Abstract Background Transoesophageal echocardiography (TOE) is essential for identifying cardiac sources of embolism in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). As randomized controlled trials are missing, recommendations regarding echocardiography after stroke remain vague, and clinical routines and structural resources for performing TOE on stroke units may differ. We here examined structural conditions for performing TOE on certified stroke units in Germany, and evaluated factors that may influence the decision to perform TOEs. Methods In this prospective exploratory cross-sectional survey, a standardized anonymous questionnaire was sent to all clinical leads of certified stroke units in Germany, supported by the German Stroke Society. The questionnaire focused on (a) on general characteristics of stroke units and logistics of TOE examinations and (b) local indication for performing TOEs, with a focus on factors that may influence this decision. Results Data from 248 SUs (stroke units) were included into the analysis (response rate 71.1%). The reported median TOE rate was 23.0% (IQR 18–34). Lower TOE rates were related to increasing numbers of stroke patients (p = 0.048). Most TOEs were performed within 24–48 h after the request (49.6%). Longer waiting times for TOE were associated with level of certification (p < 0.001) and higher numbers of stroke patients (p = 0.002). The presence of a stroke unit cardiologist did not result into shorter waiting times (p = 0.238). In total, 23.8% of the responding stroke units do not have a standardized operating procedure (SOP) for indicating TOE. Though 50% of leads considered quantitative requirements for indicating TOEs, within certain clinical contexts and situations, our findings revealed a broad consensus among stroke unit leads concerning TOE indications. Conclusions Despite limitations, our study provides valuable insights into performing TOE in hospitalized German stroke patients. This may facilitate the optimized use of TOE in hospitals and represent a first step towards the development of future guidelines and SOPs, in particular in the context of limited resources.

Endothelial activation and stress index (EASIX) is a biomarker of endothelial dysfunction and has been validated previously as a prognostic score for mortality in various diseases, including oncologic diseases, sepsis, and cardiac disease. Since endothelial dysfunction is an established mediator of adverse outcomes in acute ischemic stroke, this study investigates the prognostic value of EASIX for risk of mortality in these patients. We analyzed data from the Heidelberg (n = 4,188) and Vienna (n = 2,273) prospective acute ischemic stroke registries. EASIX was calculated as creatinine [mg/dL] × LDH [U/L] / platelet count [109/L]. An EASIX cut-off was established using maximal Youden index. Validation was performed using Brier score and C-statistics. Higher EASIX was associated with higher risk of mortality in the training cohort in a multivariable Cox regression (HR of all-cause mortality per log2 increase: 1.20 (95

Mechanical thrombectomy (MT) is the first-line therapy for patients with acute ischemic stroke due to large vessel occlusion; however, despite substantial advances in MT techniques and devices, mechanical recanalization remains unsuccessful in up to 15

This post-hoc subanalysis of the TENSION trial evaluated the association between anesthesia strategy and neurological outcomes in patients with large-core infarcts undergoing mechanical thrombectomy (MT). We analyzed patients from the interventional arm of the TENSION trial who underwent MT under general anesthesia (GA) or conscious sedation (CS). Anesthesia strategy was not prespecified and was selected by the local stroke team. Key outcomes included early neurological improvement (ENI) or deterioration (END), modified Rankin Scale (mRS) at 90 days, procedural metrics, and safety outcomes. Multivariable logistic regression was performed to assess the independent association between anesthesia strategy and ENI, END, and favorable functional outcome, defined as mRS 0–3 at 90 days. Sensitivity analyses were conducted in patients with successful reperfusion. A total of 117 patients were included, of whom 50 were treated under GA and 67 under CS. No significant differences were observed between GA and CS for ENI (46.0

