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Globally, up to 1·5 million individuals with ischaemic stroke or transient ischaemic attack can be newly diagnosed with atrial fibrillation per year. In the past decade, evidence has accumulated supporting the notion that atrial fibrillation first detected after a stroke or transient ischaemic attack differs from atrial fibrillation known before the occurrence of as stroke. Atrial fibrillation detected after stroke is associated with a lower prevalence of risk factors, cardiovascular comorbidities, and atrial cardiomyopathy than atrial fibrillation known before stroke occurrence. These differences might explain why it is associated with a lower risk of recurrence of ischaemic stroke than known atrial fibrillation. Patients with ischaemic stroke or transient ischaemic attack can be classified in three categories: no atrial fibrillation, known atrial fibrillation before stroke occurrence, and atrial fibrillation detected after stroke. This classification could harmonise future research in the field and help to understand the role of prolonged cardiac monitoring for secondary stroke prevention with application of a personalised risk-based approach to the selection of patients for anticoagulation. [ABSTRACT FROM AUTHOR]

Source Citation: Kamel H, Longstreth WT Jr, Tirschwell DL, et al; ARCADIA Investigators. Apixaban to prevent recurrence after cryptogenic stroke in patients with atrial cardiopathy: the ARCADIA randomized clinical trial. JAMA. 2024;331:573-581. 38324415 Clinical Impact Ratings: GIM/FP/GP: 5 out of 7 Neurology: 6 out of 7 [ABSTRACT FROM AUTHOR]

Background: Cognition is an important outcome in many clinical trials. The NIH Toolbox-Cognition Battery (NIHTB-CB) is a computerized cognitive assessment designed for clinical research that is administered in-person. Here, we evaluated the equivalency of a novel videoconference protocol for administering the NIHTB-CB. Since our protocol required repeated assessments, we further explored the NIHTB-CB's practice effect. Materials and Methods: Twenty-five healthy participants completed the NIHTB-CB under two separate conditions 4 weeks apart. The standard condition followed the recommended administration protocol, whereas the videoconference condition had the examiner and participant in separate rooms but able to communicate over videoconference. A linear mixed-model analysis was performed to explore the fixed effect of testing condition and time on NIHTB-CB performance. Results: Across all three NIHTB-CB composite scores (total, fluid, and crystallized cognition), no significant fixed effect of administration condition was found. A significant practice effect was observed for the fluid and total cognition composite scores over a 29.0 (±2.1) day test–retest interval. Conclusions: Our novel videoconference protocol for the NIHTB-CB is equivalent to the standard protocol in healthy participants, and may provide a solution for researchers seeking to engage study participants at remote sites. If the NIHTB-CB is used longitudinally to monitor patients, corrections for repeated measures may be required. [ABSTRACT FROM AUTHOR]

Background and purpose: Among members of the health care team, nurses play a large role in actively engaging stroke survivors in secondary stroke prevention programs. This systematic review and meta-analysis examines the effectiveness of interventions in which nurses have a primary role on modification of risk factors among stroke survivors. Methods: We systematically searched for randomized controlled trials in relevant databases investigating the role of nurses in secondary stroke prevention. Meta-analyses were conducted using Cochrane Review Manager Software. The mean pooled effect size, a 95% confidence interval (CI), and I-squared (I²) for heterogeneity were calculated. Results: Sixteen randomized controlled trials were included with a total of 3568 stroke and transient ischemic attack patients. After removing one outlier, the models demonstrated a statistically significant effect on reducing systolic blood pressure (SMD = -0.14 (95% CI = -0.23, -0.05), I² = 0%; p = 0.002, six studies, n =1885) and diastolic blood pressure (SMD = -0.16 (95% CI = -0.27, -0.05), I² = 0%; p = 0.003, four studies, n =1316). The interventions also significantly improved physical activity (five studies, n=1234), diet (three studies, n=425), medication adherence (two studies, n=270), and knowledge of risk factors (three studies, n=516). However, there was no effect on smoking cessation or reduction in use of alcohol. Conclusion: We found that interventions in which nurses had a primary role were effective on improving medical and behavioral risk factors, as well as knowledge of risk factors as part of secondary prevention of stroke. [ABSTRACT FROM AUTHOR]

Although there were more LVO-associated strokes, with worse stroke severity, in the KAF group without OAC (44.2%, vs. 36.4% with OAC), both KAF groups had lower rates of LVO-associated stroke than the AFDAS group (58.2%). The use of prolonged cardiac monitoring (PCM) in patients with a recent ischemic stroke or transient ischemic attack has led to a renewed interest in the clinical and prognostic significance of atrial fibrillation (AF) detected after stroke (AFDAS). [Extracted from the article]

Background: Pain is a common complication after stroke and is associated with the presence of depression, cognitive dysfunction, and impaired quality of life. It remains underdiagnosed and undertreated, despite evidence that effective treatment of pain may improve function and quality of life. Summary: We provide an overview of the means for clinical assessment and risk factors for the development of post-stroke pain, then review the newest available literature regarding the commonest post-stroke pain syndromes, including central post-stroke pain, complex regional pain syndrome, musculoskeletal pain including shoulder subluxation, spasticity-related pain, and post-stroke headache, as well as the available epidemiology and current treatment options. Key Messages: In the best interests of optimizing quality of life and function after stroke, clinicians should be aware of pain as a common complication after stroke, identify those patients at highest risk, directly inquire as to the presence and characteristics of pain, and should be aware of the options for treatment for the various pain syndromes. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

AbstractPurposeMethodsResultsConclusion\nIMPLICATIONS FOR REHABILITATIONStroke is often regarded as a disease of the elderly. However, 10–15% of strokes occur in people aged 18 to 50, and rates continue to rise. Young stroke survivors face unique challenges due to their occupational, family and personal commitments, which current stroke rehabilitation services may not fully address. Our qualitative study aimed to identify gaps in patient care and resources for young stroke survivors. We used these findings to develop recommendations to inform clinical care, healthcare system design, and health policy.Using Interpretive Description, we conducted semi-structured interviews with 19 stroke survivors aged 18–55 living in British Columbia, Canada, to explore their experiences during stroke recovery and assess current gaps in support and resources. We applied broad-based coding and thematic analysis to the transcripts.Key themes included: (1) the need for longitudinal medical follow-up and information provision, (2) the need for psychological/psychiatric care, (3) the need to adapt community supports and resources to young survivors, and (4) the need to centralize and integrate community stroke services and resources.Young stroke survivors experience unique challenges and lack appropriate services and resources. Many of our findings may be representative of remediable gaps that persist nationally and internationally.Young Adult Stroke Survivors face unique challenges due to their occupational, family, and personal commitments, resulting in unmet needs during stroke recovery and rehabilitation.Policymakers, healthcare providers and community organizations need to re-think follow-up and information provision, psychological/psychiatric care, and community support and resources for young adult stroke survivors.Centralization and integration of different community stroke services and resources specific to young stroke survivors are key in stroke rehabilitation and recovery pathways.Young Adult Stroke Survivors face unique challenges due to their occupational, family, and personal commitments, resulting in unmet needs during stroke recovery and rehabilitation.Policymakers, healthcare providers and community organizations need to re-think follow-up and information provision, psychological/psychiatric care, and community support and resources for young adult stroke survivors.Centralization and integration of different community stroke services and resources specific to young stroke survivors are key in stroke rehabilitation and recovery pathways. [ABSTRACT FROM AUTHOR]

This commentary is on the original article by Flanigan et al. on pages 379–385 of this issue. [ABSTRACT FROM AUTHOR]

We read with interest the I CMAJ i Analysis by Aubin and colleagues,[1] which identified issues in developing and measuring the impact of patient-oriented research. We collaborated with these patients to identify patient-centred outcomes in CVT and are employing validated metrics to measure these. [Extracted from the article]

