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Increase of Stroke Incidence in Young Adults in a Middle-Income Country [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—The incidence of stroke is on the rise in young adults in high-income countries. However, there is a gap of knowledge about trends in stroke incidence in young adults from low- and middle-income countries. We aimed to measure trends in incidence of ischemic stroke (IS) and intracerebral hemorrhage (IH) in young people from 2005 to 2015 in Joinville, Brazil.Methods—We retrospectively ascertained all first-ever IS subtypes and IH that occurred in Joinville in the periods of 2005 to 2006, 2010 to 2011, and 2014 to 2015. Poisson regression was used to calculate incidence rate ratios of all strokes, IS, and IH. We also compared the prevalence of risk factors and extension of diagnostic work-up across the 3 periods.Results—For 10 years, we registered 2483 patients (7.5% aged <45 years). From 2005 to 2006 to 2014 to 2015, overall stroke incidence significantly increased by 62% (incidence rate ratios, 1.62; 95% confidence interval, 1.10–2.40) in subjects <45 years and by 29% in those <55 years (incidence rate ratios, 1.29; 95% confidence interval, 1.04–1.60). Incidence of IS increased by 66% (incidence rate ratios, 1.66; 95% confidence interval, 1.09–2.54), but there was no significant change in incidence of IH in subjects <45 years. Smoking rates decreased by 71% (odds ratio, 0.29; 95% confidence interval, 0.12–0.68).Conclusions—Stroke incidence is rising in young adults in Joinville, Brazil, because of increase in rates of ischemic but not hemorrhagic strokes. We urgently need better policies of cardiovascular prevention in the young.



Incidence and Outcomes of Myocardial Infarction in Patients Admitted With Acute Ischemic Stroke [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—Data on the incidence and outcomes of acute myocardial infarction (AMI) complicating acute ischemic stroke (AIS) are limited. We aim to evaluate the incidence, treatment patterns, and outcomes of AMI in patients with AIS using a nationwide database.Methods—The National Inpatient Sample was used to identify patient with AIS between 2003 and 2014. Trends of incidence of AMI and its associated in-hospital mortality were evaluated. Univariate and multivariate logistic regressions were used to evaluate predictors of AMI. The impact of AMI on in-hospital outcomes was assessed in a comparative analysis of propensity-matched groups of patients with and without AMI.Results—Patients with AIS (n=864 043) were identified in the national inpatient sample, of whom 13 573 patients (1.6%) had an AMI (79.5% non–ST-segment–elevation myocardial infarction and 20.5% ST-segment–elevation myocardial infarction). In-hospital mortality was 21.4% and 7.1% in propensity-matched cohorts of patients with and without AMI, P<0.001. In-hospital length of stay and cost of care were 50% higher in the AMI group. In a multivariate logistical regression analysis, the strongest predictors of having AMI after AIS were older age, history of coronary artery disease, chronic renal insufficiency, undergoing mechanical thrombectomy, and rhythm and conduction abnormalities. In the AMI group, undergoing coronary angiography and undergoing percutaneous coronary intervention both strongly correlated with lower in-hospital mortality (odds ratio, 0.34 [confidence interval, 0.23–0.51] and 0.26 [confidence interval, 0.20–0.34], respectively, P<0.001). However, these were only performed in 7.5% and 2% of patients, respectively.Conclusions—AMI complicating stroke carries a substantial in-hospital mortality and cost of care. Patients who underwent coronary angiography with or without intervention may have improved survival although it was only utilized in a minority of patients. Further studies needed to discern the ideal approach in AMI in patients with AIS.



National Trends in Patients Hospitalized for Stroke and Stroke Mortality in France, 2008 to 2014 [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—Stroke is the leading cause of death in women and the third leading cause in men in France. In young adults (ie, <65 years old), an increase in the incidence of ischemic stroke was observed at a local scale between 1985 and 2011. After the implementation of the 2010 to 2014 National Stroke Action Plan, this study investigates national trends in patients hospitalized by stroke subtypes, in-hospital mortality, and stroke mortality between 2008 and 2014.Methods—Hospitalization data were extracted from the French national hospital discharge databases and mortality data from the French national medical causes of death database. Time trends were tested using a Poisson regression model.Results—From 2008 to 2014, the age-standardized rates of patients hospitalized for ischemic stroke increased by 14.3% in patients <65 years old and decreased by 1.5% in those aged ≥65 years. The rate of patients hospitalized for hemorrhagic stroke was stable (+2.0%), irrespective of age and sex. The proportion of patients hospitalized in stroke units substantially increased. In-hospital mortality decreased by 17.1% in patients with ischemic stroke. From 2008 to 2013, stroke mortality decreased, except for women between 45 and 64 years old and for people aged ≥85 years.Conclusions—An increase in cardiovascular risk factors and improved stroke management may explain the increase in the rates of patients hospitalized for ischemic stroke. The decrease observed for in-hospital stroke mortality may be because of recent improvements in acute-phase management.



Minimal Clinically Important Difference for Safe and Simple Novel Acute Ischemic Stroke Therapies [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—Determining the minimal clinically important difference (MCID) is essential for evaluating novel therapies. For acute ischemic stroke, expert surveys have yielded MCIDs that are substantially higher than the MCIDs observed in actual expert behavior in guideline writing and clinical practice, potentially because of anchoring bias.Methods—We administered a structured, internet-based survey to a cross-section of academic stroke neurologists in the United States. Survey responses assessed demographic and clinical experience, and expert judgment of the MCID of the absolute increase needed in the proportion of patients achieving functional independence at 3 months to consider a novel, safe neuroprotective agent as clinically worthwhile. To mitigate anchoring bias, the survey response framework used a base 1000 rather than base 100 patient framework.Results—Survey responses were received from 122 of 333 academic stroke neurologists, there were 23% women, 72.8% had ≥6 years of practice experience, and neurovascular disease accounted for more than half of practice time in >70%. Responder–nonresponder and continuum of resistance tests indicated that responders were representative of the full expert population. Among respondents, the median MCID was 1.3% (interquartile range, 0.8% to >2%).Conclusions—Stroke expert responses to MCID surveys are affected by anchoring and centrality bias. When survey design takes these into account, the expert-derived MCID for a safe acute ischemic stroke treatment is 1.1% to 1.5%, in accord with actual physician behavior in guideline writing and clinical practice. This revised MCID value can guide clinical trial design and grant-funding and regulatory agency decisions.