INTRODUCTION:Mechanical thrombectomy is a highly effective treatment for acute ischemic stroke (AIS) caused by large vessel occlusions (LVO). However, our understanding of the pathophysiology of AIS is still limited, particularly regarding the ischemic microenvironment distal to the occlusion. AIM:To investigate the relationship between the intracerebral blood pressure (BP) distal to an LVO and clinical and imaging parameters. METHODS:In this single-center prospective study, intracerebral BPs proximal and distal to the occluding clot were measured during thrombectomy in patients with AIS of the anterior circulation caused by LVO. BPs were correlated with imaging parameters and clinical data using Spearman's rank correlation and linear regression. RESULTS:25 patients were included. A significant correlation was found between the mean arterial pressure (MAP) distal to the occlusion and the baseline Alberta Stroke Program Early CT Score (Spearman r=0.503, P=0.014) and baseline National Institutes of Health Stroke Scale score (r=-0.439, P=0.036). No significant correlation was observed between the MAP distal to the occlusion and collateral scores (eg, MAP vs American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology score (r=0.307, P=0.165) or modified Rankin Scale (mRS) score (pre-mRS vs 90-day mRS; r=0.013, P=0.952)). Systemic MAPs did not correlate with the MAP distal to the clot (eg, R2=0.029, P=0.593). CONCLUSION:The intracerebral BP measured in the ischemic vasculature distal to the LVO correlates with the extent of the ischemic core and the clinical severity at baseline, but not with collateral scores, systemic BPs, or functional outcome. These results shed light on the pathophysiology of BP mechanisms in AIS and can be the basis for further research in this field.

Introduction: Previous studies have shown the efficacy and safety of time-based intravenous thrombolysis (IVT) in elderly patients with ischemic stroke. However, there are safety concerns about bleeding associated with IVT due to their low body weight, renal dysfunction, and the concomitant use of antithrombotic drugs. Robust evidence on the effect of IVT, particularly in elderly patients with unknown onset stroke, is limited. This study aimed to evaluate the efficacy and safety of imaging-based IVT in this population. Methods: Patients with an unknown onset stroke were evaluated using an individual patient-level database of randomized controlled trials comparing IVT with placebo or standard treatment from the Evaluation of unknown Onset Stroke thrombolysis trials (EOS) collaboration. The primary outcome was favorable outcome, defined as a mRS score of 0-1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) at 22–36 hours and 90-day mortality. The effect of IVT was evaluated in each of patients aged ≥85 and <85 years using a mixed-effect logistic regression analysis. Results: Among the 843 patients in the EOS dataset, 56 were aged 85 years or older (6.7%), and 787 were under 85 years (93.3%). The elderly group had a higher prevalence of atrial fibrillation (42.9% vs. 17.2%), hypertension (78.6% vs. 58.7%), and premorbid anticoagulation (13.6% vs. 3.1%). The baseline NIHSS score was also higher (median, 12 vs. 7) (all p<0.05). Overall, there was no significant interaction between age (≥85 or <85 years) and treatment on efficacy or safety outcomes (P interaction for the primary outcome 0.689). In the elderly group, favorable outcomes were observed in 33.3% of the IVT group and 19.2% of the control group, with an adjusted odds ratio (aOR) of 3.06 (95% CI 0.68-13.8). Mortality at 90 days was not significantly different between the IVT and control groups (20.0% vs. 19.2%, aOR 1.32 [0.30-5.79]), and there was only one case of sICH in the IVT group. In patients under 85 years, favorable outcomes were observed in 48.5% of the IVT group compared to 40.5% in controls (aOR 1.50, 95% CI 1.09-2.06). The IVT group had higher mortality (5.8% vs. 2.3%, aOR 2.56, [1.16-5.67]) and more frequent sICH (2.7% vs. 0.5%, aOR 5.35, [1.18-24.3]). Conclusion: Imaging-based IVT with alteplase may improve outcomes in elderly patients with unknown onset stroke without significantly increasing the risk of death or sICH.

