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Background: The benefit of distinguishing between disabling versus nondisabling deficit in mild acute ischemic stroke due to endovascular thrombectomy-targetable vessel occlusion (EVT-tVO; including anterior circulation large and medium-vessel occlusion) is unknown. We compared safety and efficacy of acute reperfusion treatments in disabling versus nondisabling mild EVT-tVO. Methods: From the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register, we included consecutive acute ischemic stroke patients (2015–2021) treated within 4.5 hours, with full NIHSS items availability and score ≤5, evidence of intracranial internal carotid artery, M1, A1-2, or M2-3 occlusion. After propensity score matching, we compared efficacy (3-month modified Rankin Scale score of 0–1, modified Rankin Scale score of 0–2, and early neurological improvement) and safety (nonhemorrhagic early neurological deterioration, any intracerebral or subarachnoid hemorrhage, symptomatic intracranial hemorrhage, and death at 3-month) outcomes in disabling versus nondisabling patients—adopting an available definition. Results: We included 1459 patients. Propensity score matched analysis of disabling versus nondisabling EVT-tVO (n=336 per group) found no significant differences in efficacy (modified Rankin Scale score 0–1: 67.4% versus 71.5%, P =0.336; modified Rankin Scale score 0–2: 77.1% versus 77.6%, P =0.895; early neurological improvement: 38.3% versus 44.4%, P =0.132) and safety (nonhemorrhagic early neurological deterioration: 8.5% versus 8.0%, P =0.830; any intracerebral hemorrhage or subarachnoid hemorrhage: 12.5% versus 13.3%, P =0.792; symptomatic intracranial hemorrhage: 2.6% versus 3.4%, P =0.598; and 3-month death: 9.8% versus 9.2%, P =0.844) outcomes. Conclusions: We found similar safety and efficacy outcomes after acute reperfusion treatment in disabling versus nondisabling mild EVT-tVO; our findings suggest to adopt similar acute treatment approaches in the 2 groups. Randomized data are needed to clarify the best reperfusion treatment in mild EVT-tVO.

Background: The association between cholesterol levels and cerebral edema (CED) or hemorrhagic transformation (HT) as an expressions of blood-brain barrier (BBB) dysfunction after ischemic stroke is not well established. The aim of this study is to determine the association of total cholesterol (TC) levels with the incidence of HT and CED after reperfusion therapies. Methods: We analyzed SITS Thrombolysis and Thrombectomy Registry data from January 2011 to December 2017. We identified patients with data on TC levels at baseline. TC values were categorized in three groups (reference group ⩾200 mg/dl). The two primary outcomes were any parenchymal hemorrhage (PH) and moderate to severe CED on follow up imaging. Secondary outcomes included death and functional independence (mRS 0–2) at 3 months. Multivariable logistic regression analysis adjusted for baseline factors including statin pretreatment was used to assess the association between TC levels and outcomes. Results: Of 35,314 patients with available information on TC levels at baseline, 3372 (9.5%) presented with TC levels ⩽130 mg/dl, 8203 (23.2%) with TC 130–200 mg/dl and 23,739 (67.3%) with TC ⩾ 200 mg/dl. In the adjusted analyses, TC level as continuous variable was inversely associated with moderate to severe CED (OR 0.99, 95% CI 0.99–1.00, p = 0.025) and as categorical variable lower TC levels were associated with a higher risk of moderate to severe CED (aOR 1.24, 95% CI 1.10–1.40, p = 0.003). TC levels were not associated with any PH, functional independence, and mortality at 3 months. Conclusions: Our findings indicate an independent association between low levels of TC and higher odds of moderate/severe CED. Further studies are needed to confirm these findings.

In adult human brain, neurogenesis seems to persist throughout life and ischemic stroke was proved to stimulate this process. Using magnetic resonance spectroscopy (MRS), a 1.28-ppm peak, putative biomarker of neural progenitor cells (NPCs), was identified both in vitro and in vivo, i.e., in normal rat and healthy human brain. The aim of our study was to identify a 1.28-ppm peak in adult human ischemic brain by using 3.0 T multivoxel MRS.We studied 10 patients, six males, and four females, with a mean (± SD) age of 59.3 (± 17.3), at three different time points from ischemic stroke onset (T0: 5 days; T14: 14 ± 2 days; T30: 30 ± 2 days).In all patients except one, a 1.28-ppm peak at T14 was detected at the ischemic boundary (all p values 0.05). MRS performed on six voluntary age-matched healthy subjects did not detect any 1.28-ppm peak.The nature of this 1.28-pm peak is uncertain; however, our data support the hypothesis that it might represent a marker of NPCs in post-stroke human brain.

Background: Although chronic kidney disease (CKD) is associated with worse stroke outcomes, data regarding the influence of CKD on intravenous thrombolysis outcomes are scarce. We sought to assess the efficacy and safety of intravenous thrombolysis for acute ischemic stroke with unknown onset time in patients with CKD. Methods: Patients with an acute stroke of unknown onset time from the EOS trials (Evaluation of Unknown Onset Stroke Thrombolysis) collaboration were evaluated using an individual patient-level database of randomized controlled trials comparing intravenous thrombolysis with placebo/standard treatment. CKD was defined as baseline estimated glomerular filtration rate of 2 Mixed-effect logistic-regression analysis was performed to evaluate treatment effects. A favorable outcome was defined as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality. Results: Baseline data on renal function were available for 688 of 843 patients. Of these, CKD was present in 146 (21%), including 69 of 351 patients receiving alteplase and 77 of 337 patients receiving placebo/standard treatment. Overall, treatment with alteplase was associated with higher odds of favorable outcome, and CKD did not modify the treatment effect ( P interaction =0.834). A favorable outcome was observed in 31 of 69 (46%) patients with CKD in the alteplase group and in 28 of 77 (36%) patients with CKD in the control group (adjusted odds ratio, 1.19 [95% CI, 0.55–2.58]). Among patients with CKD, symptomatic intracranial hemorrhage occurred in 2 patients (3%) in the alteplase group but in none of the controls ( P =0.133). At 90 days, death was reported in 3 patients (4%) in the alteplase group compared with 2 patients (3%) in the controls ( P =0.539). Conclusions: The present analysis indicates that the benefit of alteplase does not differ between stroke patients with unknown onset time with and without CKD, although the statistical power was lacking to confirm the efficacy in subgroups. This study only applies to mild-to-moderate or predialysis CKD.

