Search

BACKGROUND: The Get With The Guidelines-Stroke program is a quality improvement initiative designed to enhance adherence to evidence-based stroke care. Since its inception in 2003, over 2800 hospitals in the United States have participated in the program. METHODS: We examined patient characteristics, adherence to performance measures, and in-hospital outcomes in patients hospitalized for acute ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, and transient ischemic attack in The Get With The Guidelines-Stroke hospitals from 2003 through 2022. We quantified temporal changes in performance measure adherence and clinical outcomes over time. Performance measure denominators consisted of patients who were eligible, excluding those with contraindications. RESULTS: Over the 20 years of the program, a total of 7837 849 stroke cases (median age 71 years, 51.0% female; 69.2% ischemic strokes, 3.9% SAHs, 11.5% ICHs, and 15.3% TIAs) were entered into the registry. Except for antithrombotics at discharge, in which the baseline performance was >92%, there was sustained improvement in all performance metrics regardless of type of cerebrovascular event (P

AIMS: The clinical correlates and outcomes of asymptomatic atrial fibrillation (AF) in hospitalized patients are largely unknown. We aimed to investigate the clinical correlates and in-hospital outcomes of asymptomatic AF in hospitalized Chinese patients. METHODS AND RESULTS: We conducted a cross-sectional registry study of inpatients with AF enrolled in the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation Project between February 2015 and December 2019. We investigated the clinical characteristics of asymptomatic AF and the association between the clinical correlates and the in-hospital outcomes of asymptomatic AF. Asymptomatic and symptomatic AF were defined according to the European Heart Rhythm Association score. Asymptomatic patients were more commonly males (56.3%) and had more comorbidities such as hypertension (57.4%), diabetes mellitus (18.6%), peripheral artery disease (PAD; 2.3%), coronary artery disease (55.5%), previous history of stroke/transient ischaemic attack (TIA; 17.9%), and myocardial infarction (MI; 5.4%); however, they had less prevalent heart failure (9.6%) or left ventricular ejection fractions ≤40% (7.3%). Asymptomatic patients were more often hospitalized with a non-AF diagnosis as the main diagnosis and were more commonly first diagnosed with AF (23.9%) and long-standing persistent/permanent AF (17.0%). The independent determinants of asymptomatic presentation were male sex, long-standing persistent AF/permanent AF, previous history of stroke/TIA, MI, PAD, and previous treatment with anti-platelet drugs. The incidence of in-hospital clinical events such as all-cause death, ischaemic stroke/TIA, and acute coronary syndrome (ACS) was higher in asymptomatic patients than in symptomatic patients, and asymptomatic clinical status was an independent risk factor for in-hospital all-cause death, ischaemic stroke/TIA, and ACS. CONCLUSION: Asymptomatic AF is common among hospitalized patients with AF. Asymptomatic clinical status is associated with male sex, comorbidities, and a higher risk of in-hospital outcomes. The adoption of effective management strategies for patients with AF should not be solely based on clinical symptoms.

Background and objectivesTo understand the role of premature (defined as ≤ 60 years) cardiovascular disease (CVD) in brain health earlier in life, we examined the associations of premature CVD with midlife cognition and white matter health.MethodsWe studied a prospective cohort in the Coronary Artery Risk Development in Young Adults study, who were 18-30 years at baseline (1985-1986) and followed up to 30 years when 5 cognitive tests measuring different domains were administered. A subset (656 participants) had brain MRI measures of white matter hyperintensity (WMH) and white matter integrity. A premature CVD event was adjudicated based on medical records of coronary heart disease, stroke/TIA, congestive heart failure, carotid artery disease, and peripheral artery disease. We conducted linear regression to determine the associations of nonfatal premature CVD with cognitive performance (z-standardized), cognitive decline, and MRI measures.ResultsAmong 3,146 participants, the mean age (57% women and 48% Black) was 55.1 ± 3.6 years, with 5% (n = 147) having premature CVD. Adjusting for demographics, education, literacy, income, depressive symptoms, physical activity, diet, and APOE, premature CVD was associated with lower cognition in 4 of 5 domains: global cognition (-0.22, 95% CI -0.37 to -0.08), verbal memory (-0.28, 95% CI -0.44 to -0.12), processing speed (-0.46, 95% CI -0.62 to -0.31), and executive function (-0.38, 95% CI -0.55 to -0.22). Premature CVD was associated with greater WMH (total, temporal, and parietal lobes) and higher white matter mean diffusivity (total and temporal lobes) after adjustment for covariates. These associations remained significant after adjusting for cardiovascular risk factors (CVRFs) and excluding those with stroke/TIA. Premature CVD was also associated with accelerated cognitive decline over 5 years (adjusted OR 3.07, 95% CI 1.65-5.71).DiscussionPremature CVD is associated with worse midlife cognition and white matter health, which is not entirely driven by stroke/TIA and even independent of CVRFs. Preventing CVD in early adulthood may delay the onset of cognitive decline and promote brain health over the life course.

BACKGROUND AND PURPOSE: Dual antiplatelet therapy has been shown to reduce the risk of recurrent stroke in patients with minor stroke or transient ischemic attack. However, whether the effect of dual antiplatelet therapy is modified by pretreatment antiplatelet status is unclear. METHODS: This is a post hoc analysis of the POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke). Patients were divided into 2 groups based on pretreatment antiplatelet use. The primary outcome was ischemic stroke within 90 days of randomization. RESULTS: We included 4881 patients of whom 41% belonged to the no pretreatment antiplatelet. Ischemic stroke occurred in 6% and 5% in the antiplatelet pretreatment and no antiplatelet pretreatment, respectively. Antiplatelet pretreatment was not associated with the risk of ischemic stroke (adjusted hazard ratio, 1.05 [95% CI, 0.81-137]) or risk of major hemorrhage (hazard ratio, 1.10 [95% CI, 0.55-2.21]; P=0.794). The effect of dual antiplatelet therapy on recurrent ischemic stroke risk was not different in patients who were on antiplatelet before randomization (adjusted hazard ratio, 0.69 [95% CI, 0.50-0.94]) as opposed to those who were not (adjusted hazard ratio, 0.75 [95% CI, 0.50-1.12]), P for interaction = 0.685. CONCLUSIONS: In patients with minor stroke and high-risk transient ischemic attack, dual antiplatelet therapy reduces the risk of ischemic stroke regardless of premorbid antiplatelet use.

BACKGROUND AND PURPOSE: Perfusion imaging can risk stratify patients with symptomatic intracranial stenosis. We aim to determine the association between perfusion delay and length of hospital stay (LOS) in symptomatic middle cerebral artery (MCA) stenosis patients. METHODS: This is a retrospective study of consecutive patients admitted to a comprehensive stroke center over 5 years with ischemic stroke or transient ischemic attack (TIA) within 7 days of symptom onset due to MCA stenosis (50-99%) and underwent perfusion imaging. Patients were divided into three groups: mismatch volume ≥ 15 cc based on T max > 6 second delay, T max 4-6 second delay, and 6 second mismatch was associated with prolonged LOS (OR 2.94 95% CI 1.06-8.18; P = .039), but T max 4-6 second was not (OR 1.45 95% CI .46-4.58, P = .528). We found similar associations when LOS was a continuous variable for T max > 6 second (β coefficient = 2.01, 95% CI .05-3.97, P = .044) and T max 4-6 second (β coefficient = 1.24, 95% CI -.85 to 3.34, P = .244). CONCLUSION: In patients with symptomatic MCA stenosis, T max > 6 second perfusion delay is associated with prolonged LOS. Prospective studies are needed to validate our findings.

Background Atrial fibrillation/flutter (AF) after transient ischemic attack (TIA) has not been well studied. We compared the likelihood of new AF diagnosis after ischemic stroke versus TIA. Methods and Results The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) trial enrolled adults within 12 hours of minor ischemic stroke or high-risk TIA. Our exposure was index event type (ischemic stroke versus TIA). The primary analysis used the original trial definition of TIA (resolution of symptoms/signs). In secondary analyses, TIA cases with infarction on neuroimaging were reclassified as strokes. Our primary outcome was a new AF diagnosis, ascertained from adverse event and treatment interruption/discontinuation reports. We calculated C-statistics for variables associated with newly diagnosed AF. We used Kaplan-Meier survival statistics and Cox models adjusted for demographics and vascular risk factors. Excluding 49 subjects with baseline AF, 2746 patients had index stroke and 2086 patients had index TIA. During the 90-day follow-up, 106 patients had newly diagnosed AF. Cumulative risks of AF were 2.7% (95% CI, 2.1%-3.4%) after stroke and 2.0% (95% CI, 1.5%-2.7%) after TIA (P=0.15). After reclassifying index events by neuroimaging, cumulative AF risk was higher after stroke (2.7%; 95% CI, 2.2%-3.4%) than TIA (1.8%; 95% CI, 1.3%-2.5%) (P=0.04). Index event type had negligible predictive utility (C-statistic, 0.54). Conclusions Among patients with cerebral ischemia, the distinction between TIA versus minor stroke did not stratify the risk of subsequent AF diagnosis, implying that patients with TIA should undergo similar heart-rhythm monitoring strategies as patients with ischemic stroke.