Background: Almost half of acute ischemic stroke patients present with mild symptoms and there are large practice variations in their treatment globally. Individuals with an intracranial occlusion who present with minor stroke are at an increased risk of early neurological deterioration and poor outcomes. Individual patient data meta-analysis in the subgroup of patients with minor deficits showed benefit of alteplase in improving outcomes; however, this benefit has not been seen with intravenous alteplase in published randomized trials. Design: TEMPO-2 (A Randomized Controlled Trial of Tenecteplase Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion) is a prospective, open label with blinded outcome assessment, randomized controlled trial, designed to test the superiority of intravenous tenecteplase (0.25 mg/kg) over nonthrombolytic standard of care, with an estimated sample size of 1274 patients. Adult patients presenting with acute ischemic stroke with the National Institutes of Health Stroke Scale (NIHSS) ⩽ 5 and visible arterial occlusion or perfusion deficit within 12 h of onset are randomized to receive either tenecteplase (0.25 mg/kg) or standard of care. The primary outcome is return to baseline neurological functioning, measured by the modified Rankin scale (mRS) at 90 days. Safety outcomes include death and symptomatic hemorrhage (intra or extra-cranial). Other secondary outcomes include mRS 0–1, mRS 0–2, ordinal shift analysis of the mRS, partial, and full recanalization on follow-up computed tomography angiogram. Conclusion: Results of this trial will aid in determining whether there is benefit of using tenecteplase (0.25 mg/kg) in treating patients presenting with minor stroke who are at high risk of developing poor outcomes due to presence of an intracranial occlusion. Data access statement: Data will be available upon reasonable request. [ABSTRACT FROM AUTHOR]

Background: Due to the rarity of cerebral venous thrombosis (CVT), performing high-quality scientific research in this field is challenging. Providing answers to unresolved research questions will improve prevention, diagnosis, and treatment, and ultimately translate to a better outcome of patients with CVT. We present an international research agenda, in which the most important research questions in the field of CVT are prioritized. Aims: This research agenda has three distinct goals: (1) to provide inspiration and focus to research on CVT for the coming years, (2) to reinforce international collaboration, and (3) to facilitate the acquisition of research funding. Summary of review: This international research agenda is the result of a research summit organized by the International Cerebral Venous Thrombosis Consortium in Amsterdam, the Netherlands, in June 2023. The summit brought together 45 participants from 15 countries including clinical researchers from various disciplines, patients who previously suffered from CVT, and delegates from industry and non-profit funding organizations. The research agenda is categorized into six pre-specified themes: (1) epidemiology and clinical features, (2) life after CVT, (3) neuroimaging and diagnosis, (4) pathophysiology, (5) medical treatment, and (6) endovascular treatment. For each theme, we present two to four research questions, followed by a brief substantiation per question. The research questions were prioritized by the participants of the summit through consensus discussion. Conclusions: This international research agenda provides an overview of the most burning research questions on CVT. Answering these questions will advance our understanding and management of CVT, which will ultimately lead to improved outcomes for CVT patients worldwide. [ABSTRACT FROM AUTHOR]

Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality. In this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged ≥18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0–5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov , NCT02398656 , and is closed to accrual. The trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88–1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4–10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4·2; 95% CI 0·9–19·7, p=0·059). There was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis. Heart and Stroke Foundation of Canada, Canadian Institutes of Health Research, and the British Heart Foundation. [ABSTRACT FROM AUTHOR]

Housing insecurity is associated with co-occurring depression and pain interfering with daily activities. Network analysis of depressive symptoms along with associated risk or protective exposures may identify potential targets for intervention in patients with co-occurring bodily pain. In a community-based sample of adults (n = 408) living in precarious housing or homelessness in Vancouver, Canada, depressive symptoms were measured by the Beck Depression Inventory; bodily pain and impact were assessed with the 36-item Short Form Health Survey. Network and bootstrap permutation analyses were used to compare depressive symptoms endorsed by Low versus Moderate-to-Severe (Mod + Pain) groups. Multilayer networks estimated the effects of risk and protective factors. The overall sample was comprised of 78% men, mean age 40.7 years, with 53% opioid use disorder and 14% major depressive disorder. The Mod + Pain group was characterized by multiple types of pain, more persistent pain, more severe depressive symptoms and a higher rate of suicidal ideation. Global network connectivity did not differ between the two pain groups. Suicidal ideation was a network hub only in the Mod + Pain group, with high centrality and a direct association with exposure to lifetime trauma. Antidepressant medications had limited impact on suicidal ideation. Guilt and increased feelings of failure represented symptoms from two other communities of network nodes, and completed the shortest pathway from trauma exposure through suicidal ideation, to the non-prescribed opioid exposure node. Interventions targeting these risk factors and symptoms could affect the progression of depression among precariously housed patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to Doctor M. Trusler's article regarding novel oral anticoagulants (NOAC) for prevention of stroke in nonvalvular atrial fibrillation, published in the previous issue.

Purpose: To explore the changes in perceived barriers and facilitators associated with participation in secondary prevention activities of stroke survivors and their caregivers over the early stroke recovery period. Method: We conducted two individual interviews (at 2 weeks and 6 months post-discharge) with stroke survivors and their family members. Using purposive sampling, participants were recruited from the stroke units of two acute care hospitals. Results: About 11 male and 8 female stroke survivors and nine caregivers participated in the study. Thematic analysis identified three themes. (1) "A soul searching experience" indicating that the stroke was anxiety provoking leading to a soul searching experience into exploring its causes to adopt a healthy lifestyle; (2) "Old habits die hard" revealing that stroke survivors encountered barriers to adopt healthy lifestyle changes; (3) "Making a fresh start" recognizing that participants were motivated to make their lifestyle healthier and most sustained some lifestyle changes over the past 6 months. Conclusion: Despite experiencing some barriers, stroke survivors adopted lifestyle changes transitioning through different stages of change. Stroke prevention education and interventions from experts would be helpful later in the rehabilitation phase (once at home) and adopting a patient-family centered approach may assist stroke survivors and their caregivers in the uptake of secondary stroke prevention activities. Stroke is perceived as a soul searching experience by stroke survivors and their caregivers motivating them to enquire its causes and adopting lifestyle changes to prevent a future stroke. Despite experiencing some barriers, stroke survivors adopted lifestyle changes transitioning through different stages of change. Stroke prevention education and interventions from experts would be helpful later in the rehabilitation phase (once at home). Adopting a patient-family centered approach may assist stroke survivors and their caregivers in the uptake of secondary stroke prevention activities. [ABSTRACT FROM AUTHOR]

A recent article in the Canadian Medical Association Journal discusses the importance of considering cerebral venous thrombosis (CVT) as a potential diagnosis for postpartum patients experiencing seizures and headaches. CVT refers to the formation of blood clots in the veins of the brain and is a significant cause of pregnancy-associated strokes. Unlike other types of strokes, CVT often presents with nonfocal symptoms such as headaches and visual changes. Diagnosis of CVT can be challenging and may require specialized imaging techniques. Timely diagnosis is crucial for appropriate management and better outcomes. [Extracted from the article]

Prognosis following cerebral venous thrombosis (CVT) is more favorable than other stroke types, but longer-term literature is limited, and trends over time are under-explored. Using administrative data, we examined factors associated with mortality in the inpatient setting, at 30 days and at one year following hospital discharge among a large consecutive cohort of Canadian patients with CVT. CVT patients from British Columbia (BC), Canada from 2000 to 2017 were identified using ICD diagnosis codes from the BC subset of the Canadian Institute for Health Information's Discharge Abstract Database. Logistic regression was used to investigate factors associated with inpatient mortality and survival analysis with Cox regression was used to explore factors associated with mortality at 30 days and one year. Of 554 incident CVT patients identified, 508 (92 %) survived their index admission. Older age (OR 1.04, 95 % CI 1.03–1.06, p < 0.01) and the presence of seizures (OR 2.31, 95 % CI 1.08–4.94, p = 0.03) or intracranial bleeding (OR 2.28, 95 % CI 1.08–4.85, p = 0.03) were associated with increased odds of inpatient mortality. Mortality after hospital discharge was 3.0 % at 30 days and 9.4 % at one year. Older age (HR 1.05, 95 % CI 1.02–1.08, p < 0.01 at 30 days; HR 1.05, 95 % CI 1.04–1.07, p < 0.01 at 1 year) and having recent or active malignancy (HR 4.17, 95 % CI 1.51–11.52, p < 0.01 at 30 days; HR 4.60, 95 % CI 2.60–8.11, p < 0.01 at 1 year) were significantly associated with higher risks of mortality at 30 days and one year after discharge. There were decreases in inpatient mortality over the study period, but this was offset by higher mortality within 30 days after discharge in the later study epochs. Among patients discharged with a diagnosis of CVT, one-year mortality was high at 9.4 %. Older age and a history of cancer were associated with higher mortality after discharge. • Reported mortality rates in cerebral venous thrombosis (CVT) have been variable. • We report mortality in an inclusive Canadian population based CVT cohort. • The 8.3 % inpatient and 17 % one-year mortality are higher than previously reported. • Age and CVT presentation (hemorrhage/seizure) informed inpatient mortality risk. • Age and malignancy status informed mortality risk after discharge. [ABSTRACT FROM AUTHOR]