BACKGROUND:While thrombectomy benefits patients with large infarcts, it is unclear whether this benefit persists across different levels of reperfusion. AIMS:This study investigates how the degree of reperfusion influences the effectiveness of endovascular thrombectomy (EVT) combined with best medical treatment (BMT), compared to BMT alone, in patients with large infarcts. METHODS:This post hoc analysis of the TENSION trial, a randomized controlled study, assessed EVT versus BMT in patients with extensive infarction (Alberta Stroke Program Early CT Score (ASPECTS) 3-5). Primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included infarct volume at 24 h, mortality, and symptomatic hemorrhage. Outcomes were stratified by final reperfusion level, measured with the modified thrombolysis in cerebral infarction (mTICI) scale. Confounder-adjusted common odds ratios (cORs) and average treatment effects (ATEs) were estimated using inverse probability weighting with regression adjustment. RESULTS:A total of 246 patients (median age, 74 years (interquartile range (IQR), 65-80); median baseline ASPECTS, 4 (IQR, 3-5)) were included. Compared to BMT alone, unsuccessful EVT (mTICI ⩽ 2a) was not associated with worse functional outcomes (cOR:1.2, 95% CI, 0.95 to 1.52; p = 0.131), higher mortality (ATE: -11.6%; 95% CI, -28.82 to 5.61; p = 0.187), or larger infarct volumes on follow-up (ATE:0.99 mL; 95% CI, -45.30 to 45.32; p = 0.965). First-pass complete reperfusion (mTICI 3) showed the greatest treatment benefit, significantly improving all endpoints, with a cOR of 4.85 (95% CI, 3.74-6.31; p < 0.001) for improved mRS scores and a 29% absolute reduction in mortality. CONCLUSION:In this post hoc analysis of the TENSION trial, unsuccessful EVT did not worsen outcomes compared to BMT alone. The highest benefit of EVT occurred with first-pass complete reperfusion, emphasizing the importance of achieving optimal reperfusion in this vulnerable stroke subgroup. These findings do not justify general treatment recommendations.

ImportanceThe net clinical effect of early vs later direct oral anticoagulant (DOAC) initiation after atrial fibrillation–associated ischemic stroke is unclear.ObjectiveTo investigate whether early DOAC treatment is associated with a net clinical benefit (NCB).Design, Setting, and ParticipantsThis was a post hoc analysis of the Early Versus Late Initiation of Direct Oral Anticoagulants in Post–Ischaemic Stroke Patients With Atrial Fibrillation (ELAN) open-label randomized clinical trial conducted across 103 sites in 15 countries in Europe, the Middle East, and Asia between November 6, 2017, and September 12, 2022, with a 90-day follow-up. Participants included patients with atrial fibrillation–associated acute ischemic stroke, excluding those with therapeutic anticoagulation at stroke onset or with severe hemorrhagic transformation of the ischemic infarct.InterventionEarly DOAC initiation (<48 hours after minor and moderate stroke, 6-7 days after major stroke) vs later initiation (3-4 days after minor stroke, 6-7 days after moderate stroke, and 12-14 days after major stroke).Main Outcomes and MeasuresThe main measure was the NCB of early treatment over later treatment, calculated by subtracting the weighted rate of excess bleeding events (major extracranial or intracranial hemorrhage) attributable to early treatment from the rate of excess ischemic events (recurrent stroke or systemic embolism) possibly prevented by early treatment within 30 days (main analysis) or 90 days (ancillary analysis). An established weighting scheme was used to account for the different clinical impact of bleeding relative to ischemic outcomes. Event rates were derived from adjusted logistic models. The analysis included all evaluable randomized ELAN participants.ResultsOf the original 2013 ELAN participants, 1966 were eligible for analysis (977 [49.7%] assigned to early DOAC initiation, 989 [50.3%] assigned to later DOAC initiation; median [IQR] age 77 [70-84] years; 1075 [54.7%] male). The 30-day NCB of early treatment over later treatment ranged from 1.73 (95% CI, 0.06-3.40) to 1.72 (95% CI, −0.63 to 3.98) weighted events possibly prevented per 100 participants for intracranial hemorrhage weights 1.5 to 3.3. The 90-day NCB ranged from 2.16 (95% CI, 0.30-3.87) to 2.14 (95% CI, −0.26 to 4.41) weighted events per 100 participants.Conclusions and RelevanceThis post hoc analysis of a randomized clinical trial estimated a sizeable NCB of early anticoagulation for patients after atrial fibrillation–associated ischemic stroke. Although estimates cannot exclude the possibility of no benefit or small net harm, the findings suggest that early treatment may be more favorable.Trial RegistrationClinicalTrials.gov Identifier: NCT03148457

