Importance:In the Left Atrial Appendage Occlusion Study III (LAAOS III), surgical occlusion of the LAA during cardiac surgery for patients with known history of atrial fibrillation (AF) substantially reduced the risk of stroke. Objective:To assess the impact of LAAO on ischemic stroke subtype and outcome. Design, Setting, and Participants:This was a post hoc exploratory analysis of the LAAOS III randomized clinical trial. Data were adjudicated from June 28, 2023, to November 29, 2023, and the main analyses took place from December 18, 2023, to April 29, 2024. The LAAOS III trial recruited participants from 105 centers in 27 countries between July 2012 and October 2018. Patients with AF and a CHA2DS2-VASc score of at least 2 undergoing cardiac surgery for other indications were included in the analysis. Interventions:Surgical LAAO plus standard care vs standard care alone. Main Outcomes and Measures:For strokes occurring during the trial, the functional outcome as measured by the modified Rankin Scale (mRS) score at day 7 or discharge, mortality, the presence of cortical infarcts, and the occurrence of infarcts of presumed cardioembolic origin were examined. Results:Of 4811 participants in the LAAOS III trial followed up for 3.8 years, 273 had a first ischemic stroke. The mean (SD) age of participants at the time of the first ischemic stroke was 75 (7) years, 104 were female (38%), and 169 were male (62%). Participants allocated to receive LAAO had reduced (common odds ratio [OR], 0.80; 95% CI, 0.65-0.99) mRS scores at 7 days or discharge and a lower risk for mortality at 30 days (16.5% vs 20.1%; hazard ratio [HR], 0.55; 95% CI, 0.31-0.97) after a stroke event. Participants allocated to LAAO had fewer cortical infarcts on neuroimaging (46.2% vs 61.3%; difference in proportions: -15.2%; 95% CI, -26.7% to -3.7%), as well as a lower proportion of ischemic strokes of presumed cardioembolic etiology when compared with ischemic strokes in the no-LAAO group (42.9% vs 57.9%; difference in proportions: -15.1%; 95% CI, -26.5% to -3.7%). Conclusions and Relevance:This study found that LAAO in patients with AF undergoing cardiac surgery was associated with a decreased risk of presumed cardioembolic stroke, reduced disability, and mortality from stroke. These findings underscore the benefit of LAAO for patients with AF undergoing cardiac surgery. Trial Registration:ClinicalTrials.gov Identifier: NCT01561651.

Abstract Background and aims The existence of sex-based differences in outcomes after endovascular thrombectomy (EVT) remains controversial. We aimed to evaluate whether sex is independently associated with process measures and outcomes after EVT in a real-world cohort. Methods We conducted a retrospective cohort study of adult patients with acute ischemic stroke treated with EVT at a comprehensive stroke center between January 1, 2022, and June 20, 2023. Baseline characteristics, procedural variables, and outcomes were compared between males and females. The primary outcome was favorable functional outcome at 3–6 months, defined as modified Rankin Scale (mRS) 0–2. Secondary outcomes included workflow metrics, successful reperfusion, EVT technical details, and intracerebral hemorrhage. Multivariable logistic regression was used to evaluate the independent association between sex and outcome. Results Among 514 patients, 247 (48%) were male and 267 (52%) female. Females were older (p < 0.001), had a higher prevalence of atrial fibrillation (p < 0.001), and lower rates of tandem lesions (p < 0.001) and basilar artery occlusion (p = 0.03). Favorable functional outcome was achieved in 44% of the overall cohort, with no significant difference between sexes. EVT techniques, workflow times, successful reperfusion rates, and periprocedural complications, including symptomatic intracranial hemorrhage, were comparable between groups. After adjustment for age and stroke severity, sex was not independently associated with functional outcome at 90 days. Conclusions In this cohort, functional outcomes did not differ between males and females after adjustment for baseline clinical differences. This is consistent with recent literature reporting comparable functional and radiological outcomes after EVT between sexes. Conflict of interest nothing to disclose

