Diagnosis and Management of Cerebral Venous Thrombosis: A Scientific Statement From the American Heart Association.

Cerebral venous thrombosis accounts for 0.5% to 3% of all strokes. The most vulnerable populations include young individuals, women of reproductive age, and patients with a prothrombotic state. The clinical presentation of cerebral venous thrombosis is diverse (eg, headaches, seizures), requiring a high level of clinical suspicion. Its diagnosis is based primarily on magnetic resonance imaging/magnetic resonance venography or computed tomography/computed tomographic venography. The clinical course of cerebral venous thrombosis may be difficult to predict. Death or dependence occurs in 10% to 15% of patients despite intensive medical treatment. This scientific statement provides an update of the 2011 American Heart Association scientific statement for the diagnosis and management of cerebral venous thrombosis. Our focus is on advances in the diagnosis and management decisions of patients with suspected cerebral venous thrombosis. We discuss evidence for the use of anticoagulation and endovascular therapies and considerations for craniectomy. We also provide an algorithm to optimize the management of patients with cerebral venous thrombosis and those with progressive neurological deterioration or thrombus propagation despite maximal medical therapy.

World Stroke Organization Brain & hEart globAl iniTiative Program.

INTRODUCTION: The World Stroke Organization (WSO) Brain & Heart Task Force developed the Brain & hEart globAl iniTiative (BEAT), a pilot feasibility implementation program to establish clinical collaborations between cardiologists and stroke physicians who work at large healthcare facilities. METHODS: The WSO BEAT pilot project focused on atrial fibrillation (AF) and patent foramen ovale (PFO) detection and management, and poststroke cardiovascular complications known as the stroke-heart syndrome. The program included 10 sites from 8 countries: Brazil, China, Egypt, Germany, Japan, Mexico, Romania, and the USA The primary composite feasibility outcome was the achievement of the following 3 implementation metrics (1) developing site-specific clinical pathways for the diagnosis and management of AF, PFO, and the stroke-heart syndrome; (2) establishing regular Neurocardiology rounds (e.g., monthly); and (3) incorporating a cardiologist to the stroke team. The secondary objectives were (1) to identify implementation challenges to guide a larger program and (2) to describe qualitative improvements. RESULTS: The WSO BEAT pilot feasibility program achieved the prespecified primary composite outcome in 9 of 10 (90%) sites. The most common challenges were the limited access to specific medications (e.g., direct oral anticoagulants) and diagnostic (e.g., prolonged cardiac monitoring) or therapeutic (e.g., PFO closure devices) technologies. The most relevant qualitative improvement was the achievement of a more homogeneous diagnostic and therapeutic approach. CONCLUSION: The WSO BEAT pilot program suggests that developing neurocardiology collaborations is feasible. The long-term sustainability of the WSO BEAT program and its impact on quality of stroke care and clinical outcomes needs to be tested in a larger and longer duration program.

Neuropsychiatric symptoms and brain morphology in patients with mild cognitive impairment, cerebrovascular disease and Parkinson disease: A cross sectional and longitudinal study.

OBJECTIVES: Neuropsychiatric symptoms (NPS) increase risk of developing dementia and are linked to various neurodegenerative conditions, including mild cognitive impairment (MCI due to Alzheimer's disease [AD]), cerebrovascular disease (CVD), and Parkinson's disease (PD). We explored the structural neural correlates of NPS cross-sectionally and longitudinally across various neurodegenerative diagnoses. METHODS: The study included individuals with MCI due to AD, (n = 74), CVD (n = 143), and PD (n = 137) at baseline, and at 2-years follow-up (MCI due to AD, n = 37, CVD n = 103, and PD n = 84). We assessed the severity of NPS using the Neuropsychiatric Inventory Questionnaire. For brain structure we included cortical thickness and subcortical volume of predefined regions of interest associated with corticolimbic and frontal-executive circuits. RESULTS: Cross-sectional analysis revealed significant negative correlations between appetite with both circuits in the MCI and CVD groups, while apathy was associated with these circuits in both the MCI and PD groups. Longitudinally, changes in apathy scores in the MCI group were negatively linked to the changes of the frontal-executive circuit. In the CVD group, changes in agitation and nighttime behavior were negatively associated with the corticolimbic and frontal-executive circuits, respectively. In the PD group, changes in disinhibition and apathy were positively associated with the corticolimbic and frontal-executive circuits, respectively. CONCLUSIONS: The observed correlations suggest that underlying pathological changes in the brain may contribute to alterations in neural activity associated with MBI. Notably, the difference between cross-sectional and longitudinal results indicates the necessity of conducting longitudinal studies for reproducible findings and drawing robust inferences.