Introduction: Recent anticoagulant intake represents a contraindication for thrombolysis in acute ischemic stroke. Idarucizumab reverses the anticoagulant effect of dabigatran, potentially allowing for thrombolysis. This nation-wide observational cohort study, systematic review, and meta-analysis evaluated the efficacy and safety of thrombolysis preceded by dabigatran-reversal in people with acute ischemic stroke. Patients and methods: We recruited people undergoing thrombolysis following dabigatran-reversal at 17 stroke centers in Italy (reversal-group), people on dabigatran treated with thrombolysis without reversal (no-reversal group), and age, sex, hypertension, stroke severity, and reperfusion treatment-matched controls in 1:7 ratio (control-group). We compared groups for symptomatic intracranial hemorrhage (sICH, main outcome), any brain hemorrhage, good functional outcome (mRS 0–2 at 3 months), and death. The systematic review followed a predefined protocol (CRD42017060274), and odds ratio (OR) meta-analysis was implemented to compare groups. Results: Thirty-nine patients in dabigatran-reversal group and 300 matched controls were included. Reversal was associated with a non-significant increase in sICH (10.3% vs 6%, aOR = 1.32, 95% CI = 0.39–4.52), death (17.9% vs 10%, aOR = 0.77, 95% CI = 0.12–4.93) and good functional outcome (64.1% vs 52.8%, aOR = 1.41, 95% CI = 0.63–3.19). No hemorrhagic events or deaths were registered in no-reversal group (n = 12). Pooling data from 3 studies after systematic review (n = 1879), reversal carried a non-significant trend for sICH (OR = 1.53, 95% CI = 0.67–3.50), death (OR = 1.53, 95% CI = 0.73–3.24) and good functional outcome (OR = 2.46, 95% CI = 0.85–7.16). Discussion and conclusion: People treated with reperfusion strategies after dabigatran reversal with idarucizumab seem to have a marginal increase in the risk of sICH but comparable functional recovery to matched patients with stroke. Further studies are needed to define treatment cost-effectiveness and potential thresholds in plasma dabigatran concentration for reversal.

IMPORTANCE Cryptogenic strokes constitute approximately 40% of ischemic strokes in young adults, and most meet criteria for the embolic stroke of undetermined source (ESUS). Two randomized clinical trials, NAVIGATE ESUS and RESPECT ESUS, showed a high rate of stroke recurrence in older adults with ESUS but the prognosis and prognostic factors among younger individuals with ESUS is uncertain. OBJECTIVE To determine rates of and factors associated with recurrent ischemic stroke and death and new-onset atrial fibrillation (AF) among young adults. DESIGN, SETTING, AND PARTICIPANTS This multicenter longitudinal cohort study with enrollment from October 2017 to October 2019 and a mean follow-up period of 12 months ending in October 2020 included 41 stroke research centers in 13 countries. Consecutive patients 50 years and younger with a diagnosis of ESUS were included. Of 576 screened, 535 participants were enrolled after 1 withdrew consent, 41 were found to be ineligible, and 2 were excluded for other reasons. The final follow-up visit was completed by 520 patients. MAIN OUTCOMES AND MEASURES Recurrent ischemic stroke and/or death, recurrent ischemic stroke, and prevalence of patent foramen ovale (PFO). RESULTS The mean (SD) age of participants was 40.4 (7.3) years, and 297 (56%) participants were male. The most frequent vascular risk factors were tobacco use (240 patients [45%]), hypertension (118 patients [22%]), and dyslipidemia (109 patients [20%]). PFO was detected in 177 participants (50%) who had transthoracic echocardiograms with bubble studies. Following initial ESUS, 468 participants (88%) were receiving antiplatelet therapy, and 52 (10%) received anticoagulation. The recurrent ischemic stroke and death rate was 2.19 per 100 patient-years, and the ischemic stroke recurrence rate was 1.9 per 100 patient-years. Of the recurrent strokes, 9 (64%) were ESUS, 2 (14%) were cardioembolic, and 3 (21%) were of other determined cause. AF was detected in 15 participants (2.8%; 95% CI, 1.6-4.6). In multivariate analysis, the following were associated with recurrent ischemic stroke: history of stroke or transient ischemic attack (hazard ratio, 5.3; 95% CI, 1.8-15), presence of diabetes (hazard ratio, 4.4; 95% CI, 1.5-13), and history of coronary artery disease (hazard ratio, 10; 95% CI, 4.8-22). CONCLUSIONS AND RELEVANCE In this large cohort of young adult patients with ESUS, there was a relatively low rate of subsequent ischemic stroke and a low frequency of new-onset AF. Most recurrent strokes also met the criteria for ESUS, suggesting the need for future studies to improve our understanding of the underlying stroke mechanism in this population.

Background: The “1-3-6-12-day rule” for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severity. Methods: The combined data of prospective registries in Japan, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-nonvalvular atrial fibrillation (September 2011 to March 2014) and RELAXED (February 2014 to April 2016) were used. Patients were divided into transient ischemic attack and 3 stroke subgroups by the National Institutes of Health Stroke Scale score: mild (0–7), moderate (8–15), and severe (≥16). The early treatment group was defined as patients starting DOACs earlier than the median initiation day in each subgroup. Outcomes included a composite of recurrent stroke or systemic embolism, ischemic stroke, and severe bleeding within 90 days. Six European prospective registries were used for validation. Results: In the 1797 derivation cohort patients, DOACs were started at median 2 days after transient ischemic attack and 3, 4, and 5 days after mild, moderate, and severe strokes, respectively. Stroke or systemic embolism was less common in Early Group (n=785)—initiating DOACS within 1, 2, 3, and 4 days, respectively—than Late Group (n=1012) (1.9% versus 3.9%; adjusted hazard ratio, 0.50 [95% CI, 0.27–0.89]), as was ischemic stroke (1.7% versus 3.2%, 0.54 [0.27–0.999]). Major bleeding was similarly common in the 2 groups (0.8% versus 1.0%). On validation, both ischemic stroke (2.4% versus 2.2%) and intracranial hemorrhage (0.2% versus 0.6%) were similarly common in Early (n=547) and Late (n=1483) Groups defined using derivation data. Conclusions: In Japanese and European populations, early DOAC initiation within 1, 2, 3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding. These findings support ongoing randomized trials to better establish the optimal timing of DOAC initiation.

