092~19.758, P=0.038), and use of intravenous thrombolysis (OR 3.438; 95% CI 1.029~11.483, P=0.045). Independent risk factors for PH were associated with higher NIHSS Score (OR 1.227; 95% CI 1.085~1.387, P=0.001, per 1 score increase) and history of oral antiplatelet and/or anticoagulation drugs (OR 6.694; 95% CI 1.245~35.977, P=0.027). Independent risk factors for sICH were associated with higher NIHSS Score (OR 1.393; 95% CI 1.138~1.704, P=0.001, per 1 score increase), increased systolic blood pressure (OR 1.061; 95% CI 1.006~1.120, P=0.030, per 1 mmHg increase) and history of coronary heart disease (OR 13.699; 95% CI 1.019~184.098, P=0.048). Patients who had PH were more likely to cause mortality at 90 days (OR 10.15; 95% CI 1.455~70.914, P=0.019).

Higher NIHSS Score was associated with HI, PH, and sICH. History of coronary heart was associated with HI and sICH. Use of intravenous thrombolysis was associated with HI. History of oral antiplatelet and/or anticoagulation drugs was associated with PH. Increased systolic blood pressure was associated with sICH. PHs was remarkably associated with mortality at 90 days.

Randomized controlled trials comparing endovascular thrombectomy (EVT) versus EVT preceded by intravenous thrombolysis (EVT + IVT) for acute ischemic stroke due to large artery occlusion remain controversial. This systematic review and meta-analysis seek to compare these 2 modalities.

Online Protocol is available at PROSPERO (york.ac.uk) (registration# CRD42022357506). MEDLINE, PubMed, and Embase were searched. The primary outcome was 90-day modified Rankin scale (mRS) ≤2. Secondary outcomes were 90-day mRS ≤1, 90-day mean mRS, National Institutes of Health Stroke Scale (NIHSS) at 1-3 and 3-7 days, 90-day Barthel Index, 90-day EQ-5D-5L (EuroQoL Group 5-Dimension 5-Level), the volume of infarction (mL), successful reperfusion, complete reperfusion, recanalization, 90-day mortality, any intracranial hemorrhage (ICH), symptomatic ICH, embolization in new territory, new infarction, puncture site complications, vessel dissection, and contrast extravasation. The certainty in the evidence was determined by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

Six randomized controlled trials yielding 2332 patients were included, of which 1163 and 1169 underwent EVT and EVT + IVT, respectively. The relative risk (RR) of 90-day mRS ≤2 was similar between the groups (RR = 0.96[0.88, 1.04]; P = 0.28). EVT was non-inferior to EVT + IVT because the lower bond of 95% confidence interval of the risk difference (RD = -0.02 [-0.06, 0.02]; P = 0.36) exceeded the -0.1 non-inferiority margin. The certainty in the evidence was high. The RR of successful reperfusion (RR = 0.96 [0.93, 0.99]; P = 0.006), any ICH (RR = 0.87 [0.77, 0.98]; P = 0.02), and puncture site complications (RR = 0.47 [0.25, 0.88]; P = 0.02) were lower with EVT. For EVT + IVT, the number needed to treat for successful reperfusion was 25, and the number needed to harm for any ICH was 20. The 2 groups were similar in other outcomes.

EVT is non-inferior to EVT + IVT. In centers capable of both EVT and IVT, if timely EVT is feasible, it is reasonable to skip bridging IVT and keep rescue thrombolysis at the discretion of the interventionist for patients presenting within 4.5 hours of anterior ischemic stroke.

Several reports have identified that clinical outcomes such as death or disability in acute ischemic stroke (AIS) patients following intravenous (IV) tissue plasminogen activator (tPA) treatment can vary according to race and ethnicities. We determined the effect of race/ethnicity on rates of arterial recanalization in AIS patients with large vessel occlusion (LVO) after IV tPA.

We analyzed 234 patients with LVO detected on computed tomographic angiography (CTA) who received IV tPA and subsequently underwent angiography for potential thrombectomy. The primary occlusion sites on CTA and digital subtracted angiography (DSA) were compared and a score was given to the level of recanalization with values ranging from 1 (complete recanalization), 2 (partial recanalization), or 3 (no recanalization).The effect of race/ethnicity were assessed for predicting vessel recanalization using the covariates of age, gender, time since stroke onset, tPA dose received, NIHSS (National Institute of Health Stroke Scale) score at baseline, and location of the occlusion, using logistic regression analysis.