BackgroundIntracranial atherosclerotic disease (ICAD) is a common cause of ischemic stroke with a high risk of clinical stroke recurrence. Multiple mechanisms may underlie cerebral ischemia in this condition. The study's objective is to discern the mechanisms of recurrent ischemia in ICAD through imaging biomarkers of impaired antegrade flow, poor distal perfusion, abnormal vasoreactivity, and artery-to-artery embolism.MethodsThis prospective multicenter observational study enrolled patients with recent (≤21 days) ischemic stroke or transient ischemic attack (TIA) caused by ICAD with 50-99% stenosis treated medically. We obtained baseline quantitative MRA (QMRA), perfusion MRI (PWI), transcranial Doppler vasoreactivity (VMR), and emboli detection studies (EDS). The primary outcome was ischemic stroke in the territory of the stenotic artery within 1 year of follow-up; secondary outcomes were TIA at 1 year and new infarcts in the territory on MRI at 6-8 weeks.ResultsAmongst 102 of 105 participants with clinical follow-up (mean 253±131 days), the primary outcome occurred in 8.8% (12.7/100 patient-years), while 5.9% (8.5/100 patient-years) had a TIA. A new infarct in the territory of the symptomatic artery was noted in 24.7% at 6-8 weeks. A low flow state on QMRA was noted in 25.5%, poor distal perfusion on PWI in 43.5%, impaired vasoreactivity on VMR in 67.5%, and microemboli on EDS in 39.0%. No significant association was identified between these imaging biomarkers and primary or secondary outcomes.ConclusionsDespite intensive medical management in ICAD, there is a high risk of clinical cerebrovascular events at 1 year and an even higher risk of new imaging-evident infarcts in the subacute period after index stroke. Hemodynamic and plaque instability biomarkers did not identify a higher risk group. Further work is needed to identify mechanisms of ischemic stroke and infarct recurrence and their consequence on long-term physical and cognitive outcomes.Trial registrationClinicalTrials.gov: NCT02121028.

ObjectiveThere is an interest in identifying a metabolic OA phenotype. We therefore assessed the relation of diabetes and cardiovascular disease to prevalent and incident radiographic (ROA) and symptomatic knee osteoarthritis (SxOA).DesignIn two large cohort studies of individuals with or at risk for knee OA, the Multicenter Osteoarthritis Study (MOST) and Osteoarthritis Initiative (OAI), participants self-reported diabetes and cardiovascular disease (CVD) at baseline. We assessed the relation of baseline diabetes and CVD (exposures) to ROA and SxOA cross-sectionally and after 60 (MOST) or 48 (OAI) months of follow-up using logistic regression with GEE to account for 2 knees within an individual, adjusting for potential confounders.ResultsIn MOST, 6,020 knees of 3,021 participants (60.1% female, mean ± SD age 62.5 ± 8.1, mean BMI 30.7 ± 6.0, 83.3% Caucasian) were included in the analyses. In OAI, 8,645 knees of 4,339 participants (58.2% female, mean ± SD age 61.1 ± 9.2, mean BMI 28.6 ± 4.8, 80.3% Caucasian) were included. We found no significant associations between prevalent diabetes or CVD and prevalent or incident ROA or SxOA. Effect estimates for prevalent ROA and SxOA ranged from 0.80 (95% CI 0.63-1.03) to 1.17 (0.91-1.51). Effect estimates for incident ROA ranged from 0.80 (0.58-1.11) to 0.88 (0.60-1.29) in MOST and from 0.75 (0.50-1.14) to 1.19 (0.81-1.74) in OAI, and for incident SxOA from 0.93 (0.65-1.31) to 1.22 (0.89-1.67) in MOST and from 0.82 (0.59-1.16) to 1.19 (0.85-1.66) in OAI).ConclusionsDiabetes and CVD were not associated with prevalent or incident knee OA.

BACKGROUND AND PURPOSE: The role of regional hypoperfusion as a contributor to stroke risk in atherosclerotic vertebrobasilar disease has recently been confirmed by the observational VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) Study. We examined the stability of hemodynamic status over time and its relationship to stroke risk in patients from this prospective cohort. METHODS: VERiTAS enrolled patients with recently symptomatic ≥50% atherosclerotic stenosis/occlusion of vertebral and/or basilar arteries. Large vessel flow in the vertebrobasilar territory was assessed using quantitative magnetic resonance angiography, and patients were designated as low or normal flow based on distal territory regional flow, incorporating collateral capacity. Patients underwent standard medical management and follow-up for primary outcome event of vertebrobasilar territory stroke. Quantitative magnetic resonance angiography imaging was repeated at 6, 12, and 24 months. Flow status over time was examined relative to baseline and relative to subsequent stroke risk using a cause-specific proportional hazard model, with flow status treated as a time-varying covariate. Mean blood pressure was examined to assess for association with changes in flow status. RESULTS: Over 19±8 months of follow-up, 132 follow-up quantitative magnetic resonance angiography studies were performed in 58 of the 72 enrolled patients. Of the 13 patients with serial imaging who had low flow at baseline, 7 (54%) had improvement to normal flow at the last follow-up. Of the 45 patients who had normal flow at baseline, 3 (7%) converted to low flow at the last follow-up. The mean blood pressure did not differ in patients with or without changes in flow status. The time-varying flow status remained a strong predictor of subsequent stroke (hazard ratio, 10.3 [95% CI, 2.2-48.7]). CONCLUSIONS: There is potential both for improvement and worsening of hemodynamics in patients with atherosclerotic vertebrobasilar disease. Flow status, both at baseline and over time, is a risk factor for subsequent stroke, thus serving as an important prognostic marker. Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT00590980.

Background and purposeClinical methods have incomplete diagnostic value for early diagnosis of acute stroke and large vessel occlusion (LVO). Electroencephalography is rapidly sensitive to brain ischemia. This study examined the diagnostic utility of electroencephalography for acute stroke/transient ischemic attack (TIA) and for LVO.MethodsPatients (n=100) with suspected acute stroke in an emergency department underwent clinical exam then electroencephalography using a dry-electrode system. Four models classified patients, first as acute stroke/TIA or not, then as acute stroke with LVO or not: (1) clinical data, (2) electroencephalography data, (3) clinical+electroencephalography data using logistic regression, and (4) clinical+electroencephalography data using a deep learning neural network. Each model used a training set of 60 randomly selected patients, then was validated in an independent cohort of 40 new patients.ResultsOf 100 patients, 63 had a stroke (43 ischemic/7 hemorrhagic) or TIA (13). For classifying patients as stroke/TIA or not, the clinical data model had area under the curve=62.3, whereas clinical+electroencephalography using deep learning neural network model had area under the curve=87.8. Results were comparable for classifying patients as stroke with LVO or not.ConclusionsAdding electroencephalography data to clinical measures improves diagnosis of acute stroke/TIA and of acute stroke with LVO. Rapid acquisition of dry-lead electroencephalography is feasible in the emergency department and merits prehospital evaluation.

Background and purposeSelf-management programs may improve quality of life and self-efficacy for stroke survivors, but participation is low. In a randomized controlled trial of a complex, multidisciplinary, team-based secondary stroke prevention intervention, we offered participants Chronic Disease Self-Management Program (CDSMP) workshops in addition to clinic visits and home visits. To enhance participation, workshops were facilitated by community health workers who were culturally and linguistically concordant with most participants and scheduled CDSMP sessions at convenient venues and times. Over time, we implemented additional strategies such as free transportation and financial incentives. In this study, we aimed to determine factors associated with CDSMP participation and attendance.MethodsFrom 2014 to 2018, 18 CDSMP workshop series were offered to 241 English and Spanish-speaking individuals (age ≥40 years) with recent stroke or transient ischemic attack. Zero-inflated Poisson regression was used to identify factors associated with participation and attendance (ie, number of sessions attended) in CDSMP. Missing values were imputed using multiple imputation methods.ResultsNearly one-third (29%) of intervention subjects participated in CDSMP. Moderate disability and more clinic/home visits were associated with participation. Participants with higher numbers of clinic and home visits (incidence rate ratio [IRR], 1.06 [95% CI, 1.01-1.12]), severe (IRR, 2.34 [95% CI, 1.65-3.31]), and moderately severe disability (IRR, 1.55 [95% CI, 1.07-2.23]), and who enrolled later in the study (IRR, 1.12 [95% CI, 1.08-1.16]) attended more sessions. Individuals with higher chaos scores attended fewer sessions (IRR, 0.97 [95% CI, 0.95-0.99]).ConclusionsLess than one-third of subjects enrolled in the SUCCEED (Secondary Stroke Prevention by Uniting Community and Chronic Care Model Teams Early to End Disparities) intervention participated in CDSMP; however, participation improved as transportation and financial barriers were addressed. Strategies to address social determinants of health contributing to chaos and engage individuals in healthcare may facilitate attendance. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01763203.