Validation of the Telephone Interview of Cognitive Status and Telephone Montreal Cognitive Assessment Against Detailed Cognitive Testing and Clinical Diagnosis of Mild Cognitive Impairment After Stroke [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—Assessment of cognitive status poststroke is recommended by guidelines but follow-up can often not be done in person. The Telephone Interview of Cognitive Status (TICS) and the Telephone Montreal Cognitive Assessment (T-MoCA) are considered useful screening instruments. Yet, evidence to define optimal cut-offs for mild cognitive impairment (MCI) after stroke is limited.Methods—We studied 105 patients enrolled in the prospective DEDEMAS study (Determinants of Dementia After Stroke; NCT01334749). Follow-up visits at 6, 12, 36, and 60 months included comprehensive neuropsychological testing and the Clinical Dementia Rating scale, both of which served as reference standards. The original TICS and T-MoCA were obtained in 2 separate telephone interviews each separated from the personal visits by 1 week (1 before and 1 after the visit) with the order of interviews (TICS versus T-MoCA) alternating between subjects. Area under the receiver-operating characteristic curves was determined.Results—Ninety-six patients completed both the face-to-face visits and the 2 interviews. Area under the receiver-operating characteristic curves ranged between 0.76 and 0.83 for TICS and between 0.73 and 0.94 for T-MoCA depending on MCI definition. For multidomain MCI defined by multiple-tests definition derived from comprehensive neuropsychological testing optimal sensitivities and specificities were achieved at cut-offs <36 (TICS) and <18 (T-MoCA). Validity was lower using single-test definition, and cut-offs were higher compared with multiple-test definitions. Using Clinical Dementia Rating as the reference, optimal cut-offs for MCI were <36 (TICS) and approximately 19 (T-MoCA).Conclusions—Both the TICS and T-MoCA are valid screening tools poststroke, particularly for multidomain MCI using multiple-test definition.



Predictors of Outcome in Aneurysmal Subarachnoid Hemorrhage Patients [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—The mortality and morbidity after aneurysmal subarachnoid hemorrhage has improved because of better diagnosis, early treatment to secure the aneurysm, and better management of disease-specific complications. With these improvements in care, it is not clear if the previously identified independent predictors of a negative outcome have changed. The aim of this study was to identify the independent predictors of an unfavorable outcome (Glasgow Outcome Score 1, 2, and 3) in aneurysmal subarachnoid hemorrhage patients.Methods—Univariate and multivariate analysis of prospectively collected data on patients presenting with an aneurysmal subarachnoid hemorrhage was performed. Outcome was assessed at discharge. Data were collected from 14 centers in the United Kingdom over a period of 4 years (September 2011–2015).Results—The median age (interquartile range) at presentation of 3341 patients with aneurysmal subarachnoid hemorrhage was 55 (18) years. Most patients were female (n=2288 [68.5%]), presented in good grade (2397 [70%]; World Federation of Neurological Surgeons grade 1 and 2), and were treated by endovascular coiling (n=2600; 75%). The independent predictors of an unfavorable outcome (95% confidence interval [CI]) were increasing age (odds ratio [OR], 1.04; 95% CI, 1.03–1.05; P<0.001), World Federation of Neurological Surgeons grade (OR, 2.06; 95% CI, 1.91–2.22; P<0.001), preoperative rebleeding (OR, 7.41; 95% CI, 4.48–12.30; P<0.001), need for cerebrospinal fluid diversion (OR, 3.25; 95% CI, 2.58–4.09; P<0.001), and delayed cerebral ischemia (OR, 2.21; 95% CI, 1.72–2.83; P<0.001).Conclusions—These data suggest that potentially modifiable risk factors of preoperative rebleeding and delayed cerebral ischemia are associated with unfavorable outcomes. Understanding the reasons why patients requiring cerebrospinal fluid diversion have 3.25-fold higher adjusted odds of a poor outcome at discharge needs to be studied.



Neuroimaging Correlates of Cerebral Microbleeds [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—Cerebral microbleed (CMB) location (deep versus strictly lobar) may elucidate underlying pathology with deep CMBs being more associated with hypertensive vascular disease and lobar CMBs being more associated with cerebral amyloid angiopathy. The objective of this study was to determine whether neuroimaging signs of vascular disease and Alzheimer pathology are associated with different types of CMBs.Methods—Among 1677 nondemented ARIC (Atherosclerosis Risk in Communities) participants (mean age=76±5 years; 40% men; 26% black) with 3-Tesla MRI scans at the fifth examination (2011–2013), we fit multinomial logistic regression models to quantify relationships of brain volumes (Alzheimer disease signature regions, total gray matter, frontal gray matter, and white matter hyperintensity volumes), infarct frequencies (lacunar, nonlacunar, and total), and apolipoprotein E (number of ε4 alleles) with CMB location (none, deep/mixed, or strictly lobar CMBs). Models were weighted for the sample selection scheme and adjusted for age, sex, education, hypertension, ever smoking status, diabetes mellitus, race site membership, and estimated intracranial volume (brain volume models only).Results—Deep/mixed and strictly lobar CMBs had prevalences of 8% and 16%, respectively. Larger white matter hyperintensity burden, greater total infarct frequency, smaller frontal volumes (in women only), and smaller total gray matter volume were associated with greater risk of both deep and lobar CMBs relative to no CMBs. Greater white matter hyperintensity volume was also associated with greater risk of deep relative to lobar CMBs. Higher lacunar and nonlacunar infarct frequencies were associated with higher risk of deep CMBs, whereas smaller Alzheimer disease signature region volume and apolipoprotein E ε4 homozygosity were associated with greater risk of lobar CMBs.Conclusions—CMBs are a common vascular pathology in the elderly. Markers of hypertensive small-vessel disease may contribute to deep CMBs while cerebral amyloid angiopathy may drive development of lobar CMBs.