The risk of stroke and cerebrovascular disease complicating infection with SARS-CoV-2 has been extensively reported since the onset of the pandemic. The striking efforts of many scientists in cooperation with regulators and governments worldwide have rapidly brought the development of a large landscape of vaccines against SARS-CoV-2. The novel DNA and mRNA vaccines have offered great flexibility in terms of antigen production and led to an unprecedented rapidity in effective and safe vaccine production. However, as mass vaccination has progressed, rare but catastrophic cases of thrombosis have occurred in association with thrombocytopenia and antibodies against PF4 (platelet factor 4). This catastrophic syndrome has been named vaccine-induced immune thrombotic thrombocytopenia. Rarely, ischemic stroke can be the symptom onset of vaccine-induced immune thrombotic thrombocytopenia or can complicate the course of the disease. In this review, we provide an overview of stroke and cerebrovascular disease as a complication of the SARS-CoV-2 infection and outline the main clinical and radiological characteristics of cerebrovascular complications of vaccinations, with a focus on vaccine-induced immune thrombotic thrombocytopenia. Based on the available data from the literature and from our experience, we propose a therapeutic protocol to manage this challenging condition. Finally, we highlight the overlapping pathophysiologic mechanisms of SARS-CoV-2 infection and vaccination leading to thrombosis.

Background and Purpose: Sex-related differences exist in many aspects of acute stroke and were mainly investigated in the early time window with conflicting results. However, data regarding sex disparities in late presenters are scarce. Therefore, we sought to investigate differences in outcomes between women and men treated with endovascular treatment in the late time window. Methods: Analyses were based on the SOLSTICE Consortium (Selection of Late-Window Stroke for Thrombectomy by Imaging Collateral Extent), which was an individual-patient level analysis of seven trials and registries. Baseline characteristics, 90-day functional independence (modified Rankin Scale score ≤2), mortality, and symptomatic intracranial hemorrhage were compared between women and men. Effect of sex on the association of age and successful reperfusion (final Thrombolysis in Cerebral Infarction 2b–3) with outcomes was assessed using multivariable logistic regression adjusted for age, National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score, time from onset to puncture, occlusion location, intravenous thrombolysis, and successful reperfusion, with interaction terms. Results: Among 608 patients treated with endovascular treatment, 50.5% were women. Women were older than men (median age of 72 versus 68 years, P =0.02) and had a lower prevalence of tandem occlusions (14.0% versus 22.9%, P =0.005). Workflow times were similar between sexes. Adjusted outcomes did not differ between women and men. Functional independence at 90 days was achieved by 127 out of 292 women (43.5%) and 135 out of 291 men (46.4%). Mortality at 90 days (54 [18.5%] versus 48 [16.5%]) and symptomatic intracranial hemorrhage (37 [13.3%] versus 33 [11.6%]) were similar between women and men. There was no sex-by-age interaction on functional outcomes. However, men had higher likelihood of mortality ( P interaction =0.003) and symptomatic intracranial hemorrhage ( P interaction =0.017) with advancing age. Sex did not influence the relation between successful reperfusion and outcomes. Conclusions: In this multicenter analysis of late patients treated with endovascular treatment, sex was not associated with functional outcome. However, sex influenced the association between age and safety outcomes, with men experiencing worse outcomes with advancing age.

Background: Randomized controlled trials (RCTs) proved that short-term (21–90 days) dual antiplatelet therapy (DAPT) reduces the risk of early ischemic recurrences after a noncardioembolic minor stroke or high-risk transient ischemic attack (TIA) without substantially increasing the hemorrhagic risk. We aimed at understanding whether and how real-world use of DAPT differs from RCTs. Methods: READAPT (Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or TIA) is a prospective cohort study including >18-year-old patients treated with DAPT after a noncardioembolic minor ischemic stroke or high-risk TIA from 51 Italian centers. The study comprises a 90-day follow-up from symptom onset. In the present work, we reported descriptive statistics of baseline data of patients recruited up to July 31, 2022, and proportions of patients who would have been excluded from RCTs. We compared categorical data through the χ² test. Results: We evaluated 1070 patients, who had 72 (interquartile range, 62–79) years median age, were mostly Caucasian (1045; 97.7%), and were men (711; 66.4%). Among the 726 (67.9%) patients with ischemic stroke, 226 (31.1%) did not meet the RCT inclusion criteria because of National Institutes of Health Stroke Scale score >3 and 50 (6.9%) because of National Institutes of Health Stroke Scale score >5. Among the 344 (32.1%) patients with TIA, 69 (19.7%) did not meet the RCT criteria because of age, blood pressure, clinical features, duration of TIA, presence of diabetes score 24 hours) DAPT initiation; 776 (72.5%) and 676 (63.2%) patients did not take loading doses of aspirin and clopidogrel, respectively. Overall, 84 (7.8%) patients met the RCT inclusion/exclusion criteria. Conclusions: The real-world use of DAPT is broader than RCTs. Most patients did not meet the RCT criteria because of the severity of ischemic stroke, lower risk of TIA, late DAPT start, or lack of antiplatelet loading dose. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05476081.