Perivascular spaces, plasma GFAP, and speeded executive function in neurodegenerative diseases.

INTRODUCTION: We investigated the effect of perivascular spaces (PVS) volume on speeded executive function (sEF), as mediated by white matter hyperintensities (WMH) volume and plasma glial fibrillary acidic protein (GFAP) in neurodegenerative diseases. METHODS: A mediation analysis was performed to assess the relationship between neuroimaging markers and plasma biomarkers on sEF in 333 participants clinically diagnosed with Alzheimer's disease/mild cognitive impairment, frontotemporal dementia, or cerebrovascular disease from the Ontario Neurodegenerative Disease Research Initiative. RESULTS: PVS was significantly associated with sEF (c = -0.125 ± 0.054, 95% bootstrap confidence interval [CI] [-0.2309, -0.0189], p = 0.021). This effect was mediated by both GFAP and WMH. DISCUSSION: In this unique clinical cohort of neurodegenerative diseases, we demonstrated that the effect of PVS on sEF was mediated by the presence of elevated plasma GFAP and white matter disease. These findings highlight the potential utility of imaging and plasma biomarkers in the current landscape of therapeutics targeting dementia. HIGHLIGHTS: Perivascular spaces (PVS) and white matter hyperintensities (WMH) are imaging markers of small vessel disease. Plasma glial fibrillary protein acidic protein (GFAP) is a biomarker of astroglial injury. PVS, WMH, and GFAP are relevant in executive dysfunction from neurodegeneration. PVS's effect on executive function was mediated by GFAP and white matter disease.

Association of plasma biomarkers with cognition, cognitive decline, and daily function across and within neurodegenerative diseases: Results from the Ontario Neurodegenerative Disease Research Initiative.

INTRODUCTION: We investigated whether novel plasma biomarkers are associated with cognition, cognitive decline, and functional independence in activities of daily living across and within neurodegenerative diseases. METHODS: Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p-tau)181 and amyloid beta (Aß)42/40 were measured using ultra-sensitive Simoa immunoassays in 44 healthy controls and 480 participants diagnosed with Alzheimer's disease/mild cognitive impairment (AD/MCI), Parkinson's disease (PD), frontotemporal dementia (FTD) spectrum disorders, or cerebrovascular disease (CVD). RESULTS: GFAP, NfL, and/or p-tau181 were elevated among all diseases compared to controls, and were broadly associated with worse baseline cognitive performance, greater cognitive decline, and/or lower functional independence. While GFAP, NfL, and p-tau181 were highly predictive across diseases, p-tau181 was more specific to the AD/MCI cohort. Sparse associations were found in the FTD and CVD cohorts and for Aß42/40 . DISCUSSION: GFAP, NfL, and p-tau181 are valuable predictors of cognition and function across common neurodegenerative diseases, and may be useful in specialized clinics and clinical trials.

Cytoprotective agents in stroke: Still uncertainty in the next frontier.

