Treatment Of Acute Stroke Research Articles

The feasibility of mechanical thrombectomy versus medical management for acute stroke with a large ischemic territory

BackgroundMechanical thrombectomy (MT) for acute ischemic stroke is generally avoided when the expected infarction is large (defined as an Alberta Stroke Program Early CT Score of <6).ObjectiveTo perform a meta-analysis...

Rationale and design of Treatment of Acute Ischaemic Stroke with Edaravone Dexborneol II (TASTE-2): a multicentre randomised controlled trial

BackgroundEdaravone dexborneol is believed to be a novel cytoprotective drug, demonstrating a synergistic combination of antioxidative and anti-inflammatory properties in animal models. The Treatment of Acute Ischaemic Stroke with Edaravone...

Orbital infarction syndrome following mechanical thrombectomy in internal carotid artery occlusion: a case report

BackgroundOrbital ischemic syndrome is a rare entity. The clinical signs typically demonstrate acute loss of visual acuity, chemosis, proptosis, ptosis, and total ophthalmoparesis. We report a case of a man who suffered an acute internal carotid artery occlusion and developed orbital ischemic syndrome after a mechanical thrombectomy.Case presentationA 57-year-old Vietnamese (Kinh ethnicity) man was brought to the emergency room with complaints of a speech disturbance, facial palsy, and severe weakness of the left arm and leg, which had started 4 hours earlier, after waking up. The National Institutes of Health Stroke Scale 12 (NIHSS 12) revealed the neurological score at admission. A head computed tomography scan showed no intracranial bleeding and an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 8 on the right brain. Computed tomography angiography showed an occlusion of the right internal carotid artery. After that, a mechanical thrombectomy was performed, and the internal carotid artery was completely reperfused. After 10 hours, he experienced orbital pain, proptosis, ptosis, chemosis, and ophthalmoplegia of the right orbit. He also had acute loss of visual acuity, and fundoscopic examination revealed papilledema, no retinal hemorrhage, and no bruit in orbital auscultation. Intraocular pressure in the right eye was measured at 50.5 mmHg. Computed tomography angiography showed no carotid–cavernous fistula, but slight enlargement of the right medial and lateral rectus muscles. He was treated with steroids and hyperosmolar agents and recovered 7 days later, but had persistent loss of visual acuity in the right eye.ConclusionOrbital ischemic syndrome is a rare complication after mechanical thrombectomy treatment in acute ischemic stroke that can lead to loss of visual acuity.

Targeting lipid nanoparticles to the blood-brain barrier to ameliorate acute ischemic stroke

Effective delivery of mRNA or small molecule drugs to the brain is a significant challenge in developing treatment for acute ischemic stroke. To address the problem, we have developed targeted nanomedicine to increase drug concentrations in endothelial cells of the blood-brain barrier (BBB) of the injured brain. Inflammation during ischemic stroke causes continuous neuronal death and increase of the infarct volume. To enable targeted delivery to the inflamed BBB, we conjugated lipid nanocarriers with antibodies that bind cell adhesion molecules expressed at the BBB. In the transient middle cerebral artery occlusion mouse model, nanocarriers targeted to VCAM achieved the highest level of brain delivery, nearly 2 orders of magnitude higher than untargeted ones. VCAM-targeted lipid nanoparticles with luciferase-encoding mRNA and Cre-recombinase showed selective expression in the ischemic brain. Anti-inflammatory drugs administered intravenously after ischemic stroke reduced cerebral infarct volume by 62% (IL-10 mRNA) or 35% (dexamethasone) only when they were encapsulated in VCAM-targeted nanocarriers. Thus, VCAM-targeted lipid nanocarriers represent a new platform for strongly concentrating drugs within the compromised BBB of penumbra, thereby ameliorating acute ischemic stroke.