Background: The effects of intravenous alteplase in patients with prior antiplatelet therapy (APT) remain controversial. We aimed to assess the efficacy and safety of imaging-based intravenous alteplase in patients with unknown onset stroke with prior APT. Methods: Data from randomized controlled trials comparing alteplase with placebo/standard care in patients with unknown onset acute ischemic stroke from the Evaluation of Unknown Onset Stroke Thrombolysis (EOS) individual patient data meta-analysis collaboration were analyzed. Favorable outcome was defined as a modified Rankin Scale score of 0–1 at 90 days post-stroke. Safety outcomes included symptomatic intracranial hemorrhage (sICH) at 22–36 h and 90-day mortality. Results: Overall, 780 patients had available baseline data on prior APT. Compared with the no prior APT group (n = 523), the prior APT group (n = 257) was older (72 vs. 66 years) and had a higher prevalence of vascular risk factors. There was no interaction between prior APT and treatment effects of alteplase (p for interaction = 0.23). In the prior APT patients, 55/125 (45%) patients in the alteplase group and 39/132 (30%) patients in the control group had a favorable outcome (adjusted odds ratio [aOR], 2.07 [95% confidence interval, 1.18–3.64]). The rates of sICH and mortality in the alteplase and control groups were 5.6% and 0.8% (aOR, 7.78 [0.94–63.37]) and 6.5% and 6.1% (aOR, 1.12 [0.38–3.36]), respectively. In the no prior APT patients, 136 patients (50%) in the alteplase group and 112 patients (45%) in the control group had a favorable outcome (aOR, 1.39 [0.94–2.05]). Safety outcomes were not significantly different between the groups (sICH: 3 [1.1%] vs. 1 [0.4%]; mortality: 13 [4.9%] vs. 3 [1.2%]). Conclusions: Alteplase has consistent efficacy regardless of prior APT in patients with unknown onset stroke. In addition, prior APT does not significantly increase the risk of sICH or mortality.

Introduction: Evidence regarding the benefit of endovascular therapy (EVT) in patients with acute ischemic stroke (AIS) due to isolated cervical internal carotid artery occlusion (c-ICA-O) is lacking. We assessed the outcomes and safety of EVT in patients with isolated c-ICA-O. Methods: Retrospective multicenter cohort study of patients with an AIS due to isolated c-ICA-O, within 24-h since last-seen-well. Comparisons were made between EVT and best medical therapy (BMT). The primary outcome was 3-months modified Rankin Scale (mRS) ordinal shift. Secondary outcomes included 3-month favorable outcome (mRS 0–2, or return to pre-stroke mRS), symptomatic intracranial hemorrhage (sICH) and any parenchymal hemorrhage. Outcomes were compared combining inverse probability of treatment weighting with regression models and propensity score matching (PSM) as sensitivity analysis. Results: We analyzed 998 patients (66.2% male, mean age 71.1 ± 13.2 years). 487 (48.8%) patients received EVT and 511 (51.2%) received BMT. Patients receiving EVT had a higher admission NIHSS [13 (7–18) vs 5 (2–13)] compared to BMT. There was no difference between EVT and BMT groups in 3-month mRS shift (adjusted common odds ratio [OR], 1.01 [95% CI 0.76–1.34]) and favorable outcome (adjusted OR [aOR] 1.16 [95% CI 0.84–1.60]). No patient (0%) in the BMT group had sICH versus 1.6% in the EVT group. Parenchymal hemorrhage was numerically higher in EVT patients (2.7% vs 0.6%; aOR 3.85 [95% CI 0.98–15.23]). PSM analysis revealed similar results. Discussion and conclusion: In patients with isolated c-ICA-O, EVT was associated with similar odds of disability and intracranial bleeding compared to BMT. Randomized-controlled clinical trials in patients with isolated c-ICA-O are warranted.