INTRODUCTION: Despite substantial improvement of acute ischemic stroke (AIS) care with the advent of extended time windows for intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT), a substantial portion of patients still suffer poor outcomes. Additional adjuvant therapies are needed but pharmacologic interactions among therapies may dictate how they could be used. We conducted a survey to determine physician decision-making regarding the use of cytoprotective agents in patients presenting with AIS. METHODS: The survey was structured, web-based, anonymous, and invite-only among physicians across the world treating patients presenting with AIS. Respondents were asked about the use of a hypothetical cytoprotective agent (that provided an added 10% benefit) in the context of a treatment interaction with IVT or its timing in relation to IVT. RESULTS: A total of 282 stroke physicians (74.9% males, mean age 46 years) participated in the survey. When the respondent could give both the cytoprotective agent and IVT with no treatment interaction, 177 (78.0%) chose to administer both. In the presence of treatment interaction, 88 (38.3%) would withhold IVT, 83 (36.1%) would withhold the cytoprotective agent and 56 (24.4%) were uncertain. Lastly, 111 (48.9%) were willing to administer the cytoprotective agent if it meant a necessary 10-minute delay in IVT administration. CONCLUSIONS: Pharmacologic interactions result in major uncertainty about cytoprotective treatment choices.

Cognitive biases in surgery: systematic review.

BACKGROUND: Although numerous studies have established cognitive biases as contributors to surgical adverse events, their prevalence and impact in surgery are unknown. This review aimed to describe types of cognitive bias in surgery, their impact on surgical performance and patient outcomes, their source, and the mitigation strategies used to reduce their effect. METHODS: A literature search was conducted on 9 April and 6 December 2021 using MEDLINE, Embase, PsycINFO, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. Included studies investigated how cognitive biases affect surgery and the mitigation strategies used to combat their impact. The National Institutes of Health tools were used to assess study quality. Inductive thematic analysis was used to identify themes of cognitive bias impact on surgical performance. RESULTS: Thirty-nine studies were included, comprising 6514 surgeons and over 200 000 patients. Thirty-one types of cognitive bias were identified, with overconfidence, anchoring, and confirmation bias the most common. Cognitive biases differentially influenced six themes of surgical performance. For example, overconfidence bias associated with inaccurate perceptions of ability, whereas anchoring bias associated with inaccurate risk-benefit estimations and not considering alternative options. Anchoring and confirmation biases associated with actual patient harm, such as never events. No studies investigated cognitive bias source or mitigation strategies. CONCLUSION: Cognitive biases have a negative impact on surgical performance and patient outcomes across all points of surgical care. This review highlights the scarcity of research investigating the sources that give rise to cognitive biases in surgery and the mitigation strategies that target these factors.

Responsiveness of the Reaching Performance Scale for Stroke.

OBJECTIVE: The objective of the study was to estimate the internal and external responsiveness of the Reaching Performance Scale for Stroke (RPSS) in individuals with stroke. DESIGN: Retrospective analysis of data from 4 randomized controlled trials. SETTING: Recruitment locations spanning rehabilitation centers and hospitals in Canada, Italy, Argentina, Peru, and Thailand. PARTICIPANTS: Data from 567 participants (acute to chronic stroke; N=567) were available. INTERVENTIONS: All 4 studies involved training using virtual reality for upper limb rehabilitation. MAIN OUTCOME MEASURES: RPSS and upper extremity Fugl-Meyer Assessment (FMA-UE) scores. Responsiveness was quantified for all data and across different stages of stroke. Internal responsiveness of the RPSS was quantified as effect-sizes calculated using post and preintervention change data. External responsiveness was quantified using orthogonal regressions between FMA-UE and RPSS scores. The area under the Receiver Operating Characteristic curve (AUC) was quantified based on the ability of RPSS scores to detect change above FMA-UE minimal clinically important different values across different stages of stroke. RESULTS: The RPSS had high internal responsiveness overall and across the acute or subacute and chronic stages of stroke. For external responsiveness, orthogonal regression analyses indicated that change in FMA-UE scores had positive moderate correlations with both RPSS Close and Far Target scores for all data and across the acute or subacute and chronic stages of stroke (0.6

Neuropsychiatric Symptom Burden across Neurodegenerative Disorders and its Association with Function.