Impact of dementia status on intravenous thrombolysis and endovascular treatment for acute ischemic stroke: Retrospective study

IntroductionIndividuals with dementia are underrepresented in interventional studies for acute ischemic stroke (AIS). This research gap creates a bias against their treatment in clinical practice. Our goal was to compare the safety and efficacy of intravenous-thrombolysis (t-PA) and endovascular treatment (EVT) in individuals with or without pre-AIS dementia. MethodA retrospective study of AIS patients receiving t-PA or EVT between 2019 and 2022. Patients were classified as dementia on a case-by-case review of baseline assessment. Additional variables included demographic, vascular risk factors, AIS severity and treatment. Outcomes of interest were intracerebral hemorrhage, mortality in 90-days, and the difference in modified rankin scale (mRS) before AIS and in 90-days follow-up. Outcomes were compared across non-matched groups and following propensity-score matching. ResultsAltogether, 628 patients were included, of which 68 had pre-AIS dementia. Compared to non-dementia group, dementia group were older, had a higher rate of vascular risk factors, higher pre-stroke mRS and higher baseline NIHSS. Individuals with dementia had higher rates of mortality (25% vs.11%,p < 0.01) on non-matched comparison. All cohort and restricted t-PA EVT matched analysis showed no difference in any outcome. Regression analysis confirmed that AIS severity at presentation and its treatment, not dementia, were the chief contributors to patients' outcomes. DiscussionOur results indicate that pre-AIS dementia does not impact the efficacy or safety of EVT or t-PA for AIS. We thus call for more inclusive research on stroke therapy with regards to baseline cognitive status. Such studies are urgently required to inform stroke guidelines and enhance care.

Effect of Postoperative Prolonged sedation with Dexmedetomidine after successful reperfusion with Endovascular Thrombectomy on long-term prognosis in patients with acute ischemic stroke (PPDET): study protocol for a randomized controlled trial

BackgroundEndovascular thrombectomy (EVT) is a standard treatment for acute ischemic stroke (AIS) with large vessel occlusion. Hypertension and increased blood pressure variability within the first 24 h after successful reperfusion are related to a higher risk of symptomatic intracerebral hemorrhage and higher mortality. AIS patients might suffer from ischemia-reperfusion injury following reperfusion, especially within 24 h. Dexmedetomidine (DEX), a sedative commonly used in EVT, can stabilize hemodynamics by inhibiting the sympathetic nervous system and alleviate ischemia-reperfusion injury through anti-inflammatory and antioxidative properties. Postoperative prolonged sedation for 24 h with DEX might be a potential pharmacological approach to improve long-term prognosis after EVT.MethodsThis single-center, open-label, prospective, randomized controlled trial will include 368 patients. The ethics committee has approved the protocol. After successful reperfusion (modified thrombolysis in cerebral infarction scores 2b–3, indicating reperfusion of at least 50% of the affected vascular territory), participants are randomly assigned to the intervention or control group. In the intervention group, participants will receive 0.1~1.0 μg/kg/h DEX for 24 h. In the control group, participants will receive an equal dose of saline for 24 h. The primary outcome is the functional outcome at 90 days, measured with the categorical scale of the modified Rankin Scale, ranging from 0 (no symptoms) to 6 (death). The secondary outcome includes (1) the changes in stroke severity between admission and 24 h and 7 days after EVT, measured by the National Institute of Health Stroke Scale (ranging from 0 to 42, with higher scores indicating greater severity); (2) the changes in ischemic penumbra volume/infarct volume between admission and 7 days after EVT, measured by neuroimaging scan; (3) the length of ICU/hospital stay; and (4) adverse events and the all-cause mortality rate at 90 days.DiscussionThis randomized clinical trial is expected to verify the hypothesis that postoperative prolonged sedation with DEX after successful reperfusion may promote the long-term prognosis of patients with AIS and may reduce the related socio-economic burden.Trial registrationClinicalTrials.gov NCT04916197. Prospectively registered on 7 June 2021.

Pharmacological preclinical comparison of tenecteplase and alteplase for the treatment of acute stroke

Alteplase (rtPA) remains the standard thrombolytic drug for acute ischemic stroke. However, new rtPA-derived molecules, such as tenecteplase (TNK), with prolonged half-lives following a single bolus administration, have been developed. Although TNK is currently under clinical evaluation, the limited preclinical data highlight the need for additional studies to elucidate its benefits. The toxicities of rtPA and TNK were evaluated in endothelial cells, astrocytes, and neuronal cells. In addition, their in vivo efficacy was independently assessed at two research centers using an ischemic thromboembolic mouse model. Both therapies were tested via early (20 and 30 min) and late administration (4 and 4.5 h) after stroke. rtPA, but not TNK, caused cell death only in neuronal cultures. Mice were less sensitive to thrombolytic therapies than humans, requiring doses 10-fold higher than the established clinical dose. A single bolus dose of 2.5 mg/kg TNK led to an infarct reduction similar to perfusion with 10 mg/kg of rtPA. Early administration of TNK decreased the hemorrhagic transformations compared to that by the early administration of rtPA; however, this result was not obtained following late administration. These two independent preclinical studies support the use of TNK as a promising reperfusion alternative to rtPA.