ObjectiveTo test the hypothesis that IV thrombolysis (IVT) treatment before endovascular thrombectomy (EVT) is associated with better outcomes in patients with anterior circulation large artery occlusion (LAO) stroke, we examined a large real-world database, the Safe Implementation of Treatment in Stroke–International Stroke Thrombectomy Register (SITS-ISTR).MethodsWe identified centers recording ≥10 consecutive patients in the SITS-ISTR, with at least 70% available modified Rankin Scale (mRS) scores at 3 months during 2014 to 2019. We defined LAO as intracranial internal carotid artery, first and second segment of middle cerebral artery, and first segment of anterior cerebral artery. Main outcomes were functional independence (mRS score 0–2) and death at 3 months and symptomatic intracranial hemorrhage (SICH) per modified SITS–Monitoring Study. We performed propensity score–matched (PSM) and multivariable logistic regression analyses.ResultsOf 6,350 patients from 42 centers, 3,944 (62.1%) received IVT. IVT + EVT–treated patients had less frequent atrial fibrillation, ongoing anticoagulation, previous stroke, heart failure, and prestroke disability. PSM analysis showed that IVT + EVT–treated patients had a higher rate of functional independence than patients treated with EVT alone (46.4% vs 40.3%,p< 0.001) and a lower rate of death at 3 months (20.3% vs 23.3%,p= 0.035). SICH rates (3.5% vs 3.0%,p= 0.42) were similar in both groups. Multivariate adjustment yielded results consistent with PSM.ConclusionPretreatment with IVT was associated with favorable outcomes in EVT-treated LAO stroke in the SITS-ISTR. These findings, while indicative of international routine clinical practice, are limited by observational design, unmeasured confounding, and possible residual confounding by indication.Classification of EvidenceThis study provides Class II evidence that IVT before EVT increases the probability of functional independence at 3 months compared to EVT alone.

Background Covert brain infarcts are associated with important neurological morbidity. Their incidence in patients with embolic stroke of undetermined source (ESUS) is unknown. Aims To assess the incidence of covert brain infarcts and cerebral microbleeds using MRI in a prospective substudy of the NAVIGATE ESUS randomized trial and to evaluate the effects of antithrombotic therapies. Methods At 87 sites in 15 countries, substudy participants were randomly assigned to receive rivaroxaban 15 mg daily or aspirin 100 mg daily and underwent brain MRI near randomization and after study termination. The primary outcome was incident brain infarct (clinical ischemic stroke or covert brain infarct). Brain infarcts and microbleeds were ascertained centrally by readers unaware of treatment. Treatment effects were estimated using logistic regression. Results Among the 718 substudy participants with interpretable, paired MRIs, the mean age was 67 years and 61% were men with a median of 52 days between the qualifying ischemic stroke and randomization and a median of seven days between randomization and baseline MRI. During the median (IQR) 11 (12) month interval between scans, clinical ischemic strokes occurred in 27 (4%) participants, while 60 (9%) of the remaining participants had an incident covert brain infarct detected by MRI. Assignment to rivaroxaban was not associated with reduction in the incidence of brain infarct (OR 0.77, 95% CI 0.49, 1.2) or of covert brain infarct among those without clinical stroke (OR 0.85, 95% CI 0.50, 1.4). New microbleeds were observed in 7% and did not differ among those assigned rivaroxaban vs. aspirin (HR 0.95, 95% CI 0.52–1.7). Conclusions Incident covert brain infarcts occurred in twice as many ESUS patients as a clinical ischemic stroke. Treatment with rivaroxaban compared with aspirin did not significantly reduce the incidence of covert brain infarcts or increase the incidence of microbleeds, but the confidence intervals for treatment effects were wide. Registration: https://www.clinicaltrials.gov . Unique identifier: NCT 02313909

Background and Purpose Cerebral edema (CED) in ischemic stroke can worsen prognosis and about 70% of patients who develop severe CED die if treated conservatively. We aimed to describe incidence, risk factors and outcomes of CED in patients with extensive ischemia.Methods Oservational study based on Safe Implementation of Treatments in Stroke-International Stroke Treatment Registry (2003–2019). Severe hemispheric syndrome (SHS) at baseline and persistent SHS (pSHS) at 24 hours were defined as National Institutes of Health Stroke Score (NIHSS) >15. Outcomes were moderate/severe CED detected by neuroimaging, functional independence (modified Rankin Scale 0–2) and death at 90 days.Results Patients (n=8,560) presented with SHS and developed pSHS at 24 hours; 82.2% received intravenous thrombolysis (IVT), 10.5% IVT+thrombectomy, and 7.3% thrombectomy alone. Median age was 77 and NIHSS 21. Of 7,949 patients with CED data, 3,780 (47.6%) had any CED and 2,297 (28.9%) moderate/severe CED. In the multivariable analysis, age 128.5 mg/dL (RR, 1.21), and decreased level of consciousness (RR, 1.14) were associated with moderate/severe CED (for all P

Background and Purpose: Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non–vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHA 2 DS 2 -VASc and HAS-BLED scores in the same setting. Methods: Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHA 2 DS 2 -VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events. Results: Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHA 2 DS 2 -VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468–0.525) and 0.530 (95% CI, 0.500–0.560), respectively. Conclusions: Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHA 2 DS 2 -VASc scores.

BackgroundThe benefit, safety, and time intervals of mechanical thrombectomy (MT) in patients with in-hospital stroke (IHS) are unclear. We sought to evaluate the outcomes and treatment times for IHS patients compared with out-of-hospital stroke (OHS) patients receiving MT.MethodsWe analyzed data from the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) between 2015 and 2019. We compared the functional outcomes (modified Rankin Scale (mRS) scores) at 3 months, recanalization rates, and symptomatic intracranial hemorrhage (sICH) after MT. Time intervals from stroke onset-to-imaging, onset-to-groin, and onset-to-end MT were recorded for both groups, as were door-to-imaging and door-to-groin for OHS. A multivariate analysis was performed.ResultsOf 5619 patients, 406 (7.2%) had IHS. At 3 months, IHS patients had a lower rate of mRS 0–2 (39% vs 48%, PConclusionDespite favorable time intervals for MT, IHS patients had worse functional outcomes than OHS patients. Delays in IHS management were detected.