OBJECTIVE: Neuropsychiatric symptoms (NPS) are prevalent in neurodegenerative disorders, however, their frequency and impact on function across different disorders is not well understood. We compared the frequency and severity of NPS across Alzheimer's disease (AD) (either with mild cognitive impairment or dementia), Cerebrovascular disease (CVD), Parkinson's disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), and explored the association between NPS burden and function. METHODS: We obtained data from Ontario Neurodegenerative Disease Research Initiative (ONDRI) that included following cohorts: AD (N = 111), CVD (N = 148), PD (N = 136), FTD (N = 50) and ALS (N = 36). We compared the frequency and severity of individual NPS (assessed by the neuropsychiatric inventory questionnaire) across cohorts using generalized estimating equations and analysis of variance. Second, we assessed the relationship of NPS burden with instrumental (iADLs) and basic (ADLs) activities of living across cohorts using multivariate linear regression while adjusting for relevant demographic and clinical covariates. RESULTS: Frequency of NPS varied across cohorts (χ2(4) = 34.4, p < .001), with post-hoc tests showing that FTD had the greatest frequency as compared to all other cohorts. The FTD cohort also had the greatest severity of NPS (H(4) = 34.5, p < .001). Further, there were differences among cohorts in terms of the association between NPS burden and ADLs (F(4,461) = 3.1, p = 0.02). Post-hoc comparisons suggested that this finding was driven by the FTD group, however, the differences did not remain significant following Bonferroni correction. There were no differences among cohorts in terms of the association between NPS burden and IADLs. CONCLUSIONS: NPS frequency and severity are markedly greater in FTD as compared to other neurodegenerative diseases. Further, NPS burden appears to be associated differently with function across neurodegenerative disorders, highlighting the need for individualized clinical interventions.

Characteristics of the Ontario Neurodegenerative Disease Research Initiative cohort.

INTRODUCTION: Understanding synergies between neurodegenerative and cerebrovascular pathologies that modify dementia presentation represents an important knowledge gap. METHODS: This multi-site, longitudinal, observational cohort study recruited participants across prevalent neurodegenerative diseases and cerebrovascular disease and assessed participants comprehensively across modalities. We describe univariate and multivariate baseline features of the cohort and summarize recruitment, data collection, and curation processes. RESULTS: We enrolled 520 participants across five neurodegenerative and cerebrovascular diseases. Median age was 69 years, median Montreal Cognitive Assessment score was 25, median independence in activities of daily living was 100% for basic and 93% for instrumental activities. Spousal study partners predominated; participants were often male, White, and more educated. Milder disease stages predominated, yet cohorts reflect clinical presentation. DISCUSSION: Data will be shared with the global scientific community. Within-disease and disease-agnostic approaches are expected to identify markers of severity, progression, and therapy targets. Sampling characteristics also provide guidance for future study design.

Rare neurovascular genetic and imaging markers across neurodegenerative diseases.

INTRODUCTION: Cerebral small vessel disease (SVD) is common in patients with cognitive impairment and neurodegenerative diseases such as Alzheimer's and Parkinson's. This study investigated the burden of magnetic resonance imaging (MRI)-based markers of SVD in patients with neurodegenerative diseases as a function of rare genetic variant carrier status. METHODS: The Ontario Neurodegenerative Disease Research Initiative study included 520 participants, recruited from 14 tertiary care centers, diagnosed with various neurodegenerative diseases and determined the carrier status of rare non-synonymous variants in five genes (ABCC6, COL4A1/COL4A2, NOTCH3/HTRA1). RESULTS: NOTCH3/HTRA1 were found to significantly influence SVD neuroimaging outcomes; however, the mechanisms by which these variants contribute to disease progression or worsen clinical correlates are not yet understood. DISCUSSION: Further studies are needed to develop genetic and imaging neurovascular markers to enhance our understanding of their potential contribution to neurodegenerative diseases.

