Cost-Effectiveness of Late Endovascular Thrombectomy vs. Best Medical Management in a Clinical Trial Setting and Real-World Setting.

BACKGROUND AND PURPOSE: To assess cost-effectiveness of late time-window endovascular treatment (EVT) in a clinical trial setting and a "real-world" setting. METHODS: Data are from the randomized ESCAPE trial and a prospective cohort study (ESCAPE-LATE). Anterior circulation large vessel occlusion patients presenting > 6 hours from last-known-well were included, whereby collateral status was an inclusion criterion for ESCAPE but not ESCAPE-LATE. A Markov state transition model was built to estimate lifetime costs and quality-adjusted life-years (QALYs) for EVT in addition to best medical care vs. best medical care only in a clinical trial setting (comparing ESCAPE-EVT to ESCAPE control arm patients) and a "real-world" setting (comparing ESCAPE-LATE to ESCAPE control arm patients). We performed an unadjusted analysis, using 90-day modified Rankin Scale(mRS) scores as model input and analysis adjusted for baseline factors. Acceptability of EVT was calculated using upper/lower willingness-to-pay thresholds of 100,000 USD/50,000 USD/QALY. RESULTS: Two-hundred and forty-nine patients were included (ESCAPE-LATE:n = 200, ESCAPE EVT-arm:n = 29, ESCAPE control-arm:n = 20). Late EVT in addition to best medical care was cost effective in the unadjusted analysis both in the clinical trial and real-world setting, with acceptability 96.6%-99.0%. After adjusting for differences in baseline variables between the groups, late EVT was marginally cost effective in the clinical trial setting (acceptability:49.9%-61.6%), but not the "real-world" setting (acceptability:32.9%-42.6%). CONCLUSION: EVT for LVO-patients presenting beyond 6 hours was cost effective in the clinical trial setting and "real-world" setting, although this was largely related to baseline patient differences favoring the "real-world" EVT group. After adjusting for these, EVT benefit was reduced in the trial setting, and absent in the real-world setting.

Vertebral to Basilar Thrombus Migration Post Intravenous Thrombolysis.

Recombinant tissue plasminogen activator improves outcomes in acute ischemic stroke. Alteplase may result in thrombus migration (TM) distally to a critical arterial supply that can worsen perfusion to eloquent brain tissue. Alteplase-related stroke recanalization and clot migration in vertebral artery (VA) occlusion whereby the clot migrates to the basilar artery (BA) may be harmful. We identified seven subjects with isolated symptomatic vertebral occlusion. Two cases suffered early neurologic deterioration due to TM from VA to BA following alteplase. Precautionary transfer to thrombectomy centers may be warranted in alteplase-treated symptomatic VA occlusions in case of migration to basilar occlusion.

Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial.

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.

Radiologic Patterns of Intracranial Hemorrhage and Clinical Outcome after Endovascular Treatment in Acute Ischemic Stroke: Results from the ESCAPE-NA1 Trial.

