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Background: Early ischemic changes on baseline imaging are commonly evaluated for acute stroke decision-making and prognostication., Aims: We assess the association of early ischemic changes on clinical outcomes and whether it differs between intravenous tenecteplase and Alteplase., Methods: Data are from the phase 3, Alteplase compared to Tenecteplase (AcT) trial. Subjects with anterior circulation stroke were included. Early ischemic changes were assessed using the Alberta Stroke Program Early CT score (ASPECTS). Efficacy outcomes included modified Rankin scale (mRS) 0-1, mRS 0-2, and ordinal mRS at 90 days. Safety outcomes included 24-h symptomatic intracerebral hemorrhage (sICH), any hemorrhage on follow-up scan, and 90-day mortality rate. Mixed-effects logistic regression was used to assess the association of ASPECTS (continuous and categorical (0-4 vs 5-7 vs 8-10)) with outcomes and if these associations were modified by thrombolytic type after adjusting for age, sex, and baseline stroke severity., Results: Of the 1577 patients in the trial, 901 patients (56.3%; median age 75 years (IQR 65-84), 50.8% females, median National Institute of Health Stroke Scale (NIHSS) 14 (IQR 17-19)) with anterior circulation stroke were included. mRS 0-1 at 90 days was achieved in 1/14 (0.3%), 43/160 (14.7%), and 252/726 (85.1%) in the ASPECTS 0-4, 5-7, and 8-10 groups respectively. Every one-point decrease in ASPECTS was associated with 2.7% and 1.9% decrease in chances of mRS 0-1 and mRS 0-2 at 90 days, respectively, and 1.9% chances of increase in mortality at 90 days. Subgroup analysis in endovascular thrombectomy (EVT)-treated population showed similar results. Thrombolytic type did not modify this association between ASPECTS and 90-day mRS 0-1 (P-interaction 0.75). There was no significant interaction by thrombolytic type with any other outcomes., Conclusion: Similar to prior studies, we found that every one-point decrease in ASPECTS was associated with poorer clinical and safety outcomes. This effect did not differ between alteplase and tenecteplase., Data Access Statement: Data shall made available on reasonable request from the PI (BMM)., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: L.C. received payments from Servier, consulting fees from iSchemaView RAPID, Circle Neurovascular Imaging (NVI), and Canadian Medical Protective Association. T.T.S. has received consulting fees from Circle NVI. R.H.S. has stock options in FollowMD and gets salary support for research from the Heart and Stroke Foundation of Canada, the Sandra Black Center for Brain Resilience & Recovery, and Ontario Brain Institute. B.M. has stock options in Circle NVI and has consulted for Biogen and Boehringer Ingelheim. M.A. reports grants from Canadian Institute of Health Research during the conduct of the study. No other disclosures are reported. N.S. gets salary support for research from the Heart and Stroke Foundation of Canada, Research Manitoba and University of Manitoba.

Introduction: In stroke patients with acute large vessel occlusion, endovascular therapy (EVT) may be performed with or without sedation. Our aim is to describe self-reported intraprocedural comfort in patients undergoing EVT depending on sedation type., Methods: We performed a prospective observational single-center study of patients undergoing EVT. Patients were systematically interviewed on the day following intervention using a structured questionnaire addressing five domains (nausea/vomiting, pain of any kind, physical discomfort, emotional discomfort, and medical team interaction). Each domain scored 0 to 2 points for a maximum total of 10 points (a higher score indicating greater discomfort). In addition, satisfaction with procedural comfort was rated on a visual analog scale (VAS), and patients reported whether they would have preferred more, less, or the same amount of sedation. Patients who underwent EVT without sedation (local anesthesia, LA) were compared to those who received procedural sedation (conscious sedation, CS)., Results: Seventy-seven questionnaires were completed: 37 (48%) patients underwent EVT with CS while 40 (52%) were treated under LA. Median scores on the self-reported discomfort scale (1[0-2] vs 1[0-2], p = 0.70) and mean scores on VAS (76 ± 25 vs 81 ± 24, p = 0.37) were similar between the CS and the LA group. The proportion of patients who were satisfied with the adopted sedation strategy was similar between groups., Conclusion: EVT without prior sedation seems to be well tolerated. Systematic self-evaluation of patient comfort appears feasible and may become integrated into routine clinical care. Patient-oriented outcomes should be included in future trials of sedation during thrombectomy., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Little guidance exists on the conduct of randomised clinical trials (RCT) that seek to randomise patients away from standard of care. We sought to test the technique of network meta-analysis (NMA) to ascertain best available evidence for the purposes of informing the ethical evaluation of RCTs under these circumstances. We used the example of RCTs for patients with symptomatic, moderate to severe carotid stenosis that seek to compare surgical intervention plus medical therapy (standard of care) versus medical therapy (less than standard of care)., Study Design and Setting: Network meta-analysis of RCTs of adults with symptomatic carotid artery stenosis of 50%-99% who were treated with carotid