Perivascular spaces mediate a relationship between diabetes and other cerebral small vessel disease markers in cerebrovascular and neurodegenerative diseases.

Type 2 diabetes mellitus (T2DM) and hypertension are risk factors for cerebral small vessel disease (SVD); however, few studies have characterised their relationships with MRI-visible perivascular spaces (PVS). MRI was used to quantify deep (d) and periventricular (p) white matter hyperintensities (WMH), lacunes, PVS in the white matter (wmPVS) or basal ganglia (bgPVS), and diffusion metrics in white matter. Patients with T2DM had greater wmPVS volume and there were greater wmPVS volumes in patients with T2DM and hypertension together. Counterfactual moderated mediation models found indirect effects of T2DM on volumes of other SVD and diffusion markers that were mediated by wmPVS: pWMH, dWMH, periventricular lacunes, and deep lacunes, and progression of deep lacunes over 1 year, in patients with hypertension, but not in patients without hypertension. Studying the regulation of cortical perivascular fluid dynamics may reveal mechanisms that mediate the impact of T2DM on cerebral small vessels.

Caregiving concerns and clinical characteristics across neurodegenerative and cerebrovascular disorders in the Ontario neurodegenerative disease research initiative.

OBJECTIVES: Caregiving burdens are a substantial concern in the clinical care of persons with neurodegenerative disorders. In the Ontario Neurodegenerative Disease Research Initiative, we used the Zarit's Burden Interview (ZBI) to examine: (1) the types of burdens captured by the ZBI in a cross-disorder sample of neurodegenerative conditions (2) whether there are categorical or disorder-specific effects on caregiving burdens, and (3) which demographic, clinical, and cognitive measures are related to burden(s) in neurodegenerative disorders? METHODS/DESIGN: N = 504 participants and their study partners (e.g., family, friends) across: Alzheimer's disease/mild cognitive impairment (AD/MCI; n = 120), Parkinson's disease (PD; n = 136), amyotrophic lateral sclerosis (ALS; n = 38), frontotemporal dementia (FTD; n = 53), and cerebrovascular disease (CVD; n = 157). Study partners provided information about themselves, and information about the clinical participants (e.g., activities of daily living (ADL)). We used Correspondence Analysis to identify types of caregiving concerns in the ZBI. We then identified relationships between those concerns and demographic and clinical measures, and a cognitive battery. RESULTS: We found three components in the ZBI. The first was "overall burden" and was (1) strongly related to increased neuropsychiatric symptoms (NPI severity r = 0.586, NPI distress r = 0.587) and decreased independence in ADL (instrumental ADLs r = -0.566, basic ADLs r = -0.43), (2) moderately related to cognition (MoCA r = -0.268), and (3) showed little-to-no differences between disorders. The second and third components together showed four types of caregiving concerns: current care of the person with the neurodegenerative disease, future care of the person with the neurodegenerative disease, personal concerns of study partners, and social concerns of study partners. CONCLUSIONS: Our results suggest that the experience of caregiving in neurodegenerative and cerebrovascular diseases is individualized and is not defined by diagnostic categories. Our findings highlight the importance of targeting ADL and neuropsychiatric symptoms with caregiver-personalized solutions.

Perceptions on basilar artery occlusion management in China versus other countries: Analysis of the after the BEST of BASICS (ABBA) survey.