Five patients (2.1%) were Hispanic or Latino, 8 (3.4%) Asian, 24 (10.3%) African American, and 197 (84.2%) White. A total of 50% had a distal ICA/proximal M1 occlusion, 20% distal M1 occlusion, and 16% single M2 occlusion. At the primary occlusion site, 44 (18.8%) had complete recanalization on post IV tPA angiogram, 17 (7.3%) had partial recanalization, and 165 (70.5%) had no recanalization. We did not find any association between race/ethnicity and vessel recanalization post IV tPA (Nonwhite combined [OR=1.49, p=0.351]; Asian [OR=1.460, p=0.650]; African American [OR=1.508, p=0.415]; White [OR=0.672, p=0.351]; ethnicity (Hispanic or Latino) [OR= 1.008, p=0.374]); Occlusion location (OR=0.189, p<0.001). Final TICI scores and mRS at 90 days were similar among the different groups.

Approximately 19% of patients had complete recanalization after IV tPA, but race and ethnicity did not seem to have an effect on arterial recanalization. Arterial recanalization was only affected by location of occlusion.

The purpose of this study was to evaluate the effectiveness and safety of drip and ship (DS) for acute ischemic stroke (AIS) by comparing three treatment strategies: 1) patients seen at a primary stroke center, started on emergency intravenous thrombolysis and then transported to a comprehensive stroke center (drip and ship, DS); 2) patients immediately transferred to comprehensive stroke center without starting intravenous thrombolysis, for mechanical thrombectomy (non-drip and ship, non-DS); and 3) patients admitted directly to the comprehensive stroke center for assessment and subsequent bridging thrombolysis (mothership, MS).

We retrospectively reviewed the data of patients that underwent mechanical thrombectomy for AIS from November 2020 to May 2022 at our institution. Patients were divided into three groups: DS, non-DS, and MS. Time course, multimodal CT features and clinical results were compared among the three groups.

The study included 62 patients, with 19, 18, and 25 patients in DS, non-DS, and MS groups, respectively. Baseline characteristics did not differ among the three groups. The DS group had a significantly longer median onset to groin time than the MS group (395 min vs 244 min; P < 0.001), a significantly shorter onset to primary stroke center time than the non-DS group (90 min vs 463 min; P < 0.001), and a longer primary stroke center to groin puncture time than the non-DS group (277 min vs 162 min; P = 0.002). The onset to needle time was longer in the MS group than the DS group (151.2 min vs 111.8 min; P = 0.041). The intravenous thrombolysis to puncture time was shorter in the MS group compared with DS (56 min vs 278 min; P < 0.001). No significant differences were present among groups in post-operative variables measured.

DS is a safe and effective method, with no increased risk of postoperative complications or death compared to non-DS and MS methods. The study provides a reference for the selection of transport modes for AIS patients.

Current published guidelines and meta-analyses comparing endovascular thrombectomy (EVT) alone versus EVT with bridging intravenous thrombolysis (IVT) suggest that EVT alone is non-inferior to EVT with bridging thrombolysis in achieving favourable functional outcome. Because of this controversy, we aimed to systematically update the evidence and meta-analyse data from randomised trials comparing EVT alone versus EVT with bridging thrombolysis, and performed an economic evaluation comparing both strategies.

We will conduct a systematic review of randomised controlled trials comparing EVT with or without bridging thrombolysis in patients presenting with large vessel occlusions. We will identify eligible studies by systematically searching the following databases from inception without any language restrictions: MEDLINE (through Ovid), Embase and the Cochrane Library. The following criteria will be used to assess eligibility for inclusion: (1) adult patients ≥18 years old; (2) randomised patients to EVT alone or to EVT with IVT; and (3) measured outcomes, including functional outcomes, at least 90 days after randomisation. Pairs of reviewers will independently screen the identified articles, extract information and assess the risk of bias of eligible studies. We will use the Cochrane Risk-of-Bias tool to evaluate risk of bias. We will also use the Grading of Recommendations, Assessment, Development and Evaluation approach to assess the certainty in evidence for each outcome. We will then perform an economic evaluation based on the extracted data.