Background Intracranial hemorrhage is a known complication after endovascular treatment in patients with acute ischemic stroke due to large vessel occlusion, but the association between radiologic hemorrhage severity and outcome is controversial. Purpose To investigate the prevalence and impact on outcome of intracranial hemorrhage and hemorrhage severity after endovascular stroke treatment. Materials and Methods The Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke (ESCAPE-NA1) trial enrolled participants with acute large vessel occlusion stroke who underwent endovascular treatment from March 1, 2017, to August 12, 2019. Evidence of any intracranial hemorrhage, hemorrhage multiplicity, and radiologic severity, according to the Heidelberg classification (hemorrhagic infarction type 1 [HI1], hemorrhagic infarction type 2 [HI2], parenchymal hematoma type 1 [PH1], and parenchymal hematoma type 2 [PH2]) was assessed at CT or MRI 24 hours after endovascular treatment. Good functional outcome, defined as a modified Rankin score of 0-2 at 90 days, was compared between participants with intracranial hemorrhage and those without intracranial hemorrhage at follow-up imaging and between hemorrhage subtypes. Poisson regression was performed to obtain adjusted effect size estimates for the presence of any intracranial hemorrhage and hemorrhage subtypes at good functional outcome. Results Of 1097 evaluated participants (mean age, 69 years ± 14 [standard deviation]; 551 men), any degree of intracranial hemorrhage was observed in 372 (34%). Good outcomes were less often achieved among participants with hemorrhage than among those without hemorrhage at follow-up imaging (164 of 372 participants [44%] vs 500 of 720 [69%], respectively; P < .01). After adjusting for baseline variables and infarct volume, intracranial hemorrhage was not associated with decreased chances of good outcome (adjusted risk ratio [RR] = 0.91 [95% CI: 0.82, 1.02], P = .10), but there was a graded relationship of radiologic hemorrhage severity and outcomes, whereby PH1 (RR = 0.77 [95% CI: 0.61, 0.97], P = .03) and PH2 (RR = 0.41 [95% CI: 0.21, 0.81], P = .01) were associated with decreased chances of good outcome. Conclusion Any degree of intracranial hemorrhage after endovascular treatment was seen in one-third of participants. A graded association existed between radiologic hemorrhage severity and outcome. Hemorrhagic infarction was not associated with outcome, whereas parenchymal hematoma was strongly associated with poor outcome, independent of infarct volume. © RSNA, 2021 Clinical trial registration no. NCT01778335 Online supplemental material is available for this article.

A Detailed Analysis of Infarct Patterns and Volumes at 24-hour Noncontrast CT and Diffusion-weighted MRI in Acute Ischemic Stroke Due to Large Vessel Occlusion: Results from the ESCAPE-NA1 Trial.

Background The effect of infarct pattern on functional outcome in acute ischemic stroke is incompletely understood. Purpose To investigate the association of qualitative and quantitative infarct variables at 24-hour follow-up noncontrast CT and diffusion-weighted MRI with 90-day clinical outcome. Materials and Methods The Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke, or ESCAPE-NA1, randomized controlled trial enrolled patients with large-vessel-occlusion stroke undergoing mechanical thrombectomy from March 1, 2017, to August 12, 2019. In this post hoc analysis of the trial, qualitative infarct variables (predominantly gray [vs gray and white] matter involvement, corticospinal tract involvement, infarct structure [scattered vs territorial]) and total infarct volume were assessed at 24-hour follow-up noncontrast CT or diffusion-weighted MRI. White and gray matter infarct volumes were assessed in patients by using follow-up diffusion-weighted MRI. Infarct variables were compared between patients with and those without good outcome, defined as a modified Rankin Scale score of 0-2 at 90 days. The association of infarct variables with good outcome was determined with use of multivariable logistic regression. Separate regression models were used to report effect size estimates with adjustment for total infarct volume. Results Qualitative infarct variables were assessed in 1026 patients (mean age ± standard deviation, 69 years ± 13; 522 men) and quantitative infarct variables were assessed in a subgroup of 358 of 1026 patients (mean age, 67 years ± 13; 190 women). Patients with gray and white matter involvement (odds ratio [OR] after multivariable adjustment, 0.19; 95% CI: 0.14, 0.25; P < .001), corticospinal tract involvement (OR after multivariable adjustment, 0.06; 95% CI: 0.04, 0.10; P < .001), and territorial infarcts (OR after multivariable adjustment, 0.22; 95% CI: 0.14, 0.32; P < .001) were less likely to achieve good outcome, independent of total infarct volume. Conclusion Infarct confinement to the gray matter, corticospinal tract sparing, and scattered infarct structure at 24-hour noncontrast CT and diffusion-weighted MRI were highly predictive of good 90-day clinical outcome, independent of total infarct volume. Clinical trial registration no. NCT02930018 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Mossa-Basha in this issue.

Clinical outcomes of isolated deep grey matter infarcts after endovascular treatment of large vessel occlusion stroke.