INTRODUCTION: Uncertainty remains on the optimal management of basilar artery occlusion (BAO). Two large randomized controlled trials (RCTs) in 2019 and 2021 demonstrated neutral results with respect to the use of endovascular therapy (EVT) for BAO. This study aimed to understand regional variation in physicians' perceptions towards the treatment of BAO as stratified by physician respondents from China versus outside China, prior to the publication of studies demonstrating a benefit of EVT for BAO. METHODS: An international online survey was conducted of stroke neurologists and neurointerventionalists from January to March 2022. Survey questions evaluated physician opinions toward the use of EVT in BAO, as well as the clinical and imaging features underlying treatment decisions. Respondents were dichotomized as either from China or from other countries and differences between groups were analyzed. RESULTS: There were 1245 physician respondents across 73 countries of which 295 (23.7%) were from China. Compared to respondents from the rest of the world, respondents from China were more likely to be interventionalists (71.5% vs 35.0%; p < 0.0001). Overall, more than 95% of respondents believed that EVT was superior to medical therapy under certain circumstances. Chinese respondents were more likely to believe that further RCTs were necessary than respondents from other countries (93.6% vs 76.2%; p < 0.0001). Chinese respondents were more likely to use advanced imaging in later time windows and use a premorbid mRS threshold of ≤2 for BAO selection to EVT. CONCLUSION: Most stroke physicians believe EVT is beneficial in selected patients with BAO. Clinical and imaging modality differences were observed in the selection criteria used for EVT. There was greater inclination to enroll all trial eligible patients in a BAO RCT by respondents from China as compared to other parts of the world.

Endovascular Therapy or Alteplase in Patients with Comorbidities: Insights from UNMASK EVT.

OBJECTIVE: Decisions to treat large-vessel occlusion with endovascular therapy (EVT) or intravenous alteplase depend on how physicians weigh benefits against risks when considering patients' comorbidities. We explored EVT/alteplase decision-making by stroke experts in the setting of comorbidity/disability. METHODS: In an international multi-disciplinary survey, experts chose treatment approaches under current resources and under assumed ideal conditions for 10 of 22 randomly assigned case scenarios. Five included comorbidities (cancer, cardiac/respiratory/renal disease, mild cognitive impairment [MCI], physical dependence). We examined scenario/respondent characteristics associated with EVT/alteplase decisions using multivariable logistic regressions. RESULTS: Among 607 physicians (38 countries), EVT was chosen less often in comorbidity-related scenarios (79.6% under current resources, 82.7% assuming ideal conditions) versus six "level-1A" scenarios for which EVT/alteplase was clearly indicated by current guidelines (91.1% and 95.1%, respectively, odds ratio [OR] [current resources]: 0.38, 95% confidence interval 0.31-0.47). However, EVT was chosen more often in comorbidity-related scenarios compared to all other 17 scenarios (79.6% versus 74.4% under current resources, OR: 1.34, 1.17-1.54). Responses favoring alteplase for comorbidity-related scenarios (e.g. 75.0% under current resources) were comparable to level-1A scenarios (72.2%) and higher than all others (60.4%). No comorbidity independently diminished EVT odds when considering all scenarios. MCI and dependence carried higher alteplase odds; cancer and cardiac/respiratory/renal disease had lower odds. Being older/female carried lower EVT odds. Relevant respondent characteristics included performing more EVT cases/year (higher EVT-, lower alteplase odds), practicing in East Asia (higher EVT odds), and in interventional neuroradiology (lower alteplase odds vs neurology). CONCLUSION: Moderate-to-severe comorbidities did not consistently deter experts from EVT, suggesting equipoise about withholding EVT based on comorbidities. However, alteplase was often foregone when respondents chose EVT. Differences in decision-making by patient age/sex merit further study.

Rethinking adherence to home care in heart failure: the lessons learned from Diego Maradona's death.

Heart failure (HF) is complex and prevalent cardiac condition associated with high hospitalization rates and mortality. Early recognition and risk categorization of vulnerable patients is essential prior to discharge. Following the recent death of Diego A. Maradona, the 60 year old universally known soccer player, we highlighted critical aspects of ambulatory home care after hospital discharge. We raised three relevant clinical questions regarding home care services: its effectiveness in patients with HF while also providing practical summary tables for the identification of high-risk patients with HF and critical elements for an effective ambulatory home care delivery. A comprehensive home care program for high-risk patients with HF requires the coordination of multiple health services, including personal and nursing care, cardiac monitoring, physio- and occupational therapy, pharmacists, as well as nutritional and emotional support to avoid recurrent hospitalizations while improving clinical outcomes.