This secondary analysis of the Left Atrial Appendage Occlusion Study III (LAAOS III) randomized clinical trial investigates the impact of LAAO on ischemic stroke subtype and outcome. QuestionAre ischemic stroke events after surgical occlusion of the left atrial appendage (LAAO) during cardiac surgery for patients with known history of atrial fibrillation (AF) of milder severity and less likely to be cardioembolic compared with ischemic stroke events occurring in individuals with AF and without LAAO?FindingsThis post hoc exploratory analysis of the Left Atrial Appendage Occlusion Study III (LAAOS III) trial, which randomized 4811 participants with a history of atrial fibrillation undergoing cardiac surgery to receive surgical LAAO or no LAAO, found that LAAO reduced the mortality and disability from ischemic stroke and the proportion of cardioembolic strokes.MeaningStudy findings complement the reduction in stroke occurrence observed in the primary analysis of the LAAOS III trial and further highlight the benefit of LAAO in stroke prevention among patients with AF undergoing cardiac surgery. ImportanceIn the Left Atrial Appendage Occlusion Study III (LAAOS III), surgical occlusion of the LAA during cardiac surgery for patients with known history of atrial fibrillation (AF) substantially reduced the risk of stroke.ObjectiveTo assess the impact of LAAO on ischemic stroke subtype and outcome.Design, Setting, and ParticipantsThis was a post hoc exploratory analysis of the LAAOS III randomized clinical trial. Data were adjudicated from June 28, 2023, to November 29, 2023, and the main analyses took place from December 18, 2023, to April 29, 2024. The LAAOS III trial recruited participants from 105 centers in 27 countries between July 2012 and October 2018. Patients with AF and a CHA2DS2-VASc score of at least 2 undergoing cardiac surgery for other indications were included in the analysis.InterventionsSurgical LAAO plus standard care vs standard care alone.Main Outcomes and MeasuresFor strokes occurring during the trial, the functional outcome as measured by the modified Rankin Scale (mRS) score at day 7 or discharge, mortality, the presence of cortical infarcts, and the occurrence of infarcts of presumed cardioembolic origin were examined.ResultsOf 4811 participants in the LAAOS III trial followed up for 3.8 years, 273 had a first ischemic stroke. The mean (SD) age of participants at the time of the first ischemic stroke was 75 (7) years, 104 were female (38%), and 169 were male (62%). Participants allocated to receive LAAO had reduced (common odds ratio [OR], 0.80; 95% CI, 0.65-0.99) mRS scores at 7 days or discharge and a lower risk for mortality at 30 days (16.5% vs 20.1%; hazard ratio [HR], 0.55; 95% CI, 0.31-0.97) after a stroke event. Participants allocated to LAAO had fewer cortical infarcts on neuroimaging (46.2% vs 61.3%; difference in proportions: -15.2%; 95% CI, -26.7% to -3.7%), as well as a lower proportion of ischemic strokes of presumed cardioembolic etiology when compared with ischemic strokes in the no-LAAO group (42.9% vs 57.9%; difference in proportions: -15.1%; 95% CI, -26.5% to -3.7%).Conclusions and RelevanceThis study found that LAAO in patients with AF undergoing cardiac surgery was associated with a decreased risk of presumed cardioembolic stroke, reduced disability, and mortality from stroke. These findings underscore the benefit of LAAO for patients with AF undergoing cardiac surgery.Trial RegistrationClinicalTrials.gov Identifier: NCT01561651

Abstract Background and aims Stroke patients with tandem carotid lesions constitute about 15-20% of patients undergoing endovascular thrombectomy (EVT). However, the optimal treatment of acute stroke in these patients remains uncertain with regards to addressing the ICA lesion during EVT or not. Methods To determine if acute cervical ICA stenting in addition to intracranial thrombectomy is superior to intracranial thrombectomy alone without acute cervical ICA stenting with regards to functional outcome at 90 days. Results EASI-TOC is an ongoing Canadian, pragmatic Phase III, multi-centre, prospective, randomized, open-label, blinded endpoint (PROBE) controlled trial. It will enroll 458 adult tandem patients undergoing EVT and randomize them (1:1) to either undergo acute ICA stenting during EVT (either before or after intracranial thrombectomy, as per clinician judgement) or undergo intracranial thrombectomy alone without ICA stenting. Conclusions The primary outcome is the proportion of patients achieving a favorable modified Rankin scale score (mRS 0-2) at 90 days and primary analysis will be by intention-to-treat. Our primary hypothesis assumes a greater proportion of patients with 90-day mRS 0-2 in the stenting group versus the no stenting group (55% versus 40%). Safety outcomes will include symptomatic intracerebral hemorrhage, procedural complications and death. Conflict of interest

BACKGROUND:Patients with stroke due to symptomatic intracranial occlusion and concurrent symptomatic high-grade cervical internal carotid artery (ICA) stenosis (≥70%) or occlusion constitute 15%-20% of patients undergoing EVT. The optimal management of the cervical ICA in these tandem lesions remains unknown. We hypothesise that acute carotid artery stenting in addition to EVT will improve functional outcomes when compared with EVT alone. STUDY DESIGN:Endovascular Acute Stroke Intervention-Tandem Occlusion (EASI-TOC) is a multicentre, prospective, randomised, open-label, blinded end-point (PROBE) controlled trial. Adult patients with a disabling acute anterior circulation stroke (intracranial carotid, M1 or M2 segment occlusion) and salvageable brain tissue who undergo EVT within 24 h of onset, are eligible for enrolment if they have an angiographically confirmed atherosclerotic carotid tandem lesion. Patients are randomised 1:1 to acute carotid stenting or no stenting during EVT. STUDY ENDPOINTS:The primary outcome is the proportion of patients achieving a favourable functional outcome (mRS 0-2) at 90 days. Secondary outcomes include 12-month mRS, recanalisation, the 90-day rate of recurrent ipsilateral stroke or retinal ischaemia, the proportion of patients with ICA thrombosis, 90-day Montreal Cognitive Assessment score and quality of life. Safety outcomes include any ICH, sICH, all-cause mortality and procedural complications. SUMMARY:Endovascular Acute Stroke Intervention-Tandem Occlusion is a pragmatic trial addressing a critical gap in the acute management of patients with tandem carotid lesions by evaluating whether acute carotid stenting provides a functional benefit over no stenting in patients undergoing EVT. TRIAL REGISTRATION:ClinicalTrials.gov NCT04261478.