PURPOSE: There are few data on the prevalence and impact of isolated deep grey matter infarction in acute stroke. In this study, we aimed to investigate the prevalence of isolated deep grey matter infarcts and their impact on the outcome. METHODS: Infarcts on 24-h follow-up imaging (non-contrast head CT or diffusion-weighted MRI) in the ESCAPE-NA1 trial were categorized into predominantly deep grey matter infarcts vs. infarcts involving additional territories ("other infarcts"). Total infarct volume was manually segmented. Baseline characteristics and proportions of good outcome (primary outcome, defined as modified Rankin Score [mRS] 0-2 at 90 days), excellent outcome (mRS 0-1) and mortality were compared between patients with and without predominantly deep grey matter infarcts. Multivariable logistic regression with adjustment for baseline variables and total infarct volume was used to determine a possible association of predominantly deep grey matter infarcts and clinical outcome. RESULTS: Predominantly deep grey matter infarcts were seen in 316/1026 patients (30.8%). Compared to other patients, their ASPECTS was higher, collateral status and reperfusion quality were better and time to treatment was shorter. Good outcome was seen in 239/316 (75.6%) with vs. 374/704 (53.1%) without predominantly deep grey matter infarcts. After adjusting for baseline variables and total infarct volume, predominantly deep grey matter infarcts were independently associated with excellent outcome (adjOR: 1.45 [CI95: 1.04-2.02]), but not with good outcome (adjOR: 1.24 [CI95: 0.86-1.80]) or mortality (adjOR: 0.73 [CI95:0.39-1.35]) CONCLUSION: Predominantly deep grey matter infarct patterns were seen in 1/3rd of patients and were significantly associated with increased chances of excellent outcome, independent of patient baseline status and infarct size.

Sex Differences in Endovascular Treatment for Stroke: A Population-based Analysis.

BACKGROUND: Acute ischemic stroke may affect women and men differently. We aimed to evaluate sex differences in outcomes of endovascular treatment (EVT) for ischemic stroke due to large vessel occlusion in a population-based study in Alberta, Canada. METHODS AND RESULTS: Over a 3-year period (April 2015-March 2018), 576 patients fit the inclusion criteria of our study and constituted the EVT group of our analysis. The medical treatment group of the ESCAPE trial had 150 patients. Thus, our total sample size was 726. We captured outcomes in clinical routine using administrative data and a linked database methodology. The primary outcome of our study was home-time. Home-time refers to the number of days that the patient was back at their premorbid living situation without an increase in the level of care within 90 days of the index stroke event. In adjusted analysis, EVT was associated with an increase of 90-day home-time by an average of 6.08 (95% CI -2.74-14.89, p-value 0.177) days in women compared to an average of 11.20 (95% CI 1.94-20.46, p-value 0.018) days in men. Further analysis revealed that the association between EVT and 90-day home-time in women was confounded by age and onset-to-treatment time. CONCLUSIONS: We found a nonsignificant nominal reduction of 90-day home-time gain for women compared to men in this province-wide population-based study of EVT for large vessel occlusion, which was only partially explained by confounding.

In What Scenarios Does a Mobile Stroke Unit Predict Better Patient Outcomes?: A Modeling Study.