Background: Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). Remarkably, cases of cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) have rarely been reported from LMICs. Aims: We studied the frequency, manifestations, treatment, and outcomes of CVST-VITT in LMICs. Methods: We report data from an international registry on CVST after COVID-19 vaccination. VITT was classified according to the Pavord criteria. We compared CVST-VITT cases from LMICs to cases from high-income countries (HICs). Results: Until August 2022, 228 CVST cases were reported, of which 63 were from LMICs (all middle-income countries [MICs]: Brazil, China, India, Iran, Mexico, Pakistan, Turkey). Of these 63, 32 (51%) met the VITT criteria, compared to 103 of 165 (62%) from HICs. Only 5 of the 32 (16%) CVST-VITT cases from MICs had definite VITT, mostly because anti-platelet factor 4 antibodies were often not tested. The median age was 26 (interquartile range [IQR] 20–37) versus 47 (IQR 32–58) years, and the proportion of women was 25 of 32 (78%) versus 77 of 103 (75%) in MICs versus HICs, respectively. Patients from MICs were diagnosed later than patients from HICs (1/32 [3%] vs. 65/103 [63%] diagnosed before May 2021). Clinical manifestations, including intracranial hemorrhage, were largely similar as was intravenous immunoglobulin use. In-hospital mortality was lower in MICs (7/31 [23%, 95% confidence interval (CI) 11–40]) than in HICs (44/102 [43%, 95% CI 34–53], p = 0.039). Conclusions: The number of CVST-VITT cases reported from LMICs was small despite the widespread use of adenoviral vaccines. Clinical manifestations and treatment of CVST-VITT cases were largely similar in MICs and HICs, while mortality was lower in patients from MICs. [ABSTRACT FROM AUTHOR]

BACKGROUND: The risk-benefit balance of antithrombotic therapy administration for blunt cerebrovascular injuries (BCVI) patients with concomitant injuries at high risk for bleeding is an ongoing therapeutic conundrum for trauma clinicians. We performed a systematic review to assess the reported efficacy and safety of treatment in this population with respect to prevention of ischemic stroke and risk of hemorrhagic complications. STUDY DESIGN: A systematic electronic literature search of MEDLINE, EMBASE, Cochrane Library, and Web of Science databases was performed from January 1, 1996 to December 31, 2021. Studies were included if they reported treatment-stratified clinical outcomes after antithrombotic therapy in BCVI patients with concomitant injuries at high risk of bleeding into a critical site. Data were extracted from selected studies by two independent reviewers, including the main outcomes of interest were BCVI-related ischemic stroke rates and rates of hemorrhagic complications. RESULTS: Of the 5,999 studies reviewed, 10 reported on the effects of treating BCVI patients with con- current traumatic injuries and were included for review. In the pooled data, among patients with BCVI and concomitant injury who received any form of antithrombotic therapy, the BCVI-related stroke rate was 7.6%. The subgroup of patients who did not receive therapy had an overall BCVI-related stroke rate of 34%. The total rate of hemorrhagic complications in the treated population was 3.4%. CONCLUSIONS: In BCVI patients with concomitant injuries at high risk for bleeding, antithrombotic use reduces the risk of ischemic strokes with a low reported risk of serious hemorrhagic complications. [ABSTRACT FROM AUTHOR]

Women, especially following menopause, are known to have worse outcomes following acute ischemic stroke. One primary postulated biological mechanism for worse outcomes in older women is a reduction in the vasculoprotective effects of estrogen. Using the INTERRseCT cohort, a multicentre international observational cohort studying recanalization in acute ischemic stroke, we explored the effects of sex, and modifying effects of age, on neuroradiological predictors of recanalization including robustness of leptomeningeal collaterals, thrombus burden and thrombus permeability. Ordinal regression analyses were used to examine the relationship between sex and each of the neuroradiological markers. Further, we explored both multiplicative and additive interactions between age and sex. All patients (n = 575) from INTERRseCT were included. Mean age was 70.2 years (SD: 13.1) and 48.5% were women. In the unadjusted model, female sex was associated with better collaterals (OR 1.37, 95% CIs: 1.01–1.85), however this relationship was not significant after adjusting for age and relevant comorbidities. There were no significant interactions between age and sex. In a large prospective international cohort, we found no association between sex and radiological predictors of recanalization including leptomeningeal collaterals, thrombus permeability and thrombus burden. [ABSTRACT FROM AUTHOR]

Introduction: Precise risk of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) remains unknown, leading to delays in anticoagulation initiation for secondary stroke prevention. We sought to assess the rate of HT associated with direct oral anticoagulant (DOAC) initiation within and beyond 48 h post-AIS. Methods: A pooled analysis of DOAC initiation within 14 days of AIS or transient ischemic attack (TIA) was conducted with six studies (four prospective open label treatment, blinded outcome studies and two randomized trials; NCT02295826 and NCT02283294). The primary endpoint was incident radiographic HT on follow-up imaging (days 7–30). Secondary endpoints included symptomatic HT, new parenchymal hemorrhage, recurrent ischemic events, extracranial hemorrhage, study period mortality, and follow-up modified Rankin Scale score. The results were reported as odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI). Results: We evaluated 509 patients; median infarct volume was 1.5 (0.1–7.8) ml, and median National Institutes of Health Stroke Scale was 2 (0–3). Incident radiographic HT was seen on follow-up scan in 34 (6.8%) patients. DOAC initiation within 48 h from index event was not associated with incident HT (adjusted OR 0.67, [0.30–1.50] P = 0.32). No patients developed symptomatic HT. Conversely, 31 (6.1%) patients developed recurrent ischemic events, 64% of which occurred within 14 days. Initiating a DOAC within 48 h of onset was associated with similar recurrent ischemic event rates compared with those in which treatment was delayed (HR: 0.42, [0.17–1.008] P = 0.052). In contrast to HT, recurrent ischemic events were associated with poor functional outcomes (OR = 6.8, [2.84–16.24], p < 0.001). Conclusions: In this pooled analysis, initiation of DOAC within 48 h post-stroke was not associated with increased incident risk of HT, and none developed symptomatic HT. The analysis was underpowered to determine the effect of early DOAC use upon recurrent ischemic events. [ABSTRACT FROM AUTHOR]