Stroke in sickle cell disease (SCD) has been well characterized in children, but data in adults remain insufficient, particularly regarding long-term functional consequences. The objective was to determine lifetime prevalence of symptomatic stroke, followed by characterization of stroke type, aetiology, treatments and functional status at last follow-up. We retrospectively reviewed adults (≥18 years) with any SCD phenotype followed at a tertiary centre from 2011 to 2023. Functional status was assessed using the Montreal Cognitive Assessment (MoCA) and Modified Rankin Scale (mRS). Among 454 adults with all major phenotypes of SCD, median age was 32 years [range 18-79] and 261 (57.5%) were women. At last follow-up, 21 individuals (4.6%) had a confirmed history of symptomatic stroke (median age at stroke onset of 42 years [range 4-68]), including 14 (3.1%) with cerebral infarction (median age 32 years [4-68]) and 7 (1.5%) with intracranial haemorrhage (median age 45 years [20-65]). Stroke was associated with marked long-term impairment, represented by lower MoCA (20.6 (±1.3) vs. 26.1 (±0.2), p < 0.001) and higher mRS (2 [1-3] vs. 0 [0-1], p < 0.001). These findings fill a critical evidence gap and underscore the urgency of targeted prevention and intervention strategies in this high-risk population.

Background: Studies have found similar rates of functional independence for men and women after endovascular thrombectomy (EVT). Less is known regarding EVT-related procedural complications and symptomatic intracerebral hemorrhage (sICH) between sexes. Methods: Using the OPTIMISE registry including data from 20 comprehensive stroke centers across Canada between 1/1/2018 and 12/31/2022, we performed a retrospective descriptive analysis of patients divided between men and women. Hemorrhagic transformation on follow-up imaging with associated clinical deterioration was required to define sICH. Results: 3631 patients were included (1778 men and 1853 women) for analysis. Female patients were older (71.8±14.6 vs 68.0±13.1 years, p<0.001). There were no differences in sICH rates (2.5% men vs. 2% women, p= 0.388}. Procedural complication rates were not different between men and women (5.8 vs 5.6% p=0.76): dissection {26 (1.5%) vs. 30 (1.6%), p=0.804}, perforation {11 (0.6%) vs. 7 (0.4%), p=0.426}, embolization {25 (1.4%) vs. 25 (1.3%), p=0.996} and arterial access complications {45 (2.5%) vs. 43 (2.3%), p=0.761}. Conclusions: In this large multicentre registry of stroke patients undergoing EVT, men and women had similarly low and reassuring rates of sICH and procedural complications. This complements previous data showing similar functional outcomes for men and women after EVT.

Background Silent cerebral infarcts (SCI) are well-known risk factors for stroke and cognitive impairment in children with sickle cell disease (SCD), with IQ declining as abnormalities on magnetic resonance imaging (MRI) increase. These lesions accumulate with age, but their long-term impact in adults is less well characterized. Importantly, SCI represent only one category of cerebral vascular injury. Other radiological features—such as white matter hyperintensities, microangiopathy, and aneurysms—may also reflect chronic cerebrovascular damage but remain poorly studied in adults with SCD. Few studies have evaluated how the full spectrum of structural and vascular lesions correlates with cognitive function, education, and employment. The primary objective of this study was to determine the prevalence of the different structural and vascular brain lesions in adults with SCD. Secondly, we aimed to assess their association with cognitive performance and thirdly, examine relationships with educational attainment, occupational status and functional outcomes. Methods We conducted a retrospective cross-sectional study (2016–2024) at a tertiary SCD center. Adults (≥18 years) with any SCD genotype, at least one hematology clinic visit, and cerebral MRI and magnetic resonance angiography (MRI/MRA) with a formal neuroradiology report were included. Patients with prior symptomatic stroke were excluded. Radiological findings included SCI, white matter hyperintensities (WMH) consistent with small vessel disease, microangiopathy, aneurysms, intracranial artery stenosis, and Moya-Moya. SCI were defined as infarct-like lesions ≥3 mm on T2-weighted MRI without neurological symptoms. WMH were categorized based on descriptive terminology consistent with STRIVE-2 guidance. Outcomes included results on MoCA, mRS, educational attainment, years of schooling, and occupational status. Cognitive and functional assessments (MoCA, mRS) were obtained at last follow-up by vascular neurologists in a dedicated neurovascular-SCD clinic. Group differences were assessed using t-tests, Mann-Whitney U, or chi-square tests, as appropriate. A univariate ANCOVA model was used to adjust for age, sex and hypertension. Ethics approval was obtained. Results Among 391 adults (median age 32 [range 18–79]; 56.3% female), 54.2% had HbSS/HbSβ⁰ and 45.8% had HbSC/HbSβ⁺. Treatments included hydroxyurea (66.0%), transfusions (14.8%), and both (5.4%). Antiplatelets were used in 37.9%, anticoagulants in 5.6%, and antihypertensives in 8.7%. At least one silent structural or vascular brain lesion was identified in 259 (66.2%). SCI were found in 30 (7.7%). WMH were observed in 172 (44.0%), microangiopathy in 46 (11.7%), aneurysms in 57 (14.8%), intracranial stenosis in 12 (3.0%), and Moya-Moya in 2 (0.5%). MRI/A was normal in 132 (33.8%). Patients with any abnormality had lower mean MoCA scores (26 vs. 27; p=0.06), although there were no significant differences in mRS (0 [0–1] vs. 1 [0–1]; p=0.54), years of schooling (13 vs. 14; p=0.27), education (χ² (5)=3.40; p=0.64), or occupation (χ² (5)=2.98; p=0.70). SCI were not significantly associated with cognitive or functional outcomes. However, microangiopathy was associated with lower MoCA scores (24 vs. 26; p=0.03), suggesting potential clinical relevance. No significant differences were seen for WMH, aneurysms, or stenosis. Age was significantly associated with MoCA scores (B=-0.095, 95% CI: -0.132 to –0.057, p<0.001), with older age predicting lower scores, while sex (p=0.09) and hypertension (p=0.30) were not. After adjusting for age, sex and hypertension, presence of microangiopathy was significantly associated with lower MoCA scores ((ANCOVA) F (1, 237) = 8.486, p=0.004). Neither SCI (F(1,237) = 0.104, p=0.75), WMH (F(1, 237) = 0.054, p=0.82), aneurysms (F(1, 237) = 0.223, p=0.64), nor stenosis (F(1, 237) = 0.011, p=0.92) were significantly associated with MoCA after adjustment. These findings suggest that microangiopathy may reflect a clinically relevant marker of cognitive vulnerability in adults with SCD, independent of age-related decline. Discussion Subclinical neurovascular injury is common in adults with SCD, with microangiopathy emerging as the only lesion independently associated with lower cognitive performance. These findings underscore the need to look beyond SCI and integrate broader markers of small vessel disease in surveillance strategies aimed at preserving cognitive health in adults with SCD.