Background and Purpose- The mobile stroke unit (MSU) brings imaging and thrombolysis to patients in the field. The MSU has the potential to decrease time from onset to thrombolysis; however, this depends on the location of the patient, the MSU, and the hospital. The MSU will only be able to treat a small subset of patients it is dispatched to. Using conditional probability modeling, we evaluate in which scenarios the MSU exhibits clear benefit over the direct-to-mothership method. Methods- Previously published conditional probability models for drip-and-ship versus mothership transport were modified to reflect MSU workflow. It was assumed that the MSU was dispatched from the endovascular therapy center. Eight scenarios were generated, varying treatment efficiency on the MSU and at the endovascular therapy center and the threshold for dispatching the MSU (low threshold: low treatment rate but few missed patients; high threshold: higher treatment rate, potential for missed treatment opportunities). Results- The relative difference in outcomes between the MSU and mothership was small. Geographic areas where the MSU is superior to mothership increase in size as treatment time on the MSU decreases. When a high-threshold dispatch system is used, the area where the MSU is superior decreases, but the relative difference in predicted outcomes between the MSU and mothership increases. The largest relative difference favoring the MSU was found in areas where the patient would forgo access to alteplase, based upon a 4.5-hour treatment threshold, using mothership transport. Conclusions- There are few scenarios where MSU transport predicts substantially superior outcomes to the mothership method when the MSU is dispatched from the endovascular therapy center. Outcomes using the MSU are maximized when dispatch criteria that maximize patients eligible for thrombolysis treatment are used and treatment times on the MSU are short relative to those of the endovascular therapy center.

White Matter Hyperintensity Volume Influences Symptoms in Patients Presenting With Minor Neurological Deficits.

Background and Purpose- Acute minor neurological deficits are a common complaint in the emergency department and differentiation of transient ischemic attack/minor stroke from a stroke mimic is difficult. We sought to assess the ability of white matter hyperintensity (WMH) volume to aid the diagnosis in such patients. Methods- This is a post hoc analysis of the previously published SpecTRA study (Spectrometry in TIA Rapid Assessment) of adult patients that presented to the emergency department with acute minor neurological deficits between December 2013 and March 2017. WMH volumes were measured if fluid-attenuated inversion recovery imaging was available. Outcomes of interest were final diagnosis, symptoms at presentation, and 90-day stroke recurrence. Results- WMH volume was available for 1485 patients. Median age was 70 years (interquartile range, 59-80), and 46.7% were female. Mean WMH volume was higher in transient ischemic attack/minor strokes compared with stroke mimics (1.71 ln mL [95% CI, 1.63-1.79 ln mL] versus 1.15 ln mL [95% CI, 1.02-1.27 ln mL], P<0.001). In multivariable-adjusted logistic regression analysis, WMH volume was not associated with final diagnosis. However, the combination of both diffusion-weighted imaging positivity and high WMH volume led to lower odds of focal symptoms at presentation (P=0.035). Conclusions- The combination of diffusion-weighted imaging positivity and high WMH volume was associated with lower odds of focal symptoms at presentation in patients seen with minor neurological deficits in the emergency department. This suggests that WMH volume might be an important consideration and the absence of focal symptoms at presentation should not discourage clinicians from further investigating patients with suspected cerebral ischemia.

Current practice and future directions in the diagnosis and acute treatment of ischaemic stroke.

Even though stroke presents as a variety of clinical syndromes, neuroimaging is the most important biomarker to help differentiate between stroke subtypes and assess treatment eligibility. Therapeutic advances have led to intravenous thrombolysis with tissue-type plasminogen activator and endovascular treatment for proximal vessel occlusion in the anterior cerebral circulation being standard care for acute ischaemic stroke. Providing access to this care has implications for existing systems of care for stroke and their organisation and has reintroduced the possibility of adjuvant and neuroprotective treatment strategies in acute ischaemic stroke. The use of neuroimaging for patient selection and speed of diagnosis and delivery of treatment are the dominant themes of modern ischaemic stroke care.

Systolic blood pressure as a predictor of transient ischemic attack/minor stroke in emergency department patients under age 80: a prospective cohort study.