Background Randomized clinical trials have demonstrated that endovascular thrombectomy reduces functional disability in patients with large ischemic stroke; arterial collateral status might be used to select these patients for endovascular thrombectomy. Purpose To investigate whether arterial collateral status modifies the treatment effect of endovascular thrombectomy in patients with large ischemic stroke. Materials and Methods The Efficacy and Safety of Thrombectomy in Stroke with Extended Lesion and Extended Time Window (TENSION) trial was a prospective, multicenter, randomized study investigating participants with acute large ischemic stroke due to anterior circulation large-vessel occlusion. Participants with an Alberta Stroke Program Early CT Score of 3-5 were enrolled at 41 participating centers between July 2018 and February 2023. Participants were randomly assigned to undergo either endovascular thrombectomy with best medical treatment or best medical treatment alone within 12 hours from stroke onset. Collateral status was graded on pretreatment single-phase CT angiography (CTA) images using the Tan score and dichotomized into poor (grade, 0-1) or good (grade, 2-3) based on the extent of collateral supply filling the affected middle cerebral artery territory. The primary outcome was the shift on the 90-day modified Rankin Scale (mRS). Results Of 253 randomized patients, 201 with pretreatment CTA were included (median age, 74 years; IQR, 66-80 years; 103 [51.2%] female patients; 103 [51.2%] patients underwent endovascular thrombectomy). Endovascular thrombectomy compared with best medical treatment (adjusted common odds ratio [OR], 3.69; 95% CI: 2.12, 6.54; P < .001) and good collaterals compared with poor collaterals (adjusted common OR, 2.88; 95% CI: 1.63, 5.11; P < .001) were independently associated with a shift in the 90-day mRS scores toward better functional outcomes. The treatment effect of endovascular thrombectomy over best medical treatment was not modified by collateral status (interaction, P = .88). The treatment effect of endovascular thrombectomy versus best medical treatment was found in patients with good collaterals (adjusted common OR, 3.93; 95% CI: 1.65, 9.69; P = .002) and poor collaterals (adjusted common OR, 3.92; 95% CI: 1.86, 8.52; P < .001). Conclusion In this secondary analysis of data from the TENSION trial, endovascular thrombectomy reduced 90-day functional disability compared with best medical treatment in patients with good and poor collaterals. These findings suggest that patients with large ischemic stroke manifesting within 12 hours after onset should undergo endovascular thrombectomy irrespective of single-phase CTA collateral status. ClinicalTrials.gov Identifier: NCT03094715 © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Benomar and Raymond in this issue.

Adequate secondary prevention in survivors of intracerebral hemorrhage (ICH) who also have atrial fibrillation (AF) is a long-standing clinical dilemma because these patients are at increased risk of recurrent ICH as well as of ischemic stroke. The efficacy and safety of oral anticoagulation, the standard preventive medication for ischemic stroke patients with AF, in ICH patients with AF are uncertain. PRESTIGE-AF is an international, phase 3b, multi-center, randomized, open, blinded end-point assessment (PROBE) clinical trial that compared the efficacy and safety of direct oral anticoagulants (DOACs) with no DOAC (either no antithrombotic treatment or any antiplatelet drug). Randomization occurred in a 1:1 ratio and stratification was based on ICH location and sex. The two co-primary binary endpoints included ischemic stroke and recurrent ICH which will be analyzed hierarchically according to the intention-to-treat principle. Secondary efficacy endpoints encompassed all-stroke and systemic embolism, all-cause and cardiovascular mortality, major adverse cardiac events, and net clinical benefit. Secondary safety endpoints included any major hemorrhage and intracranial hemorrhage. All outcome events were adjudicated by an independent committee. Results of PRESTIGE-AF are expected to support risk-adjusted secondary prevention in ICH survivors with AF and to inform clinical guideline recommendations.

Intravenous thrombolysis (IVT) and endovascular therapy (EVT) are the cornerstones of acute ischemic stroke treatment. While IVT has been an integral part of acute therapy since the mid-1990s, EVT has evolved as one of the most effective treatments in medicine over the past decade. Traditionally, systemic thrombolysis has been performed with alteplase (rtPA). More recently, tenecteplase (TNK) has been shown to be non-inferior to rtPA. TNK has some pharmacological advantages over rtPA and may lead to earlier recanalization, particularly in large vessel occlusions. All recanalization therapies are highly time dependent. To ensure rapid treatment, standard operating procedures (SOPs) should be established and followed in clinical practice. The optimal time window for IVT is 4.5 h after symptom onset and can be extended up to 9 h using specialized imaging techniques. For EVT, studies suggest a time window up to 24 h after symptom onset. In some cases, EVT has been successfully performed beyond this time window. To select patients for EVT, advanced imaging identifying salvageable brain tissue might be necessary. Even in large ischemic stroke, EVT can still improve outcome. Compared to EVT, IVT requires fewer technical and human resources, so more stroke patients can potentially be treated. In contrast, EVT requires highly trained personnel with sophisticated equipment and can, therefore, only be performed in specialized centers. Both procedures should be combined within the 4.5 h time window for patients without contraindications.