This systematic review will not require a research ethics approval because no confidential patient data will be used. We will disseminate our findings by publishing the results in a peer-reviewed journal and via presentation at conferences.

CRD42022315608.

It is unclear whether thrombectomy alone is non-inferior to thrombectomy with intravenous thrombolysis in patients with acute ischemic stroke due to large-vessel occlusion.

To 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.

The 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.

Six 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).

Compared 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.

Early neurological deterioration (END) is associated with a poor survival after mechanical thrombectomy (MT) in acute ischemic stroke (AIS). To assess risk factors and functional outcomes of END after MT in patients, we analyzed data from 79 patients who received MT with large-vessel occlusion. END after MT in patients is defined as an increase of two points or more in the National Institute of Health Stroke Scale (NIHSS) score, compared with the best neurological status within 7 days. The mechanism of END can be classified into: AIS progression, sICH, and encephaledema. A total of 32 AIS patients (40.5%) had END after MT. Risk factors for END after MT included: history of oral antiplatelet and/or anticoagulation drugs before MT (OR = 9.56,95% CI = 1.02-89.57), higher NIHSS score when admitted to hospital (OR = 1.24, 95% CI = 1.04-1.48), under the subtype of atherosclerotic stroke (OR = 17.36, 95% CI = 1.51-199.56), ASITN/SIR< 2 (OR = 15.78, 95% CI = 1.65-151.26), and prolonged period from AIS onset to the first revascularization (OR = 1.01, 95% CI = 1.00-1.02). AIS patients who had END at early stages were more likely to experience poor outcomes (Modified Rankin Scale [mRS] >2) at 90 days after MT (OR = 6.829, 95% CI = 1.573-29.655). Thus, AIS patients who had experienced END at early stages were more likely to have poor outcomes (mRS >2) at 90 days after MT, and the risk factors of END were connected to the mechanism of END.

Tandem occlusion accounts for 10%-20% of all large vessel occlusion strokes and often yields a poor recanalization rate. The endovascular treatment of tandem lesions is still controversial. This study uses an endovascular treatment strategy, "guided catheter recovery balloon (GRB)" for the treatment of acute anterior circulation tandem occlusion.

A retrospective design was adopted. The population included patients with acute tandem occlusion who received emergency GRB endovascular treatment. And the choice of stenting was made based on intraoperative radiography imaging. Recanalization was evaluated by the thrombolysis in cerebral infarction score after the operation. Three-month modified Rankin Scale follow-up results were recorded, and modified Rankin Scale ≤2 was considered favorable recovery.

A total of 55 patients aged 66.9 ± 8.5 years were enrolled, 37 of whom received stenting. The mean overall recanalization time was 46 minutes. Fifty (90.9%) patients achieved successful recanalization with a thrombolysis in cerebral infarction score of 2b-3. At the 3-month follow-up, the number of patients with favorable functional recovery was 28 (50.9%). The presence of hypertension was correlated with a favorable recovery outcome: 82.1% of the favorable recovery population had hypertension, and 55.6% of the unfavorable outcome population had hypertension (P = 0.033). There was no statistically significant association between stent application and favorable recovery outcomes (P = 0.504).

GRB technique showed a high recanalization rate when applied to the treatment of acute anterior circulation tandem occlusion.

Acute ischemic stroke remains the major cause of death and disability and conclusive evidence of Tenecteplase in treating stroke is lacking.

To conduct a meta-analysis to determine whether Tenecteplase produces better outcomes than Alteplase and a network meta-analysis comparing the different dosing regimens of Tenecteplase.

Searches were made in MEDLINE, CENTRAL, and ClinicalTrials.gov. The outcome measures are recanalization, early neurological improvement, functional outcomes at 90 days (modified Rankin Scale 0-1 and 0-2), intracranial hemorrhage, symptomatic intracranial hemorrhage, and mortality within 90 days from treatment.