Background and purpose: Cerebral venous sinus thrombosis due to vaccine‐induced immune thrombotic thrombocytopenia (CVST‐VITT) is an adverse drug reaction occurring after severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination. CVST‐VITT patients often present with large intracerebral haemorrhages and a high proportion undergoes decompressive surgery. Clinical characteristics, therapeutic management and outcomes of CVST‐VITT patients who underwent decompressive surgery are described and predictors of in‐hospital mortality in these patients are explored. Methods: Data from an ongoing international registry of patients who developed CVST within 28 days of SARS‐CoV‐2 vaccination, reported between 29 March 2021 and 10 May 2022, were used. Definite, probable and possible VITT cases, as defined by Pavord et al. (N Engl J Med 2021; 385: 1680–1689), were included. Results: Decompressive surgery was performed in 34/128 (27%) patients with CVST‐VITT. In‐hospital mortality was 22/34 (65%) in the surgical and 27/94 (29%) in the non‐surgical group (p < 0.001). In all surgical cases, the cause of death was brain herniation. The highest mortality rates were found amongst patients with preoperative coma (17/18, 94% vs. 4/14, 29% in the non‐comatose; p < 0.001) and bilaterally absent pupillary reflexes (7/7, 100% vs. 6/9, 67% with unilaterally reactive pupil, and 4/11, 36% with bilaterally reactive pupils; p = 0.023). Postoperative imaging revealed worsening of index haemorrhagic lesion in 19 (70%) patients and new haemorrhagic lesions in 16 (59%) patients. At a median follow‐up of 6 months, 8/10 of surgical CVST‐VITT who survived admission were functionally independent. Conclusions: Almost two‐thirds of surgical CVST‐VITT patients died during hospital admission. Preoperative coma and bilateral absence of pupillary responses were associated with higher mortality rates. Survivors often achieved functional independence. [ABSTRACT FROM AUTHOR]

Abstract: Pain and related consequences could contribute to comorbid illness and premature mortality in homeless and precariously housed persons. We analyzed longitudinal data from an ongoing naturalistic prospective study of a community-based sample (n = 370) to characterize risk factors and consequences of bodily pain. The aims were to describe bodily pain and associations with symptoms and psychosocial function, investigate factors that may increase or ameliorate pain, and examine the consequences of pain for symptoms, functioning, and all-cause mortality. Bodily pain severity and impact were rated with the 36-item Short Form Health Survey Bodily Pain Scale monthly over 5 years. Mixed-effects linear regression models estimated the effects of time-invariant and time-varying risk factors for pain, verified by reverse causality and multiple imputation analysis. Regression models estimated the associations between overall person-mean pain severity and subsequent functioning and suicidal ideation, and Cox proportional hazard models assessed association with all-cause mortality. Bodily pain of at least moderate severity persisted (>3 months) in 64% of participants, exceeding rates expected in the general population. Greater pain severity was associated with depressive symptom severity and month-to-month opioid use, overlaid on enduring risk associated with age, arthritis, and posttraumatic stress disorder. The frequency of prescribed and nonprescribed opioid use had nonlinear relationships with pain: intermittent use was associated with severe pain, without reverse association or change with the overdose epidemic. Greater longitudinal mean pain severity was associated with premature mortality, poorer functioning, and suicidal ideation. Considering the relationships between pain, intermittent opioid use, and depressive symptoms could improve health care for precariously housed patients. [ABSTRACT FROM AUTHOR]

Background: Intravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care.Methods: In this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90-120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than -5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual.Findings: Between Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63-83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0-1 at 90-120 days (unadjusted risk difference 2·1% [95% CI - 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment INTERPRETATION: Intravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis.Funding: Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit. [ABSTRACT FROM AUTHOR]

Background While living with others has been associated with improved functional outcome after acute stroke, it is unclear if this affects adherence to stroke prevention measures. Aims We examined the relationship between living arrangements and adherence to antiplatelet therapy assignment and participation status in an international randomized trial for secondary stroke prevention. Method Antiplatelet therapy adherence, trial retention outcomes, and baseline characteristics for participants enrolled in the Secondary Prevention of Small Subcortical Strokes study were compared between those who lived alone vs. with others ( n = 2374). Participant status at end-of-trial was categorized into (1) on assigned antiplatelet, (2) off assigned antiplatelet by participant request, or (3) participant withdrew consent/lost to follow-up. Multivariable multivariate logistic regression was used to identify patient features at entry predictive of participant status at trial end. Results Living arrangement, alone vs. with other(s), was not significantly associated with participant status. Participants enrolled in the United States/ Canada (odds ratio 3·1, confidence intervals 2·0-5·0, vs. Latin America), taking more (7+) prescription medications (odds ratio 1·7, confidence intervals 1·1-2·7, vs. 0-2 medications), and scoring lower on the Stroke Specific Quality of Life scale (odds ratio 1·3, confidence intervals 1·1-1·5, per 10 points) were more likely to withdraw or become lost to follow-up in the study vs. completing the study on assigned antiplatelet therapy. Participants enrolled in the United States/ Canada (odds ratio 5·0, confidence intervals 2·4-10·0, vs. Latin America) and taking fewer (0-2) medications (odds ratio 1·9, confidence intervals 1·2-3·1 vs. 3-6 medications) were more likely to request discontinuation of assigned antiplatelet medication vs. completing the study. Conclusion Living with others was not independently predictive of protocol adherence in this cohort. Number of medications and Stroke Specific Quality of Life scale score may be more indicative of likelihood of trial participation and acceptance of long-term antiplatelet regimen. [ABSTRACT FROM AUTHOR]

Background: Untreated blunt cerebrovascular injuries (BCVIs) are associated with high rates of death and disability due to stroke. We assessed alignment of clinical practice at our centre with current recommendations for management of BCVIs and examined rates of new and recurrent in-hospital stroke.Methods: We retrospectively reviewed the BC Trauma Registry to identify all adult (age > 18 yr) patients with trauma with BCVIs at the largest level 1 trauma centre in British Columbia, Canada, from Apr. 1, 2013, to Mar. 31, 2018. We evaluated the registry, hospital databases and patient charts to assess alignment with guidelines for early initiation of appropriate antithrombotic therapy and follow-up imaging, and to ascertain short-term outcomes.Results: A total of 186 patients met the inclusion criteria. Just over half of BCVIs (97 [52.2%]) were Biffl grade 1-2. The majority of patients were treated with acetylsalicylic acid monotherapy (144/162 [88.9%]) or low-molecular-weight heparin (2/162 [1.2%]). Although guidelines recommend repeat imaging at 7-10 days to reassess the injury and guide duration of therapy, only 61/171 patients (35.7%) underwent repeat imaging within 7 days. Neuroimaging within 3 months after injury showed brain infarction in 29 patients (15.6%).Conclusion: Antithrombotic therapy was initiated in the majority of eligible patients with BCVIs, but completion of follow-up imaging and documentation of clear outpatient care plans were suboptimal. This finding shows the need for routine multidisciplinary management to facilitate standardization of care for this complex population. [ABSTRACT FROM AUTHOR]

Objective: Traumatic brain injury (TBI) is increasingly recognized as a common and impactful health determinant in homeless and precariously housed populations. We sought to describe the history of TBI in a precariously housed sample and evaluate how TBI was associated with the initial loss and lifetime duration of homelessness and precarious housing. Method: We characterized the prevalence, mechanisms, and sex difference of lifetime TBI in a precariously housed sample. We also examined the impact of TBI severity and timing on becoming and staying homeless or precariously housed; 285 precariously housed participants completed the Brain Injury Screening Questionnaire in addition to other health assessments. Results: A history of TBI was reported in 82.1% of the sample, with 64.6% reporting > 1 TBI, and 21.4% reporting a moderate or severe TBI. Assault was the most common mechanism of injury overall, and females reported significantly more traumatic brain injuries due to physical abuse than males (adjusted OR = 1.26, 95% CI = 1.14 to 1.39, P < 0.0001). The first moderate or severe TBI was significantly closer to the first experience of homelessness (b = 2.79, P = 0.003) and precarious housing (b = 2.69, P < 0.0001) than was the first mild TBI. In participants who received their first TBI prior to becoming homeless or precariously housed, traumatic brain injuries more proximal to the initial loss of stable housing were associated with a longer lifetime duration of homelessness (RR = 1.04, 95% CI = 1.02 to 1.06, P < 0.0001) and precarious housing (RR = 1.03, 95% CI = 1.01 to 1.04, P < 0.0001). Conclusions: These findings demonstrate the high prevalence of TBI in this vulnerable population, and that aspects of TBI severity and timing are associated with the loss and lifetime duration of stable housing. [ABSTRACT FROM AUTHOR]