Background: Anterior (ACS) and posterior circulation (PCS) stroke patients have different clinical presentations and prognoses, though both benefit from endovascular thrombectomy (EVT). We sought to determine whether ACS and PCS patients treated with EVT differed with regards to treatment metrics and functional outcomes. Methods: We retrospectively analysed the Canadian OPTIMISE registry which included data from 20 comprehensive stroke centers across Canada between January 1, 2018, and December 31, 2022. We performed a descriptive analysis of patients divided in two groups (ACS= carotid artery and its branches, PCS= vertebrobasilar system). Results: Of the 6391 patients included (5929 ACS and 462 PCS), PSC patients were younger (67 vs. 71.3, p<0.001), more often male (61.9% vs. 48.6%, p<0.001), had longer (in minutes) onset-to-door (362 vs. 256, p<0.001), door-to-needle (172 vs. 144, p=0.0016), and onset-to-puncture (459 vs. 329, p<0.001) times. They were less often thrombolyzed (39.8% vs. 50.4%, p<0.001), and more frequently underwent general anesthesia (47.6% vs. 10.6%, p<0.001). Successful reperfusion and functional independence at 90 days were similar between the two groups. Conclusions: Patients with PCS had worst treatment metrics than ACS. Strategies to improve PCS management times are critical to decrease these disparities, including faster pre-hospital recognition and in-hospital workflows.

Background: Telemedicine evaluation for treatment of acute stroke patients with IV thrombolysis has been shown to be beneficial. Its usefulness for the evaluation of patients transferred from a primary stroke centre (PSC) to a comprehensive stroke centre (CSC) for endovascular thrombectomy (EVT) is less well defined. Methods: We retrospectively analyzed the Canadian OPTIMISE registry which included data from 20 comprehensive stroke centers across Canada between January 1, 2018, and December 31, 2022 to compare treatment metrics and early outcomes between two groups: patients evaluated by telemedicine (TM) and patients evaluated in person (non-TM) at the PSC prior to CSC transfer. Results: We included 3317 patients who were transferred from a PSC to a CSC for: 888 TM and 2429 non-TM. There were no major differences in baseline characteristics, including intravenous thrombolysis administration, though the TM group included more men. TM patients had longer onset-to-puncture times (441 vs 403 minutes, p<0.001) and higher symptomatic intracerebral hemorrhage (sICH) rates (7.4% vs 3.7%, p<0.001), but CSC door-to-puncture times and successful recanalization rates did not differ. Conclusions: Patients transferred to a CSC for EVT first evaluated by TM had similar characteristics to those evaluated in person at the PSC, but longer onset-to-puncture times and higher sICH rates.