Fourteen studies are included in the meta-analyses and 18 studies in the network meta-analyses. In the meta-analysis, Tenecteplase 0.25 mg/kg has significant results in early neurological improvement (OR = 2.35, and 95% CI = 1.16-4.72) and excellent functional outcome (OR = 1.20, and 95% CI = 1.02-1.42). In the network meta-analysis, Tenecteplase 0.25 mg/kg produces significant results in early neurological improvement (OR = 1.52 [95% CI = 1.13-2.05], p-value = 0.01), functional outcomes (mRS 0-1 and 0-2) (OR = 1.19 [95% CI = 1.03-1.37], p-value = 0.02; OR = 1.21 [95% CI = 1.05-1.39], p-value = 0.01; respectively) and mortality (OR = 0.78 [95% CI = 0.64-0.96], p-value = 0.02) whereas Tenecteplase 0.40 mg/kg increases the chances of symptomatic intracranial hemorrhage (OR = 2.35 [95% CI = 1.19-4.64], p-value = 0.01).

While not conclusive, our study lends evidence to 0.25 mg/kg Tenecteplase dose for ischemic stroke treatment. Further randomized trials need to be done to validate this finding.

International prospective register of systematic reviews (PROSPERO) - CRD42022339774URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=339774.

Stroke caused from large vessel occlusion (LVO) has emerged as the most common stroke subtype worldwide. Intravenous tissue plasminogen activator administration (IV-tPA) and additional intraarterial thrombectomy (IA-Tx) is regarded as standard treatment. In this study, the authors try to find the early recanalization rate of IV-tPA in LVO stroke patients.

Total 300 patients undertook IA-Tx with confirmed anterior circulation LVO, were analyzed retrospectively. Brain computed tomography angiography (CTA) was the initial imaging study and acute stroke magnetic resonance angiography (MRA) followed after finished IV-tPA. Early recanalization rate was evaluated by acute stroke MRA within 2 hours after the IV-tPA. In 167 patients undertook IV-tPA only and 133 non-recanalized patients by IV-tPA, additional IA-Tx tried (IV-tPA + IA-Tx group). And 131 patients, non-recanalized by IV-tPA (IV-tPA group) additional IA-Tx recommend and tried according to the patient condition and compliance.

Early recanalization rate of LVO after IV-tPA was 12.0% (36/300). In recanalized patients, favorable outcome (modified Rankin Scale, 0-2) was 69.4% (25/36) while it was 32.1% (42/131, p<0.001) in non-recanalized patients. Among 133 patients, nonrecanalized after intravenous recombinant tissue plasminogen activator and undertook additional IA-Tx, the clinical outcome was better than not undertaken additional IA-Tx (favorable outcome was 42.9% vs. 32.1%, p=0.046). Analysis according to the perfusion/diffusion (P/D)-mismatching or not, in patient with IV-tPA with IA-Tx (133 patients), favorable outcome was higher in P/ D-mismatching patient (52/104; 50.0%) than P/D-matching patients (5/29; 17.2%; p=0.001). Which treatment tired, P/D-mismatching was favored in clinical outcome (iv-tPA only, p=0.008 and IV-tPA with IA-Tx, p=0.001).

The P/D-mismatching influences on the recanalization and clinical outcomes of IV-tPA and IA-Tx. The authors would like to propose that we had better prepare IA-Tx when LVO is diagnosed on initial diagnostic imaging. Furthermore, if the patient shows P/D-mismatching on MRA after IV-tPA, additional IA-Tx improves treatment results and lessen the futile recanalization.

Treatment of distal vessel occlusions causing incomplete reperfusion after mechanical thrombectomy (MT) is debated. We hypothesized that pretreatment with intravenous thrombolysis (IVT) may facilitate delayed reperfusion (DR) of residual vessel occlusions causing incomplete reperfusion after MT.

Retrospective analysis of patients with incomplete reperfusion after MT, defined as extended thrombolysis in cerebral infarction (eTICI) 2a-2c, and available perfusion follow-up imaging at 24 ± 12 h after MT. DR was defined as absence of any perfusion deficit on time-sensitive perfusion maps, indicating the absence of any residual occlusion. The association of IVT with the occurrence of DR was evaluated using a logistic regression analysis adjusted for confounders. Sensitivity analyses based on IVT timing (time between IVT start and the occurrence incomplete reperfusion following MT) were performed.