Background: Left ventricular assist devices (LVADs) are artificial pumps used in end-stage heart failure to support the circulatory system. These cardiac assist devices work in parallel to the heart, diverting blood from the left ventricle through an outflow graft and into the ascending aorta. LVADs have allowed patients with end-stage heart failure to live longer and with improved quality of life compared to best medical therapy alone. However, they are associated with significant risks related to both thrombosis and bleeding in this medically complex patient population. As LVADs continue to be used more widely, stroke neurologists need to become familiar with the unique physical exam and vascular imaging findings associated with this population. Summary: Reported rates of LVAD-associated stroke at 2 years post-implantation range from 10 to 30%, which is significantly higher than in age-matched controls. There are approximately equal rates of ischemic and hemorrhagic strokes, and rates are highest during the peri-implantation period and in the first year of therapy. Risk factors associated with ischemic and hemorrhagic stroke in this cohort can be grouped into treatment-related factors, including specific devices and antithrombotic/anticoagulation strategy, and patient-related factors. Evidence for reperfusion therapy for acute stroke in this population is limited. Intravenous tissue plasminogen activator (IV-tPA) is often contraindicated as events may occur in the perioperative setting, or in the context of therapeutic anticoagulation. Endovascular therapy with successful recanalization is reported, but there is little experience documented in the published literature. Key messages: LVAD use is increasingly common. Given the high associated risks of stroke, neurologists will need to become increasingly familiar with an approach to assessment and therapy for LVAD patients with cerebrovascular issues. [ABSTRACT FROM AUTHOR]

Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to provide contemporary estimates of the prevalence of lower extremity motor impairment and walking limitation after first-ever stroke and to characterize the predictive nature of early walking ability for being discharged home after acute hospitalization. Methods: In this cohort study, data were collected from a metropolitan acute care hospital in Canada at admission for 487 adults with first-ever acute ischemic or hemorrhagic stroke. Lower extremity motor impairment and walking limitation were measured using the National Institutes of Health Stroke Scale and AlphaFIM, respectively. Parallel multivariable logistic regression models were built to predict discharge home after acute hospitalization compared with further hospitalization. Results: For patients surviving a first-ever stroke, 44.1% presented with some degree of lower extremity motor impairment and 46.0% were unable to walk. In a multivariable model built around a binary classification of walking (Nagelkerke R2 = 0.41), those with any ability to walk at admission (with or without therapist assistance) had 9.48 times greater odds of being discharged home (odds ratio = 9.48, 95% CI = 6.11–14.92) than those who were unable. In a parallel multivariable model built around an ordinal classification of walking (Nagelkerke R2 = 0.49), patients had 2.07 times greater odds (odds ratio = 2.07, 95% CI = 1.82–2.38) of being discharged home for each increment on a 6-point walking scale (total dependence to complete independence) assessed at acute admission. Conclusion: Approximately one-half of patients with first-ever stroke present with lower extremity weakness and walking limitation. Early walking ability is a significant predictor of returning home after acute hospitalization, independent of stroke severity. Discharge planning may be facilitated early after stroke with the familiar assessment of walking ability. Impact: An early assessment of walking function within days of stroke admission can help to streamline discharge planning. Lay Summary: Nearly one-half of all individuals who experience a first-time stroke have walking difficulty when they arrive at the hospital. The severity of the walking limitation can predict whether a patient will eventually be discharged home or go on to further hospitalization. [ABSTRACT FROM AUTHOR]

Importance: Cases of cerebral venous sinus thrombosis in combination with thrombocytopenia have recently been reported within 4 to 28 days of vaccination with the ChAdOx1 nCov-19 (AstraZeneca/Oxford) and Ad.26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccines. An immune-mediated response associated with platelet factor 4/heparin antibodies has been proposed as the underlying pathomechanism.Objective: To determine the frequencies of admission thrombocytopenia, heparin-induced thrombocytopenia, and presence of platelet factor 4/heparin antibodies in patients diagnosed with cerebral venous sinus thrombosis prior to the COVID-19 pandemic.Design, Setting, and Participants: This was a descriptive analysis of a retrospective sample of consecutive patients diagnosed with cerebral venous sinus thrombosis between January 1987 and March 2018 from 7 hospitals participating in the International Cerebral Venous Sinus Thrombosis Consortium from Finland, the Netherlands, Switzerland, Sweden, Mexico, Iran, and Costa Rica. Of 952 patients, 865 with available baseline platelet count were included. In a subset of 93 patients, frozen plasma samples collected during a previous study between September 2009 and February 2016 were analyzed for the presence of platelet factor 4/heparin antibodies.Exposures: Diagnosis of cerebral venous sinus thrombosis.Main Outcomes and Measures: Frequencies of admission thrombocytopenia (platelet count <150 ×103/μL), heparin-induced thrombocytopenia (as diagnosed by the treating physician), and platelet factor 4/heparin IgG antibodies (optical density >0.4, in a subset of patients with previously collected plasma samples).Results: Of 865 patients (median age, 40 years [interquartile range, 29-53 years], 70% women), 73 (8.4%; 95% CI, 6.8%-10.5%) had thrombocytopenia, which was mild (100-149 ×103/μL) in 52 (6.0%), moderate (50-99 ×103/μL) in 17 (2.0%), and severe (<50 ×103/μL) in 4 (0.5%). Heparin-induced thrombocytopenia with platelet factor 4/heparin antibodies was diagnosed in a single patient (0.1%; 95% CI, <0.1%-0.7%). Of the convenience sample of 93 patients with cerebral venous sinus thrombosis included in the laboratory analysis, 8 (9%) had thrombocytopenia, and none (95% CI, 0%-4%) had platelet factor 4/heparin antibodies.Conclusions and Relevance: In patients with cerebral venous sinus thrombosis prior to the COVID-19 pandemic, baseline thrombocytopenia was uncommon, and heparin-induced thrombocytopenia and platelet factor 4/heparin antibodies were rare. These findings may inform investigations of the possible association between the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines and cerebral venous sinus thrombosis with thrombocytopenia. [ABSTRACT FROM AUTHOR]

Background: Subcortical ischemic vascular cognitive impairment (SIVCI) is the most common form of vascular cognitive impairment. Importantly, SIVCI is considered the most treatable form of cognitive impairment in older adults, due to its modifiable risk factors such as hypertension, diabetes mellitus, and hypercholesterolemia. Exercise training is a promising intervention to delay the progression of SIVCI, as it actively targets these cardiometabolic risk factors. Despite the demonstrated benefits of resistance training on cognitive function and emerging evidence suggesting resistance training may reduce the progression of white matter hyperintensities (WMHs), research on SIVCI has predominantly focused on the use of aerobic exercise. Thus, the primary aim of this proof-of-concept randomized controlled trial is to investigate the efficacy of a 12-month, twice-weekly progressive resistance training program on cognitive function and WMH progression in adults with SIVCI. We will also assess the efficiency of the intervention.Methods: Eighty-eight community-dwelling adults, aged > 55 years, with SIVCI from metropolitan Vancouver will be recruited to participate in this study. SIVCI will be determined by the presence of cognitive impairment (Montreal Cognitive Assessment < 26) and cerebral small vessel disease using computed tomography or magnetic resonance imaging. Participants will be randomly allocated to a twice-weekly exercise program of (1) progressive resistance training or (2) balance and tone training (i.e., active control). The primary outcomes are cognitive function measured by the Alzheimer's Disease Assessment Scale-Cognitive-Plus (ADAS-Cog-13 with additional cognitive tests) and WMH progression.Discussion: The burden of SIVCI is immense, and to our knowledge, this will be the first study to quantify the effect of progressive resistance training on cognitive function and WMH progression among adults with SIVCI. Slowing the rate of cognitive decline and WMH progression could preserve functional independence and quality of life. This could lead to reduced health care costs and avoidance of early institutional care.Trial Registration: ClinicalTrials.gov NCT02669394 . Registered on February 1, 2016. [ABSTRACT FROM AUTHOR]