BackgroundClinical trials and observational studies have demonstrated the benefit of thrombectomy up to 16 or 24 hours after the patient was last known to be well. This study aimed to evaluate the outcome of stroke patients treated beyond 24 hours from onset.MethodsWe analyzed the outcome of 34 stroke patients (mean age 70.7±12.3 years; median National Institutes of Health Stroke Scale (NIHSS) score 13) treated with endovascular thrombectomy beyond 24 hours from onset who were recruited in the Italian Registry of Endovascular Thrombectomy in Acute Stroke. Selection criteria for patients were: pre-stroke modified Rankin scale (mRS) score of ≤2, non-contrast CT Alberta Stroke Program Early CT score of ≥6, good collaterals on single phase CT angiography (CTA) or multiphase CTA, and CT perfusion mismatch with an infarct core size ≤50% of the total hypoperfusion extent or involving less than one-third of the extent of the middle cerebral artery territory evaluated by visual inspection. The primary outcome measure was functional independence assessed by the mRS at 90 days after onset. Safety outcomes were 90 day mortality and the occurrence of symptomatic intracranial hemorrhage (sICH).ResultsSuccessful recanalization (Thrombolysis in Cerebral Infarction score of 2b or 3) was present in 76.5% of patients. Three month functional independence (mRS score 0–2) was observed in 41.1% of patients. The case fatality rate was 26.5%. and the incidence of sICH was 8.8%.ConclusionsThese findings suggest that, in a real world setting, very late endovascular therapy is feasible in appropriately selected patients.

Acute ischemic stroke with isolated occlusion of the M2-segment middle cerebral artery (MCA) has not been a focus of trials on mechanical thrombectomy (MT) thus far. We aimed to assess outcomes in stroke patients treated with different endovascular procedures versus direct MT alone for isolated M2-MCA occlusion. We conducted a cohort study on data from 506 stroke patients with isolated M2-MCA occlusion who were enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke cohort. We calculated odds ratio (OR) with confidence interval (CI) of different endovascular procedures (vs direct MT alone) for outcomes after adjustment for age, enrollment period, pre-stroke mRS score, NIHSS score, ASPECT score, onset-to-groin time, and procedure time. Endovascular procedures were direct MT alone (n = 156), intravenous thrombolysis (IVT) plus MT (n = 266), MT plus intra-arterial thrombolysis (IAT) (n = 43), and IAT alone (n = 41). MT plus IAT was associated with higher rates of TICI 2b/3 (OR 3.281, 95% CI 1.006-10.704), 3-month mRS 0-1 (OR 4.153, 95% CI 1.267-13.612), and 3-month mRS 0-2 (OR 4.497, 95% CI 1.485-13.617). IAT alone was associated with lower rates of TICI 3 (OR 0.348, 95% CI 0.139-0.874) and TICI 2b/3 (OR 0.369, 95% CI 0.144-0.948). IVT plus MT was associated with higher rate of asymptomatic ICH (OR 2.526, 95% CI 1.145-5.571). No significant difference was found between different endovascular procedures and direct MT alone as regards symptomatic ICH and 3-month death. In stroke patients with isolated M2-MCA occlusion, MT plus IAT was associated with better outcomes as compared with direct MT alone.

Background: Uncertainties remain about the role of common thrombophilia markers as determinants of the ischemic stroke (IS) risk. Polymorphism His1299Arg in the FV gene, named R2 haplotype (FVHR2), has been poorly investigated. The aim of the present study was to assess the prevalence of common thrombophilia markers and of FVHR2 in a cohort of IS patients compared to a nonmatched group of healthy individuals. Methods: We studied 156 consecutive patients survivors of a first ever IS and 124 healthy controls. All subjects were investigated for the gene polymorphisms factor V (FV) Leiden, prothrombin (PTH) G20210A, MTHFR C677T, and FVHR2. Protein C (PC), protein S (PS), antithrombin (ATIII), and lupus anticoagulant (LAC) activity was measured. Homocysteinemia was assessed within 48 hours and after 30 days from stroke onset. Univariate and multivariate analyses were performed. Results: Compared with controls, patients were significantly older (mean [SD] age, 50.5 [12.9] vs 37.5 [15.5] years, P < .001), less frequently females (48.1% vs 67.7%, P = .001) and had more frequently hyperhomocysteinemia (45.9% vs 11.0%) only in the acute phase (OR 6.899, CI 95% 2.993-15.899; P < .001). No differences were found in the prevalence of FV Leiden, PTH G20210A, and MTHFR C677T between patients and controls, whereas FVHR2 was present in 34/156 (22%) stroke patients and in 5/124 (4%) controls (OR 6.632, 95% CI 2.509-17.535, P < .001). In a multivariate logistic regression analysis, the FVHR2 resulted independently associated with the occurrence of IS (OR 6.071, 95% CI 1.762-20.923; P = .004). Conclusions: In our study, hyperhomocysteinemia was confirmed to be a transient consequence of the thrombotic event. FVHR2 seems to be a possible candidate prothrombotic condition related to arterial IS irrespective of age and sex in an Italian sample population.

Background: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. Methods: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. Results: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA 2 DS 2 -VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0–1.3] for each point increase; P =0.05) and hypertension (OR, 2.3 [95% CI, 1.0–5.1]; P =0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0–1.2] for each year increase; P =0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4–14.2]; P =0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4–5.5]; P =0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8–1.7]). Conclusions: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.