Background Cerebral vasculopathy in sickle cell disease (SCD) is associated with thrombotic and hemorrhagic stroke. Magnetic resonance angiography (MRA) can detect SCD-related arterial stenosis and aneurysms across the lifespan. In children, transcranial Doppler (TCD) is widely used to screen for elevated stroke risk and guide early intervention. In adults, however, the optimal neurosurveillance strategy remains undefined. While advanced modalities such as transcranial color-coded duplex sonography (TCCD) have shown high diagnostic accuracy compared to MRA, their availability and technical complexity may limit widespread implementation. Standard TCD, a simpler and more accessible tool, remains underexplored in this context. At our institution, all adults with SCD have access to routine TCD as part of standard care since 2021. If TCD-measured cerebral blood flow velocities correlate with MRA-defined vasculopathy, TCD could serve as a resource-efficient first step to identify adults who require further neurovascular imaging, particularly in resource-constrained settings. Objective The primary objective of this study was to assess whether mean flow velocities (MFV) measured by standard transcranial Doppler (TCD) correlate with MRA-defined cerebral vasculopathy (stenosis or aneurysm) in adults with SCD. We also explored whether a threshold MFV in the middle cerebral artery (MCA), the most routinely assessed vessel, could help rule out significant abnormalities on MRA, positioning TCD as a resource-efficient first step in neurosurveillance. Methods We conducted a retrospective study of adults (≥18 years) with SCD who underwent both routine TCD and MRA between 09/2021 and 07/2024 at a tertiary care center. TCD was performed by one of two certified vascular neurologists, measuring MFV in the middle (MCA), anterior (ACA), and posterior (PCA) cerebral arteries; bilateral values were averaged. MRA was performed using gadolinium-enhanced sequences, and radiology reports were reviewed for the presence of arterial stenosis or aneurysm. MFV were compared between patients with and without MRA-defined vasculopathy using independent samples t-tests. The study was approved by the local research ethics board. Results A total of 187 patients were included. The mean age was 35 ±13 years (range 18–79), and 104 (56%) were women. Hemoglobin phenotypes were evenly distributed, with 91 patients (49%) having SS or Sβ⁰-thalassemia and 96 (51%) having SC or Sβ⁺-thalassemia. The mean hemoglobin level was 11 ± 17 g/dL. One patient had a history of overt stroke. Nine patients (4.8%) had at least one MRA-defined stenosis in any of the 3 large vessels. These patients displayed significantly higher MFV in the MCA, but not in the ACA and PCA, as shown below: MCA MFV (cm/s); stenosis / no stenosis: (81 +/- 20) / (67 +/- 17), p = 0.012*. ACA MFV (cm/s); stenosis / no stenosis: (56 +/- 12) / (53 +/- 13), p = 0.230. PCA MFV (cm/s); stenosis / no stenosis: (47 +/- 9) / (38 +/- 11), p = 0.339. Additionally, all but 3 patients with at least one MRA-defined stenosis (any territory) had TCD-measured MFV ≥ 60 cm/s in the MCA (positive predictive value [PPV] 5%, negative predictive value [NPV] 96%). Thirty-three patients (17.6%) had at least one MRA-defined aneurysm. Likewise, they also displayed significantly higher MFV in the MCA, but not in the ACA and PCA, as shown below: MCA MFV (cm/s); aneurysm / no aneurysm: (75 +/- 17) / (66 +/- 17), p = 0.005*. ACA MFV (cm/s); aneurysm / no aneurysm: (56 +/- 12) / (52 +/- 13), p = 0.069. PCA MFV (cm/s); aneurysm / no aneurysm: (39 +/- 9) / (38 +/- 11), p = 0.353 Similarly, all but 2 patients with at least one MRA-defined aneurysm (any territory) had TCD-measured MFV ≥ 60 cm/s in the MCA territory (PPV 28%, NPV 97%). Conclusions Higher MFV in the MCA territory is associated with both MRA-defined stenoses and aneurysm across the 3 major cerebral arteries. An MCA MFV below 60 cm/s demonstrated a high negative predictive value for excluding these abnormalities. As an inexpensive and accessible tool, standard TCD may serve as a useful first-line screening modality in adults with SCD, particularly in resource-limited settings. These associations may reflect compensatory hyperemia or shear stress–related vascular remodeling, both of which warrant further investigation. Longitudinal studies are needed to validate the role of TCD in neurosurveillance and risk stratification.

IntroductionThere are several possible anesthetic strategies during endovascular therapy (EVT) for acute ischemic stroke (AIS), including general anesthesia (GA), conscious sedation (CS), and local anesthesia (LA). While randomized trials have not shown a clear advantage of GA or CS, LA remains understudied. We aimed to determine if LA is associated with better functional outcomes compared to CS in a Canadian EVT registry.Patients and MethodsA retrospective analysis of the OPTIMISE registry was conducted, focusing on adult patients with anterior circulation AIS treated with EVT between January 2018 and December 2021. Patients with available information regarding anesthetic modality and 3-month functional outcome were included. The primary endpoint was a favorable functional outcome at 3 months (defined as a modified Rankin Scale score of 0-2) when using LA compared to CS (average treatment effect [ATE] determined by targeted maximum likelihood estimation). Secondary outcomes included procedural time, favorable reperfusion, complications, and symptomatic intracranial hemorrhage.ResultsA total of 2204 patients were included in the analysis (763 LA, 1441 CS). In the LA group, 57.5% (n = 439) had a favorable outcome at 3 months compared to 55.6% (n = 801) in the CS group (ATE 0.04 [0.00-0.07]; adjusted odds ratio 1.16 [1.01-1.34]; p = 0.04). No significant difference was found between groups regarding reperfusion rates, procedural times, and symptomatic intracranial hemorrhage.ConclusionIn this large, Canadian multicenter cohort of patients undergoing EVT for anterior circulation AIS, LA was safe and led to better functional outcomes at 3 months compared to CS. Given its simplicity and potential benefits, LA warrants greater consideration in clinical practice and inclusion as a treatment arm in future randomized controlled trials studying the optimal anesthetic strategy for EVT.

Background The optimal management of tandem carotid lesions during endovascular thrombectomy (EVT) remains uncertain. The safety and efficacy of acute carotid artery stenting (aCAS) are debated, including safety concerns such as procedural complications and symptomatic intracerebral hemorrhage (sICH). We aimed to assess aCAS safety among EVT-treated patients using a large Canadian registry. Methods We retrospectively analyzed the OPTIMISE registry and compared adult patients undergoing EVT and aCAS versus EVT only. The primary outcome was a composite of in-hospital death, long-term care facility destination at discharge, sICH, or any EVT-related procedural complications. Secondary outcomes included individual components of the primary outcome, EVT workflow times, final modified Thrombolysis in Cerebral Ischemia score and 90-day modified Rankin Scale score. Statistical significance was evaluated by a multivariate logistic regression model. Results 4205 patients were included (330 with EVT-aCAS and 3875 with EVT-only). Both groups were similar with regard to baseline National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score and use of IV thrombolysis, but differed in age (EVT-aCAS group 67.2±12.1 years vs EVT-only group 71.3±14.1 years, P<0.001), proportion of women (28.2% vs 53.3%, P<0.001), and occlusion location (internal carotid artery terminus 44% vs 16%, P<0.001). The EVT-aCAS group showed a non-significant increase in odds of composite safety outcomes (adjusted OR 1.35 (95% CI 0.97 to 1.84), P=0.06) with a significantly higher proportion of procedural complications (10.0% vs 6.2%, P=0.002). Conclusion In a large national registry, EVT-aCAS was associated with a higher proportion of unfavorable safety outcomes, driven by more frequent procedural complications. Further research is needed to clarify the role of aCAS in tandem occlusion stroke.