RationaleIntracranial atherosclerotic disease (ICAD) is the most common cause of ischemic stroke with the highest rate of recurrence, despite aggressive medical management. Diverse mechanisms may be responsible for ICAD-related cerebral ischemia, with potential therapeutic implications. Here we present the rationale, design and methods of the Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD) study. The aim of MyRIAD is to determine the mechanisms of stroke in ICAD through physiologic imaging biomarkers that evaluate impaired antegrade flow, poor distal perfusion, abnormal vasoreactivity, artery to artery embolism, and their interaction.Methods and designThis is a prospective observational study of patients with recently symptomatic (

Background and purposeClopidogrel is an antiplatelet drug that is metabolized to its active form by the CYP2C19 enzyme. The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) found a significant interaction between loss-of-function allele status for the CYP2C19 gene and the effect of dual antiplatelet therapy with aspirin and clopidogrel on the rate of early recurrent stroke following acute transient ischemic attack/minor stroke. The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial), similar in design to CHANCE but performed largely in North America and Europe, demonstrated a reduction in early recurrent stroke with dual antiplatelet therapy compared with aspirin alone. This substudy was done to evaluate a potential interaction between loss-of-function CYP2C19 alleles and outcome by treatment group in POINT.MethodsOf the 269 sites in 10 countries that enrolled patients in POINT, 134 sites participated in this substudy. DNA samples were genotyped for CYP2C19 *2, *3, and *17 alleles and classified as being carriers or noncarriers of loss-of-function alleles. Major ischemia consisted of ischemic stroke, myocardial infarction, or ischemic vascular death.ResultsNine hundred thirty-two patients provided analyzable DNA. The rates of major ischemia were 6.7% for the aspirin group versus 2.3% for the dual antiplatelet therapy group (hazard ratio, 0.33 [95% CI, 0.09-1.21]; P=0.09) among carriers of loss-of-function allele. The rates of major ischemia were 5.6% for the aspirin group versus 3.7% for the dual antiplatelet therapy group (hazard ratio, 0.65 [95% CI, 0.32-1.34]; P=0.25) among noncarriers. There was no significant interaction by genotype for major ischemia (P=0.36) or stroke (P=0.33).ConclusionsThis substudy of POINT found no significant interaction with CYP2C19 loss-of-function carrier status and outcome by treatment group. Failure to confirm the findings from the CHANCE trial may be because the loss-of-function alleles tested are not clinically important in this context or because the 2 trials had differences in racial/ethnic composition. Additionally, differences between the 2 trials might be due to chance as our statistical power was limited to 50%. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00991029.

BackgroundResidual shunt is observed in up to 25% of patients after patent foramen ovale (PFO) closure, but its long-term influence on stroke recurrence currently is unknown.ObjectiveTo investigate the association of residual shunt after PFO closure with the incidence of recurrent stroke and transient ischemic attack (TIA).DesignProspective cohort study comparing stroke or TIA recurrence in patients with and without residual shunt after PFO closure.SettingSingle hospital center.Participants1078 consecutive patients (mean age, 49.3 years) with PFO-attributable cryptogenic stroke who were undergoing percutaneous PFO closure were followed for up to 11 years.MeasurementsResidual shunt was evaluated by transthoracic echocardiography with saline contrast. Primary outcome was a composite of the first recurrent ischemic stroke or TIA after PFO closure.ResultsCompared with complete closure, the presence of residual shunt after PFO closure was associated with an increased incidence of recurrent stroke or TIA: 2.32 versus 0.75 events per 100 patient-years (hazard ratio [HR], 3.05 [95% CI, 1.65 to 5.62]; P < 0.001). This result remained robust after adjustment for important covariates, namely age; study period; device; presence of atrial septal aneurysm, hypertension, hyperlipidemia, diabetes, hypercoagulability, or hypermobile septum; and medication use (HR, 3.01 [CI, 1.59 to 5.69]; P < 0.001). Further stratification based on shunt size revealed that moderate or large residual shunts were associated with a higher risk for stroke or TIA recurrence (HR, 4.50 [CI, 2.20 to 9.20]; P < 0.001); the result for small residual shunts was indeterminate (HR, 2.02 [CI, 0.87 to 4.69]; P = 0.102).LimitationNonrandomized study with potential unmeasured confounding.ConclusionAmong patients undergoing PFO closure to prevent future stroke, the presence of residual shunt, particularly a moderate or large residual shunt, was associated with an increased risk for stroke or TIA recurrence.Primary funding sourceNational Institutes of Health.

Background There is growing recognition that positive health beliefs may promote blood pressure (BP) reduction, which is critical to stroke prevention but remains a persistent challenge. Yet, studies that examine the association between positive health beliefs and BP among stroke survivors are lacking. Methods and Results Data came from the DESERVE (Discharge Educational Strategies for Reduction of Vascular Events) study, a randomized controlled trial of a skills-based behavioral intervention to reduce vascular risk in a multiethnic cohort of 552 transient ischemic attack and mild/moderate stroke patients in New York City. The exposure was perception that people can protect themselves from having a stroke (ie, prevention self-efficacy) at baseline. The association between systolic BP (SBP) reduction at 12-month follow-up and self-efficacy was examined using linear regression adjusted for key confounders, overall and stratified by age, sex, race/ethnicity, and intervention trial arm. Approximately three quarters endorsed self-efficacy. These participants had, on average, 5.6 mm Hg greater SBP reduction compared with those who did not endorse it (95% CI, 0.5-10.7 mm Hg; P=0.032). Self-efficacy was significantly associated with greater SBP reduction, particularly among female versus male, younger versus older, and Hispanic versus non-Hispanic white patients. Sensitivity analysis adjusting for baseline SBP instead of elevated BP yielded no association between self-efficacy and SBP reduction, but showed sex differences in this association (women: β=5.3; 95% CI, -0.2 to 10.8; P=0.057; men: β=-3.3; 95% CI, -9.4 to 2.9; P=0.300; interaction P=0.064). Conclusions Self-efficacy was linked with greater SBP reduction among female stroke survivors. Targeted strategies to improve health beliefs after stroke may be important for risk factor management. REGISTRATION URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT01836354.

Background and Purpose- While combination aspirin and clopidogrel reduces recurrent stroke compared with aspirin alone in patients with transient ischemic attack (TIA) or minor stroke, the effect on disability is uncertain. Methods- The POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) randomized patients with TIA or minor stroke (National Institutes of Health Stroke Scale score ≤3) within 12 hours of onset to dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel versus aspirin alone. The primary outcome measure was a composite of stroke, myocardial infarction, or vascular death. We performed a post hoc exploratory analysis to examine the effect of treatment on overall disability (defined as modified Rankin Scale score >1) at 90 days, as well as disability ascribed by the local investigator to index or recurrent stroke. We also evaluated predictors of disability. Results- At 90 days, 188 of 1964 (9.6%) of patients enrolled with TIA and 471 of 2586 (18.2%) of those enrolled with stroke were disabled. Overall disability was similar between patients assigned DAPT versus aspirin alone (14.7% versus 14.3%; odds ratio, 0.97 [95% CI, 0.82-1.14]; P=0.69). However, there were numerically fewer patients with disability in conjunction with a primary outcome event in the DAPT arm (3.0% versus 4.0%; odds ratio, 0.73 [95% CI, 0.53-1.01]; P=0.06) and significantly fewer patients in the DAPT arm with disability attributed by the investigators to either the index event or recurrent stroke (5.9% versus 7.4%; odds ratio, 0.78 [95% CI, 0.62-0.99]; P=0.04). Notably, disability attributed to the index event accounted for the majority of this difference (4.5% versus 6.0%; odds ratio, 0.74 [95% CI, 0.57-0.96]; P=0.02). In multivariate analysis, age, subsequent ischemic stroke, serious adverse events, and major bleeding were significantly associated with disability in TIA; for those with stroke, female sex, hypertension, or diabetes mellitus, National Institutes of Health Stroke Scale score, recurrent ischemic stroke, subsequent myocardial infarction, and serious adverse events were associated with disability. Conclusions- In addition to reducing recurrent stroke in patients with acute minor stroke and TIA, DAPT might reduce stroke-related disability. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00991029.

AimsStroke is often a devastating event among patients with heart failure with reduced ejection (HFrEF). In COMMANDER HF, rivaroxaban 2.5 mg b.i.d. did not reduce the composite of first occurrence of death, stroke, or myocardial infarction compared with placebo in patients with HFrEF, coronary artery disease (CAD), and sinus rhythm. We now examine the incidence, timing, type, severity, and predictors of stroke or a transient ischaemic attack (TIA), and seek to establish the net clinical benefit of treatment with low-dose rivaroxaban.Methods and resultsIn this double-blind, randomized trial, 5022 patients who had HFrEF(≤40%), elevated natriuretic peptides, CAD, and who were in sinus rhythm were treated with rivaroxaban 2.5 mg b.i.d. or placebo in addition to antiplatelet therapy, after an episode of worsening HF. The primary neurological outcome for this post hoc analysis was time to first event of any stroke or TIA. Over a median follow-up of 20.5 (25th-75th percentiles 20.0-20.9) months, 150 all-cause stroke (127) or TIA (23) events occurred (ischaemic stroke in 82% and haemorrhagic stroke in 11% of stroke events). Overall, 47.5% of first-time strokes were either disabling (16.5%) or fatal (31%). Prior stroke, low body mass index, geographic region, and the CHA2DS2-VASc score were predictors of stroke/TIA. Rivaroxaban significantly reduced the primary neurological endpoint of all-cause stroke or TIA compared with placebo by 32% (1.29 events vs. 1.90 events per 100 patient-years), adjusted for the time from index HF event to randomization and stratified by geographic region (adjusted hazard ratio 0.68, 95% confidence interval 0.49-0.94), with a number needed to treat of 164 patients per year to prevent one stroke/TIA event. The principal safety endpoint of fatal bleeding or bleeding into a critical space, occurred at a similar rate on rivaroxaban and placebo (0.44 events vs. 0.55 events per 100 patient-years).ConclusionsPatients with HFrEF and CAD are at risk for stroke or TIA in the period following an episode of worsening heart failure in the absence of atrial fibrillation. Most strokes are of ischaemic origin and nearly half are either disabling or fatal. Rivaroxaban at a dose of 2.5 mg b.i.d. reduced rates of stroke or TIA compared with placebo in this population.Trial registrationCOMMANDER HF (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure); ClinicalTrials.gov NCT01877915.