Objective: To evaluate an abbreviated NIH Toolbox Cognition Battery (NIHTB-CB) protocol that can be administered remotely without any in-person assessments, and explore the agreement between prorated scores from the abbreviated protocol and standard scores from the full protocol. Methods: Participant-level age-corrected NIHTB-CB data were extracted from six studies in individuals with a history of stroke, mild traumatic brain injury (mTBI), treatment-resistant psychosis, and healthy controls, with testing administered under standard conditions. Prorated fluid and total cognition scores were estimated using regression equations that excluded the three fluid cognition NIHTB-CB instruments which cannot be administered remotely. Paired t tests and intraclass correlations (ICCs) were used to compare the standard and prorated scores. Results: Data were available for 245 participants. For fluid cognition, overall prorated scores were higher than standard scores (mean difference = +4.5, SD = 14.3; p < 0.001; ICC = 0.86). For total cognition, overall prorated scores were higher than standard scores (mean difference = +2.7, SD = 8.3; p < 0.001; ICC = 0.88). These differences were significant in the stroke and mTBI groups, but not in the healthy control or psychosis groups. Conclusions: Prorated scores from an abbreviated NIHTB-CB protocol are not a valid replacement for the scores from the standard protocol. Alternative approaches to administering the full protocol, or corrections to scoring of the abbreviated protocol, require further study and validation. [ABSTRACT FROM AUTHOR]

Background: The Alberta Stroke Program Early CT Score (ASPECTS) is a systematic method of assessing the extent of early ischemic change on non-contrast computed tomography in patients with acute ischemic stroke. Our objective was to validate an automated ASPECTS scoring method we recently developed on a large data set. Materials and methods: We retrospectively collected 602 acute ischemic stroke patients' non-contrast computed tomography scans. Expert ASPECTS readings on non-contrast computed tomography were compared to automated ASPECTS. Statistical analyses on the total ASPECTS, region level ASPECTS, and dichotomized ASPECTS (≤4 vs. >4) score were conducted. Results: In total, 602 scans were evaluated and 6020 (602 × 10) ASPECTS regions were scored. Median time from stroke onset to computed tomography was 114 min (interquartile range: 73–183 min). Total ASPECTS for the 602 patients generated by the automated method agreed well with expert readings (intraclass correlation coefficient): 0.65 (95% confidence interval (CI): 0.60–0.69). Region level analysis showed that the automated method yielded accuracy of 81.25%, sensitivity of 61.13% (95% CI: 58.4%–63.8%), specificity of 86.56% (95% CI: 85.6%–87.5%), and area under curve of 0.74 (95% CI: 0.73–0.75). For dichotomized ASPECTS (≤4 vs. >4), the automated method demonstrated sensitivity 97.21% (95% CI: 95.4%–98.4%), specificity 57.81% (95% CI: 44.8%–70.1%), accuracy 93.02%, and area under the curve of 0.78 (95% CI: 0.74–0.81). For each individual region (M1–6, lentiform, insula, and caudate), the automated method demonstrated acceptable performance. Conclusion: The automated system we developed approached the stroke expert in performance when scoring ASPECTS on non-contrast computed tomography scans of acute ischemic stroke patients. [ABSTRACT FROM AUTHOR]

Background: In a cross-sectional stepped-wedge trial with unequal cluster sizes, attained power in the trial depends on the realized allocation of the clusters. This attained power may differ from the expected power calculated using standard formulae by averaging the attained powers over all allocations the randomization algorithm can generate. We investigated the effect of design factors and allocation characteristics on attained power and developed models to predict attained power based on allocation characteristics.Method: Based on data simulated and analyzed using linear mixed-effects models, we evaluated the distribution of attained powers under different scenarios with varying intraclass correlation coefficient (ICC) of the responses, coefficient of variation (CV) of the cluster sizes, number of cluster-size groups, distributions of group sizes, and number of clusters. We explored the relationship between attained power and two allocation characteristics: the individual-level correlation between treatment status and time period, and the absolute treatment group imbalance. When computational time was excessive due to a scenario having a large number of possible allocations, we developed regression models to predict attained power using the treatment-vs-time period correlation and absolute treatment group imbalance as predictors.Results: The risk of attained power falling more than 5% below the expected or nominal power decreased as the ICC or number of clusters increased and as the CV decreased. Attained power was strongly affected by the treatment-vs-time period correlation. The absolute treatment group imbalance had much less impact on attained power. The attained power for any allocation was predicted accurately using a logistic regression model with the treatment-vs-time period correlation and the absolute treatment group imbalance as predictors.Conclusion: In a stepped-wedge trial with unequal cluster sizes, the risk that randomization yields an allocation with inadequate attained power depends on the ICC, the CV of the cluster sizes, and number of clusters. To reduce the computational burden of simulating attained power for allocations, the attained power can be predicted via regression modeling. Trial designers can reduce the risk of low attained power by restricting the randomization algorithm to avoid allocations with large treatment-vs-time period correlations. [ABSTRACT FROM AUTHOR]

Background: Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke.Methods: For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1:1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0-1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018.Findings: Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups.Interpretation: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo.Funding: Canadian Institutes for Health Research, Alberta Innovates, and NoNO. [ABSTRACT FROM AUTHOR]

Background: Persistent post‐stroke headache is a clinical entity that has recently entered the International Classification of Headache Disorders, 3rd edition. In contrast to acute headache attributed to stroke, the epidemiology, clinical features, potential pathophysiology, and management of persistent post‐stroke headache have not been reviewed. Methods: We summarize the literature describing persistent headache attributed to stroke. Results: Persistent headache after ischemic or hemorrhagic stroke affects up to 23% of patients. These persistent headaches tend to have tension‐type features and are more frequent and severe than acute stroke‐related headaches. Risk factors include younger age, female sex, pre‐existing headache disorder, and comorbid post‐stroke fatigue or depression. Other factors including obstructive sleep apnea or musculoskeletal imbalances may contribute to headache persistence. Although more evidence is needed, it may be reasonable to treat persistent post‐stroke headache according to headache semiology. Conclusion: Recognition of persistent post‐stroke headache as a separate clinical entity from acute stroke‐attributed headache is the first step toward better defining its natural history and most effective treatment strategies. [ABSTRACT FROM AUTHOR]