Serum Potassium Is Positively Associated With Stroke and Mortality in the Large, Population-Based Malmo Preventive Proȷect Cohort [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—Low serum potassium is associated with stroke in populations with cardiovascular disease, hypertension, and diabetes mellitus but has not been studied in a mainly healthy population. We aimed to study the relation between serum potassium and incident stroke and mortality in the Malmö Preventive Project, a large cohort with screening in early mid-life and follow-up >25 years.Methods—Serum potassium measurements and covariates were available in 21 353 individuals (79% men, mean age 44 years). Mean follow-up time was 26.9 years for stroke analyses and 29.3 years for mortality analyses. There were 2061 incident stroke events and 8709 deaths. Cox regression analyses adjusted for multiple stroke risk factors (age, sex, height, weight, systolic blood pressure, fasting blood glucose, serum sodium, current smoking, prevalent diabetes mellitus, prevalent coronary artery disease, and treatment for hypertension) were fitted.Results—There was an independent, linear association between serum potassium, per mmol/L increase, and both stroke (hazard ratio, 1.33; 95% confidence interval, 1.17–1.52; P<0.0001) and mortality (hazard ratio, 1.20; 95% confidence interval, 1.13–1.28; P<0.0001). This was significant in subjects both older and younger than the median age (46.5 years), and there was evidence of an interaction with serum sodium. The association was positive and significant for both ischemic stroke and intracerebral hemorrhage and in both hypertensive and normotensive subjects.Conclusions—Serum potassium, measured in early mid-life, was linearly associated with both incidence of ischemic stroke and intracerebral hemorrhage and all-cause mortality. An interaction with serum sodium implies that factors related to electrolyte balance and incident hypertension may be mediating factors.



Dietary Sodium to Potassium Ratio and Risk of Stroke in a Multiethnic Urban Population [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—There is growing evidence that increased dietary sodium (Na) intake increases the risk of vascular diseases, including stroke, at least in part via an increase in blood pressure. Higher dietary potassium (K), seen with increased intake of fruits and vegetables, is associated with lower blood pressure. The goal of this study was to determine the association of a dietary Na:K with risk of stroke in a multiethnic urban population.Methods—Stroke-free participants from the Northern Manhattan Study, a population-based cohort study of stroke incidence, were followed-up for incident stroke. Baseline food frequency questionnaires were analyzed for Na and K intake. We estimated the hazard ratios and 95% confidence intervals for the association of Na:K with incident total stroke using multivariable Cox proportional hazards models.Results—Among 2570 participants with dietary data (mean age, 69±10 years; 64% women; 21% white; 55% Hispanic; 24% black), the mean Na:K ratio was 1.22±0.43. Over a mean follow-up of 12 years, there were 274 strokes. In adjusted models, a higher Na:K ratio was associated with increased risk for stroke (hazard ratio, 1.6; 95% confidence interval, 1.2–2.1) and specifically ischemic stroke (hazard ratio, 1.6; 95% confidence interval, 1.2–2.1).Conclusions—Na:K intake is an independent predictor of stroke risk. Further studies are required to understand the joint effect of Na and K intake on risk of cardiovascular disease.



CHA2DS2-VASc Score for Identifying Truly Low-Risk Atrial Fibrillation for Stroke [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—As the threshold of stroke risk for initiating oral anticoagulants is lowered after the introduction of the nonvitamin K antagonist oral anticoagulants, the focus of stroke prevention in patients with nonvalvular atrial fibrillation has shifted away from predicting high-risk patients toward initially identifying patients with a truly low risk of ischemic stroke, who do not need antithrombotic therapy. We tested the predictive ability of the congestive heart failure, hypertension, age ≥75, diabetes mellitus, prior stroke or transient ischemic attack (doubled; CHADS2), congestive heart failure, hypertension, age ≥75 (doubled), diabetes mellitus, prior stroke or transient ischemic attack (doubled), vascular disease, age 65 to 74, female (CHA2DS2-VASc), and Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) risk stratification schemes in oral anticoagulants naive patients with atrial fibrillation in a Korean nationwide sample cohort.Methods—From January 2002 to December 2008, a total of 5855 oral anticoagulant naive patients with nonvalvular atrial fibrillation aged ≥20 years were enrolled from Korea National Health Insurance Service-Sample Cohort database and were followed-up until December 2013.Results—At baseline, the proportions categorized as low risk using CHADS2, CHA2DS2-VASc, and ATRIA risk stratification schemes were 1049 (17.9%), 860 (14.7%), and 3280 (56.0%), respectively. During follow-up, the low-risk category using CHADS2, CHA2DS2-VASc, and ATRIA scores was retained in 811 (13.9%), 667 (11.4%), and 2729 (46.6%) patients, respectively. Rates of ischemic stroke (100 person-years) in the low risk categories of CHADS2, CHA2DS2-VASc, and ATRIA scores were 0.42, 0.26, and 1.43, respectively. CHA2DS2-VASc had the best sensitivity (98.8% versus 85.7% in CHADS2 and 74.8% in ATRIA) and negative predictive value (98.8% versus 95.3% for CHADS2 and 93.7% for ATRIA) for the prediction of stroke incidence and was best for the prediction of the absence of ischemic stroke during 5 years of follow-up (odds ratio, 16.4 [95% confidence interval, 8.8–30.8]).Conclusions—The CHA2DS2-VASc score shows good performance in defining truly low-risk Asian patients with atrial fibrillation for stroke compared with CHADS2 and ATRIA scores.