Background Direct oral anticoagulants (DOACs) reduce the rate of thromboembolism in patients with atrial fibrillation but the benefits and risks in survivors of intracerebral haemorrhage are uncertain. We aimed to determine whether DOACs reduce the risk of ischaemic stroke without substantially increasing the risk of recurrent intracerebral haemorrhage. Methods PRESTIGE-AF is a multicentre, open-label, randomised, phase 3 trial conducted at 75 hospitals in six European countries. Eligible patients were aged 18 years or older with spontaneous intracerebral haemorrhage, atrial fibrillation, an indication for anticoagulation, and a score of 4 or less on the modified Rankin Scale. Patients were randomly assigned (1:1) to a DOAC or no anticoagulation, stratified by intracerebral haemorrhage location and sex. Only the events adjudication committee was masked to treatment allocation. The coprimary endpoints were first ischaemic stroke and first recurrent intracerebral haemorrhage. Hierarchical testing for superiority and non-inferiority, respectively, was performed in the intention-to-treat population. The margin to establish non-inferiority regarding intracerebral haemorrhage was less than 1·735. The safety analysis was done in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT03996772, and is complete. Findings Between May 31, 2019, and Nov 30, 2023, 319 participants were enrolled and 158 were randomly assigned to the DOAC group and 161 to the no anticoagulant group. Patients' median age was 79 years (IQR 73–83). 113 (35%) of 319 patients were female and 206 (65%) were male. Median follow-up was 1·4 years (IQR 0·7–2·3). First ischaemic stroke occurred less frequently in the DOAC group than in the no anticoagulant group (hazard ratio [HR] 0·05 [95% CI 0·01–0·36]; log-rank p<0·0001). The rate of all ischaemic stroke events was 0·83 (95% CI 0·14–2·57) per 100 patient-years in the DOAC group versus 8·60 (5·43–12·80) per 100 patient-years in the no anticoagulant group. For first recurrent intracerebral haemorrhage, the DOAC group did not meet the prespecified HR for the non-inferiority margin of less than 1·735 (HR 10·89 [90% CI 1·95–60·72]; p=0·96). The event rate of all intracerebral haemorrhage was 5·00 (95% CI 2·68–8·39) per 100 patient-years in the DOAC group versus 0·82 (0·14–2·53) per 100 patient years in the no anticoagulant group. Serious adverse events occurred in 70 (44%) of 158 patients in the DOAC group and 89 (55%) of 161 patients in the no anticoagulant group. 16 (10%) patients in the DOAC group and 21 (13%) patients in the no anticoagulant group died. Interpretation DOACs effectively prevent ischaemic strokes in survivors of intracerebral haemorrhage with atrial fibrillation but a part of this benefit is offset by a substantially increased risk of recurrent intracerebral haemorrhage. To optimise stroke prevention in these vulnerable patients, further evidence from ongoing trials and a meta-analysis of randomised data is needed, as well as the evaluation of safer medical or mechanical alternatives for selected patients. Funding European Commission.