Importance: Recanalization of intracranial thrombus is associated with improved clinical outcome in patients with acute ischemic stroke. The association of intravenous alteplase treatment and thrombus characteristics with recanalization over time is important for stroke triage and future trial design.Objective: To examine recanalization over time across a range of intracranial thrombus occlusion sites and clinical and imaging characteristics in patients with ischemic stroke treated with intravenous alteplase or not treated with alteplase.Design, Setting, and Participants: Multicenter prospective cohort study of 575 patients from 12 centers (in Canada, Spain, South Korea, the Czech Republic, and Turkey) with acute ischemic stroke and intracranial arterial occlusion demonstrated on computed tomographic angiography (CTA).Exposures: Demographics, clinical characteristics, time from alteplase to recanalization, and intracranial thrombus characteristics (location and permeability) defined on CTA.Main Outcomes and Measures: Recanalization on repeat CTA or on first angiographic acquisition of affected intracranial circulation obtained within 6 hours of baseline CTA, defined using the revised arterial occlusion scale (rAOL) (scores from 0 [primary occlusive lesion remains the same] to 3 [complete revascularization of primary occlusion]).Results: Among 575 patients (median age, 72 years [IQR, 63-80]; 51.5% men; median time from patient last known well to baseline CTA of 114 minutes [IQR, 74-180]), 275 patients (47.8%) received intravenous alteplase only, 195 (33.9%) received intravenous alteplase plus endovascular thrombectomy, 48 (8.3%) received endovascular thrombectomy alone, and 57 (9.9%) received conservative treatment. Median time from baseline CTA to recanalization assessment was 158 minutes (IQR, 79-268); median time from intravenous alteplase start to recanalization assessment was 132.5 minutes (IQR, 62-238). Successful recanalization occurred at an unadjusted rate of 27.3% (157/575) overall, including in 30.4% (143/470) of patients who received intravenous alteplase and 13.3% (14/105) who did not (difference, 17.1% [95% CI, 10.2%-25.8%]). Among patients receiving alteplase, the following factors were associated with recanalization: time from treatment start to recanalization assessment (OR, 1.28 for every 30-minute increase in time [95% CI, 1.18-1.38]), more distal thrombus location, eg, distal M1 middle cerebral artery (39/84 [46.4%]) vs internal carotid artery (10/92 [10.9%]) (OR, 5.61 [95% CI, 2.38-13.26]), and higher residual flow (thrombus permeability) grade, eg, hairline streak (30/45 [66.7%]) vs none (91/377 [24.1%]) (OR, 7.03 [95% CI, 3.32-14.87]).Conclusions and Relevance: In patients with acute ischemic stroke, more distal thrombus location, greater thrombus permeability, and longer time to recanalization assessment were associated with recanalization of arterial occlusion after administration of intravenous alteplase; among patients who did not receive alteplase, rates of arterial recanalization were low. These findings may help inform treatment and triage decisions in patients with acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Purpose:We applied cluster analysis to identify discrete patterns of concomitant responses of systolic (SBP), diastolic (DBP) and pulse pressure (PP) during intensive BP lowering; and to evaluate their clinical relevance and association with risk of mortality, major vascular events (MVEs), and stroke. Material and methods:We used an unsupervised cluster procedure to identify distinct patterns of BP change during the first 9 months of anti-hypertensive therapy intensification among 1,331 participants in the Secondary Prevention of Small Subcortical Strokes Trial who were previously randomized to lower BP target (SBP < 130 mm Hg) after lacunar stroke. Results:The cluster procedure partitioned participants into three groups in the lower SBP target arm, persons with: 1) mildly elevated baseline SBP and minimal visit-to-visit BP variability (mild reducers); 2) moderately elevated baseline SBP and moderate visit-to-visit BP variability (moderate reducers); and 3) very elevated baseline SBP with very large visit-to-visit BP variability during intensification (large reducers). In the lower SBP target group, moderate reducers had a higher risk of death (adjusted HR 1.6 [95% CI 1.0–2.7]), MVE (adjusted HR 2.1 [95% CI 1.4–3.2]), and stroke (adjusted HR 2.6[95% CI 1.7–4.1]) compared to mild reducers. Large reducers had the highest risk of death (adjusted HR 2.3 [95% CI 1.2–4.4]), but risk of MVE (HR = 1.7 [95%CI 0.9–3.1]) and stroke (HR = 1.6 [95%CI: 0.8–3.5]) were not statistically significantly different compared to mild reducers. Conclusions:Among persons with prior lacunar stroke, baseline BP levels, and BP variability in the setting of intensive BP lowering can identify discrete groups of persons at higher risk of adverse outcomes. [ABSTRACT FROM PUBLISHER]

We characterized traumatic brain injury (TBI) and studied its associations with mental and physical health in a community cohort of homeless and vulnerably housed individuals. Detailed mental and physical health structured interviews, neuropsychological testing, and multimodal magnetic resonance imaging (MRI) were performed on 283 participants. Two TBI participant groups were defined for primary analyses: those with a self-reported history of TBI and those with MRI confirmation of TBI. By self-report, 174 participants (61.5%) reported a previous serious head or face injury (symptomatic or asymptomatic), with 100 (35.3%) experiencing symptoms consistent with TBI (any post-injury loss of consciousness, confusion, or memory loss). Persons self-reporting TBI had poorer current mental and physical health, more ongoing neurological symptoms, and a higher rate of mood disorders, compared to those with no TBI. The presence of a mood disorder, a TBI history, and an interaction between these factors contributed to lower mental health. There was evidence of TBI in 20 participants (6.9%) on clinical MRI sequences. These participants had globally lower cortical gray matter volumes and lower white matter fractional anisotropy (FA) values. Neurocognitive test scores positively correlated with both FA and cortical gray matter volumes in participants with MRI evidence of trauma. Previous TBI is associated with poorer mental and physical health in homeless and vulnerably housed individuals and interacts with mood disorders to exacerbate poor mental health. Focal traumatic lesions evident on MRI are associated with diffusely lower gray matter volumes and white matter integrity, which predict cognitive functioning. [ABSTRACT FROM AUTHOR]

Rationale: Patients with transient ischemic attack or minor stroke are at high risk of early recurrent cerebrovascular events. Anticoagulation with heparin or warfarin acutely after ischemic stroke is at least as efficacious as aspirin for preventing recurrent events but is associated with an increased risk of clinical worsening due to hemorrhagic transformation. Aim and hypothesis: We aim to demonstrate the safety of early anticoagulation with dabigatran, an oral direct thrombin inhibitor, in acute cerebrovascular syndrome patients. The primary hypothesis is that symptomatic hemorrhagic transformation rates in dabigatran and aspirin-treated patients will be similar. Sample size estimates: At least 136 participants in two groups required to demonstrate an absolute between-group difference in the rate of hemorrhagic transformation of 5.6% with 80% power, assuming alpha=5%. Methods and design: A randomized, multicenter open-label clinical trial (NCT02295826). Three-hundred participants with a transient ischemic attack/ischemic stroke (National Institutes of Health Stroke Scale≤9) will undergo magnetic resonance imaging within 72 h of symptom onset and will be randomized to aspirin 81 mg daily or dabigatran 150 mg twice daily for 30 days. Participants undergo repeat magnetic resonance imaging at 30 days and clinical assessment to 90 days. Study outcomes: The primary outcome is the symptomatic hemorrhagic transformation rate. Secondary outcomes include recurrent stroke and new ischemic lesions on repeat magnetic resonance imaging. Discussion: This study will determine the safety of early anticoagulation with dabigatran in patients with acute transient ischemic attack/ischemic stroke and will inform the design of a phase III randomized trial aimed at demonstrating reduced recurrent early ischemic events after acute transient ischemic attack/stroke. [ABSTRACT FROM AUTHOR]

Background: Pontine infarcts are common and often attributed to small vessel disease (''small deep infarcts'') or basilar branch atherosclerosis ("wedge shaped"). A well-described morphological differentiation using magnetic resonance images has not been reported. Furthermore, whether risk factors and outcomes differ by morphology, or whether infarct morphology should guide secondary prevention strategy, is not well characterized. Methods: All participants in the Secondary Prevention of Small Subcortical Strokes Study with magnetic resonance imaging-proven pontine infarcts were included. Infarcts were classified as well-circumscribed small deep (small deep infarct, i.e. lacunar), paramedian, atypical paramedian, or other based on diffusion-weighted imaging, T2/fluid-attenuated inversion recovery, and T1-magnetic resonance images. Inter-rater reliability was high (90% agreement, Cohen's kappa=0.84). Clinical and radiologic features independently associated with small deep infarct versus paramedian infarcts were identified (multivariable logistic regression). Differences in stroke risk and death were assessed using Cox proportional hazards. Results: Of the 3020 patients enrolled, 644 had pontine infarcts; 619 images were available: 302(49%) small deep infarct, 245 (40%) paramedian wedge, 35 (6%) atypical paramedian, and 37 (6%) other. Among vascular risk factors, only smoking (OR 2.1, 95% CI 1.3-3.3) was independently associated with small deep infarct versus paramedian infarcts; on neuroimaging, old lacunes on T1/fluid-attenuated inversion recovery (OR 1.8, 1.3-2.6) and intracranial stenosis (any location) -50% (OR 0.62, 0.41-0.96). Small deep infarct versus paramedian was not predictive of either recurrent stroke or death, and there was no interaction with assigned treatment. Conclusions: Pontine infarcts can be reliably classified based on morphology using clinical magnetic resonance images. Few risk factors differed between small deep infarct and paramedian infarcts with no differences in recurrent stroke or mortality. There was no difference in response to different antiplatelet or blood pressure treatment strategies between these two groups. [ABSTRACT FROM AUTHOR]