Effect of anesthesia mode during endovascular treatment on neurological functional outcomes in patients with acute posterior circulation stroke.

To compare the effect of anesthesia mode on the neurological functional outcomes in patients undergoing endovascular treatment for acute posterior circulation ischemic stroke. Clinical data of 656 patients undergoing intravascular therapy for acute posterior circulation ischemic stroke registered in online Acute Stroke Patients for Stroke Management Quality Evaluation Database from January 2017 to December 2022 were retrospectively analyzed. The data included 163 cases with conscious sedation and 493 cases with general anesthesia during the procedure. After propensity score matching, 428 patients were included in the analysis, including 155 cases in the conscious sedation group and 273 cases in the general anesthesia group. The differences of operation mode, etiology type, vascular recanalization, hemorrhagic transformation at 24 h, modified Rankin Scale (mRS) score at 3 months and mortality within 3 months were compared between the two groups. Binary logistic regression was used to explore the effect of different anesthesia mode on neurological functional outcomes. There was a significant difference in operation mode between the two groups (P<0.01), while there were no significant differences in etiology type, vascular recanalization, hemorrhagic transformation at 24 h, mRS score at 3 months or mortality within 3 months (all P>0.05). Binary logistic regression analysis revealed that anesthesia modes were not significantly associated with functional outcomes of patients (OR=1.151, 95%CI: 0.751-1.765, P>0.05). Anesthesia mode (conscious sedation or general anesthesia) will not affect the neurological functional outcomes in patients with acute posterior circulation ischemic stroke undergoing endovascular treatment.

Anesthetic management for large vessel occlusion acute ischemic stroke with tandem lesions

BackgroundEndovascular therapy (EVT) stands as an established and effective intervention for acute ischemic stroke in patients harboring tandem lesions (TLs). However, the optimal anesthetic strategy for EVT in TL patients...

Coronary Microvascular Disease Registry (CMDR): Study design and rationale

BackgroundCoronary microvascular dysfunction (CMD) is a prevalent condition among patients with cardiovascular risk factors, leading to a reduced quality of life and an increased risk of major adverse cardiovascular events. Novel invasive techniques have emerged to more accurately diagnose CMD. However, CMD's natural history remains poorly understood due to limited data. To address this knowledge gap, the Coronary Microvascular Disease Registry (CMDR) was established with the primary aim of standardizing comprehensive coronary functional testing and understanding of CMD. DesignCMDR is a prospective, multicenter registry enrolling an unlimited number of consecutive subjects who undergo comprehensive invasive hemodynamic assessment of the entire coronary arterial vasculature. Patients undergoing acetylcholine provocation test for coronary vasospasm will also be included. Follow-up assessments will be conducted at 30 days and annually for up to 5 years. The primary endpoint is Canadian Cardiovascular Society angina grade over time. Secondary endpoints, including all-cause mortality, cardiovascular death, acute myocardial infarction, stroke, hospitalizations, medication changes, and subsequent coronary interventions, will be analyzed to establish long-term safety and clinical outcomes in patients undergoing invasive CMD assessment. SummaryCMDR aims to characterize the clinical and physiologic profile of patients undergoing comprehensive invasive coronary functional testing, simultaneously providing crucial longitudinal information on the natural history and outcomes of these patients. This will shed light on CMD's course and clinical implications, which, in turn, holds the potential to significantly improve diagnostic and treatment strategies for CMD patients, ultimately leading to the enhancement of their overall prognosis and quality of life. Clinical trial registrationclinicaltrials.gov, NCT05960474

Thrombectomy

Endovascular procedures have become the standard treatment for acute stroke caused by large vessel occlusion. Various strategies are available, including stent retrieval, aspiration catheter placement, and combined techniques. However, the first-pass effect can be maximized using the technique most familiar to each surgeon and institution. Therefore, it is necessary to understand the characteristics of each device and develop case-specific treatment strategies.