ABSTRACT: Oral anticoagulation (OAC) prevents stroke in atrial fibrillation, yet a residual stroke risk remains. In this single-center retrospective analysis of acute ischemic stroke patients despite OAC, suboptimal OAC treatment is common (30%: inappropriate dosing (17%); patient non-adherence (13%)). Other causes of stroke included OAC interruption (14.5%), a competing stroke mechanism (11.0%), and undetermined breakthrough stroke in 44.5%. Overall, easily modifiable causes of ischemic stroke despite OAC are common. Accordingly, strategies to improve treatment compliance, including appropriate dosing along with guideline-based risk factor and periprocedural OAC management, should be emphasized to improve secondary stroke prevention in this patient population.

Background Individuals with sickle cell disease (SCD) are at a high risk of stroke throughout their lifespan. Regular transcranial doppler (TCD) screening is widely adopted for children with SCD to identify those in need of treatment intensification. However, TCD screening is not routinely performed beyond ages 16-18. Data on TCD feasibility and standard velocities in adults with SCD are limited. Since 2021, all adults with SCD followed at the Centre Hospitalier de l'Université de Montréal (CHUM) Comprehensive SCD Centre are referred for TCD examination as part of routine neurovascular surveillance, regardless of their genotype, age, comorbidities, or neurologic status. ObjectivesThe primary aim of this study is to determine the feasibility of TCD in unselected adults with SCD. The secondary aim is to report the distribution of Doppler velocities in this population. We also aimed to explore associations between these measures and biological and clinical patient characteristics. Methods In this retrospective study, clinical data of all patients seen at the SCD Center between September 2021 and June 2024 were reviewed and extracted.Patients with routine TCD examination were included in the study sample. Mean flow velocity (MFV) measurements were attempted in all patients for the anterior cerebral artery (ACA), the middle cerebral artery (MCA), the posterior cerebral artery (PCA), and the basilar artery (BasA). Feasibility was assessed using the following definitions: “standard TCD” with successful insonation of both MCA, and “complete TCD” for successful insonation of bilateral MCA, ACA, PCA and BasA. Chi-squared test was used to compare feasibility across predetermined groups (age, sex, genotype and body mass index (BMI)). Distribution of MFV was calculated as mean ± standard deviation (SD). A priori determined covariates tested for univariate linear association with MFV were age, sex, genotype, BMI, hemoglobin (Hb) and hematocrit (Hct). The project was approved by the local ethics committee.Results A total of 249 SCD patients with a documented TCD examination were analyzed (mean age 35 [range 18 to 79 years], 141 (57%) were women). Overall, 115 (46%) patients had a SS/Sβ0 and 134 (54%) a SC/Sβ+ genotype. A prior diagnosis of cognitive disorder was present in 4 (2%), and of stroke in 19 (8%) cases. A majority of 156 patients (63%) were on hydroxyurea (HU) treatment alone, while 65 (26%) were on transfusions, and 18 (7%) on both treatments. A “standard” TCD examination was feasible in 229 (92%) patients, while a “complete” TCD was successfully documented in 190 (76%). There was no statistically significant effect of sex, age, genotype and BMI on TCD feasibility. Documented MFV (±SD) for cerebral arteries were as follows: MCAleft 67 (±19) cm/s; right 67 (±19) cm/s;ACAleft 53 (±16) cm/s; right 52 (±15) cm/s;PCAleft 37 (±12) cm/s; right 38 (±12) cm/s;BasA43 (±14) cm/s Linear regression showed increasing age was inversely associated with MFV in all arteries (p≤0.002). For each additional 10 years, a decrease of MFV (±SD) in the respective brain arteries was as follows: MCAleft -4.8 (±1.0); right -3.6 (±1.0) cm/s;ACAleft -3.1 (±1.0); right -2.9 (±0.9) cm/s;PCAleft -2.6 (±0.7); right -2.2 (±0.7) cm/s;BasA-3.3 (±0.7) cm/s. Female sex was associated with higher MFV in the left ACM and both PCA (p<0.05). MFV were negatively correlated with Hb and Hct for all arteries (p<0.005 for all). MFV were higher in the HbSS/Sβ0, compared to the HbSC/Sβ+ group (p<0.05). Conclusion : Our study showed that TCD can be implemented in routine follow-up of adult patients with SCD with a high (92%) success rate for standard MCA evaluation. Overall, measured intracranial velocities were in line with previously established patterns showing an inverse association with age throughout adulthood. Longitudinal TCD follow-up may help to further determine the role of intracranial flow parameters in the neurovascular risk assessment of adults with SCD.