Background Excess transmission of pressure pulsatility caused by increased arterial stiffness may incur microcirculatory damage in end organs (target organ damage [TOD] ) and, in turn, elevate risk for cardiovascular disease ( CVD ) events. Methods and Results We related arterial stiffness measures (carotid-femoral pulse wave velocity, mean arterial pressure, central pulse pressure) to the prevalence and incidence of TOD (defined as albuminuria and/or echocardiographic left ventricular hypertrophy) in up to 6203 Framingham Study participants (mean age 50±15 years, 54% women). We then related presence of TOD to incident CVD in multivariable Cox regression models without and with adjustment for arterial stiffness measures. Cross-sectionally, greater arterial stiffness was associated with a higher prevalence of TOD (adjusted odds ratios ranging from 1.23 to 1.54 per SD increment in arterial stiffness measure, P

Mitochondrial Zn2+ accumulation, particularly in CA1 neurons, occurs after ischemia and likely contributes to mitochondrial dysfunction and subsequent neurodegeneration. However, the relationship between mitochondrial Zn2+ accumulation and their disruption has not been examined at the ultrastructural level in vivo. We employed a cardiac arrest model of transient global ischemia (TGI), combined with Timm's sulfide silver labeling, which inserts electron dense metallic silver granules at sites of labile Zn2+ accumulation, and used transmission electron microscopy (TEM) to examine subcellular loci of the Zn2+ accumulation. In line with prior studies, TGI-induced damage to CA1 was far greater than to CA3 pyramidal neurons, and was substantially progressive in the hours after reperfusion (being significantly greater after 4- than 1-hour recovery). Intriguingly, TEM examination of Timm's-stained sections revealed substantial Zn2+ accumulation in many postischemic CA1 mitochondria, which was strongly correlated with their swelling and disruption. Furthermore, paralleling the evolution of neuronal injury, both the number of mitochondria containing Zn2+ and the degree of their disruption were far greater at 4- than 1-hour recovery. These data provide the first direct characterization of Zn2+ accumulation in CA1 mitochondria after in vivo TGI, and support the idea that targeting these events could yield therapeutic benefits.

ImportanceRandomized clinical trials have demonstrated that patients with asymptomatic carotid stenosis are eligible for carotid endarterectomy (CEA) if the 30-day surgical complication rate is less than 3% and the patient's life expectancy is at least 5 years.ObjectiveTo develop a risk prediction tool to improve patient selection for CEA among patients with asymptomatic carotid stenosis.Design, setting, and participantsIn this cohort study, veterans 65 years and older who received both carotid imaging and CEA in the Veterans Administration between January 1, 2005, and December 31, 2009 (n = 2325) were followed up for 5 years. Data were analyzed from January 2005 to December 2015. A risk prediction tool (the Carotid Mortality Index [CMI]) based on 23 candidate variables identified in the literature was developed using Veterans Administration and Medicare data. A simpler model based on the number of 4 key comorbidities that were prevalent and strongly associated with 5-year mortality was also developed (any cancer in the past 5 years, chronic obstructive pulmonary disease, congestive heart failure, and chronic kidney disease [the 4C model]). Model performance was assessed using measures of discrimination (eg, area under the curve [AUC]) and calibration. Internal validation was performed by correcting for optimism using 500 bootstrapped samples.Main outcome and measureFive-year mortality.ResultsAmong 2325 veterans, the mean (SD) age was 73.74 (5.92) years. The cohort was predominantly male (98.8%) and of white race/ethnicity (94.4%). Overall, 29.5% (n = 687) of patients died within 5 years of CEA. On the basis of a backward selection algorithm, 9 patient characteristics were selected (age, chronic kidney disease, diabetes, chronic obstructive pulmonary disease, any cancer diagnosis in the past 5 years, congestive heart failure, atrial fibrillation, remote stroke or transient ischemic attack, and body mass index) for the final logistic model, which yielded an optimism-corrected AUC of 0.687 for the CMI. The 4C model had slightly worse discrimination (AUC, 0.657) compared with the CMI model; however, the calibration curve was similar to the full model in most of the range of predicted probabilities.Conclusions and relevanceAccording to results of this study, use of the CMI or the simpler 4C model may improve patient selection for CEA among patients with asymptomatic carotid stenosis.

BackgroundCurrent guidelines suggest treatment for many individuals who may never develop a stroke. We hypothesized that a combination of coronary artery calcification (CAC) and carotid artery intima-media thickness (C IMT) data could better individualize risk assessment for ischemic stroke and transient ischemic attack events.MethodsA total of 4720 individuals from the Multi-Ethnic Study of Atherosclerosis were evaluated for ischemic stroke and transient ischemic attack. Cox proportional hazards models for time to incident ischemic stroke/transient ischemic attack were used to examine CAC and CIMT as ischemic stroke/transient ischemic attack predictors in addition to traditional risk factors. We calculated the 10-year number needed to treat by applying the benefit observed in ASCOT-LLA to the observed event rates within CAC and CIMT strata.ResultsMedian follow-up was 13.1 years. Compared with individuals with no CAC and with CIMT ≤ 75th percentile, stroke/transient ischemic attack risk increased progressively with each CAC category (0, 1-100, >100) among individuals with CIMT > 75th percentile. Among participants eligible for statin therapy based on the 2013 atherosclerotic cardiovascular disease (ASCVD) guidelines (ASCVD risk of >5%), 739/2906 (25%) had no CAC and CIMT ≤ 75th percentile and an observed ischemic stroke/transient ischemic attack rate of 2.49 per 1000 person-years. The predicted 10-year number needed to treat was 292 for no CAC and CIMT ≤ 75th percentile and 57 for CAC > 100 and CIMT > 75th percentile.ConclusionThe combination of CIMT and CAC could serve to further refine risk calculation for ischemic stroke/transient ischemic attack prevention and may prioritize those in most need of statin therapy to reduce ischemic stroke/transient ischemic attack risk.

Background Current American College of Cardiology/American Heart Association guidelines suggest that for patients with atrial fibrillation who are at low risk for stroke (CHA2DS2VASc=1) (or women with CHA2DS2VASc=2) a variety of treatment strategies may be considered. However, in clinical practice, patterns of treatment in these "low-risk" patients are not well described. The objective of this analysis is to define thromboembolic event rates and to describe treatment patterns in patients with low-risk CHA2DS2VASc scores. Methods and Results We compared characteristics, treatment strategies, and outcomes among patients with a CHA2DS2VASc=0, CHA2DS2VASc=1, females with a CHA2DS2VASc=2, and CHA2DS2VASc ≥2 in ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) I & II. Compared with CHA2DS2VASc ≥2 patients (84.2%), those with a CHA2DS2VASc=0 (60.3%), 1 (69.9%), and females with a CHA2DS2VASc score=2 (72.4%) were significantly less often treated with oral anticoagulation ( P

Background and aimsThe association between minimally elevated coronary artery calcification (CAC) and cerebrovascular disease is not well known. We assessed whether individuals with minimal CAC (Agatston scores of 1-10) have higher ischemic stroke or transient ischemic attack (TIA) frequencies compared with those with no CAC. We also investigated the relative prevalence of carotid atherosclerosis in these two groups.MethodsA total of 3924 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) without previous cardiovascular events, including stroke, and with baseline CAC scores of 0-10 were followed for the occurrence of incident ischemic stroke/TIA. We used carotid ultrasound to detect carotid artery plaques and to measure the intima-media thickness (IMT).ResultsDuring a median follow-up of 13.2 years, 130 participants developed incident ischemic stroke/TIA. There was no significant difference in the ischemic stroke/TIA incidence between those with minimal CAC and no CAC (3.7 versus 2.7 per 1000 person-years). In participants with minimal CAC, we observed a significant association of the condition with an internal carotid artery (ICA) that had a greater-than-average IMT (ICA-IMT; β = 0.071, p = 0.001) and a higher odds ratio (OR) for carotid artery plaques (OR 1.46; with a 95% confidence interval [CI] of 1.18-1.80; p

Background Current American College of Cardiology/American Heart Association guidelines suggest that for patients with atrial fibrillation who are at low risk for stroke (CHA2DS2VASc=1) (or women with CHA2DS2VASc=2) a variety of treatment strategies may be considered. However, in clinical practice, patterns of treatment in these "low-risk" patients are not well described. The objective of this analysis is to define thromboembolic event rates and to describe treatment patterns in patients with low-risk CHA2DS2VASc scores. Methods and Results We compared characteristics, treatment strategies, and outcomes among patients with a CHA2DS2VASc=0, CHA2DS2VASc=1, females with a CHA2DS2VASc=2, and CHA2DS2VASc ≥2 in ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) I & II. Compared with CHA2DS2VASc ≥2 patients (84.2%), those with a CHA2DS2VASc=0 (60.3%), 1 (69.9%), and females with a CHA2DS2VASc score=2 (72.4%) were significantly less often treated with oral anticoagulation ( P