One-Year Outcomes After Minor Stroke or High-Risk Transient Ischemic Attack [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—Patients with minor ischemic stroke or transient ischemic attack are at high risk of recurrent stroke and vascular events, which are potentially disabling or fatal. This study aimed to evaluate contemporary subsequent vascular event risk after minor ischemic stroke or transient ischemic attack in Korea.Methods—Patients with minor ischemic stroke or high-risk transient ischemic attack admitted within 7 days of symptom onset were identified from a Korean multicenter stroke registry database. We estimated 3-month and 1-year event rates of the primary outcome (composite of stroke recurrence, myocardial infarction, or all-cause death), stroke recurrence, a major vascular event (composite of stroke recurrence, myocardial infarction, or vascular death), and all-cause death and explored differences in clinical characteristics and event rates according to antithrombotic strategies at discharge.Results—Of 9506 patients enrolled in this study, 93.8% underwent angiographic assessment and 72.7% underwent cardiac evaluations; 25.1% had symptomatic stenosis or occlusion of intracranial arteries. At discharge, 95.2% of patients received antithrombotics (antiplatelet polytherapy, 37.1%; anticoagulation, 15.3%) and 86.2% received statins. The 3-month cumulative event rate was 5.9% for the primary outcome, 4.3% for stroke recurrence, 4.6% for a major vascular event, and 2.0% for all-cause death. Corresponding values at 1 year were 9.3%, 6.1%, 6.7%, and 4.1%, respectively. Patients receiving nonaspirin antithrombotic strategies or no antithrombotic agent had higher baseline risk profiles and at least 1.5× higher event rates for clinical event outcomes than those with aspirin monotherapy.Conclusions—Contemporary secondary stroke prevention strategies based on thorough diagnostic evaluation may contribute to the low subsequent vascular event rates observed in real-world clinical practice in Korea.



Pancreatic {beta}-Cell Function and Prognosis of Nondiabetic Patients With Ischemic Stroke [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—Pancreatic β-cell dysfunction is an important factor in the development of type 2 diabetes mellitus. This study aimed to estimate the association between β-cell dysfunction and prognosis of nondiabetic patients with ischemic stroke.Methods—Patients with ischemic stroke without a history of diabetes mellitus in the ACROSS-China (Abnormal Glucose Regulation in Patients with Acute Stroke across China) registry were included. Disposition index was estimated as computer-based model of homeostatic model assessment 2-β%/homeostatic model assessment 2-insulin resistance based on fasting C-peptide level. Outcomes included stroke recurrence, all-cause death, and dependency (modified Rankin Scale, 3–5) at 12 months after onset.Results—Among 1171 patients, 37.2% were women with a mean age of 62.4 years. At 12 months, 167 (14.8%) patients had recurrent stroke, 110 (9.4%) died, and 184 (16.0%) had a dependency. The first quartile of the disposition index was associated with an increased risk of stroke recurrence (adjusted hazard ratio, 3.57; 95% confidence interval, 2.13–5.99) and dependency (adjusted hazard ratio, 2.30; 95% confidence interval, 1.21–4.38); both the first and second quartiles of the disposition index were associated with an increased risk of death (adjusted hazard ratio, 5.09; 95% confidence interval, 2.51–10.33; adjusted hazard ratio, 2.42; 95% confidence interval, 1.17–5.03) compared with the fourth quartile. Using a multivariable regression model with restricted cubic spline, we observed an L-shaped association between the disposition index and the risk of each end point.Conclusions—In this large-scale registry, β-cell dysfunction was associated with an increased risk of 12-month poor prognosis in nondiabetic patients with ischemic stroke.



Stress Hyperglycemia and Prognosis of Minor Ischemic Stroke and Transient Ischemic Attack [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—We aimed to determine the association between stress hyperglycemia and risk of new stroke in patients with a minor ischemic stroke or transient ischemic attack.Methods—A subgroup of 3026 consecutive patients from 73 prespecified sites of the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) were analyzed. Stress hyperglycemia was measured by glucose/glycated albumin (GA) ratio. Glucose/GA ratio was calculated by fasting plasma glucose divided by GA and categorized into 4 even groups according to the quartiles. The primary outcome was a new stroke (ischemic or hemorrhagic) at 90 days. We assessed the association between glucose/GA ratio and risk of stroke by multivariable Cox regression models adjusted for potential covariates.Results—Among 3026 patients included, a total of 299 (9.9%) new stroke occurred at 3 months. Compared with patients with the lowest quartile, patients with the highest quartile of glucose/GA ratio was associated with an increased risk of stroke at 3 months after adjusted for potential covariates (12.0% versus 9.2%; adjusted hazard ratio, 1.46; 95% confidence interval, 1.06–2.01). Similar results were observed after further adjusted for fasting plasma glucose. We also observed that higher level of glucose/GA ratio was associated with an increased risk of stroke with a threshold of 0.29 using a Cox regression model with restricted cubic spline.Conclusions—Stress hyperglycemia, measured by glucose/GA ratio, was associated with an increased risk of stroke in patients with a minor ischemic stroke or transient ischemic attack.Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589.