[Backgroun] Statins have an important role in stroke prevention, especially in high-risk populations and may also affect the initial stroke severity and outcomes in patients taking them before an ischemic stroke., [Aims] Our aim was to evaluate the association of statin pre-treatment with the severity in acute ischemic stroke (AIS)., [Methods] We analyzed AIS patients received intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT) and recorded in the SITS International Thrombolysis and Thrombectomy Registry from 2011 to 2017. We identified patients with statin information at baseline. The primary outcome was baseline National Institutes of Health Stroke Scale (NIHSS) score. Secondary outcomes were NIHSS score at 24 h, symptomatic intracerebral hemorrhage (SICH) and functional outcome at 90 days after acute intervention. Multivariable linear and logistic regression and propensity score matching (PSM) was used to quantify the effect of statin pre-treatment., [Results] Of 93,849 patients, 23,651 (25.2%) were treated with statins prior the AIS. Statin pre-treatment group was older and had higher comorbidity. Median NIHSS at baseline was similar between groups. In the adjusted and PSM analysis, statin pre-treatment was inversely associated with baseline NIHSS (odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.6–0.99 and OR for PSM 0.73, 95% CI = 0.54–0.99, p = 0.004) and independently associated with mild stroke defined as NIHSS ⩽8 in adjusted and PSM analysis (OR = 1.21, 95% CI = 1.1–1.34, p, [Conclusion] Prior treatment with statins was associated with lower NIHSS at baseline. However, this association did not translate into any difference regarding functional outcome at 90 days. No association was found regarding SICH. These findings indicate the need of further studies to assess the effect on statin pre-treatment on initial stroke severity.

We aimed to examine the association between Careggi Collateral Score (CCS) and radiological outcomes in a large multicenter cohort of patients receiving thrombectomy for stroke with occlusion of middle cerebral artery (MCA). We conducted a study on prospectively collected data from 1785 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. According to the extension of the retrograde reperfusion in the cortical anterior cerebral artery-MCA territories, CCS ranges from 0 (absence of retrograde filling) to 4 (visualization of collaterals until the alar segment of the MCA). Radiological outcomes at 24 h were the presence and severity of infarct growth defined by the absolute change in ASPECTS from baseline to 24 h; presence and severity of cerebral bleeding defined as no ICH, HI-1, HI-2, PH-1, or PH-2; presence and severity of cerebral edema (CED) defined as no CED, CED-1, CED-2, or CED-3. Using CCS = 0 as reference, ORs of CCS grades were significantly associated in the direction of better radiological outcome on infarct growth (0.517 for CCS = 1, 0.413 for CCS = 2, 0.358 for CCS = 3, 0.236 for CCS = 4), cerebral bleeding grading (0.485 for CCS = 1, 0.445 for CCS = 2, 0.400 for CCS = 3, 0.379 for CCS = 4), and CED grading (0.734 for CCS = 1, 0.301 for CCS = 2, 0.295 for CCS = 3, 0.255 for CSS = 4) shift in ordinal regression analysis after adjustment for pre-defined variables (age, NIHSS score, ASPECTS, occlusion site, onset-to-groin puncture time, procedure time, and TICI score). Using CCS = 4 as reference, ORs of CCS grades were significantly associated in the direction of worse radiological outcome on infarct growth (1.521 for CCS = 3, 1.754 for CCS = 2, 2.193 for CCS = 1, 4.244 for CCS = 0), cerebral bleeding grading (2.498 for CCS = 0), and CED grading (1.365 for CCS = 2, 2.876 for CCS = 1, 3.916 for CCS = 0) shift. The CCS could improve the prognostic estimate of radiological outcomes in patients receiving thrombectomy for stroke with MCA occlusion.

Introduction To identify predictors of 3-month mRS score and to estimate the benefit from successful recanalization across baseline subgroups of Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) cohort of stroke patients receiving endovascular treatments according to the DIRECT-MT criteria. Methods Using a model of propensity score matching, we retrospectively identified an IRETAS cohort of 137 patients receiving bridging who were matched with 137 patients receiving MT alone according to the DIRECT-MT criteria. Results Differences were found between DIRECT-MT and IRETAS cohorts for 3-month mRS score 0 to 1 (23.5% vs. 33.1%) and 0 to 2 (36.7% vs. 47.1%), successful (82% vs. 76.7%) and complete recanalization (32.3% vs. 58.8%). Among unfavorable predictors for 3-month mRS shift, diabetes mellitus (18.9% vs. 13.9%) and asymptomatic intracerebral hemorhage (ICH) (34.8% vs. 25.5%) were more frequent in the DIRECT-MT, whereas age ≥80 years (23.7% vs. 15.3%) and pre-stroke mRS score >0 (16.1% vs. 7.8%) were more frequent in the IRETAS. The direction of effect on the 3-month mRS shift (6 to 0) favored successful recanalization across all strata. Greatest benefit from successful recanalization was observed in patients with most severe strokes (NIHSS ≥20, OR:4.002; 16–19, OR:3.292; 2–5, OR:2.470) and most proximal occlusion site (intra-cranial ICA, OR:4.092; M1-MCA, OR:3.705; M2-MCA, OR:2.001), in younger patients (18–59 years, OR:3.677; 60–79, OR:3.267; ≥80, OR:1.993), and in patients who started the treatment earlier (onset-to-groin time ≤205 min, OR:4.361; onset-to-groin time >205, OR:2.326). Conclusions The benefit from successful recanalization for 3-month mRS shift in the direction of favorable outcome was different across baseline subgroups.

Ischaemic stroke is the second leading cause of mortality and disability in the western world. Revascularization interventions are the cornerstone of the acute treatment of this pathology and must be administered as soon as possible after the patient’s arrival. They consist of intravenous thrombolysis (IVT) with alteplase, recommended by the guidelines within 4.5 h of the onset of symptoms, and endovascular treatment, recommended within 6 h of the onset of symptoms. The individualized patient selection based on the extent of the mismatch between the penumbra and the ischaemic core allowed to overcome the limits imposed by the rigid time windows, defining a benefit of mechanical revascularization therapies up to 24 h from the theoretical onset of symptoms (last time the patient was known to be well) and up to 9 h for IVT since the theoretical onset of symptoms (last time the patient was known to be well). Advanced neuroimaging methods with perfusion studies are a fundamental tool in patient selection. Their spread in the territory, together with a greater availability of neurovascular treatment units are desirable to ensure a fair delivery of treatment to all patients with ischaemic stroke.