BackgroundCombination antiplatelet therapy with clopidogrel and aspirin may reduce the rate of recurrent stroke during the first 3 months after a minor ischemic stroke or transient ischemic attack (TIA). A trial of combination antiplatelet therapy in a Chinese population has shown a reduction in the risk of recurrent stroke. We tested this combination in an international population.MethodsIn a randomized trial, we assigned patients with minor ischemic stroke or high-risk TIA to receive either clopidogrel at a loading dose of 600 mg on day 1, followed by 75 mg per day, plus aspirin (at a dose of 50 to 325 mg per day) or the same range of doses of aspirin alone. The dose of aspirin in each group was selected by the site investigator. The primary efficacy outcome in a time-to-event analysis was the risk of a composite of major ischemic events, which was defined as ischemic stroke, myocardial infarction, or death from an ischemic vascular event, at 90 days.ResultsA total of 4881 patients were enrolled at 269 international sites. The trial was halted after 84% of the anticipated number of patients had been enrolled because the data and safety monitoring board had determined that the combination of clopidogrel and aspirin was associated with both a lower risk of major ischemic events and a higher risk of major hemorrhage than aspirin alone at 90 days. Major ischemic events occurred in 121 of 2432 patients (5.0%) receiving clopidogrel plus aspirin and in 160 of 2449 patients (6.5%) receiving aspirin plus placebo (hazard ratio, 0.75; 95% confidence interval [CI], 0.59 to 0.95; P=0.02), with most events occurring during the first week after the initial event. Major hemorrhage occurred in 23 patients (0.9%) receiving clopidogrel plus aspirin and in 10 patients (0.4%) receiving aspirin plus placebo (hazard ratio, 2.32; 95% CI, 1.10 to 4.87; P=0.02).ConclusionsIn patients with minor ischemic stroke or high-risk TIA, those who received a combination of clopidogrel and aspirin had a lower risk of major ischemic events but a higher risk of major hemorrhage at 90 days than those who received aspirin alone. (Funded by the National Institute of Neurological Disorders and Stroke; POINT ClinicalTrials.gov number, NCT00991029 .).

Background and purposeSOCRATES (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes), comparing ticagrelor with aspirin in patients with acute cerebral ischemia, found a nonsignificant 11% relative risk reduction for stroke, myocardial infarction, or death (P=0.07). Aspirin intake before randomization could enhance the effect of ticagrelor by conferring dual antiplatelet effect during a high-risk period for subsequent stroke. Therefore, we explored the efficacy and safety of ticagrelor versus aspirin in the patients who received any aspirin the week before randomization.MethodsA prespecified subgroup analysis in SOCRATES (n=13 199), randomizing patients with acute ischemic stroke (National Institutes of Health Stroke Scale score of ≤5) or transient ischemic attack (ABCD2 score of ≥4) to 90-day treatment with ticagrelor or aspirin. Patients in the prior-aspirin group had received any aspirin within the week before randomization. Primary end point was time to stroke, myocardial infarction, or death. Safety end point was PLATO (Study of Platelet Inhibition and Patient Outcomes) major bleeding.ResultsThe 4232 patients in the prior-aspirin group were older, had more vascular risk factors, and vascular disease than the other patients. In the prior-aspirin group, the primary end point occurred in 138/2130 (6.5%) of patients on ticagrelor and in 177/2102 (8.3%) on aspirin (hazard ratio, 0.76; 95% confidence interval, 0.61-0.95; P=0.02); in patients with no prior-aspirin usage an event occurred in 304/4459 (6.9%) and 320/4508 (7.1%) on ticagrelor and aspirin, respectively (hazard ratio, 0.96; 95% confidence interval, 0.82-1.12; P=0.59). The treatment-by-prior-aspirin interaction was not statistically significant (P=0.10). In the prior-aspirin group, major bleeding occurred in 0.7% and 0.4% of patients on ticagrelor and aspirin, respectively (hazard ratio, 1.58; 95% confidence interval, 0.68-3.65; P=0.28).ConclusionsIn this secondary analysis from SOCRATES, fewer primary end points occurred on ticagrelor treatment than on aspirin in patients receiving aspirin before randomization, but there was no significant treatment-by-prior-aspirin interaction. A new study will investigate the benefit-risk of combining ticagrelor and aspirin in patients with acute cerebral ischemia (URL: https://www.clinicaltrials.gov. Unique identifier: NCT03354429).Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01994720.

OBJECTIVE:To investigate the incidence of first-ever stroke/transient ischemic attack (TIA) and associated risk factors in a cohort of persons living with HIV infection (PLWH). DESIGN:Observational cohort study METHODS:We determined incidence rates of first-ever stroke/TIA in PLWH after ART initiation from the AIDS Clinical Trials Group ALLRT cohort and its parent trials. Poisson regression models evaluated baseline and time-varying covariates as risk factors for stroke/TIA. RESULTS:The incidence rate of stroke/TIA was 1.69 per 1000 person-years. Incidence rates were highest in women (2.88 stroke/TIAs per 1000 person-years compared with 1.40 per 1000 person-years in men) and non-Hispanic Blacks (2.51 stroke/TIAs per 1000 person-years compared with 0.77 per 1000 person-years in Hispanic/other race/ethnicities and 1.56 per 1000 person-years in whites). In a multivariable model, we found a significant age-by-sex interaction (P = 0.01). The higher risk of stroke/TIA in women was more pronounced at younger ages, whereas older age conferred a greater increase in stroke/TIA risk in men than women. Other risk factors for stroke/TIA included hypertension, higher LDL, and HIV RNA greater than 200 copies/ml. Overweight/obese BMI and higher CD4+:CD8+ ratio protected against stroke/TIA. CONCLUSION:Women and non-Hispanic Blacks living with HIV had the highest incidence rates of stroke/TIA. A concerted effort must be made to include PLWH from these at-risk groups in observational and interventional studies aimed at understanding stroke mechanisms and reducing stroke risk in HIV infection. Strategies to modify stroke risk in PLWH should employ a multipronged approach targeting vascular risk factors and engaging and retaining patients in HIV care.

Our previous study demonstrated caspase independent DNA fragmentation after very brief cerebral ischemia, the mechanism of which was unclear. In this study, we explore whether actin is cleaved following focal cerebral ischemia, and whether these structural changes of actin might modulate DNA fragmentation observed following focal ischemia. Results showed that a cleaved β-actin fragment was identified in brains of rats 24 hours following 10-minute and 2-hour focal ischemia. Though granzyme B and caspase-3 cleaved β-actin in vitro, the fragment size of β-actin cleaved by granzyme B was the same as those found after 10-minute and 2-hour focal ischemia. This was consistent with increases of granzyme B activity after 10-minute and 2-hour ischemia compared with controls. Cerebral extracts from 10-minute and 2-hour ischemic brains degraded DNA in vitro. Adding intact β-actin to these samples completely abolished DNA degradation from the 10-minute ischemia group but not from the 2-hour ischemia group. We concluded that β-actin is likely cleaved by granzyme B by 24 hours following 10-minute and 2-hour focal cerebral ischemia. Intact β-actin inhibits DNase, and cleavage of β-actin activates DNase, which leads to DNA fragmentation observed in the brain following very brief focal ischemia.

Several studies have demonstrated that excitatory amino acid carrier-1 (EAAC1) gene deletion exacerbates hippocampal and cortical neuronal death after ischemia. However, presently there are no studies investigating the role of EAAC1 in hippocampal neurogenesis. In this study, we tested the hypothesis that reduced cysteine transport into neurons by EAAC1 knockout negatively affects adult hippocampal neurogenesis under physiological or pathological states. This study used young mice (aged 3-5 months) and aged mice (aged 11-15 months) of either the wild-type (WT) or EAAC1 -/- genotype. Ischemia was induced through the occlusion of bilateral common carotid arteries for 30 minutes. Histological analysis was performed at 7 or 30 days after ischemia. We found that both young and aged mice with loss of the EAAC1 displayed unaltered cell proliferation and neuronal differentiation, as compared to age-matched WT mice under ischemia-free conditions. However, neurons generated from EAAC1 -/- mice showed poor survival outcomes in both young and aged mice. In addition, deletion of EAAC1 reduced the overall level of neurogenesis, including cell proliferation, differentiation, and survival after ischemia. The present study demonstrates that EAAC1 is important for the survival of newly generated neurons in the adult brain under physiological and pathological conditions. Therefore, this study suggests that EAAC1 plays an essential role in modulating hippocampal neurogenesis.

Background and aimsAtherosclerosis is a systemic disease. We examined whether the cumulative burden of thoracic extra-coronary calcification (ECC) improves prediction of stroke, transient ischemic attack (TIA), and stroke mortality beyond traditional risk factors and coronary artery calcium (CAC).MethodsWe followed a total of 6805 participants (mean age 62.1 ± 10.2 years, 47.2% male) from the Multi-Ethnic Study of Atherosclerosis (MESA) over a median of 12.1 years. The presence or absence of calcification at 4 thoracic ECC sites (mitral valve annulus, aortic valve, aortic root, and thoracic aorta) was determined from baseline cardiac-gated non-contrast CT scans. A multisite thoracic ECC score, ranging 0-4, was calculated by summing the 4 individual sites, which were treated as binary variables. Multivariable Cox proportional hazards regression models, controlled for traditional risk factors and CAC, were used to estimate hazard ratios for ischemic (primary endpoint) and hemorrhagic stroke, total stroke, TIA, and stroke mortality with increasing thoracic ECC.ResultsWith an increasing number of thoracic ECC sites, there was a significant (p  0.10).ConclusionsAlthough multisite thoracic ECC is independently associated with ischemic stroke, total stroke, and TIA, the incremental predictive value of thoracic ECC beyond traditional risk factors and CAC appears to be minimal.