BACKGROUND: Elevated blood pressure (BP) at emergency department (ED) presentation and advancing age have been associated with risk of ischemic stroke; however, the relationship between BP, age, and transient ischemic attack/minor stroke (TIA/MS) is not clear. METHODS: A multi-site, prospective, observational study of 1084 ED patients screened for suspected TIA/MS (symptom onset < 24 h, NIHSS< 4) between December 2013 and April 2016. Systolic and diastolic BP measurements (SBP, DBP) were taken at ED presentation. Final diagnosis was consensus adjudication by stroke neurologists; patients were diagnosed as either TIA/MS or stroke-mimic (non-cerebrovascular conditions). Conditional inference trees were used to define age cut-points for predicting binary diagnosis (TIA/MS or stroke-mimic). Logistic regression models were used to estimate the effect of BP, age, sex, and the age-BP interaction on predicting TIA/MS diagnosis. RESULTS: Over a 28-month period, 768 (71%) patients were diagnosed with TIA/MS: these patients were older (mean 71.6 years) and more likely to be male (58%) than stroke-mimics (61.4 years, 41%; each p < 0.001). TIA/MS patients had higher SBP than stroke-mimics (p < 0.001). DBP did not differ between the two groups (p = 0.191). SBP was predictive of TIA/MS diagnosis in younger patients, after accounting for age and sex; an increase of 10 mmHg systolic increased the odds of TIA/MS 18% (odds ratio [OR] 1.18, 95% CI 1.00-1.39) in patients < 60 years, and 23% (OR 1.23, 95% CI 11.12-1.35) in those 60-79 years, while not affecting the odds of TIA/MS in patients ≥80 years (OR 0.99, 95% CI 0.89-1.07). CONCLUSIONS: Raised SBP in patients younger than 80 with suspected TIA/MS may be a useful clinical indicator upon initial presentation to help increase clinicians' suspicion of TIA/MS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03050099 (10-Feb-2017) and NCT03070067 (3-Mar-2017). Retrospectively registered.

Association of White Matter Hyperintensities With Short-Term Outcomes in Patients With Minor Cerebrovascular Events.

BACKGROUND AND PURPOSE: White matter lesions (WML) are associated with cognitive decline, increased stroke risk, and disability in old age. We hypothesized that superimposed acute cerebrovascular occlusion on chronic preexisting injury (leukoaraiosis) leads to worse outcome after minor cerebrovascular event, both using quantitative (volumetric) and qualitative (Fazekas scale) assessment, as well as relative total brain volume. METHODS: WML volume assessment was performed in 425 patients with high-risk transient ischemic attack (TIA; motor/speech deficits >5 minutes) or minor strokes from the CATCH study (CT and MRI in the Triage of TIA and Minor Cerebrovascular Events to Identify High Risk Patients). Complete baseline characteristics and outcome assessment were available in 412 patients. Primary outcome was disability at 90 days, defined as modified Rankin Scale score of >1. Secondary outcomes were stroke progression, TIA recurrence, and stroke recurrence. Analysis was performed using descriptive statistics and regression models including interaction terms. RESULTS: Median age was 69 years, 39.8% were female. Sixty-two patients (15%) had unfavorable outcome with disability at 90 days (modified Rankin Scale score >1). Higher Fazekas scores were strongly correlated with higher WML volume (r=0.79). Both higher Fazekas score and higher WMH volume were associated with disability at 90 days in univariate regression (odds ratio 1.22; 95% confidence interval, 1.04-1.43 and odds ratio, 1.25 per milliliter increase; 95% confidence interval, 1.02-1.54, respectively) but not with stroke progression, TIA recurrence, or stroke recurrence. In multivariable-adjusted analyses, additive interaction terms were associated with unfavorable outcome (adjusted odds ratio 3.99, 95% confidence interval, 1.87-8.49). CONCLUSIONS: Our data suggest that quantitative and qualitative WML assessments are highly correlated and comparable in TIA/minor stroke patients. WML burden is associated with short-term outcome of patients with good prestroke function in the presence of intracranial stenosis/occlusion.

Evolving Treatments for Acute Ischemic Stroke.

The purpose of this article is to review advances in stroke treatment in the hyperacute period. With recent evolutions of technology in the fields of imaging, thrombectomy devices, and emergency room workflow management, as well as improvement in statistical methods and study design, there have been ground breaking changes in the treatment of acute ischemic stroke. We describe how stroke presents as a clinical syndrome and how imaging as the most important biomarker will help differentiate between stroke subtypes and treatment eligibility. The evolution of hyperacute treatment has led to the current standard of care: intravenous thrombolysis with tissue-type plasminogen activator and endovascular treatment for proximal vessel occlusion in the anterior cerebral circulation. All patients with acute ischemic stroke are in need of hyperacute secondary prevention because the risk of recurrence is highest closest to the index event. The dominant themes of modern stroke care are the use of neurovascular imaging and speed of diagnosis and treatment.