Objectives Aim of this study was to evaluate the association between cerebral microbleeds (CMBs) and white matter disease (WMD) with intracerebral hemorrhage (ICH) after intravenous thrombolysis (IVT) with rt-PA. We also evaluated whether CMBs characteristics and WMD burden correlate with symptomatic ICH and outcome. Methods We included acute ischemic stroke (AIS) patients treated with IVT. The number and location of CMBs as well as severity of WMD were rated analyzing pre- or post-treatment MRI. Multivariable regression analysis was used to determine the impact of CMB and WMD on ICH subgroups and outcome measures. Results 434 patients were included. CMBs were detected in 23.3% of them. ICH occurred in 34.7% of patients with CMBs. Independent predictors of parenchymal hemorrhage were the presence of CMBs (OR 2.724, 95% CI 1.360–5.464, p = 0.005) as well as cortical-subcortical stroke (OR 3.629, 95% CI 1.841–7.151, p < 0.001) and atherothrombotic stroke subtype (OR 3.381, 95% CI 1.335–8.566, p = 0.010). Either the presence, or number, and location of CMBs, as well as WMD, was not independently associated with the development of SICH. No independent association between the presence, number, or location of CMBs or WMD and outcome measures was observed. Conclusions The results of our study suggest that the exclusion of eligible candidates to administration of IV rt-PA only on the basis of CMBs presence is not justified. The clinical decision should be weighed with a case-by-case approach. Additional data are needed to evaluate the benefit-risk profile of rt-PA in patients carrying numerous microbleeds.

Background and purpose: Early neurological deterioration (END) after stroke onset may predict severe outcomes. Estimated rates of END after intravenous thrombolysis among small patient samples have been reported up to 29.8%. We studied the incidence and factors associated with END among patients following intravenous thrombolysis. Methods: We analyzed SITS-International Stroke Thrombolysis registry patients with known outcomes enrolled in 2010 to 2017. END was defined as an increase in National Institutes of Health Stroke Scale score ≥4 or death within 24 hours from baseline National Institutes of Health Stroke Scale. We determined the incidence of END and used logistic regression models to inspect its associated factors. We adjusted for variables found significant in univariate analyses ( P Results: We excluded 53 539 patients and included 50 726 patients. The incidence of END was 3415/50 726 (6.7% [95% CI, 6.5%–7.0%]). Factors independently associated with END on multivariate analysis were intracerebral hemorrhage (OR, 3.23 [95% CI, 2.96–3.54], P P P P P P Conclusions: The routinely observed rate of END reflected by real-world data is low, but END greatly increases risk of disability and mortality. Readily identifiable factors predict END and may help with understanding causal mechanisms to assist prevention of END.

Intravenous thrombolysis (IVT)-ineligible patients undergoing direct thrombectomy tended to have poorer functional outcome as compared with IVT-eligible patients undergoing bridging therapy. We aimed to assess radiological and functional outcomes in large vessel occlusion-related stroke patients receiving direct thrombectomy in the presence of absolute exclusion criteria for IVT vs relative exclusion criteria for IVT and vs non-exclusion criteria for IVT. A cohort study on prospectively collected data from 2282 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke cohort for treatment with direct thrombectomy (n = 486, absolute exclusion criteria for IVT alone; n = 384, absolute in combination with relative exclusion criteria for IVT; n = 777, relative exclusion criteria for IVT alone; n = 635, non-exclusion criteria for IVT). After adjustment for unbalanced variables (model 1), ORs for 3-month death was higher in the presence of absolute exclusion criteria for IVT alone (vs relative exclusion criteria for IVT alone) (1.595, 95% CI 1.042–2.440) and in the presence of absolute exclusion criteria for IVT alone (vs non-exclusion criteria for IVT) (1.235, 95% CI 1.014–1.504). After adjustment for predefined variables (model 2: age, sex, pre-stroke mRS ≤ 1, NIHSS, occlusion in the anterior circulation, onset-to-groin time, and procedure time), ORs for 3-month death was higher in the presence of absolute exclusion criteria for IVT alone (vs relative exclusion criteria for IVT alone) (1.235, 95% CI 1.014–1.504) and in the presence of absolute exclusion criteria for IVT alone (vs non-exclusion criteria for IVT) (1.246, 95% CI 1.039–1.495). No significant difference was found between the groups as regards any type of intracerebral hemorrhage and parenchymal hematoma within 24 h, successful and complete recanalization after procedure, and modified Rankin Scale score 0–2 at 3 months. After adjustment for predefined variables of model 2, ORs for death were higher in the presence of recent administration of IV heparin (OR: 2.077), platelet count

Introduction The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. Materials and Methods Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39–2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16–1.80). Discussion our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. Conclusions Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.

Background and Purpose— A large infarct and expanding cerebral edema (CED) due to a middle cerebral artery occlusion confers a 70% mortality unless treated surgically. Reperfusion may cause blood-brain barrier disruption and a risk for cerebral edema and secondary parenchymal hemorrhage (PH). We aimed to investigate the effect of recanalization on development of early CED and PH after recanalization therapy. Methods— From the SITS-International Stroke Treatment Registry, we selected patients with signs of artery occlusion at baseline (either Hyperdense Artery Sign or computed tomography/magnetic resonance imaging angiographic occlusion). We defined recanalization as the disappearance of radiological signs of occlusion at 22 to 36 hours. Primary outcome was moderate to severe CED and secondary outcome was PH on 22- to 36-hour imaging scans. We used logistic regression with adjustment for baseline variables and PH. Results— Twenty two thousand one hundred eighty-four patients fulfilled the inclusion criteria (n=18 318 received intravenous thrombolysis, n=3071 received intravenous thrombolysis+thrombectomy, n=795 received thrombectomy). Recanalization occurred in 64.1%. Median age was 71 versus 71 years and National Institutes of Health Stroke Scale score 15 versus 16 in the recanalized versus nonrecanalized patients respectively. Recanalized patients had a lower risk for CED (13.0% versus 23.6%), adjusted odds ratio (aOR), 0.52 (95% CI, 0.46–0.59), and a higher risk for PH (8.9% versus 6.5%), adjusted odds ratio, 1.37 (95% CI, 1.22–1.55), than nonrecanalized patients. Conclusions— In patients with acute ischemic stroke, recanalization was associated with a lower risk for early CED even after adjustment for higher rate for PH in recanalized patients.