The MAPSTROKE project: A computational strategy to improve access to acute stroke care.

Global access to acute stroke treatment is variable worldwide, with notable gaps in low and middle-income countries (LMIC), especially in rural areas. Ensuring a standardized method for pinpointing the existing regional coverage and proposing potential sites for new stroke centers is essential to change this scenario. To create and apply computational strategies (CSs) to determine optimal locations for new acute stroke centers (ASCs), with a pilot application in nine Latin American regions/countries. Hospitals treating acute ischemic stroke (AIS) with intravenous thrombolysis (IVT) and meeting the minimum infrastructure requirements per structured protocols were categorized as ASCs. Hospitals with emergency departments, noncontrast computed tomography (NCCT) scanners, and 24/7 laboratories were identified as potential acute stroke centers (PASCs). Hospital geolocation data were collected and mapped using the OpenStreetMap data set. A 45-min drive radius was considered the ideal coverage area for each hospital based on the drive speeds from the OpenRouteService database. Population data, including demographic density, were obtained from the Kontur Population data sets. The proposed CS assessed the population covered by ASCs and proposed new ASCs or artificial points (APs) settled in densely populated areas to achieve a target population coverage (TPC) of 95%. The observed coverage in the region presented significant disparities, ranging from 0% in the Bahamas to 73.92% in Trinidad and Tobago. No country/region reached the 95% TPC using only its current ASCs or PASCs, leading to the proposal of APs. For example, in Rio Grande do Sul, Brazil, the introduction of 132 new centers was suggested. Furthermore, it was observed that most ASCs were in major urban hubs or university hospitals, leaving rural areas largely underserved. The MAPSTROKE project has the potential to provide a systematic approach to identify areas with limited access to stroke centers and propose solutions for increasing access to AIS treatment. Data used for this publication are available from the authors upon reasonable request.

The Relevance of Reperfusion Stroke Therapy for miR-9-3p and miR-9-5p Expression in Acute Stroke-A Preliminary Study.

Reperfusion stroke therapy is a modern treatment that involves thrombolysis and the mechanical removal of thrombus from the extracranial and/or cerebral arteries, thereby increasing penumbra reperfusion. After reperfusion therapy, 46% of patients are able to live independently 3 months after stroke onset. MicroRNAs (miRNAs) are essential regulators in the development of cerebral ischemia/reperfusion injury and the efficacy of the applied treatment. The first aim of this study was to examine the change in serum miRNA levels via next-generation sequencing (NGS) 10 days after the onset of acute stroke and reperfusion treatment. Next, the predictive values of the bioinformatics analysis of miRNA gene targets for the assessment of brain ischemic response to reperfusion treatment were explored. Human serum samples were collected from patients on days 1 and 10 after stroke onset and reperfusion treatment. The samples were subjected to NGS and then validated using qRT-PCR. Differentially expressed miRNAs (DEmiRNAs) were used for enrichment analysis. Hsa-miR-9-3p and hsa-miR-9-5p expression were downregulated on day 10 compared to reperfusion treatment on day 1 after stroke. The functional analysis of miRNA target genes revealed a strong association between the identified miRNA and stroke-related biological processes related to neuroregeneration signaling pathways. Hsa-miR-9-3p and hsa-miR-9-5p are potential candidates for the further exploration of reperfusion treatment efficacy in stroke patients.

Incidence and clinical outcomes of perforations during mechanical thrombectomy for medium vessel occlusion in acute ischemic stroke: A retrospective, multicenter, and multinational study.