Verification of a proteomic biomarker panel to diagnose minor stroke and transient ischaemic attack: phase 1 of SpecTRA, a large scale translational study.

OBJECTIVE: To derive a plasma biomarker protein panel from a list of 141 candidate proteins which can differentiate transient ischaemic attack (TIA)/minor stroke from non-cerebrovascular (mimic) conditions in emergency department (ED) settings. DESIGN: Prospective clinical study (#NCT03050099) with up to three timed blood draws no more than 36 h following symptom onset. Plasma samples analysed by multiple reaction monitoring-mass spectrometry (MRM-MS). PARTICIPANTS: Totally 545 participants suspected of TIA enrolled in the EDs of two urban medical centres. OUTCOMES: 90-day, neurologist-adjudicated diagnosis of TIA informed by clinical and radiological investigations. RESULTS: The final protein panel consists of 16 proteins whose patterns show differential abundance between TIA and mimic patients. Nine of the proteins were significant univariate predictors of TIA [odds ratio (95% confidence interval)]: L-selectin [0.726 (0.596-0.883)]; Insulin-like growth factor-binding protein 3 [0.727 (0.594-0.889)]; Coagulation factor X [0.740 (0.603-0.908)]; Serum paraoxonase/lactonase 3 [0.763 (0.630-0.924)]; Thrombospondin-1 [1.313 (1.081-1.595)]; Hyaluronan-binding protein 2 [0.776 (0.637-0.945)]; Heparin cofactor 2 [0.775 (0.634-0.947)]; Apolipoprotein B-100 [1.249 (1.037-1.503)]; and von Willebrand factor [1.256 (1.034-1.527)]. The scientific plausibility of the panel proteins is discussed. CONCLUSIONS: Our panel has the potential to assist ED physicians in distinguishing TIA from mimic patients.

Validation of a proteomic biomarker panel to diagnose minor-stroke and transient ischaemic attack: phase 2 of SpecTRA, a large scale translational study.

OBJECTIVE: To validate our previously developed 16 plasma-protein biomarker panel to differentiate between transient ischaemic attack (TIA) and non-cerebrovascular emergency department (ED) patients. METHOD: Two consecutive cohorts of ED patients prospectively enrolled at two urban medical centers into the second phase of SpecTRA study (training, cohort 2A, n = 575; test, cohort 2B, n = 528). Plasma samples were analyzed using liquid chromatography/multiple reaction monitoring-mass spectrometry. Logistic regression models which fit cohort 2A were validated on cohort 2B. RESULTS: Three of the panel proteins failed quality control and were removed from the panel. During validation, panel models did not outperform a simple motor/speech (M/S) deficit variable. Post-hoc analyses suggested the measured behaviour of L-selectin and coagulation factor V contributed to poor model performance. Removal of these proteins increased the external performance of a model containing the panel and the M/S variable. CONCLUSIONS: Univariate analyses suggest insulin-like growth factor-binding protein 3 and serum paraoxonase/lactonase 3 are reliable and reproducible biomarkers for TIA status. Logistic regression models indicated L-selectin, apolipoprotein B-100, coagulation factor IX, and thrombospondin-1 to be significant multivariate predictors of TIA. We discuss multivariate feature subset analyses as an exploratory technique to better understand a panel's full predictive potential.

Outcomes in Hospitalized Ischemic Stroke Patients with Dementia on Admission: A Population-Based Cohort Study.