endarterectomy (CEA), carotid artery stenting (CAS), or medical therapy (MT). The primary outcome was any stroke or death until end of follow-up, and secondary outcome was 30-day risk of ipsilateral stroke/death., Results: We analysed eight studies, with 7187 subjects with symptomatic moderate/severe stenosis (50%-99%). CEA was more efficacious than MT (HR = 0.82, 95% credible intervals [95% CrI] = 0.73-0.92) and CAS (HR 0.73, 95% CrI = 0.62-0.85) for the prevention of any stroke/death. At 30 days, the odds of experiencing an ipsilateral stroke/death were significantly lower in the CEA group compared to both MT (OR = 0.58, 95% CrI = 0.47-0.72) and CAS (OR = 0.68, 95% CrI = 0.55-0.83)., Conclusion: Our results support the feasibility of using NMA to assess best available evidence to inform the ethical evaluation of RCTs seeking to randomise patients away from standard of care. Our results suggest that a strong argument is required to ethically justify the conduct of RCTs that seek to randomise patients away from standard of care in the setting of symptomatic moderate to severe carotid stenosis., (© 2023 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

Neurovascular disease such as symptomatic stroke, silent brain infarcts and vascular cognitive impairment are common complications of sickle cell disease (SCD) that can have devastating consequences on quality of life, employment, and social functioning.  Early recognition of neurovascular disease is a prerequisite for the timely optimization of medical care and to connect patients to adaptive resources. While cognitive impairment has been well described in children, currently available data are limited in adults. As a result, guidance on the optimal cognitive screening strategies in adults is scarce. We conducted a systematic review to identify the different screening tools that have been evaluated in SCD. A meta-analysis was performed to estimate the prevalence of suspected cognitive impairment in this population. In this qualitative synthesis, we present 8 studies that evaluated 6 different screening tools. Patient characteristics that impacted on cognitive screening performance included age, education level, and a prior history of stroke. We report a pooled prevalence of 38% [14-62%] of suspected cognitive impairment. We discuss the relative benefits and limitations of the different screening tools to help clinicians select an adapted approach tailored to their specific patients' needs. Further studies are needed to establish and validate cognitive screening strategies in patients with diverse cultural and educational backgrounds., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objectives: We evaluated whether clinicians agree in the detection of non-contrast CT markers of intracerebral hemorrhage (ICH) expansion., Methods: From our local dataset, we randomly sampled 60 patients diagnosed with spontaneous ICH. Fifteen physicians and trainees (Stroke Neurology, Interventional and Diagnostic Neuroradiology) were trained to identify six density (Barras density, black hole, blend, hypodensity, fluid level, swirl) and three shape (Barras shape, island, satellite) expansion markers, using standardized definitions. Thirteen raters performed a second assessment. Inter- and intra-rater agreement were measured using Gwet's AC 1 , with a coefficient > 0.60 indicating substantial to almost perfect agreement., Results: Almost perfect inter-rater agreement was observed for the swirl (0.85, 95% CI: 0.78-0.90) and fluid level (0.84, 95% CI: 0.76-0.90) markers, while the hypodensity (0.67, 95% CI: 0.56-0.76) and blend (0.62, 95% CI: 0.51-0.71) markers showed substantial agreement. Inter-rater agreement was otherwise moderate, and comparable between density and shape markers. Inter-rater agreement was lower for the three markers that require the rater to identify one specific axial slice (Barras density, Barras shape, island: 0.46, 95% CI: 0.40-0.52 versus others: 0.60, 95% CI: 0.56-0.63). Inter-observer agreement did not differ when stratified for raters' experience, hematoma location, volume, or anticoagulation status. Intra-rater agreement was substantial to almost perfect for all but the black hole marker., Conclusion: In a large sample of raters with different backgrounds and expertise levels, only four of nine non-contrast CT markers of ICH expansion showed substantial to almost perfect inter-rater agreement., Key Points: • In a sample of 15 raters and 60 patients, only four of nine non-contrast CT markers of ICH expansion showed substantial to almost perfect inter-rater agreement (Gwet's AC 1 > 0.60). • Intra-rater agreement was substantial to almost perfect for eight of nine hematoma expansion markers. • Only the blend, fluid level, and swirl markers achieved substantial to almost perfect agreement across all three measures of reliability (inter-rater agreement, intra-rater agreement, agreement with the results of a reference reading)., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Background: The COVID-19 pandemic has disrupted acute stroke care logistics, including delays in hyperacute management and decreased monitoring following endovascular therapy (EVT). We aimed to assess the impact of the pandemic on 90-day functional outcome among patients treated with EVT., Methods: This is an observational cohort study including all patients evaluated for an acute stroke between March 30, 2020 and September 30, 2020 (pandemic cohort) and 2019 (reference cohort) in a high-volume Canadian academic stroke center. We