Mechanical thrombectomy (MT) has revolutionized the treatment of acute ischemic stroke (AIS) due to large vessel occlusion (LVO), but its efficacy and safety in medium vessel occlusion (MeVO) remain less explored. This multicenter, retrospective study aims to investigate the incidence and clinical outcomes of vessel perforations (confirmed by extravasation during an angiographic series) during MT for AIS caused by MeVO. Data were collected from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021. A total of 1373 AIS patients with MeVO underwent MT. Baseline characteristics, procedural details, and clinical outcomes were analyzed. The incidence of vessel perforation was 4.8% (66/1373). Notably, our analysis indicates variations in perforation rates across different arterial segments: 8.9% in M3 segments, 4.3% in M2 segments, and 8.3% in A2 segments (p = 0.612). Patients with perforation had significantly worse outcomes, with lower rates of favorable angiographic outcomes (TICI 2c-3: 23% vs 58.9%, p < 0.001; TICI 2b-3: 56.5% vs 88.3%, p < 0.001). Functional outcomes were also worse in the perforation group (mRS 0-1 at 3 months: 22.7% vs 36.6%, p = 0.031; mRS 0-2 at 3 months: 28.8% vs 53.9%, p < 0.001). Mortality was higher in the perforation group (30.3% vs 16.8%, p = 0.008). This study reveals that while the occurrence of vessel perforation in MT for AIS due to MeVO is relatively rare, it is associated with poor functional outcomes and higher mortality. The findings highlight the need for increased caution and specialized training in performing MT for MeVO. Further prospective research is required for risk mitigation strategies.

Registration study for the prevention and treatment of cerebral hemorrhage using naoxueshu oral liquid: Protocol for a research study

BackgroundNaoxueshu oral liquid is the only approved drug for acute treatment of cerebral hemorrhage in China. It has been used widely for the treatment of acute ischemic stroke and acute hemorrhagic stroke. However, safety and efficacy data on the early use of Naoxueshu oral liquid are lacking. The main purpose of this study is to observe the benefit and safety of early use of Naoxueshu oral liquid (< 72 h of cerebral hemorrhage) and offer evidence into the potential superiority of Naoxueshu oral liquid in patients with hemorrhagic stroke, and its healthcare costs. MethodsThis registration study for the prevention and treatment of cerebral hemorrhage using Naoxueshu oral liquid will be a quantitative, prospective, multicenter, observational clinical registry study. We aim to register 2000 patients with cerebral hemorrhage within 7 days of disease onset. This study will be an observational study and not interfere with the medication regimen of participants. Hence, we will not allocate patients. The main observation indicators will be the hematoma volume and the proportion of reduction 14 days post-cerebral hemorrhage (or at hospital discharge), onset of new stroke (ischemic stroke, hemorrhagic stroke) within 12 months of disease onset, independence in everyday life activities (modified Rankin Scale score ≤ 2), total cost during hospitalization, and treatment costs. ConclusionThis registration study will offer strong evidence for the efficacy and safety of Naoxueshu oral liquid for the prevention and treatment of cerebral hemorrhage, particularly with regard to early use (72 h after onset). It will offer evidence into the potential advantages of Naoxueshu oral liquid in patients with hemorrhagic stroke, including healthcare costs.

Effect of continuous 2MHz transcranial ultrasound as an adjunct to tenecteplase thrombolysis in acute anterior circulation ischemic stroke patients: an open labeled non-randomized clinical trial.

The treatment of acute ischemic stroke has improved in last few decades. While meta-analyses of several trials have established the safety and efficacy of Intravenous (IV) Tenecteplase thrombolysis, concomitant continuous transcranial doppler (TCD) ultrasound administration has not been assessed in any clinical trial. The aim of this study was to determine the effects of continuous 2MHz TCD ultrasound during IV Tenecteplase thrombolysis for Middle cerebral artery (MCA) stroke. A total of 19 patients were included, 13 received TCD ultrasound and 6 sham TCD with IV Tenecteplase. TCD spectrum and difference in Pre and post TCD parameters were measured. Asymptomatic hemorrhagic transformation of infarct wasseen in two patients. There was no mortality or clinical worsening in thesonothrombolysis group as against sham sonothrombolysis group. Median of peak systolic velocity wasincreased in both thesonothrombolysis (P = 0.0002) and sham sonothrombolysis group (P-value = 0.001). The difference in change in mean flow velocity between two groups, sonothrombolysis (11cm/sec)and sham sonothrombolysis (3.5cm/sec) were also significantly different (P = 0.014). This pilot work has established safety of continuous 30min TCD application along with IV Tenecteplase thrombolysis and it concludes thatconcomitant 2MHz TCD ultrasound administration significantly increased the MCA blood flow compared to chemothrombolysis alone.CTRI Registered Number: CTRI/2021/02/031418.