Background and purpose: To evaluate the reliability and accuracy of nonaneurysmal perimesencephalic subarachnoid hemorrhage (NAPSAH) on Noncontrast Head CT (NCCT) between numerous raters. Materials and methods: 45 NCCT of adult patients with SAH who also had a catheter angiography (CA) were independently evaluated by 48 diverse raters; 45 raters performed a second assessment one month later. For each case, raters were asked: 1) whether they judged the bleeding pattern to be perimesencephalic; 2) whether there was blood anterior to brainstem; 3) complete filling of the anterior interhemispheric fissure (AIF); 4) extension to the lateral part of the sylvian fissure (LSF); 5) frank intraventricular hemorrhage; 6) whether in the hypothetical presence of a negative CT angiogram they would still recommend CA. An automatic NAPSAH diagnosis was also generated by combining responses to questions 2 -5. Reliability was estimated using Gwet 's AC1 ( K G ), and the relationship between the NCCT diagnosis of NAPSAH and the recommendation to perform CA using Cramer 's V test. Multi -rater accuracy of NCCT in predicting negative CA was explored. Results: Inter -rater reliability for the presence of NAPSAH was moderate ( K G = 0.58; 95%CI: 0.47, 0.69), but improved to substantial when automatically generated ( K G = 0.70; 95%CI: 0.59, 0.81). The most reliable criteria were the absence of AIF filling ( K G = 0.79) and extension to LSF ( K G = 0.79). Mean intra-rater reliability was substantial ( K G = 0.65). NAPSAH weakly correlated with CA decision ( V = 0.50). Mean sensitivity and specificity were 58% (95%CI: 44%, 71%) and 83 % (95%CI: 72 %, 94%), respectively. Conclusion: NAPSAH remains a diagnosis of exclusion. The NCCT diagnosis was moderately reliable and its impact on clinical decisions modest. (c) 2024 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

BACKGROUND:Patients with stroke while hospitalized experience important delays in symptom recognition. This study aims to describe the overall management of an in-hospital stroke population and how it compares with an out-of-hospital community-onset stroke population. METHODS:In this retrospective observational study, we included consecutive patients with in-hospital and out-of-hospital strokes (both ischemic and hemorrhagic) over a period of one year treated at a comprehensive stroke center. Demographic and clinical data were extracted, and patient groups were compared with regard to stroke treatment time metrics. RESULTS:A total of 362 patients diagnosed with acute stroke were included, of whom 38 (10.5%) had in-hospital and 324 (89.5%) had out-of-hospital strokes. The median delay to stroke recognition (time between the last time seen well and first time seen symptomatic) was significantly longer in in-hospital compared to out-of-hospital strokes (77.5 [0-334.8] vs. 0 [0-138.5] min, p = 0.04). The median time interval from stroke code activation to the arrival of the stroke team at the bedside was significantly shorter in in-hospital versus out-of-hospital cases (10 [6-15] vs. 15 [8-24.8] min, p = 0.01). In-hospital strokes were less likely to receive thrombolysis (12.8% vs. 45.4%, p < 0.01) with significantly higher mortality (18.2% versus 2.6%, p < 0.01) and longer overall median hospital stay (3 [1-7] vs. 12 days [7-23], p < 0.01) compared to out-of-hospital strokes. CONCLUSION:This study showed significant delays in stroke symptom recognition and stroke code activation for in-hospital stroke patients despite comparable overall stroke time metrics. Development of in-hospital stroke protocols and systematic staff training on stroke symptom recognition should be implemented to improve care for hospitalized patients.

Background Adults with sickle cell disease (SCD) are at higher risk of cognitive disorder compared to the general population. The American Society of Hematology recommends cognitive screening; however, optimal surveillance strategies have not been established. The Rowland Universal Dementia Assessment Scale (RUDAS) is a short questionnaire that was specifically developed in culturally diverse populations. Objective To determine whether the RUDAS is a valid screening tool to detect cognitive disorder among adults with SCD. Methods This cross-sectional study was conducted between 2018 and 2023 in 3 large centres of excellence of SCD (Centre Hospitalier de l'Université de Montréal [CHUM] in Montréal, and University Health Network [UHN] in Toronto, Canada, and APHP-Henri Mondor French Red Blood Cell Coordinating Referral Center, Créteil, France). All outpatients (pts), ≥18 years-old, of all SCD genotypes, with documented RUDAS screening were included, unless they were unable to provide informed consent. The French or the English versions of the RUDAS were used for cognitive screening, according to pts' preference. RUDAS was adjusted for education (+1 point) if the number of years of education was ≤12. At CHUM, pts were assessed comprehensively by a multidisciplinary neurovascular team. Diagnosis of major or mild cognitive disorder was determined according to VasCog diagnostic criteria. Multistep validation was performed by an expert in measures (SB), and included reliability of repeat testing and interrater reliability, the partial credit model, and “gold standard” (criterion) validation of the RUDAS against formal diagnosis of cognitive disorder. Sensitivity (Ss), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) were calculated. For reliability testing, only 145 pts had repeat testing within 3-6 months and 92 had repeat scoring by an independent assessor. For the criterion validation, only the 117 pts evaluated at the CHUM were included in the analysis. Results A total of 440 pts met the inclusion criteria: 173 (39.3%) from CHUM, 171 from UHN (38.9%) and 96 from APHP-Henri Mondor (21.8 %); 248 were women (56.4 %) and the median [range] age was 34 [18-75] years old. Median [range] RUDAS score was 26 [16-30]. For reliability testing, the correlation coefficient for repeat RUDAS testing after 3 to 6 months was 0.6. Scores improved from a median of 26.0 [16-30] to 28.0 [19-20], suggesting a potential learning effect. The interrater reliability coefficient was 1.0 Latent class analyses using 2 classes had the best fit, compared to 3 or 4 classes, based on lowest Akaike information and Bayes information criterion values. The entropy value for this model was acceptable (0.89). RUDAS was able to discriminate two clinically distinct groups. Pts in one group had overall lower RUDAS performance (median=22 [16-27] vs. 27[18-30]), were also older, more likely to have a history of stroke, common vascular risk markers and factors, lower kidney function, lower educational attainment and higher unemployment. Clinical validity was tested by comparing the RUDAS to formal neurological and cognitive assessment in the CHUM group. The subgroup of patients who had a formal cognitive evaluation (N = 117) was divided into two groups: those with (N=42) and those without (N=75) a confirmed diagnosis of major or minor cognitive disorder. The mean RUDAS scores differed significantly in those two groups (26.5 ± 2.8 vs. 28.5 ± 2.6, t=3.5, p<0.001). A RUDAS cut-off of <27/30 detected cognitive disorder with a 50% Ss, 83% Sp, 62% PPV and a 75% NPV. When adjusted for education level, a RUDAS score of <27/30 had a 45% Ss, 89% Sp, 70% PPV and 74% NPV. Conclusion The RUDAS is an accessible, valid, and scalable screening tool for systematic cognitive surveillance of adults with SCD. It can be administered in 6 minutes by health care professionals (e.g., nurses, physicians). It has modest sensitivity, but good specificity, especially when adjusted for educational level. It could therefore assist healthcare professionals caring for adults with SCD in the detection of patients in need of specific interventions, comprehensive neurocognitive assessment, and educative or professional accommodations. Future research should evaluate the utility of the RUDAS for longitudinal surveillance of cognitive disorders and whether adaptations could improve its sensitivity in adults with SCD.