BACKGROUND: Dementia prevalence is rising, and it will double in the next 20 years. This study sought to understand the prevalence of dementia in hospitalized patients with ischemic stroke, and its impact on outcomes. METHODS: Using the Canadian Institute of Health Information's (CIHI) Discharge Abstract Database (DAD), all acute ischemic stroke admissions from April 2003 to March 2015 in Canada (excluding Quebec) were analyzed. Concurrent dementia at the time of admission was assessed based on hospital diagnostic codes. Characteristics and in-hospital outcomes were compared in patients with and without dementia using χ 2 and negative binomial, as well as Poisson regression analysis. RESULTS: During the observed period, 313,138 people were admitted to a hospital in Canada for an ischemic stroke. Of those, 21,788 (7.0%) had a concurrent diagnosis of dementia. People with dementia had older median age (84 vs. 76 years; p<0.0001), were more often female (59.6% vs. 48.4%; p<0.0001) and more often had Charlson-Deyo Comorbidity Index ≥2 (64.5% vs. 43.5%; p<0.0001). Patients with dementia were less likely to be discharged to a rehabilitation facility (adjusted risk ratio [RR] 3.089, 95% confidence interval [CI] 2.992-3.188, p<0.0001) or home independently (adjusted RR 0.756, 95% CI 0.737-0.776, p<0.0001).InterpretationApproximately 1 in 13 hospitalized ischemic stroke patients has coded dementia. Patients with ischemic stroke and concurrent dementia have higher mortality, face significantly more dependence after stroke and utilize greater healthcare resources than stroke patients without dementia. Causative conclusions are limited by the administrative data source. Early care planning and coordination could potentially optimize outcomes.

Defining Optimal Brain Health in Adults: A Presidential Advisory From the American Heart Association/American Stroke Association.

Cognitive function is an important component of aging and predicts quality of life, functional independence, and risk of institutionalization. Advances in our understanding of the role of cardiovascular risks have shown them to be closely associated with cognitive impairment and dementia. Because many cardiovascular risks are modifiable, it may be possible to maintain brain health and to prevent dementia in later life. The purpose of this American Heart Association (AHA)/American Stroke Association presidential advisory is to provide an initial definition of optimal brain health in adults and guidance on how to maintain brain health. We identify metrics to define optimal brain health in adults based on inclusion of factors that could be measured, monitored, and modified. From these practical considerations, we identified 7 metrics to define optimal brain health in adults that originated from AHA's Life's Simple 7: 4 ideal health behaviors (nonsmoking, physical activity at goal levels, healthy diet consistent with current guideline levels, and body mass index <25 kg/m2) and 3 ideal health factors (untreated blood pressure <120/<80 mm Hg, untreated total cholesterol <200 mg/dL, and fasting blood glucose <100 mg/dL). In addition, in relation to maintenance of cognitive health, we recommend following previously published guidance from the AHA/American Stroke Association, Institute of Medicine, and Alzheimer's Association that incorporates control of cardiovascular risks and suggest social engagement and other related strategies. We define optimal brain health but recognize that the truly ideal circumstance may be uncommon because there is a continuum of brain health as demonstrated by AHA's Life's Simple 7. Therefore, there is opportunity to improve brain health through primordial prevention and other interventions. Furthermore, although cardiovascular risks align well with brain health, we acknowledge that other factors differing from those related to cardiovascular health may drive cognitive health. Defining optimal brain health in adults and its maintenance is consistent with the AHA's Strategic Impact Goal to improve cardiovascular health of all Americans by 20% and to reduce deaths resulting from cardiovascular disease and stroke by 20% by the year 2020. This work in defining optimal brain health in adults serves to provide the AHA/American Stroke Association with a foundation for a new strategic direction going forward in cardiovascular health promotion and disease prevention.

Cerebral Microbleeds and Cortical Superficial Siderosis in Patients Presenting With Minor Cerebrovascular Events.