Corneal Confocal Microscopy Detects Corneal Nerve Damage in Patients Admitted With Acute Ischemic Stroke [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—Corneal confocal microscopy can identify corneal nerve damage in patients with peripheral and central neurodegeneration. However, the use of corneal confocal microscopy in patients presenting with acute ischemic stroke is unknown.Methods—One hundred thirty patients (57 without diabetes mellitus [normal glucose tolerance], 32 with impaired glucose tolerance, and 41 with type 2 diabetes mellitus) admitted with acute ischemic stroke, and 28 age-matched healthy control participants underwent corneal confocal microscopy to quantify corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length.Results—There was a significant reduction in corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length in stroke patients with normal glucose tolerance (P<0.001, P<0.001, P<0.001), impaired glucose tolerance (P=0.004, P<0.001, P=0.002), and type 2 diabetes mellitus (P<0.001, P<0.001, P<0.001) compared with controls. HbA1c and triglycerides correlated with corneal nerve fiber density (r=−0.187, P=0.03; r=−0.229 P=0.01), corneal nerve fiber length (r=−0.228, P=0.009; r=−0.285; P=0.001), and corneal nerve branch density (r=−0.187, P=0.033; r=−0.229, P=0.01). Multiple linear regression showed no independent associations between corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length and relevant risk factors for stroke.Conclusions—Corneal confocal microscopy is a rapid noninvasive ophthalmic imaging technique that identifies corneal nerve fiber loss in patients with acute ischemic stroke.



Island Sign [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—The aim of the study was to investigate the usefulness of the computed tomography (CT) island sign for predicting early hematoma growth and poor functional outcome.Methods—We included patients with spontaneous intracerebral hemorrhage (ICH) who had undergone baseline CT within 6 hours after ICH symptom onset in our hospital between July 2011 and September 2016. Two readers independently assessed the presence of the island sign on the admission noncontrast CT scan. Multivariable logistic regression analysis was used to analyze the association between the presence of the island sign on noncontrast admission CT and early hematoma growth and functional outcome.Results—A total of 252 patients who met the inclusion criteria were analyzed. Among them, 41 (16.3%) patients had the island sign on baseline noncontrast CT scans. In addition, the island sign was observed in 38 of 85 patients (44.7%) with hematoma growth. Multivariate logistic regression analysis demonstrated that the time to baseline CT scan, initial hematoma volume, and the presence of the island sign on baseline CT scan independently predicted early hematoma growth. The sensitivity of the island sign for predicting hematoma expansion was 44.7%, specificity 98.2%, positive predictive value 92.7%, and negative predictive value 77.7%. After adjusting for the patients’ age, baseline Glasgow Coma Scale score, presence of intraventricular hemorrhage, presence of subarachnoid hemorrhage, admission systolic blood pressure, baseline ICH volume, and infratentorial location, the presence of the island sign (odds ratio, 3.51; 95% confidence interval, 1.26–9.81; P=0.017) remained an independent predictor of poor outcome in patients with ICH.Conclusions—The island sign is a reliable CT imaging marker that independently predicts hematoma expansion and poor outcome in patients with ICH. The noncontrast CT island sign may serve as a potential marker for therapeutic intervention.



Added Value of Vessel Wall Magnetic Resonance Imaging for Differentiation of Nonocclusive Intracranial Vasculopathies [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—Our goal is to determine the added value of intracranial vessel wall magnetic resonance imaging (IVWI) in differentiating nonocclusive vasculopathies compared with luminal imaging alone.Methods—We retrospectively reviewed images from patients with both luminal and IVWI to identify cases with clinically defined intracranial vasculopathies: atherosclerosis (intracranial atherosclerotic disease), reversible cerebral vasoconstriction syndrome, and inflammatory vasculopathy. Two neuroradiologists blinded to clinical data reviewed the luminal imaging of defined luminal stenoses/irregularities and evaluated the pattern of involvement to make a presumed diagnosis with diagnostic confidence. Six weeks later, the 2 raters rereviewed the luminal imaging in addition to IVWI for the pattern of wall involvement, presence and pattern of postcontrast enhancement, and presumed diagnosis and confidence. Analysis was performed on per-lesion and per-patient bases.Results—Thirty intracranial atherosclerotic disease, 12 inflammatory vasculopathies, and 12 reversible cerebral vasoconstriction syndrome patients with 201 lesions (90 intracranial atherosclerotic disease, 64 reversible cerebral vasoconstriction syndrome, and 47 inflammatory vasculopathy lesions) were included. For both per-lesion and per-patient analyses, there was significant diagnostic accuracy improvement with luminal imaging+IVWI when compared with luminal imaging alone (per-lesion: 88.8% versus 36.1%; P<0.001 and per-patient: 96.3% versus 43.5%; P<0.001, respectively). There was substantial interrater diagnostic agreement for luminal imaging+IVWI (κ=0.72) and only slight agreement for luminal imaging (κ=0.04). Although there was a significant correlation for both luminal and IVWI pattern of wall involvement with diagnosis, there was a stronger correlation for IVWI finding of lesion eccentricity and intracranial atherosclerotic disease diagnosis than for luminal imaging (κ=0.69 versus 0.18; P<0.001).Conclusions—IVWI can significantly improve the differentiation of nonocclusive intracranial vasculopathies when combined with traditional luminal imaging modalities.



Thrombolysis in Postoperative Stroke [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—Intravenous thrombolysis (IVT) is beneficial in reducing disability in selected patients with acute ischemic stroke. There are numerous contraindications to IVT. One is recent surgery. The aim of this study was to analyze the safety of IVT in patients with postoperative stroke.Methods—Data of consecutive IVT patients from the Telemedical Project for Integrative Stroke Care thrombolysis registry (February 2003 to October 2014; n=4848) were retrospectively searched for keywords indicating preceding surgery. Patients were included if surgery was performed within the last 90 days before stroke. The primary outcome was defined as surgical site hemorrhage. Subgroups with major/minor surgery and recent/nonrecent surgery (within 10 days before IVT) were analyzed separately.Results—One hundred thirty-four patients underwent surgical intervention before IVT. Surgery had been performed recently (days 1–10) in 49 (37%) and nonrecently (days 11–90) in 85 patients (63%). In 86 patients (64%), surgery was classified as major, and in 48 (36%) as minor. Nine patients (7%) developed surgical site hemorrhage after IVT, of whom 4 (3%) were serious, but none was fatal. One fatal bleeding occurred remotely from surgical area. Rate of surgical site hemorrhage was significantly higher in recent than in nonrecent surgery (14.3% versus 2.4%, respectively, odds ratioadjusted 10.73; 95% confidence interval, 1.88–61.27). Difference between patients with major and minor surgeries was less distinct (8.1% and 4.2%, respectively; odds ratioadjusted 4.03; 95% confidence interval, 0.65–25.04). Overall in-hospital mortality was 8.2%. Intracranial hemorrhage occurred in 9.7% and was asymptomatic in all cases.Conclusions—IVT may be administered safely in postoperative patients as off-label use after appropriate risk–benefit assessment. However, bleeding risk in surgical area should be taken into account particularly in patients who have undergone surgery shortly before stroke onset.



Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Asian Patients With Atrial Fibrillation [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—There are limited real-world data comparing the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in Asians with nonvalvular atrial fibrillation. We aimed to compare the effectiveness and safety between NOACs and warfarin users in the Korean atrial fibrillation population, with particular focus on high-risk patients.Methods—Using the Korean National Health Insurance Service database, we analyzed the risk of ischemic stroke, intracranial hemorrhage (ICH) events, and all-cause death in NOAC users (n=11 611 total, n=5681 taking rivaroxaban, n=3741 taking dabigatran, and n=2189 taking apixaban) compared with propensity score-matched warfarin users (n=23 222) among patients with high-risk atrial fibrillation (CHA2DS2-VASc score ≥2) between 2014 and 2015.Results—NOAC treatment was associated with similar risk of ischemic stroke and lower risk of ICH and all-cause mortality compared with warfarin. All 3 NOACs were associated with a similar risk of ischemic stroke and a lower risk of ICH compared with warfarin. Dabigatran and apixaban were associated with a lower risk of total mortality and the composite net clinical outcome (ischemic stroke, ICH, and all-cause death) compared with warfarin, whereas this was nonsignificant for rivaroxaban. Among previously oral anticoagulant–naive patients (n=23 262), dabigatran and apixaban were superior to warfarin for ICH prevention, whereas rivaroxaban and warfarin were associated with similar risk of ICH.Conclusions—In real-world practice among a high-risk Asian atrial fibrillation population, all 3 NOACs demonstrated similar risk of ischemic stroke and lower risk of ICH compared with warfarin. All-cause mortality was significantly lower only with dabigatran and apixaban.



Association Between Onset-to-Door Time and Clinical Outcomes After Ischemic Stroke [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—The role of early hospital arrival in improving poststroke clinical outcomes in patients without reperfusion treatment remains unclear. This study aimed to determine whether early hospital arrival was associated with favorable outcomes in patients without reperfusion treatment or with minor stroke.Methods—This multicenter, hospital-based study included 6780 consecutive patients (aged, 69.9±12.2 years; 63.9% men) with ischemic stroke who were prospectively registered in Fukuoka, Japan, between July 2007 and December 2014. Onset-to-door time was categorized as T0-1, ≤1 hour; T1-2, >1 and ≤2 hours; T2-3, >2 and ≤3 hours; T3-6, >3 and ≤6 hours; T6-12, >6 and ≤12 hours; T12-24, >12 and ≤24 hours; and T24-, >24 hours. The main outcomes were neurological improvement (decrease in National Institutes of Health Stroke Scale score of ≥4 during hospitalization or 0 at discharge) and good functional outcome (3-month modified Rankin Scale score of 0–1). Associations between onset-to-door time and main outcomes were evaluated after adjusting for potential confounders using logistic regression analysis.Results—Odds ratios (95% confidence intervals) increased significantly with shorter onset-to-door times within 6 hours, for both neurological improvement (T0-1, 2.79 [2.28–3.42]; T1-2, 2.49 [2.02–3.07]; T2-3, 1.52 [1.21–1.92]; T3-6, 1.72 [1.44–2.05], with reference to T24-) and good functional outcome (T0-1, 2.68 [2.05–3.49], T1-2 2.10 [1.60–2.77], T2-3 1.53 [1.15–2.03], T3-6 1.31 [1.05–1.64], with reference to T24-), even after adjusting for potential confounding factors including reperfusion treatment and basal National Institutes of Health Stroke Scale. These associations were maintained in 6216 patients without reperfusion treatment and in 4793 patients with minor stroke (National Institutes of Health Stroke Scale ≤4 on hospital arrival).Conclusions—Early hospital arrival within 6 hours after stroke onset is associated with favorable outcomes after ischemic stroke, regardless of reperfusion treatment or stroke severity.



Randomized Controlled Trial of Early Versus Delayed Statin Therapy in Patients With Acute Ischemic Stroke [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—Several studies suggested that statins during hospitalization were associated with better disability outcomes in patients with acute ischemic stroke, but only 1 small randomized trial is available.Methods—We conducted a multicenter, open-label, randomized controlled trial in patients with acute ischemic strokes in 11 hospitals in Japan. Patients with acute ischemic stroke and dyslipidemia randomly received statins within 24 hours after admission in the early group or on the seventh day in the delayed group, in a 1:1 ratio. Statins were administered for 12 weeks. The primary outcome was patient disability assessed by modified Rankin Scale at 90 days.Results—A total of 257 patients were randomized and analyzed (early 131, delayed 126). At 90 days, modified Rankin Scale score distribution did not differ between groups (P=0.68), and the adjusted common odds ratio of the early statin group was 0.84 (95% confidence interval, 0.53–1.3; P=0.46) compared with the delayed statin group. There were 3 deaths at 90 days (2 in the early group, 1 in the delayed group) because of malignancy. Ischemic stroke recurred in 9 patients (6.9%) in the early group and 5 patients (4.0%) in the delayed group. The safety profile was similar between groups.Conclusions—Our randomized trial involving patients with acute ischemic stroke and dyslipidemia did not show any superiority of early statin therapy within 24 hours of admission compared with delayed statin therapy 7 days after admission to alleviate the degree of disability at 90 days after onset.Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT02549846.