Intensive vs Conventional Blood Pressure Control After Thrombectomy in Acute Ischemic Stroke

Endovascular thrombectomy (EVT) is standard treatment for acute ischemic stroke (AIS) due to large-vessel occlusion (LVO), but optimal post-EVT blood pressure (BP) control remains debated. To assess the association of different systolic BP targets following EVT with functional outcomes, mortality, and complications in patients with AIS due to LVO. Systematic review and meta-analysis of databases (PubMed, Embase, Web of Science, Scopus, and Cochrane Library) to September 8, 2023. Inclusion criteria consisted of randomized clinical trials examining post-EVT management of systolic BP in patients with AIS and LVO comparing intensive vs conventional targets. Nonrandomized studies, observational studies, noninterventional trials, meeting abstracts, duplicate studies, studies with overlapping data, and non-English language studies were excluded. Two authors independently applied these criteria through a blinded review, with discrepancies resolved through consensus. The risk of bias in the included studies was assessed using the revised tool for assessing risk of bias in randomized trials. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Three authors extracted data regarding study characteristics, baseline patient data, and outcomes of interest. The pooled data were analyzed using a random-effects meta-analysis. Rates of functional independence, 90-day mortality, symptomatic intracranial hemorrhage, and hypotensive events. A total of 4 randomized clinical trials with 1571 initially enrolled patients were included in the analysis. Lower functional independence rates were observed in the intensive control group (relative risk [RR], 0.81 [95% CI, 0.67-0.98]). No significant differences were found in 90-day mortality (RR, 1.18 [95% CI, 0.92-1.52]), symptomatic intracranial hemorrhage (RR, 1.12 [95% CI, 0.75-1.67]), or hypotensive events (RR, 1.80 [95% CI, 0.37-8.76]). There was minimal heterogeneity among the studies included in the functional independence outcome (I2 = 13% and τ2 = 0.003), which was absent among other outcomes (I2 = 0 and τ2 = 0). These findings suggest that intensive post-EVT BP reduction does not yield benefits and may carry risks. While awaiting the results of additional ongoing trials, a conservative BP management strategy after endovascular recanalization is favored in daily practice.

Are we missing an opportunity? Prehospital delay in patients with acute ischemic stroke and known atrial fibrillation

Introduction and ObjectivesThe follow-up of patients with atrial fibrillation (AF) presents an opportunity to alert patients and their families on how to recognize and act in the event of stroke. Our aim was to compare stroke recognition-to-door time and prehospital stroke code activation in patients with known AF (KAF) and AF detected after stroke (AFDAS). MethodsWe performed a retrospective cohort study of consecutive patients receiving acute recanalization treatment for acute ischemic stroke between January 2016 and August 2022, with AF as a potential stroke cause. Patients were divided into KAF and AFDAS, and stroke recognition-to-door time and prehospital stroke code activation were compared. In the KAF subgroup, we assessed whether the use of preadmission anticoagulation was associated with the studied prehospital parameters. ResultsWe included 438 patients, 290 female (66.2%), mean age 79.3±9.4 years. In total, 238 patients had KAF (54.3%) and 200 (45.7%) had AFDAS. Of those with KAF, 114 (48.1%) were pretreated with anticoagulation. Patients with KAF and AFDAS had no differences in stroke recognition-to-door time (74.0 [55.0–101.0] vs. 78.0 [60.0–112.0] min; p=0.097) or prehospital stroke code activation [148 (64.6%) vs. 128 (65.3%); p=0.965]. In the KAF subgroup, preadmission anticoagulation did not influence stroke recognition-to-door time or mode of hospital admission. ConclusionStroke recognition-to-door time and prehospital stroke code activation were similar between patients with known or newly diagnosed AF. Preadmission anticoagulation treatment also did not affect the studied parameters. Our findings highlight a missed opportunity to promote stroke knowledge in patients followed due to AF.