BACKGROUND AND PURPOSE: Transient focal neurological episodes occur in cerebral amyloid angiopathy (CAA) and can mimic transient ischemic attack (TIA). Risk factors and outcomes of minor ischemic stroke or TIA might differ in patients with and without cerebral microbleeds (CMBs), including CAA-consistent lobar CMB. METHODS: Baseline magnetic resonance imaging (MRI) was analyzed for CMBs and cortical superficial siderosis in 416 patients in the prospective computed tomography and MRI in the CATCH study (Triage of TIA and Minor Cerebrovascular Events to Identify High Risk Patients). Clinical symptoms, baseline characteristics, recurrence, and 90-day modified Rankin Scale were prospectively collected. MRI white-matter hyperintensity was measured using the Fazekas scale. RESULTS: CMBs were detected in 65 (15.6%) and cortical superficial siderosis in 11 patients (2.6%). Lobar CMBs were present in 49 (11.8%). In multivariable logistic regression adjusted for risk factors and age, subcortical Fazekas score was associated with lobar CMB (odds ratio, 2.07; 95% confidence interval, 1.23-3.48; P=0.006). Forty-two patients (10.1%) had lobar-only CMBs with or without cortical superficial siderosis consistent with modified Boston criteria for possible/probable CAA. The possible/probable CAA pattern was not predictive of recurrent TIA (odds ratio, 0.42; 95% confidence interval, 0.05-3.31; P=0.41), stroke (odds ratio, 1.24; 95% confidence interval, 0.26-5.99; P=0.79), or 90-day modified Rankin Scale score ≥2 (odds ratio, 1.38; 95% confidence interval, 0.62-3.07; P=0.42). CONCLUSIONS: CMBs in TIA and minor stroke are moderately common but do not predict recurrence or 90-day outcome. CAA-related transient focal neurological episodes and TIA have overlapping clinical symptoms, suggesting that MRI may be needed for differentiation.

Cerebral Amyloid Angiopathy Is Associated With Executive Dysfunction and Mild Cognitive Impairment.

BACKGROUND AND PURPOSE: Autopsy studies suggest that cerebral amyloid angiopathy (CAA) is associated with cognitive impairment and risk for dementia. We analyzed neuropsychological test data from a prospective cohort study of patients with CAA to identify the prevalence of cognitive impairment and its associations with brain magnetic resonance imaging features and the apolipoprotein E genotype. METHODS: Data were analyzed from 34 CAA, 16 Alzheimer's disease, 69 mild cognitive impairment, and 27 ischemic stroke participants. Neuropsychological test results were expressed as z scores in relation to normative data provided by the test manuals and then grouped into domains of memory, executive function, and processing speed. RESULTS: Mean test scores in CAA participants were significantly lower than norms for memory (-0.44±1.03; P=0.02), executive function (-1.14±1.07; P<0.001), and processing speed (-1.06±1.12; P<0.001). Twenty-seven CAA participants (79%) had mild cognitive impairment based on low cognitive performance accompanied by cognitive concerns. CAA participants had similarly low executive function scores as Alzheimer's disease, but relatively preserved memory. CAA participants' scores were lower than those of ischemic stroke controls for executive function and processing speed. Lower processing speed scores in CAA were associated with higher magnetic resonance imaging white matter hyperintensity volume. There were no associations with the apolipoprotein E ε4 allele. CONCLUSIONS: Mild cognitive impairment is very prevalent in CAA. The overall cognitive profile of CAA is more similar to that seen in vascular cognitive impairment rather than Alzheimer's disease. White matter ischemic lesions may underlie some of the impaired processing speed in CAA.

Endovascular Interventions in Acute Ischemic Stroke: Recent Evidence, Current Challenges, and Future Prospects.

After many years of clinical research, endovascular thrombectomy has been conclusively proven to be an effective treatment in acute ischemic stroke. The evidence is compelling; however, it is generated in high volume stroke centers with stroke expertise. Challenges remain ahead on translating and implementing this evidence in routine clinical care across the world. The current evidence has opened up avenues for further research and innovation in this field. In this review, we will discuss the evolution of evidence on endovascular thrombectomy followed by a discussion of challenges and future prospects in this exciting field of stroke care.