collected baseline characteristics, acute reperfusion treatment and management metrics. For EVT-treated patients, we assessed the modified Rankin score (mRS) at 90 days. We evaluated the impact of the pandemic on a 90-day favourable functional status (defined as mRS 0-2) and death using multivariable logistic regressions., Results: Among 383 and 339 patients included in the pandemic and reference cohorts, baseline characteristics were similar. Delays from symptom onset to evaluation and in-house treatment were longer during the early first wave, but returned to reference values in the subsequent months. Among the 127 and 136 EVT-treated patients in each respective cohort, favourable 90-day outcome occurred in 53/99 (53%) vs 52/109 (48%, p=0.40), whereas 22/99 (22%) and 28/109 (26%, p=0.56) patients died. In multivariable regressions, the pandemic period was not associated with 90-day favourable functional status (aOR 1.27, 95% CI 0.60 to 2.56) or death (aOR 0.74, 95% CI 0.33 to 1.63)., Conclusion: In this single-center cohort study conducted in a Canadian pandemic epicenter, the first 6 months of the COVID-19 pandemic did not impact 90-day functional outcomes or death among EVT-treated patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: No systematic review of the literature has dedicated itself to looking at the management of symptomatic carotid stenosis in female patients. In this scoping review, we aimed to identify all randomised controlled trials (RCTs) that reported sex-specific outcomes for patients who underwent carotid revascularisation, and determine whether sufficient information is reported within these studies to assess short-term and long-term outcomes in female patients., Design, Setting and Participants: We systematically searched Medline, Embase, Pubmed and Cochrane libraries for RCTs published between 1991 and 2020 that included female patients and compared either endarterectomy with stenting, or any revascularisation (endarterectomy or stenting) with medical therapy in patients with symptomatic high-grade (>50%) carotid stenosis., Results: From 1537 references examined, 27 eligible studies were identified. Sex-specific outcomes were reported in 13 studies. Baseline patient characteristics of enrolled female patients were reported in 2 of those 13 studies. Common outcomes reported included stroke and death, however, there was significant heterogeneity in the reporting of both periprocedural and long-term outcomes. Sex-specific differences relating to the degree of stenosis and time from index event to treatment are largely limited to studies comparing endarterectomy to medical therapy. Adverse events were not reported by sex., Conclusions: Only half of the previously published RCTs and systematic reviews report sex-specific outcomes. Detailed analyses on the results of carotid artery intervention for female patients with symptomatic stenosis are limited., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Women have historically been under-represented in randomised controlled trials (RCTs), including many landmark RCTs that established standards of care. In light of this fact, some modern researchers are calling for replication of earlier landmark trials with women only. This approach is ethically concerning, in that it would require some enrolled women to be deprived of treatments that are currently considered standard of care., Objective: In an attempt to better understand the justification of a women-only approach to designing clinical trials, this study looks to systematically categorise the number of women-only RCTs for conditions that affect both men and women and the reasons given within the medical and philosophical literatures to perform them., Methodology: This scoping review of the literature will search, screen and select articles based on predetermined inclusion/exclusion criteria, after which a grounded theory approach will be used to synthesise the data. It is expected that there will be a variety of reasons given for why a women-only trial may be justified. Electronic databases that will be searched include MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trials Register, Web of Science Proceedings, ClinicalTrials.gov, Philosopher's Index, Phil Papers, JSTOR, Periodicals Archive Online, Project MUSE and the National Reference Centre for Bioethics., Significance: The scope of this study is to determine published rationales used to justify women-only randomised trials, both in the case of new trials and in the repetition of landmark trials., Ethics and Dissemination: Research ethics board approval is not required for this study as there is no participant involvement. Results will be published as a stand-alone manuscript and will inform a larger project related to the ethics of a women-only RCT of carotid intervention for women with symptomatic high-grade carotid stenosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: It is unclear whether it is clinically necessary or cost-effective to routinely obtain a transthoracic echocardiogram (TTE) during inpatient admission for ischemic stroke., Methods: We assessed consecutive patients presenting with acute ischemic stroke at a comprehensive stroke center from 2015 to 2017 who underwent TTE. We assessed for findings on TTE that would warrant urgent intervention including cardiac thrombus, atrial myxoma, mitral stenosis, valve vegetation, valve dysfunction requiring surgery, and low ejection fraction. Subsequent changes in management included changes in anticoagulation, antibiotics, or