ObjectivesTo determine the impact of admission among transient ischemic attack (TIA) patients in the emergency department (ED).Study designRetrospective cohort study using national Veterans Health Administration data (2008).MethodsWe first analyzed whether admitted patients were discharged from the hospital with a diagnosis of TIA. We then analyzed whether admission was associated with a composite outcome (new stroke, new myocardial infarction, or death in the year after TIA) using multivariate logistic regression modeling with propensity score matching.ResultsAmong 3623 patients assigned a diagnosis of TIA in the ED, 2118 (58%) were admitted to the hospital or placed in observation compared with 1505 (42%) who were discharged from the ED. Among the 2118 patients who were admitted, 903 (43% of admitted group) were discharged from the hospital with a diagnosis of TIA, and 548 (26% of admitted group) were discharged with a diagnosis of stroke. Admitted patients were more likely than nonadmitted patients to receive processes of care (i.e., brain imaging, carotid imaging, echocardiography). In matched analyses using propensity scores, the 1-year composite outcome in the admitted group (15.3%) was not lower than the discharged group (13.3%, OR 1.17 [.94-1.46], P = .17).ConclusionsLess than half of patients admitted with a diagnosis of TIA retained that diagnosis at hospital discharge. Although admitted patients were more likely to receive diagnostic procedures, we did not identify improvements in outcomes among admitted patients; however, evaluating care for patients with TIA is limited by the reliability of secondary data analysis.

BACKGROUND: Despite concerns regarding hypoperfusion in patients with large-artery occlusive disease, strict blood pressure (BP) control has become adopted as a safe strategy for risk reduction of stroke. We examined the relationship between BP control, blood flow, and risk of subsequent stroke in the prospective Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) study. METHODS: The VERiTAS study enrolled patients with recent vertebrobasilar (VB) transient ischemic attack or stroke and ≥50% atherosclerotic stenosis or occlusion of vertebral or basilar arteries. Hemodynamic status was designated as low or normal based on quantitative magnetic resonance angiography. Patients underwent standard medical management and follow-up for primary outcome event of VB territory stroke. Mean BP during follow-up (

ObjectivesDetection of atrial fibrillation (AF) in post-cryptogenic stroke (CS) or transient ischemic attack (TIA) patients carries important therapeutic implications.MethodsTo risk stratify CS/TIA patients for later development of AF, we conducted a retrospective cohort study using data from 1995 to 2015 in the Stanford Translational Research Integrated Database Environment (STRIDE).ResultsOf the 9,589 adult patients (age ≥40 years) with CS/TIA included, 482 (5%) patients developed AF post CS/TIA. Of those patients, 28.4, 26.3, and 45.3% were diagnosed with AF 1-12 months, 1-3 years, and >3 years after the index CS/TIA, respectively. Age (≥75 years), obesity, congestive heart failure, hypertension, coronary artery disease, peripheral vascular disease, and valve disease are significant risk factors, with the following respective odds ratios (95% CI): 1.73 (1.39-2.16), 1.53 (1.05-2.18), 3.34 (2.61-4.28), 2.01 (1.53-2.68), 1.72 (1.35-2.19), 1.37 (1.02-1.84), and 2.05 (1.55-2.69). A risk-scoring system, i.e., the HAVOC score, was constructed using these 7 clinical variables that successfully stratify patients into 3 risk groups, with good model discrimination (area under the curve = 0.77).ConclusionsFindings from this study support the strategy of looking longer and harder for AF in post-CS/TIA patients. The HAVOC score identifies different levels of AF risk and may be used to select patients for extended rhythm monitoring.

The goal of this analysis was to evaluate the ability of insulin resistance, identified by the presence of prediabetes mellitus (PreDM) combined with either an elevated triglyceride (TG >1.7 mmol/l) or body mass index (BMI ≥27.0 kg/m2), to identify increased risk of statin-associated type 2 diabetes mellitus (T2DM). Consequently, a retrospective analysis of data from subjects without diabetes in the Treating to New Targets and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels randomized controlled trials was performed, subdividing participants into 4 experimental groups: (1) normal fasting glucose (NFG) and TG ≤1.7 mmol/l (42%); (2) NFG and TG >1.7 mmol/l (22%); (3) PreDM and TG ≤1.7 mmol/l (20%); and (4) PreDM and TG >1.7 mmol/l (15%). Comparable groupings were created substituting BMI values (kg/m2 1.7 mmol/l) with intermediate values for only an elevated TG >1.7 mmol/l (5.2%/4.3%) or only PreDM (12.8%/7.6%). Comparable differences were observed when BMI values were substituted for TG concentrations. In conclusion, these data suggest that (1) the diabetogenic impact of statin treatment is relatively modest in general; (2) the diabetogenic impact is accentuated relatively dramatically as FPG and TG concentrations and BMI increase; and (3) PreDM, TG concentrations, and BMI identify people at highest risk of statin-associated T2DM.

ImportanceAtherosclerotic vertebrobasilar (VB) occlusive disease is a significant etiology of posterior circulation stroke, with regional hypoperfusion as an important potential contributor to stroke risk.ObjectiveTo test the hypothesis that, among patients with symptomatic VB stenosis or occlusion, those with distal blood flow compromise as measured by large-vessel quantitative magnetic resonance angiography (QMRA) are at higher risk of subsequent posterior circulation stroke.Design, setting, and participantsA prospective, blinded, longitudinal cohort study was conducted at 5 academic hospital-based centers in the United States and Canada; 82 patients from inpatient and outpatient settings were enrolled. Participants with recent VB transient ischemic attack or stroke and 50% or more atherosclerotic stenosis or occlusion in vertebral and/or basilar arteries underwent large-vessel flow measurement in the VB territory using QMRA. Physicians performing follow-up assessments were blinded to QMRA flow status. Follow-up included monthly telephone calls for 12 months and biannual clinical visits (for a minimum of 12 months, and up to 24 months or the final visit). Enrollment took place from July 1, 2008, to July 31, 2013, with study completion on June 30, 2014; data analysis was performed from October 1, 2014, to April 10, 2015.ExposureStandard medical management of stroke risk factors.Main outcomes and measuresThe primary outcome was VB-territory stroke.ResultsOf the 82 enrolled patients, 72 remained eligible after central review of their angiograms. Sixty-nine of 72 patients completed the minimum 12-month follow-up; median follow-up was 23 (interquartile range, 14-25) months. Distal flow status was low in 18 of the 72 participants (25%) included in the analysis and was significantly associated with risk for a subsequent VB stroke (P = .04), with 12- and 24-month event-free survival rates of 78% and 70%, respectively, in the low-flow group vs 96% and 87%, respectively, in the normal-flow group. The hazard ratio, adjusted for age and stroke risk factors, in the low distal flow status group was 11.55 (95% CI, 1.88-71.00; P = .008). Medical risk factor management at 6-month intervals was similar between patients with low and normal distal flow. Distal flow status remained significantly associated with risk even when controlling for the degree of stenosis and location.Conclusions and relevanceDistal flow status determined using a noninvasive and practical imaging tool is robustly associated with risk for subsequent stroke in patients with symptomatic atherosclerotic VB occlusive disease. Identification of high-risk patients has important implications for future investigation of more aggressive interventional or medical therapies.

Background and purposeExhaled carbon monoxide (CO) is associated with cardiometabolic traits, subclinical atherosclerosis, and cardiovascular disease, but its specific relations with stroke are unexplored. We related exhaled CO to magnetic resonance imaging measures of subclinical cerebrovascular disease cross-sectionally and to incident stroke/transient ischemic attack prospectively in the Framingham Offspring study.MethodsWe measured exhaled CO in 3313 participants (age 59±10 years; 53% women), and brain magnetic resonance imaging was available in 1982 individuals (age 58±10 years; 54% women). Participants were analyzed according to tertiles of exhaled CO concentration.ResultsIn age- and sex-adjusted models, the highest tertile of exhaled CO was associated with lower total cerebral brain volumes, higher white-matter hyperintensity volumes, and greater prevalence of silent cerebral infarcts (P

Background and purposeGrowth differentiation factor-15 (GDF-15) and soluble (s)ST2 are markers of cardiac and vascular stress. We investigated the associations between circulating concentrations of these biomarkers and incident stroke and subclinical vascular brain injury in a sample from the Framingham Offspring cohort.MethodsWe followed 3374 stroke- and dementia-free individuals (mean age, 59.0±9.7 years; 53% women) attending the Framingham Offspring sixth examination cycle 11.8±3.0 years for incident stroke. A subsample of 2463 individuals underwent brain magnetic resonance imaging and neuropsychological testing ≈4.0±1.7 years after the sixth examination.ResultsAfter adjustment for traditional cardiovascular risk factors, B-type natriuretic peptide, high-sensitivity C-reactive protein, and urine albumin levels, higher stress biomarker levels were associated cross-sectionally with lower brain volumes (β coefficients for intracranial volume comparing fourth [Q4] versus first biomarker [Q1] quartiles: -0.71% for GDF-15; P=0.002 and 0.47% for sST2; P=0.02) and worse performance on the visual reproduction test (β coefficients for Q4 versus Q1: -0.62 for GDF-15; P=0.009 and -0.40 for sST2; P=0.04). Higher GDF-15 concentrations were also associated with greater log-transformed white-matter hyperintensity volumes (β for Q4 versus Q1=0.19; P=0.01). Prospectively, a total of 203 (6%) individuals developed incident stroke/transient ischemic attack during follow-up. After multivariable adjustment, sST2 remained significantly associated with stroke/transient ischemic attack, hazard ratio for Q4 versus Q1 of 1.76, 95% confidence interval of 1.06 to 2.92, and P=0.03.ConclusionsCirculating GDF-15 and sST2 are associated with subclinical brain injury and cognitive impairment. Higher sST2 concentrations are also associated with incident stroke, suggesting potential links between cardiac stress biomarkers and brain injury.