Development and Validation of a Prognostic Tool for Direct Enteral Tube Insertion After Acute Stroke.

Background and Purpose- We aimed to create a novel prognostic risk score to estimate outcomes after direct enteral tube placement in acute stroke. Methods- We used the Ontario Stroke Registry and linked databases to obtain clinical information on all patients with direct enteral tube insertion after ischemic stroke or intracerebral hemorrhage from July 1, 2003 to June 30, 2010 (derivation cohort) and July 1, 2010 to March 31, 2013 (validation cohort). We used multivariable regression to assign scores to predictor variables for 3 outcomes after tube placement: favorable outcome (discharge modified Rankin Scale score 0-3 and alive at 90 days), poor outcome (discharge modified Rankin Scale score 5 or death at 90 days), and 30-day mortality. Results- Variables associated with a favorable outcome were younger age, preadmission independence, ischemic stroke rather than intracerebral hemorrhage, lower stroke severity, and a shorter time between stroke and tube placement. Variables associated with a poor outcome were older age, preadmission dependence, atrial fibrillation, greater stroke severity, and tracheostomy. Age, preadmission dependence, atrial fibrillation, cancer, chronic obstructive pulmonary disease, and shorter time to tube placement were associated with increased 30-day mortality. Using these variables, we created an online calculator to facilitate estimation of individual patient risk of favorable and poor outcomes. C-statistic in the validation cohort was 0.82 for favorable outcome, 0.65 for poor outcome, and 0.62 for 30-day mortality, and calibration was adequate. Conclusions- We developed risk scores to estimate outcomes after direct enteral tube insertion for acute dysphagic stroke. This information may be useful in discussions with patients and families when there is prognostic uncertainty surrounding outcomes with direct enteral tube placement after stroke.

First-Ever Ischemic Stroke and Incident Major Adverse Cardiovascular Events in 93 627 Older Women and Men.

Background and Purpose- Stroke risk is sex-specific, but little is known about sex differences of poststroke major adverse cardiovascular events (MACEs). Stroke-related brain damage causes autonomic dysfunction and inflammation, sometimes resulting in cardiac complications. Sex-specific cardiovascular susceptibility to stroke without the confounding effect of preexisting heart disease constitutes an unexplored field because previous studies focusing on sex differences in poststroke MACE have not excluded patients with known cardiovascular comorbidities. We therefore investigated sex-specific risks of incident MACE in a heart disease-free population-based cohort of patients with first-ever ischemic stroke and propensity-matched individuals without stroke. Methods- We included Ontario residents ≥66 years, without known cardiovascular comorbidities, with first-ever ischemic stroke between 2002 and 2012 and propensity-matched individuals without stroke. We investigated the 1-year risk of incident MACE (acute coronary syndrome, myocardial infarction, incident coronary artery disease, coronary revascularization procedures, incident heart failure, or cardiovascular death) separately for females and males. For estimating cause-specific adjusted hazard ratios, we adjusted Cox models for variables with weighted standardized differences >0.10 or those known to influence MACE risk. Results- We included 93 627 subjects without known cardiovascular comorbidities; 21 931 with first-ever ischemic stroke and 71 696 propensity-matched subjects without stroke. Groups were well-balanced on propensity-matching variables. There were 53 476 women (12 421 with and 41 055 without ischemic stroke) and 40 151 men (9510 with and 30 641 without ischemic stroke). First-ever ischemic stroke was associated with increased risk of incident MACE in both sexes. The risk was time-dependent, highest within 30 days (women: adjusted hazard ratio, 25.1 [95% CI, 19.3-32.6]; men: aHR, 23.4 [95% CI, 17.2-31.9]) and decreasing but remaining significant between 31 and 90 days (women: aHR, 4.8 [95% CI, 3.8-6.0]; men: aHR, 4.2 [95% CI, 3.3-5.4]), and 91 to 365 days (aHR, 2.1 [95% CI, 1.8-2.3]; men: aHR, 2.0 [95% CI, 1.7-2.3]). Conclusions- In this large population-based study, ischemic stroke was independently associated with increased risk of incident MACE in both sexes.