BACKGROUND:It remains unclear whether outcomes of patients treated with endovascular thrombectomy with large-vessel occlusion and unwitnessed onset of stroke differ from those with witnessed onset in the extended time window. METHODS:We enrolled patients with anterior circulation large-vessel occlusion (internal carotid artery, M1, or M2 segment of the middle cerebral artery) undergoing endovascular thrombectomy within 6 to 24 hours from the time last seen well, from 2014 to 2022, at 66 sites in Europe, North America, and Asia. Patients with a prestroke modified Rankin Scale score of >3 or age <18 were excluded. We categorized patients by onset mode as witnessed or unwitnessed. The primary outcome was the modified Rankin Scale shift at 90 days. Secondary outcomes were functional independence, a composite of functional independence or return of Rankin to prestroke level, symptomatic intracranial hemorrhage, mortality, and a composite of severe disability or mortality at 90 days. We applied inverse probability of treatment weighting to compare outcomes between the groups. RESULTS:Of 5098 patients assessed for eligibility, we included 2073, of whom 1760 (84.9%) had unwitnessed onset, and 313 (15.1%) were witnessed. In the univariate comparison (before inverse probability of treatment weighting), 38.8% of the unwitnessed and 45.7% of the witnessed patients achieved functional independence (P=0.022). Mortality was 21.6% among unwitnessed and 22.0% among witnessed (P=0.847), and symptomatic intracranial hemorrhage rates were 6.6% and 5.8%, respectively (P=0.623). The primary outcome (modified Rankin Scale shift) showed no difference comparing unwitnessed to witnessed patients (odds ratio, 1.35 [95% CI, 0.82-2.20]; P=0.235) in the inverse probability of treatment weighting. Unwitnessed patients were more likely to achieve functional independence or return of Rankin (1.53 [1.01-2.33]; P=0.045). Other secondary outcomes did not differ between the witnessed and unwitnessed patients. CONCLUSIONS:In the extended time window, unwitnessed patients with large-vessel occlusion undergoing endovascular thrombectomy have at least the same likelihood of favorable outcomes as witnessed patients. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248.

BACKGROUND:There is uncertainty about whether patients with M2 occlusion benefit from endovascular therapy (EVT) in the late (6-24-hour) time window. We evaluated the clinical outcomes of patients with M2 occlusion selected for EVT compared with those who received medical management (MM) in the late window. METHODS:This multinational cohort study was conducted at 66 sites across 10 countries (January 2014 to May 2022). We included consecutive patients with late-window stroke due to M2 occlusion, baseline National Institutes of Health Stroke Scale score of ≥5, and premorbid modified Rankin Scale score of ≤2 who received EVT or MM alone. The primary end point was 90-day ordinal shift in the modified Rankin Scale score. Safety end points were symptomatic intracranial hemorrhage and 90-day mortality. Differences in outcomes were determined using inverse probability of treatment weighting-adjusted logistic regression models. RESULTS:Among 5098 patients, 496 met inclusion criteria (median [interquartile range] age, 74 years [62-81 years]; baseline National Institutes of Health Stroke Scale score, 12 [8-17]), of whom 394 (79.4%) received EVT and 102 (20.6%) MM. In inverse probability of treatment weighting adjusted analyses, there was no favorable 90-day ordinal modified Rankin Scale shift (odds ratio, 1.39 [95% CI, 0.92-2.12]) and no difference of functional independence rates (modified Rankin Scale score of 0-2; odds ratio, 1.72 [95% CI, 0.93-3.15]) with EVT compared with MM. Moreover, symptomatic intracranial hemorrhage risk (odds ratio, 3.46 [95% CI, 0.50-23.92]) and 90-day mortality (odds ratio, 1.11 [95% CI, 0.66-1.87]) were not statistically different between treatment groups. CONCLUSIONS:In patients with M2 occlusion in the 6- to 24-hour time window, there was no difference in disability outcomes or symptomatic intracranial hemorrhage risk between patients treated with EVT compared with MM. Results of ongoing randomized trials will provide further insight. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248.

Die intravenöse Thrombolyse (IVT) und die endovaskuläre Schlaganfalltherapie (EST) zählen zu den Säulen der Akuttherapie des ischämischen Schlaganfalls. Während die IVT bereits seit Mitte der 1990er-Jahre fester Bestandteil der Akuttherapie ist, hat sich die EST in den letzten 10 Jahren als eine der wirksamsten kausalen Therapien etabliert. Traditionell wurde die systemische Thrombolyse mit Alteplase (rtPA) durchgeführt. Inzwischen wurde gezeigt, dass Tenecteplase (TNK) nicht unterlegen ist. Gegenüber rtPA hat TNK einige pharmakologische Vorteile und führt evtl. bei Großgefäßverschlüssen etwas häufiger zu einer frühen Rekanalisation. Alle Rekanalisationstherapien sind stark zeitabhängig. Um eine zügige Behandlung zu gewährleisten, sollen klinikintern Standard Operating Procedures (SOP) formuliert und praktiziert werden. Das klassische Zeitfenster nach Symptombeginn für die IVT liegt bei 4,5 h und kann durch spezielle bildgebende Verfahren auf bis zu 9 h ausgedehnt werden. Für die EST gibt es studienbasiert ein Zeitfenster von 24 h nach Symptombeginn, wobei in Einzelfällen Rekanalisationen auch darüber hinaus noch erfolgreich waren. Wichtiger als bei der IVT ist für die Patientenselektion die Identifizierung von rettbarem Hirngewebe mittels spezieller Bildgebung. Auch bei ausgedehnten Ischämiefrühzeichen kann die EST dennoch mit einer Verbesserung des Outcomes verbunden sein. Der Vorteil der IVT gegenüber der EST ist, dass sie weniger technische und personelle Ressourcen benötigt und auch deswegen mehr Schlaganfallpatienten angeboten werden kann. Die EST erfordert hingegen eine hohe apparative und personelle Expertise und kann daher nur in spezialisierten Zentren durchgeführt werden. Beide Verfahren sollen vor allem bei Patienten ohne Kontraindikationen im Zeitfenster von 4,5 h kombiniert werden.