ObjectiveWe compared the effect of clopidogrel plus aspirin vs aspirin alone on functional outcome and quality of life in the Clopidogrel in High-risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial of aspirin-clopidogrel vs aspirin alone after acute minor stroke or TIA.MethodsParticipants were assessed at 90 days for functional outcome using the modified Rankin Scale (mRS) and quality of life using the EuroQol-5 Dimension (EQ-5D). Poor functional outcome was defined as mRS score of 2-6 at 90 days and poor quality of life as EQ-5D index score of 0.5 or less.ResultsPoor functional outcome occurred in 254 patients (9.9%) in the clopidogrel-aspirin group, as compared with 299 (11.6%) in the aspirin group (p = 0.046). Poor quality of life occurred in 142 (5.5%) in the clopidogrel-aspirin group and in 175 (6.8%) in the aspirin group (p = 0.06). Disabling stroke at 90 days occurred in 166 (6.5%) in the clopidogrel-aspirin group and in 219 (8.5%) in the aspirin group (p = 0.01). In stratified analysis by subsequent stroke, there was no difference in 90-day functional outcome and quality of life between the 2 groups.ConclusionsIn patients with minor stroke or TIA, the combination of clopidogrel and aspirin appears to be superior to aspirin alone in improving the 90-day functional outcome, and this is consistent with a reduction in the rate of disabling stroke in the dual antiplatelet arm.Classification of evidenceThis study provides Class II evidence that for patients with acute minor stroke or TIA, clopidogrel plus aspirin compared to aspirin alone improves 90-day functional outcome (absolute reduction of poor outcome 1.70%, 95% confidence interval 0.03%-3.42%).

BackgroundNovel oral anticoagulants (NOACs) have been shown to be at least as good as warfarin for preventing stroke or transient ischemic attack in patients with atrial fibrillation, yet diffusion of these therapies and patterns of use among atrial fibrillation patients with ischemic stroke and transient ischemic attack have not been well characterized.Methods and resultsUsing data from Get With The Guidelines-Stroke, we identified a cohort of 61 655 atrial fibrillation patients with ischemic stroke or transient ischemic attack hospitalized between October 2010 and September 2012 and discharged on warfarin or NOAC (either dabigatran or rivaroxaban). Multivariable logistic regression was used to identify factors associated with NOAC versus warfarin therapy. In our study population, warfarin was prescribed to 88.9%, dabigatran to 9.6%, and rivaroxaban to 1.5%. NOAC use increased from 0.04% to a 16% to 17% plateau during the study period, although anticoagulation rates among eligible patients did not change appreciably (93.7% versus 94.1% from first quarter 2011 to second quarter 2012), suggesting a trend of switching from warfarin to NOACs rather than increased rates of anticoagulation among eligible patients. Several bleeding risk factors and CHA2DS2-VASc scores were lower among those discharged on NOAC versus warfarin therapy (47.9% versus 40.9% with CHA2DS2-VASc ≤5, P

ObjectivesTo investigate the prevalence, knowledge, and treatment of TIA in a Chinese adult population.MethodsWe conducted a complex, multistage, probability sampling-designed, cross-sectional, nationwide survey of 98,658 Chinese adults in 2010. Possible TIA cases were first identified by symptoms recall or self-reported history of TIA through face-to-face interviews, and the final diagnosis was then made by expert neurologists through phone interviews or record review.ResultsThe age-standardized prevalence of TIA was 2.27%. Clinically, only 16.0% of the participants were diagnosed before the study. The prevalence of TIA was higher in women and in patients who were older, had less education, were current smokers, lived in rural or undeveloped areas, and had a history of stroke, hypertension, myocardial infarction, dyslipidemia, or diabetes. Based on the survey responses, approximately 3.08% of Chinese adults had knowledge of TIA. Among patients with TIA, only 5.02% received treatment and 4.07% received guideline-recommended therapy.ConclusionsTIA is prevalent and an estimated 23.9 million people in China may have experienced a TIA. Public knowledge on TIA is very limited. TIA appears to be largely undiagnosed and untreated in China. There is an urgent need to develop strategies to improve the identification and appropriate management of TIA.

Presence of coronary artery calcium (CAC), carotid plaque, and increased carotid intima-media thickness (IMT) may indicate elevated cardiovascular disease (CVD) risk; however, no large studies have compared them directly. This study compares predictive uses of CAC presence, carotid artery plaque presence, and high IMT for incident CVD events. Participants were from the Multi-Ethnic Study of Atherosclerosis (MESA). Predictive values of carotid plaque, IMT, and CAC presence were compared using Cox proportional hazards models, c-statistics, and net reclassification indices. The 6779 participants were mean (SD) 62.2 (10.2) years old; 49.9% had CAC, and 46.7% had carotid plaque. The mean left and right IMT were 0.754 (0.210) mm and 0.751 (0.187) mm, respectively. After 9.5 years (mean), 538 CVD events, 388 coronary heart disease (CHD) events, and 196 stroke/transient ischemic attacks were observed. CAC presence was a stronger predictor of incident CVD and CHD than carotid ultrasound measures. Mean IMT≥75th percentile (for age, sex, and race) alone did not predict events. Compared with traditional risk factors, c-statistics for CVD (c=0.756) and CHD (c=0.752) increased the most by the addition of CAC presence (CVD, 0.776; CHD, 0.784; P

Aquaporin-4 (AQP4) is a water channel expressed in astrocyte end-feet lining the blood-brain barrier. AQP4 deletion in mice is associated with improved outcomes in global cerebral ischemia produced by transient carotid artery occlusion, and focal cerebral ischemia produced by permanent middle cerebral artery occlusion (MCAO). Here, we investigated the consequences of 1-h transient MCAO produced by intraluminal suture blockade followed by 23 h of reperfusion. In nine AQP4(+/+) and nine AQP4(-/-) mice, infarct volume was significantly reduced by an average of 39 ± 4% at 24h in AQP4(-/-) mice, cerebral hemispheric edema was reduced by 23 ± 3%, and Evans Blue extravasation was reduced by 31 ± 2% (mean ± SEM). Diffusion-weighted magnetic resonance imaging showed greatest reduction in apparent diffusion coefficient around the occlusion site after reperfusion, with remarkably lesser reduction in AQP4(-/-) mice. The reduced infarct volume in AQP4(-/-) mice following transient MCAO supports the potential utility of therapeutic AQP4 inhibition in stroke.

ImportanceAlthough cerebral amyloid angiopathy (CAA) has important clinical implications, our understanding of it and ability to diagnose it are limited.ObjectiveTo determine pathological correlates and clinical factors identifiable during life that predict the presence of severe CAA in persons with pathologically confirmed Alzheimer disease (AD).Design, setting, and participantsWe compared demographic and clinical variables at the earliest visit during life at which participants were found to have cognitive impairment and compared pathological variables between persons ultimately found to have no or severe CAA at autopsy using logistic regression. Analyses were repeated separately for carriers and noncarriers of the APOE ε4 allele. Data were obtained from the Uniform Data Set, which comprises longitudinal clinical assessments performed in the Alzheimer's Disease Centers funded by the National Institute on Aging. Participants included 193 persons with AD and severe CAA and 232 persons with AD and no CAA. All participants had cognitive impairment and met National Institute on Aging-Reagan Institute neuropathological criteria for AD.Main outcomes and measuresPrevalence of demographic characteristics and the APOE ε4 allele and odds ratios (ORs) of clinical variables for the prediction of severe CAA.ResultsPersons with severe CAA compared with those without CAA were more likely to carry an APOE ε4 allele (64.9% vs 42.8%, respectively; P

BackgroundPhysicians treating patients with atrial fibrillation (AF) must weigh the benefits of anticoagulation in preventing stroke versus the risk of bleeding. Although empirical models have been developed to predict such risks, the degree to which these coincide with clinicians' estimates is unclear.Methods and resultsWe examined 10 094 AF patients enrolled in the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF) registry between June 2010 and August 2011. Empirical stroke and bleeding risks were assessed by using the congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and previous stroke or transient ischemic attack (CHADS2) and Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) scores, respectively. Separately, physicians were asked to categorize their patients' stroke and bleeding risks: low risk (6%). Overall, 72% (n=7251) in ORBIT-AF had high-risk CHADS2 scores (≥2). However, only 16% were assessed as high stroke risk by physicians. Although 17% (n=1749) had high ATRIA bleeding risk (score ≥5), only 7% (n=719) were considered so by physicians. The associations between empirical and physician-estimated stroke and bleeding risks were low (weighted Kappa 0.1 and 0.11, respectively). Physicians weighed hypertension, heart failure, and diabetes mellitus less significantly than empirical models in estimating stroke risk; physicians weighted anemia and dialysis less significantly than empirical models when estimating bleeding risks. Anticoagulation use was highest among patients with high stroke risk, assessed by either empirical model or physician estimates. In contrast, physician and empirical estimates of bleeding had limited impact on treatment choice.ConclusionsThere is little agreement between provider-assessed risk and empirical scores in AF. These differences may explain, in part, the current divergence of anticoagulation treatment decisions from guideline recommendations.Clinical trial registration urlhttp://www.clinicaltrials.gov. Unique identifier: NCT01165710.