valve surgery. We calculated in-hospital resource utilization and associated costs for inpatient TTE using individual direct cost details within a case-costing system., Results: Of 695 patients admitted with acute ischemic stroke, 516 (74%) had a TTE and were included in our analysis. TTE findings were potentially clinically significant in 30 patients (5.8%) and changed management in 17 patients (3.3%). Inpatient admission was prolonged to expedite TTE in 24 patients, while TTE occurred after discharge in 76 patients. After correcting for the cost of TTE, the mean difference in cost to prolong an admission for TTE was $555.52 (USD), or $16 832 per change in management., Conclusions: Given the low clinical utility of inpatient TTE after acute ischemic stroke and the costs associated with prolonging admission, discharge from hospital should not be delayed solely to obtain TTE., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Background Early insight into the possible etiology of ischemic stroke allows for early initiation of mechanism-specific secondary stroke prevention. Initial systolic blood pressure during acute ischemic stroke may relate to stroke etiology. We sought to determine whether normotension at presentation with acute ischemic stroke predicts cardioembolic etiology. Methods and Results All patients presenting with acute ischemic stroke within 12 hours of symptom onset at a comprehensive stroke center from January 2015 to December 2017 were assessed. Normotension was defined as systolic blood pressure ≤130 mm Hg. The primary exposure was blood pressure on arrival at the hospital, and the primary outcome was cardioembolic etiology. Multivariable regression with stepwise selection was used to adjust for relevant covariates. We included 683 patients in our analysis, 303 (44%) of whom were diagnosed with cardioembolic etiology at 6 months. The probability of cardioembolic etiology was inversely associated with systolic blood pressure, and initial systolic blood pressure was significantly associated with cardioembolic etiology (odds ratio: 1.15; 95% CI, 1.05 to 1.26). Normotension was associated with 2.62-fold increased odds of cardioembolic etiology (95% CI, 1.46 to 4.72). Conclusions Normotension at presentation with acute ischemic stroke strongly predicts cardioembolic etiology. These patients may especially benefit from early and prolonged cardiac investigations.

Introduction: Carotid intervention in the form of endarterectomy or stenting is the current standard of care for the majority of patients with symptomatic high-grade carotid stenosis. However, some randomised controlled trials (RCT) have demonstrated that women benefited significantly less from intervention than men. It is unclear if this is a true phenomenon or a study sampling artefact, as women were severely under-represented in all RCTs of carotid revascularisation. A systematic review is needed to summarise the existing data and to answer the question of whether a women-only trial for symptomatic patients with ipsilateral carotid stenosis is scientifically necessary and ethically permissible., Methods and Analysis: We will systematically search Medline, Embase, PubMed and the Cochrane libraries for all studies with data from RCTs that included women and compared either endarterectomy with stenting or revascularisation (by means of endarterectomy or stenting) with medical therapy in patients with symptomatic carotid stenosis. Search dates will be restricted to 1991-2018. Two reviewers will conduct screening search results, study selection, data extraction and quality assessment. We will include all studies reporting outcomes of interest. Planned subgroup analysis based on revascularisation technique, degree of stenosis and timing of intervention from the index event will be conducted with enough data., Ethics and Dissemination: This research is exempt of ethics approval as no primary data will be collected. The results will be published in peer-reviewed journals and disseminated through national and international-level conferences and scientific meetings. The result of this comprehensive review will provide useful information on whether further RCTs are required to study a women-only population with symptomatic carotid disease., Prospero Registration Number: CRD42019134967., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The presence of spasticity and pyramidal features is a hallmark of some of hereditary ataxias, such as autosomal-recessive spastic ataxia of Charlevoix-Saguenay, other primary spastic ataxias, Friedreich ataxia, or ataxia with isolated vitamin E deficiency. Certain spastic paraplegias, such as spastic paraplegia 7, may present as an ataxic phenotype and often share common pathophysiologic pathways with cerebellar ataxias. Because of the rarity and genetic heterogeneity of these conditions, their molecular diagnosis remains challenging and time consuming. Herein we review the clinical, epidemiologic, and genetic features of the best-defined spastic ataxias with a focus on autosomal-recessive spastic ataxia of Charlevoix-Saguenay, one of the most frequent ataxias worldwide, which presents with a unique early-onset spastic ataxia phenotype. We briefly discuss other genetic and metabolic multisystem disorders where spastic ataxia is a secondary feature. Emphasis is placed on their typical age of onset and key clinical and imaging features that enable discrimination between these complex diseases., (Copyright © 2018 Elsevier B.V. All rights reserved.)