Introduction: Although stroke occurs frequently in patients with cancer, there is scarce evidence regarding the safety and efficacy of endovascular treatment (EVT) in patients with acute ischemic stroke and concurrent cancer. We performed a systematic review and meta-analysis to summarize the existing literature. Methods: We searched for English written observational studies reporting data on safety and efficacy of EVT in patients with acute ischemic stroke and concurrent cancer. Outcomes of interest were: functional independence (modified Rankin Scale (mRS) ⩽ 2); mortality at 3 months; rate of successful recanalization (modified Treatment In Cerebral Ischemia (mTICI) 2b or 3); occurrence of any hemorrhagic transformation (both symptomatic and asymptomatic). We pooled data with Maentel-Haenszel model to calculate cumulative odds ratios (ORs). Results: We included seven studies with a total of 4465 patients, of whom 262 (6%) with cancer. We observed various definitions of cancer across included studies. Patients with cancer had less likely mRS⩽2 at 3 months (24% vs 42%, OR = 0.44; 95% CI = 0.32–0.60) and increased probability of death (43% vs 19%, OR = 5.02; 95% CI = 2.90–8.69). There was no difference in successful recanalization (70% vs 75%, OR = 0.84; 95% CI = 0.49–1.44); patients with cancer had increased risk of any intracerebral hemorrhage after treatment (49% vs 34%, OR = 1.95; 95% CI = 1.28–2.96), though not for symptomatic ICH (OR 1.04; 95% CI = 0.59–1.85). Conclusion: Patients with acute ischemic stroke and cancer have similar EVT recanalization but higher probability of functional dependence, death, and any hemorrhagic transformation, though not necessarily symptomatic, compared with patients without cancer. Our results may help communication with patients and carers.

Background: Efficient healthcare workflow leads to faster reperfusion and better functional outcomes of stroke in the early-time window. We investigated the impact of care delays on the outcomes of stroke patients treated with endovascular thrombectomy (EVT) in the late window. Methods: Pooled data from seven randomized clinical trials and registries that only included patients who underwent EVT in the late time window (onset/last known well (LKW) time to imaging time of 6 hours or more) were combined for this analysis. The time intervals from stroke onset to successful reperfusion were analyzed. Logistic regression was used to estimate the likelihood of a functionally independent outcome at 90 days (modified Rankin scale 0-2) for each time interval while adjusting for relevant patients’ characteristics. Negative binomial regression was used to evaluate the relationship between each time interval and the predictors. Results: 584 patients were included in this analysis. The median age was 70 years (IQR: 21), 293 [50.17%] were females, 298 (53.31%) had wake-up strokes, and the median ASPECTS was 8 (IQR: 2). All patients had CT, and CTA imaging, and 360 (61.64%) underwent perfusion imaging. Successful reperfusion was achieved in 469 (80.45%) patients, and 249 (44.54%) had independent outcomes at 90 days. For every 30 minutes delay, the estimated probability of functional independence decreased by 19% for the emergency department (ED) arrival to imaging time interval, by 25% from groin puncture to end of EVT, and by 12% from ED arrival to end of EVT. Older age and higher NIHSS were associated with longer time from imaging to groin puncture. However, only age was associated with a longer estimated times from stroke onset/LKW to arrival in ED and from stroke onset/LKW to the end of EVT. Conclusion: Faster in-hospital care is associated with improved functional independence among late-window patients. Page 1

Background and Purpose: Sex-related differences exist in many aspects of stroke and were mainly investigated in the early time window with conflicting results. However, data regarding sex disparities in late presenters are scarce. Therefore, we sought to investigate differences in outcomes between women and men treated with endovascular treatment (EVT) in the late time window. Methods: Analyses were based on the Selection Of Late-window Stroke for Thrombectomy by Imaging Collateral Extent Consortium, which was an individual-patient level analysis of seven trials and registries. Baseline characteristics, functional independence (modified Rankin Scale ≤ 2), mortality, and symptomatic intracranial hemorrhage (sICH) were compared between women and men. Effect of sex on the association between age, successful reperfusion (Thrombolysis in cerebral infarction 2b-3) and outcomes was assessed using multivariable logistic regression with interaction terms. Results: Among 608 patients treated with EVT, 50.5% were women. Women were older than men by median 4 years and had a lower prevalence of tandem occlusions (14.0% vs. 22.9%). In the subset of patients with available perfusion volumes (n= 195), women had smaller penumbra (median IQR:97 mL [60- 130] vs. 109 mL [73-189]; p= 0.008), and mismatch volumes, (79 mL [49-101] vs. 91 mL [57-158] ; p= 0.02). Pre and intrahospital times were similar between sexes. Outcomes did not differ between women and men, and there was no sex-by-age interaction on functional independence. However, men had higher likelihood of mortality (p interaction = 0.004) and sICH (p interaction = 0.016) with advancing age. Sex did not influence the relation between successful reperfusion and outcomes. Conclusions: In this multicenter analysis of late presenters treated with EVT, sex was not associated with clinical outcomes. However, sex influenced the association between age and safety outcomes with men experiencing worse outcomes with advancing age.

Background and purpose We sought to investigate whether there are gender differences in clinical outcome after stroke due to large vessel occlusion (LVO) after mechanical thrombectomy (EVT) in a large population of real-world patients. Methods From the Italian Registry of Endovascular Thrombectomy, we extracted clinical and outcome data of patients treated for stroke due to large vessel occlusion. We compared clinical and safety outcomes in men and women who underwent EVT alone or in combination with intravenous thrombolysis (IVT) in the total population and in a Propensity Score matched set. Results Among 3422 patients included in the study, 1801 (52.6%) were women. Despite older age at onset (mean 72.4 vs 68.7; p Conclusions Subject to the limitations of a non-randomized comparison, women with stroke due to LVO treated with mechanical thrombectomy had a better chance to achieve complete recanalization, and 3-month functional independence than men. The results could be driven by women who underwent combined treatment.