In 368 included patients (median age 73.7 years, 51.1% female), DR occurred in 225 (61.1%). Atrial fibrillation, higher eTICI grade, better collateral status and longer intervention-to-follow-up time were all associated with DR. IVT did not show an association with the occurrence of DR (aOR 0.80, 95% CI 0.44-1.46, even in time-sensitive strata, aOR 2.28 [95% CI 0.65-9.23] and aOR 1.53 [95% CI 0.52-4.73] for IVT to incomplete reperfusion following MT timing <80 and <100 min, respectively).

A DR occurred in 60% of patients with incomplete MT at ~24 h and did not seem to occur more often in patients receiving pretreatment IVT. Further research on potential associations of IVT and DR after MT is required.

Mechanical thrombectomy (MT) is the standard of care in eligible patients presenting with acute ischemic stroke (AIS). The question of whether intravenous thrombolysis (IVT) improves outcomes in conjunction with MT remains unanswered. We performed a systematic review and meta-analysis of published randomized controlled trials (RCT) to explore outcomes of MT with and without IVT.

Following the PRISMA guidelines, a systematic literature review of the English language literature was conducted using PubMed, Embase, Web of science, and Scopus. Outcomes of interest included 90-day modified Rankin Scale (mRS) 0-2, thrombolysis in cerebral infarction (TICI) score 2b-3, symptomatic intracranial hemorrhage (sICH), distal embolization, and mortality. We calculated pooled risk ratios (RRs) and their corresponding 95% confidence intervals (CI).

Six RCTs with 2334 patients compared outcomes of patients treated with MT alone and MT with IVT. Both treatments resulted in comparable rates of mRS 0-2 (RR = 0.96, 95% CI = 0.88-1.04; p-value = 0.282), sICH (RR = 0.80, 95% CI = 0.55-1.17; p-value = 0.253), mortality at 90-days (RR = 1.06, 95% CI = 0.88-1.28; p-value = 0.529), and distal embolization (RR = 1.10, 95% CI = 0.79-1.52; p-value = 0.572). MT alone was associated with a lower rate of TICI 2b-3 compared to MT with IVT (RR = 0.96, 95% CI = 0.93-0.99; p-value = 0.006).

In this meta-analysis of six RCTs, MT alone was comparable to MT plus IVT for mRS 0-2, sICH, mortality, and distal embolization; however, MT alone resulted in lower rates of TICI 2b-3. Further trials are needed to determine which patient populations benefit from MT plus IVT and to increase the power of future meta-analyses.

The current guideline recommends using an intravenous tissue-type plasminogen activator (IV tPA) prior to mechanical thrombectomy (MT) in eligible acute ischemic stroke (AIS) with emergent large vessel occlusion (ELVO). Some recent studies found no significant differences in the long-term functional outcomes between bridging therapy (BT, i.e., IV tPA prior to MT) and direct MT (dMT).

We conducted a systematic review and meta-analysis to compare the safety and functional outcomes between BT and dMT in AIS patients with ELVO who were eligible for IV tPA administration. Based on the ELVO location, patients were categorized as the anterior group (occlusion of the anterior circulation), or the combined group (occlusion of the anterior and/or posterior circulation). A subgroup analysis was performed based on the study type, i.e., RCT and non-RCT.

Thirteen studies (3985 patients) matched the eligibility criteria. Comparing the BT and dMT groups, no significant differences in terms of mortality and good functional outcome were observed at 90 days. Symptomatic intracranial hemorrhagic (sICH) events were more frequent in BT patients in the combined group (OR = 0.73, p = 0.02); this result remained significant only in the non-RCT subgroup (OR = 0.67, p = 0.03). The RCT subgroup had a significantly higher rate of successful revascularization in BT patients (OR = 0.73, p = 0.02).

Our meta-analysis uncovered no significant differences in functional outcome and mortality rate at 90 days between dMT and BT in patients with AIS who had ELVO. Although BT performed better in terms of successful recanalization rate, there is a risk of increased sICH rate in this group.