Objectives To determine safety and tolerability of lowering blood pressure in older adults with lacunar stroke. Design Cohort study. Setting The Secondary Prevention of Small Subcortical Strokes ( SPS3) Trial, which compared the efficacy of two systolic blood pressure ( SBP) targets (<130 mmHg and 130-149 mmHg) for secondary stroke prevention. Participants Of 3,020 SPS3 participants, 494 aged 75 and older at baseline were used in these analyses. Measurements Rates of side effects related to lowering SBP and clinical outcomes, including stroke recurrence and vascular death, were examined. Results Older participants achieved SBP levels similar to those of younger participants (mean SBP of 125 mmHg and 137 mmHg in lower and higher SBP target groups, respectively). At least once during the approximately 3.5 years of follow-up, 21% reported dizziness, and 15% reported lightheadedness when standing; the only significant difference between the younger and older groups was unsteadiness when standing (23% vs 32% respectively, P < .001). There was no difference according to treatment group. In younger adults, recurrent stroke was less likely in the lower than the higher SBP group (hazard ratio ( HR) = 0.77, 95% confidence interval ( CI) = 0.59-1.01) but not in older participants ( HR = 1.01, 95% CI = 0.59-1.73), although the interaction was not significant ( P = .39). The lower SBP target was associated with a significant reduction in vascular death in older participants ( HR = 0.42, 95% CI = 0.18-0.98), with a significant interaction between age and SBP group ( P = .049). Conclusion Except for unsteadiness when standing, there was no difference according to age in individuals with lacunar stroke with respect to side effects potentially related to lowering blood pressure. Although the lower SBP target was not associated with lower likelihood of recurrent stroke, these exploratory analyses suggested a possible benefit related to vascular death. [ABSTRACT FROM AUTHOR]

The prevalence and risk factors of hemorrhagic transformation (HT) after acute ischemic stroke HT have not been adequately delineated. We performed a systematic review and meta-analysis to identify English-language prospective observational MEDLINE and EMBASE-listed reports of acute ischemic stroke with HT published from 1985–2017. Studies that used the ECASS-2 definitions of hemorrhagic transformation subtypes, hemorrhagic infarction (HI), and parenchymal hematoma (PH) were included. Patients treated with intravenous thrombolysis with tissue plasminogen activator (IV-tPA) were compared with those who did not receive thrombolysis. A total of 65 studies with 17,259 patients met inclusion criteria. Overall, HT prevalence was 27%; 32% in patients receiving IV-tPA vs. 20% in those without. Overall PH prevalence was 9%; 12% in IV-tPA treated patients vs. 5% in those without. HT was associated with a history of atrial fibrillation (OR 2.94) and use of anticoagulants (OR 2.47). HT patients had higher NIHSS (Hedge's-G 0.96) and larger infarct volume (diffusion-weighted MRI, Hedge's-G 0.8). In IV-tPA treated patients, PH correlated with antiplatelet (OR 3) and statin treatment (OR 4). HT (OR 3) and PH (OR 8) were associated with a poor outcome at 90-day (mRS 5–6). Hemorrhagic transformation is a frequent complication of acute ischemic stroke and is associated with poor outcome. Recognition of risk factors for HT and PH may reduce their incidence and severity. [ABSTRACT FROM AUTHOR]

• We use neural network models for dementia prediction to avoid task-specific features. • Our model for combining multimodal features give performances comparable to baselines. • Coherence scores are not different between dementia patients and healthy controls. • Our HAN-AGE model achieves state-of-the-art performance for dementia detection. Early prediction of neurodegenerative disorders such as Alzheimer's disease (AD) and related dementias may facilitate earlier access to medical and social supports. Further, detection of individuals with preclinical disease may help to enrich clinical trial populations for studies examining disease-modifying interventions. Changes in speech and language patterns may occur in the early stages of neurodegenerative diseases such as AD and frontotemporal dementia, with worsening as the disease progresses. This has led to recent attempts to create automatic methods that predict cognitive impairment and dementia through language analysis. Previous works have improved the prediction accuracy by introducing some task-specific features in addition to task-agnostic linguistic and acoustic features. However, task-specific features prevent the model from generalizing to other tests and languages. In this paper, we focus on exploring the effectiveness of neural network models that require no task-specific feature for dementia prediction in three different ways. First, we use a multimodal neural model to fuse linguistic features and acoustic features, and investigate the performance change compared to simply concatenating these features. Second, we propose a novel coherence feature generated by a neural coherence model, and investigate the predictiveness of this new feature for dementia prediction. Finally, we apply an end-to-end neural method which is free from feature engineering and achieves state-of-the-art classification result on a widely used dementia dataset. [ABSTRACT FROM AUTHOR]

Background: Successful stroke trials require adequate recruitment. In this observational study, we assessed reasons for refusal to provide informed consent in eligible patients approached for clinical trial participation at the Vancouver Stroke Program.Methods: We assessed screening logs from four trials that were actively recruiting at our center: three randomized trials, two of which investigated different antithrombotic strategies for secondary prevention (NAVIGATE-ESUS, NCT02313909 12/2014; DATAS-II, NCT02295826 11/2014) and one that investigated surgery plus medical management versus medical management alone for primary prevention (CREST-2, NCT02089217 03/2014). The fourth study was observational and non-randomized; all participants received an external monitoring device (PROPHECY, NCT03712865 10/2018). Screening logs from June 2015 to April 2017 were reviewed retrospectively. Subsequently, we used a prospective structured case report form for screening (May 2017-March 2018). We assessed and compared refusal rates between trials, demographics of those refusing consent, and their reasons for doing so. We used descriptive statistics, chi-square and Fisher's exact tests as appropriate for non-parametric data, and t-tests for parametric data. We examined likelihood of refusal by sex using multivariable logistic regression models including age and trial intervention as co-variables.Results: A total of 235 patients (43% women) were approached for consent. More patients refused the surgical (59%) and antithrombotic trials (53%) compared with the non-randomized external monitoring device study (13%) (p < 0.001). Surgical trial refusals were primarily due to a desire for certainty in receiving a particular intervention (39%), with the majority of those patients wanting surgery. Refusals for the antithrombotic trials were mainly due to concerns with the potential side effects of the study drug (41%); refusals in the device trial were mainly due to disinterest (46%). Women refused participation more often than men (48% vs 33%). Women remained less likely to consent than men, even after adjustment for age and trial intervention (OR 0.46, 95% CI 0.26-0.82, p = 0.009).Conclusions: Concern surrounding drug safety, randomization, and disinterest were the chief deterrents to enrolment; there were also differences in rates of consent by gender. A better understanding of why patients refuse participation in stroke trials may help to develop future patient-directed communication strategies to improve enrolment. Further research is required to better understand the reasons underlying gender disparities in consent rates. [ABSTRACT FROM AUTHOR]

Background Suboccipital decompressive craniectomy (SDC) for cerebellar infarction has been traditionally performed with minimal high-quality evidence. The aim of this systematic review and meta-analysis is to investigate the impact of SDC on functional outcomes, mortality, and adverse events in patients with cerebellar infarcts. Methods A systematic review and meta-analysis in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Our primary outcome was the proportion of patients with moderate-severe disability after SDC. Secondary outcomes included mortality and adverse events. A sensitivity analysis was conducted to examine the roles of age, preoperative neurologic status, external ventricular drain insertion, and debridement of infarcted tissue on SDC outcomes. Results Eleven studies (with 283 patients) met our inclusion criteria. The pooled event rate for moderate-severe disability was 28% (95% confidence interval [CI], 20%–37%) and for mortality, it was 20% (95% CI, 12%–31%). The estimated overall rate of adverse events for SDC was 23% (95% CI, 14%–35%). Sensitivity analysis found less mortality with mean age <60 years, higher rates of concomitant external ventricular drain insertion, and debridement of infarcted tissue. Several factors were identified for heterogeneity between studies, including follow-up time, outcomes scale, extent of infarction, and other neuroimaging features. Conclusions The best available evidence for SDC is based on retrospective observational studies. SDC for cerebellar infarction is associated with better outcomes compared with decompressive surgery for hemispheric infarctions. Lack of standardized reporting methods for SDC is a considerable drawback to the development of a better understanding of the impact of this surgery on patient outcomes. [ABSTRACT FROM AUTHOR]