Remote Ischemic Conditioning May Improve Outcomes of Patients With Cerebral Small-Vessel Disease [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—We aimed to evaluate the efficacy of remote ischemic conditioning (RIC) in patients with cerebral small-vessel disease.Methods—Thirty patients with cerebral small-vessel disease–related mild cognitive impairment were enrolled in this prospective, randomized controlled study for 1 year. Besides routine medical treatment, participants were randomized into the experimental group (n=14) undergoing 5 cycles consisting of ischemia followed by reperfusion for 5 minutes on both upper limbs twice daily for 1 year or the control group (n=16) who were treated with sham ischemia–reperfusion cycles. The primary outcome was the change of brain lesions, and secondary outcomes were changes of cognitive function, plasma biomarkers, and cerebral hemodynamic parameters both at baseline and at the end of 1-year follow-up.Results—Compared with pretreatment, the post-treatment white matter hyperintensities volume in the RIC group was significantly reduced (9.10±7.42 versus 6.46±6.05 cm3; P=0.020), whereas no significant difference was observed in the sham-RIC group (8.99±6.81 versus 8.07±6.56 cm3; P=0.085). The reduction of white matter hyperintensities volume in the RIC group was more substantial than that in sham group (−2.632 versus −0.935 cm3; P=0.049). No significant difference was found in the change of the number of lacunes between 2 groups (0 versus 0; P=0.694). A significant treatment difference at 1 year on visuospatial and executive ability was found between the 2 groups (0.639 versus 0.191; P=0.048). RIC showed greater effects compared with sham-RIC on plasma triglyceride (−0.433 versus 0.236 mmol/L; P=0.005), total cholesterol (−0.975 versus 0.134 mmol/L; P<0.001), low-density lipoprotein (−0.645 versus −0.029 mmol/L; P=0.034), and homocysteine (−4.737 versus −1.679 µmol/L; P=0.044). Changes of the pulsation indices of middle cerebral arteries from the baseline to 1 year were different between the 2 groups (right: −0.075 versus 0.043; P=0.030; left: −0.085 versus 0.043; P=0.010).Conclusions—RIC seems to be potentially effective in patients with cerebral small-vessel disease in slowing cognition decline and reducing white matter hyperintensities.Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01658306.



Safety Outcomes After Percutaneous Transcatheter Closure of Patent Foramen Ovale [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—We sought to evaluate the real-world rate of safety outcomes after patent foramen ovale (PFO) closure in patients with ischemic stroke or transient ischemic attack (TIA).Methods—We performed a retrospective cohort study using administrative claims data on all hospitalizations from 2005 to 2013 in New York, California, and Florida. Using International Classification of Diseases, Ninth Revision, Clinical Modification codes, we identified patients who underwent percutaneous transcatheter PFO closure within 1 year of ischemic stroke or TIA. Our outcome was an adverse event occurring during the hospitalization for PFO closure, defined as in prior studies as atrial fibrillation or flutter, cardiac tamponade, pneumothorax, hemothorax, a vascular access complication, or death. Crude rates were reported with exact confidence intervals.Results—We identified 1887 patients who underwent PFO closure after ischemic stroke or TIA. The rate of any adverse outcome during the hospitalization for PFO closure was 7.0% (95% confidence interval [CI], 5.9%–8.2%). Rates of adverse outcomes varied by age and type of preceding cerebrovascular event. In patients >60 years of age, the rate of adverse outcomes was 10.9% (95% CI, 8.6%–13.6%) versus 4.9% (95% CI, 3.8%–6.3%) in patients ≤60 years of age. The rate of adverse outcomes was 9.9% (95% CI, 7.3%–12.5%) in patients with preceding ischemic stroke versus 5.9% (95% CI, 4.7%–7.1%) after TIA.Conclusions—Approximately 1 in 14 patients who underwent percutaneous transcatheter PFO closure after ischemic stroke or TIA experienced a serious periprocedural adverse outcome or death. The risk of adverse outcomes was highest in older patients and in those with preceding ischemic stroke.



Baseline Quality of Life and Risk of Stroke in the ALLHAT Study (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—The visual analogue scale is a self-reported, validated tool to measure quality of life (QoL). Our purpose was to determine whether baseline QoL predicted strokes in the ALLHAT study (Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial) and evaluate determinants of poststroke change in QoL. In the ALLHAT study, among the 33 357 patients randomized to treatment arms, 1525 experienced strokes; 1202 (79%) strokes were nonfatal. This study cohort includes 32 318 (97%) subjects who completed the baseline visual analogue scale QoL estimate.Methods—QoL was measured on a visual analogue scale and adjusted using a Torrance transformation (transformed QoL [TQoL]). Kaplan–Meier curves and adjusted proportional hazards analyses were used to estimate the effect of TQoL on the risk of stroke, on a continuous scale (0–1) and by quartiles (≤0.81, >0.81≤0.89, >0.89≤0.95, >0.95). We analyzed the change from baseline to first poststroke TQoL using adjusted linear regression.Results—After adjusting for multiple stroke risk factors, the hazard ratio for stroke events for baseline TQoL was 0.93 (95% confidence interval, 0.89–0.98) per 0.1 U increase. The lowest baseline TQoL quartile had a 20% increased stroke risk (hazard ratio=1.20 [95% confidence interval, 1.00–1.44]) compared with the reference highest quartile TQoL. Poststroke TQoL change was significant within all treatment groups (P≤0.001). Multivariate regression analysis revealed that baseline TQoL was the strongest predictor of poststroke TQoL with similar results for the untransformed QoL.Conclusions—The lowest baseline TQoL quartile had a 20% higher stroke risk than the highest quartile. Baseline TQoL was the only factor that predicted poststroke change in TQoL.Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542.