Introduction: The effects of imaging-based intravenous thrombolysis on outcomes based on patient sex remain unclear. We aimed to investigate whether outcomes among patients with stroke with an unknown onset time and treated with imaging-based intravenous thrombolysis are influenced by their sex.Patients and Methods: This study was a pooled analysis of individual patient-level data acquired from the Evaluation of unknown Onset Stroke thrombolysis trials. Patients treated with imaging-based intravenous thrombolysis for stroke with an unknown onset time were included. The primary outcome was a favourable outcome (modified Rankin Scale score 0-1) at 90 days. The sex-based difference in outcomes was studied using mixed-effect logistic or ordinal regression models, considering potential heterogeneity across trials.Results: Out of 509 patients in total, 204 (40.1%) were women. Compared with men, women were older and more likely to have atrial fibrillation. Baseline National Institutes of Health Stroke Scale score was higher and hours from last-known-well to treatment were longer for women than for men. Favourable outcomes occurred less often among women than among men. However, multivariate adjustment revealed a non-significant association between female sex and favourable outcome (adjusted odds ratio: 1.04 [95% confidence interval: 0.66-1.52], p = 0.98).Discussion and conclusion: Pooled data from the included clinical trials showed that women with ischaemic stroke with an unknown onset time had worse functional outcomes following imaging-based intravenous thrombolysis than did men. However, this sex-based difference can be explained by the higher age and more severe clinical status at onset among women.

BackgroundThe optimal anesthetic strategy for endovascular therapy (EVT) in acute ischemic stroke is still under debate. The aim of this study was to compare the clinical outcomes of patients with isolated posterior cerebral artery (PCA) occlusion stroke undergoing EVT by anesthesia modality with conscious sedation (non-GA) versus general anesthesia (GA).MethodsPatients from the Posterior CerebraL Artery Occlusion (PLATO) study were analyzed with regard to anesthetic strategy. GA was compared with non-GA using multivariable logistic regression and inverse probability of weighting treatment (IPTW) methods. The primary endpoint was the 90-day distribution of the modified Rankin Scale (mRS) score. Secondary outcomes included functional independence or return to Rankin at day 90, and successful reperfusion, defined as expanded Thrombolysis in Cerebral Infarction (eTICI) 2b to 3. Safety endpoints were symptomatic intracranial hemorrhage and mortality.ResultsAmong 376 patients with isolated PCA occlusion stroke treated with EVT, 183 (49%) had GA. The treatment groups were comparable, although the GA group contained more patients with severe stroke and lower posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS). On IPTW analysis, there was no difference between groups with regard to ordinal mRS shift analysis (common OR 0.89, 95% CI 0.53 to 1.51, P=0.67) or functional independence (OR 0.84, 95% CI 0.50 to 1.39, P=0.49). There were greater odds for successful reperfusion with GA (OR 1.70, 95% CI 1.17 to 2.47, P=0.01). Safety outcomes were comparable between groups.ConclusionIn patients with isolated PCA occlusion undergoing EVT, patients treated with GA had higher reperfusion rates compared with non-GA. Both GA and non-GA strategies were safe and functional outcomes were similar.

ClinicalTrials.gov NCT03996772; first submitted June 21, 2019; first patient enrolled: May 31, 2019; available at clinicaltrials.gov/study/NCT03996772.