Background Stroke is a potentially devastating complication among patients with sickle cell disease (SCD). Stroke has been well described in children with SCD and can now be prevented in most cases through early screening by transcranial doppler and intensification of treatment for those at risk. In adult patients with SCD, systematic data on stroke prevalence, etiology, and long-term functional impacts are limited. The primary goal of this study was to determine the lifetime prevalence of stroke within an adult population with SCD followed in a specialized referral centre. Secondary objectives included stratification by stroke type, etiology, treatment received and functional outcome. Methods The study was designed as a retrospective cross-sectional study that quantified the prevalence of stroke at the end of the observation period (December 2023 or at the last visit) in a large monocentric cohort. All adult patients (≥18 years old) with any SCD genotype (HbSS, HbS β°/β+-thalassemia and HbSC), that had at least one visit between 2011 and 2023 at CHUM were included. Patients were evaluated by vascular neurologists in a specialized clinic in which standard assessment included a National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Montreal Cognitive Assessment (MoCA) test. Symptomatic stroke was defined as any cerebral infarction or intracranial hemorrhage on brain imaging with a corresponding focal neurological deficit or related symptoms. Clinical patient characteristics were extracted from the electronic medical record. Summary statistics were calculated as mean (standard deviation), median [range] and proportions, as appropriate. The project was approved by the local ethics committee. Results Overall, 450 patients met the inclusion criteria, 258 (57%) of which were women. The median age was 32 years [range 18-79]. Genotypes included 215 patients with HbSS (48%), 10 HbSβ0 (2%), 190 HbSC (42%) and 35 HbSβ+ (8%). Sixteen patients (3.6%) were identified with at least one symptomatic stroke (median age at presentation 36 years [range 4-65]), including 10 (2.2%) with cerebral infarction (median age 25 years [range 4-58], 6 (1.3%) with intracranial hemorrhage (median age 45 years [range 20-65]). For the SS/Sβ0 and SC/Sβ+ genotypes, stroke prevalence was 9/225 (4.0%) and 7/225 (3.1%), respectively. Three patients (0.7%) suffered at least one recurrent stroke during follow-up. Etiologies for ischemic strokes included carotid stenosis (n=1), Moya-Moya syndrome (n=1), cardio-embolic origin (n=3), acute vaso-occlusive crisis (n=2) and unknown etiology (n=3). Underlying causes for intracranial hemorrhage included aneurysm rupture (n=5) and underlying severe microangiopathy (n=1). Acute hematological treatment included blood transfusions within 24 hours of admission for 3 patients. None received acute reperfusion therapy (including IV thrombolysis or mechanical thrombectomy). Aneurysms were treated by endovascular (n=4) or neurosurgical procedures (n= 1). Thirteen patients began long-term exchange transfusions, 10 antiplatelet therapy, and 2 oral anticoagulants. On the last follow-up, nine stroke patients had residual neurological deficits with a median NIHSS score of 0 [range 0-9] and a median mRS of 2 [range 0-3]; seven patients were unable to work. Patients after stroke had a median MoCA of 20 [range 11-29]; 11 had MoCA scores below 26. Discussion This large cross-sectional study confirms that the lifetime prevalence of symptomatic stroke in adults with SCD is high with at times long term functional impairment. Stroke etiologies include intracranial large vessel disease, but also common causes such as underlying carotid stenosis or cardiac embolism. Studies with longitudinal neurovascular follow-up are needed to identify risk factors and opportunities for improving primary and secondary stroke prevention.