Short-Term and Long-Term Risk of Recurrent Vascular Event by Cause After Ischemic Stroke in Young Adults

Cause of ischemic stroke in young people is highly variable; however, the risk of recurrence is often presented with all subtypes of stroke grouped together in classification systems such as the Trial of ORG (danaparoid sodium [Orgaran]) 10172 in Acute Stroke Treatment (TOAST) criteria, which limits the ability to individually inform young patients with stroke about their risk of recurrence. To determine the short-term and long-term risk of recurrent vascular events after ischemic stroke at a young age by stroke cause and to identify factors associated with recurrence. This cohort study used data from the Observational Dutch Young Symptomatic Stroke Study, a prospective, multicenter, hospital-based cohort study, conducted at 17 hospitals in the Netherlands between 2013 and 2021. Eligible participants included 30-day survivors of an initial, neuroimaging-proven ischemic stroke (aged 18-49 years). Data analysis was conducted from June to July 2023. Diagnosis of a first-ever, ischemic stroke via neuroimaging. The primary outcome was short-term (within 6 months) and long-term (within 5 years) recurrence risk of any vascular event, defined as fatal or nonfatal recurrent ischemic stroke, transient ischemic attack, myocardial infarction, and revascularization procedure. Predefined characteristics were chosen to identify factors associated with risk of recurrence (cause of stroke, age, sex, stroke severity, and cardiovascular health factors). A total of 1216 patients (median [IQR] age, 44.2 [38.4-47.7] years; 632 male [52.0%]; 584 female [48.0%]) were included, with a median (IQR) follow-up of 4.3 (2.6-6.0) years. The 6-month risk of any recurrent ischemic event was 6.7% (95% CI, 5.3%-8.1%), and the 5-year risk was 12.2% (95% CI, 10.2%-14.2%)The short-term risk was highest for patients with cervical artery dissections (13.2%; 95% CI, 7.6%-18.7%). Other factors associated with a recurrent short-term event were atherothrombotic stroke, rare causes of stroke, and hypertension. The long-term cumulative risk was highest for patients with atherothrombotic stroke (22.7%; 95% CI, 10.6%-34.7%) and lowest for patients with cryptogenic stroke (5.8%; 95% CI, 3.0%-8.5%). Cardioembolic stroke was associated with a recurrent long-term event, as were diabetes and alcohol abuse. The findings of this cohort study of 1216 patients with an ischemic stroke at a young age suggest that the risk of recurrent vascular events was high and varied by cause of stroke both for short-term and long-term follow-up, including causes that remained concealed when combined into 1 category in the routinely used TOAST criteria. This knowledge will allow for more personalized counseling of young patients with stroke.

Sex Differences in Perihematomal Edema Volume and Outcome After Intracerebral Hemorrhage.

Although larger hematoma volume is associated with worse outcome after intracerebral hemorrhage (ICH), the association between perihematomal edema (PHE) volume and outcome remains uncertain, as does the impact of sex on PHE and outcome. Here we aimed to determine whether larger PHE volume is associated with worse outcome and whether PHE volume trajectories differ by sex. We conducted a post hoc analysis of the Factor VIIa for Acute Hemorrhagic Stroke Treatment (FAST) trial, which randomized patients with ICH to receive recombinant activated factor VIIa or placebo. Computerized planimetry calculated PHE and ICH volumes on serial computed tomography (CT) scans (at baseline [within 3h of onset], at 24h, and at 72h). Generalized estimating equations examined interactions between sex, CT time points, and FAST treatment arm on PHE and ICH volumes. Mixed and multivariable logistic models examined associations between sex, PHE, and outcomes. A total of 781 patients with supratentorial ICH (mean age 65years) were included. Compared to women (n = 296), men (n = 485) had similar median ICH (14.9 vs. 13.6mL, p = 0.053) and PHE volumes (11.1 vs. 10.5mL, p = 0.56) at baseline but larger ICH and PHE volumes at 24h (19.0 vs. 14.0mL, p < 0.001; 22.2 vs. 15.7mL, p < 0.001) and 72h (16.0 vs. 11.8mL, p < 0.001; 28.7 vs. 19.9mL, p < 0.001). Men had higher absolute early PHE expansion (p < 0.001) and more hematoma expansion (growth ≥ 33% or 6mL at 24h, 33% vs. 22%, p < 0.001). An interaction between sex and CT time points on PHE volume (p < 0.001), but not on ICH volume, confirmed a steeper PHE trajectory in men. PHE expansion (per 5mL, odds radio 1.19, 95% confidence interval 1.10-1.28), but not sex, was associated with poor outcome. Early PHE expansion and trajectory in men were significantly higher. PHE expansion was associated with poor outcomes independent of sex. Mechanisms leading to sex differences in PHE trajectories merit further investigation.