Background and purposeA substantial portion of clinically diagnosed TIA cases is imaging-negative. The purpose of the current study is to determine if arterial spin-labeling is helpful in detecting perfusion abnormalities in patients presenting clinically with TIA.Materials and methodsPseudocontinuous arterial spin-labeling with 3D background-suppressed gradient and spin-echo was acquired on 49 patients suspected of TIA within 24 hours of symptom onset. All patients were free of stroke history and had no lesion-specific findings on general MR, DWI, and MRA sequences. The calculated arterial spin-labeling CBF maps were scored from 1-3 on the basis of presence and severity of perfusion disturbance by 3 independent observers blinded to patient history. An age-matched cohort of 36 patients diagnosed with no cerebrovascular events was evaluated as a control. Interobserver agreement was assessed by use of the Kendall concordance test.ResultsScoring of perfusion abnormalities on arterial spin-labeling scans of the TIA cohort was highly concordant among the 3 observers (W = 0.812). The sensitivity and specificity of arterial spin-labeling in the diagnosis of perfusion abnormalities in TIA was 55.8% and 90.7%, respectively. In 93.3% (70/75) of the arterial spin-labeling CBF map readings with positive scores (≥2), the brain regions where perfusion abnormalities were identified by 3 observers matched with the neurologic deficits at TIA onset.ConclusionsIn this preliminary study, arterial spin-labeling showed promise in the detection of perfusion abnormalities that correlated with clinically diagnosed TIA in patients with otherwise normal neuroimaging results.

Background and purposeStatins reduce stroke risk when initiated months after transient ischemic attack (TIA)/stroke and reduce early vascular events in acute coronary syndromes, possibly via pleiotropic plaque stabilization. Few data exist on acute statin use in TIA. We aimed to determine whether statin pretreatment at TIA onset modified early stroke risk in carotid stenosis.MethodsWe analyzed data from 2770 patients with TIA from 11 centers, 387 with ipsilateral carotid stenosis. ABCD2 score, abnormal diffusion weighted imaging, medication pretreatment, and early stroke were recorded.ResultsIn patients with carotid stenosis, 7-day stroke risk was 8.3% (95% confidence interval [CI], 5.7-11.1) compared with 2.7% (CI, 2.0%-3.4%) without stenosis (P

BACKGROUND: Individuals with TIA/stroke symptoms often do not seek urgent medical attention. We assessed the feasibility of identifying individuals searching for information on TIA/stroke symptoms online as a target for future interventions to encourage urgent evaluation and we evaluated the performance of a self-reported risk score to identify subjects with true TIA or stroke. METHODOLOGY/PRINCIPAL FINDINGS: We placed online advertisements to target English-speaking adults in the United States searching for TIA/stroke-related keywords. After completing an online questionnaire, participants were telephoned by a vascular neurologist to assess the likelihood of TIA/stroke. We used logistic regression and the c-statistic to assess associations and model discrimination respectively. Over 122 days, 251 (1%) of 25,292 website visitors completed the online questionnaire and 175 were reached by telephone (mean age 58.5 years; 63% women) for follow-up. Of these participants, 37 (21%) had symptoms within 24 hours, 60 (34%) had not had a medical evaluation yet, and 68 (39%) had TIA/stroke. Applying a modified ABCD(2) score yielded a c-statistic of 0.66, but 2 of 12 with a zero score had a TIA/stroke. Those with new symptoms were more likely to have TIA/stroke (OR 4.90, 95% CI 2.56-9.09). CONCLUSIONS/SIGNIFICANCE: Individuals with TIA/stroke that are seeking real-time information on symptoms online can be readily identified, in some cases before they have sought formal medical evaluation. Although a simple self-reported risk score was unable to identify a low-risk population in this selected group, this population may still present an attractive target for future interventions designed to encourage urgent medical evaluation.

Background and purposeThere were limited data on the long-term outcome of patients with symptomatic intracranial atherosclerotic stenosis ≥70% after Wingspan stenting. Using our Wingspan cohort data and the data from the Warfarin and Aspirin for Symptomatic Intracranial Atherosclerotic Disease (WASID) as a historical control, we tested the hypothesis that stenting provided no benefit over antithrombotic therapy alone for these high-risk patients.MethodsBetween January 2007 and February 2009, 100 consecutive patients with intracranial atherosclerotic stenosis ≥70% and symptoms within 90 days were enrolled into this prospective single-center Wingspan cohort study and followed up until the end of February 2010. Stenosis was measured per the WASID criteria. One-year risk of primary end point (any stroke or death within 30 days and ipsilateral ischemic stroke afterward) was compared with that of ipsilateral ischemic stroke in the WASID patients with ≥70% stenosis.ResultsThe stent placement success rate was 99%. All patients but 1 had clinical follow-up of ≥12 months. During a mean follow-up of 1.8 years, 9 patients developed primary end point events (5 within 30 days and 4 afterward). The 1-year risk of the outcome events was lower than that in similar WASID patients: 7.3% (95% CI, 2.0% to 12.5%) versus 18% (95% CI, 13% to 24%; P

BackgroundA patent foramen ovale (PFO) is a risk factor for cerebral events such as cryptogenic stroke, transient ischemic attacks, and migraine headaches. Far less commonly, PFO is associated with non-cerebral, paradoxical systemic embolic events such as myocardial infarction (MI), renal infarct, and limb ischemia. This report details the incidence of systemic paradoxical emboli at our institution.Methods416 patients were referred for evaluation of PFO related conditions from 2001 to 2009. Clinical history and medical records of the patients were reviewed for incidence of cryptogenic stroke, transient ischemic attack (TIA), migraine headache, arterial desaturation, and noncerebral systemic embolism.ResultsAs the primary presenting symptom, 219 patients had a diagnosis of cryptogenic stroke, 38 patients had migraine headaches, and 80 patients had transient neurologic deficits consistent with a TIA or complex headache. Twelve patients (2.9% of the total population) presented with a presumptive diagnosis of systemic embolism. Eight of these patients had acute MI diagnosed by elevated cardiac biomarkers, electrocardiogram changes, and/or imaging evidence of a left ventricular wall motion abnormality, without evidence of obstructive coronary disease on angiography. Four patients had evidence of peripheral embolism to a systemic artery, including the popliteal artery, ophthalmic artery, and brachial artery. PFO closure was performed in 197 patients (47.4% of the total population), including eight patients in the systemic embolism group. All closure procedures were successful.ConclusionAlthough most paradoxical emboli travel to the brain, noncerebral paradoxical embolism is also associated with PFO. In addition to embolism of thrombus, there may be paradoxical passage of vasoactive chemicals that induce intense coronary spasm and myocardial infarction. Diagnosis is often challenging, given the lack of definitive criteria and the need to exclude other potential etiologies.

Background and aimIntracranial vertebrobasilar artery (VBA) stenosis portends a stroke and death rate of 8.5-22.8% annually despite medical therapy. Stenting has emerged as a treatment option but also carries substantial risk. Awake stenting under local anesthesia to minimize major procedural complication was investigated.MethodsBetween January 2007 and December 2008, 43 of 46 consecutive patients with severe symptomatic intracranial VBA stenosis underwent elective angioplasty assisted with self-expanding Wingspan stent under local anesthesia at our institute. All data were collected prospectively.ResultsAll 43 patients tolerated the stenting procedure under local anesthesia well. Forty-two patients (97.7%) were stented successfully. Within 30 days, there were three periprocedural strokes, including thromboembolic infarct, pontine perforator infarct and intracranial hemorrhage, without fatality. In addition, five patients had intraoperative brainstem transient ischemic attacks (TIAs) seconds after the deployment of the stent delivery system across the tortuous VBA. The symptoms and signs included impaired consciousness (n=5), dysarthria (n=3), convulsion (n=2), conjugate horizontal gaze palsy (n=2), nystagmus (n=2) and pinpoint pupils (n=1). There was angiographic evidence of VBA straightening without thromboembolism. The TIAs resolved within minutes of prompt removal of the delivery catheter.ConclusionsVBA stenting under local anesthesia is feasible with a 7% periprocedural stroke risk. Awake stenting allows timely detection of intraoperative TIAs. The mechanism of intraoperative TIA appears to be stent delivery system induced VBA straightening and distortion of its vascular tree. A devastating stroke may ensue if the TIA is not detected and distortion of VBA perforators is not reversed promptly.