Endovascular treatment decision-making in acute ischemic stroke patients with large vessel occlusion and low National Institutes of Health Stroke Scale: insights from UNMASK EVT, an international multidisciplinary survey.

PURPOSE: Many stroke patients with large vessel occlusion present with a low National Institutes of Health Stroke Scale (NIHSS). There is currently no level 1A recommendation for endovascular treatment (EVT) for this patient subgroup. From a physician's standpoint, the deficits might only be slight, but they are often devastating from a patient perspective. Furthermore, early neurologic deterioration is common. The purpose of this study was to explore endovascular treatment attitudes of physicians in acute ischemic stroke patients presenting with low admission NIHSS. METHODS: In an international cross-sectional survey among stroke physicians, participants were presented the scenario of a 76-year-old stroke patient with an admission NIHSS of 2. Survey participants were then asked how they would treat the patient (A) given their current local resources, and (B) under assumed ideal conditions, i.e., without external (monetary or infrastructural) constraints. Overall, country-specific and specialty-specific decision rates were calculated and clustered multivariable logistic regression performed to provide adjusted measures of effect size. RESULTS: Two hundred seventy-five participants (150 neurologists, 84 interventional neuroradiologists, 30 neurosurgeons, 11 affiliated to other specialties) from 33 countries provided their treatment approach to this case scenario. Most physicians favored an endovascular treatment approach, either combined with intravenous alteplase (55.3% under assumed ideal and 52.0% under current working conditions) or as single treatment (11.3% under assumed ideal and 8.4% under current conditions). CONCLUSION: Despite the limited evidence for endovascular therapy in acute stroke patients with low NIHSS, most physicians in this survey decided to proceed with endovascular therapy. A randomized controlled trial seems warranted.

Endovascular Treatment Decision Making in Patients with Low Baseline ASPECTS: Insights from UNMASK EVT, an International Multidisciplinary Study.

BACKGROUND: Current stroke treatment guidelines restrict level 1A recommendations for endovascular therapy to patients with baseline ASPECTS score > 5. However, a recent meta-analysis from the HERMES-group showed treatment benefit in patients with ASPECTS ≤ 5. We aimed to explore how physicians across different specialties and countries approach endovascular treatment decision-making in acute ischemic stroke patients with low baseline ASPECTS. METHODS: In a multidisciplinary survey, 607 stroke physicians were randomly assigned 10 out of a pool of 22 case-scenarios, 3 of which involved patients with low baseline ASPECTS (A:40-year old with ASPECTS 4, B:33-year old with ASPECTS 2 C:72-year old with ASPECTS 3), otherwise fulfilling all EVT-eligibility criteria. Participants were asked how they would treat the patient A) under their current local resources and B) under assumed ideal conditions, without any external (monetary, policy-related or infrastructural) restraints. Overall and scenario-specific decision rates were calculated. Clustered multivariable logistic regression analysis was used to determine the association of baseline ASPECTS with endovascular treatment-decision. RESULTS: Baseline ASPECTS score was significantly associated with current (OR:1.09, CI 1.05-1.13) and ideal endovascular treatment-decision (OR:1.12, CI 1.08-1.16). Overall current and ideal treatment decision-rates for the low ASPECTS scenarios were 57.1% and 57.6%. Current and ideal rates for the two younger patients were higher (scenario A:69.9/60.4%, scenario B:60.0/61.5%) compared to the 72-year old patient (41.3/40.2%). CONCLUSION: Most physicians decided to proceed with endovascular treatment despite low baseline ASPECTS, particularly in younger patients. This may have implications on the design and execution of low ASPECTS randomized trials.