Outcomes of Primary and Secondary Carotid Artery Stenting [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—Little is known of the excess risk attributable to secondary carotid angioplasty and stenting (CAS). This study evaluates outcomes of redo-CAS and CAS after prior ipsilateral carotid endarterectomy (CASAPICEA) relative to primary-CAS.Methods—We studied all patients in the Vascular Quality Initiative, who underwent primary-CAS, CASAPICEA, or redo-CAS (2003–2016). Kaplan–Meier, multivariable logistic and Cox regression analyses were used to evaluate outcomes within 30 days and up to 1 year and identify their predictors.Results—There were 11 742 CAS procedures performed: 8519 (72%) primary-, 2645 (23%) CASAPICEA, and 578 (5%) redo-CAS. Comparing primary-CAS versus CASAPICEA versus redo-CAS, 30-day stroke/death was 2.5% versus 2.0% versus 1.3% for asymptomatic patients (P=0.23) and 5.2% versus 2.6% versus 5.0% for symptomatic patients (P=0.003). CASAPICEA was associated with significantly lower 30-day stroke/death (odds ratio: 0.60; 95% confidence interval: 0.37–0.98; P=0.04) compared with primary-CAS among symptomatic patients. The odds of bradycardia were lower following CASAPICEA (odds ratio: 0.32; 95% confidence interval: 0.26–0.39; P<0.001) and redo-CAS (odds ratio: 0.55; 95% confidence interval: 0.39–0.78; P=0.001) compared with primary-CAS. Similarly, the odds of hypotension were significantly lower in both groups compared with primary-CAS (CASAPICEA: 0.41 [0.35–0.48], P<0.001; redo-CAS: 0.66 [0.50–0.86] P=0.003). There were no significant differences in the hazards of stroke/death at 1 year for CASAPICEA and redo-CAS compared with primary-CAS.Conclusions—CASAPICEA is associated with significantly lower odds of periprocedural stroke/death compared with primary-CAS among symptomatic patients. CASAPICEA and redo-CAS are associated with significantly lower odds of periprocedural hypotension and bradycardia but higher odds of hypertension compared with primary-CAS.



Effects of Physical Activity on Poststroke Cognitive Function [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—Despite the social, health, and economic burdens associated with cognitive impairment poststroke, there is considerable uncertainty about the types of interventions that might preserve or restore cognitive abilities. The objective of this systematic review and meta-analysis was to evaluate the effects of physical activity (PA) training on cognitive function poststroke and identify intervention and sample characteristics that may moderate treatment effects.Methods—Randomized controlled trials examining the association between structured PA training and cognitive performance poststroke were identified using electronic databases EMBASE and MEDLINE. Intervention effects were represented by Hedges’ g and combined into pooled effect sizes using random- and mixed-effects models. Effect sizes were subjected to moderation analyses using the between-group heterogeneity test.Results—Fourteen studies met inclusion criteria, representing data from 736 participants. The primary analysis yielded a positive overall effect of PA training on cognitive performance (Hedges’ g [95% confidence interval]=0.304 [0.14–0.47]). Mixed-effects analyses demonstrated that combined aerobic and strength training programs generated the largest cognitive gains and that improvements in cognitive performance were achieved even in the chronic stroke phase (mean=2.6 years poststroke). Positive moderate treatment effects were found for attention/processing speed measures (Hedges’ g [confidence interval]=0.37 [0.10–0.63]), while the executive function and working memory domains did not reach significance (P>0.05).Conclusions—We found a significant positive effect of PA training on cognition poststroke with small to moderate treatment effects that are apparent even in the chronic stroke phase. Our findings support the use of PA training as a treatment strategy to promote cognitive recovery in stroke survivors.



Incorporating Stroke Severity Into Hospital Measures of 30-Day Mortality After Ischemic Stroke Hospitalization [Clinical Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—The Centers for Medicare one that includes other risk variables derived from claims and clinical variables that could be obtained from electronic health record data (hybrid model); and one that includes other risk variables that could be derived only from electronic health record data (electronic health record model).Results—The cohort used to develop and validate the risk models consisted of 188 975 hospital admissions at 1511 hospitals. The claims, hybrid, and electronic health record risk models included 20, 21, and 9 risk-adjustment variables, respectively; the C statistics were 0.81, 0.82, and 0.79, respectively (as compared with the current publicly reported model C statistic of 0.75); the risk-standardized mortality rates ranged from 10.7% to 19.0%, 10.7% to 19.1%, and 10.8% to 20.3%, respectively; the median risk-standardized mortality rate was 14.5% for all measures; and the odds of mortality for a high-mortality hospital (+1 SD) were 1.51, 1.52, and 1.52 times those for a low-mortality hospital (−1 SD), respectively.Conclusions—We developed 3 quality measures that demonstrate better discrimination than the Centers for Medicare & Medicaid Services’ existing stroke mortality measure, adjust for stroke severity, and could be implemented in a variety of settings.



Bosutinib Attenuates Inflammation via Inhibiting Salt-Inducible Kinases in Experimental Model of Intracerebral Hemorrhage on Mice [Basic Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—Intracerebral hemorrhage (ICH) is a subtype of stroke with highest mortality and morbidity. Pronounced inflammation plays a significant role in the development of the secondary brain injury after ICH. Recently, SIK-2 (salt-inducible kinase-2) was identified as an important component controlling inflammatory response. Here we sought to investigate the role of SIK-2 in post-ICH inflammation and potential protective effects of SIK-2 inhibition after ICH.Methods—Two hundred and ninety-three male CD-1 mice were used. ICH was induced via injection of 30 μL of autologous blood. Recombinant SIK-2 was administrated 1 hour after ICH intracerebroventricularly. SIK-2 small interfering RNA was injected intracerebroventricularly 24 hours before ICH. Bosutinib, a clinically approved tyrosine kinase inhibitor with affinity to SIK-2, was given intranasally 1 hour or 6 hours after ICH. Effects of treatments were evaluated by neurological tests and brain water content calculation. Molecular pathways were investigated by Western blots and immunofluorescence studies.Results—Endogenous SIK-2 was expressed in microglia and neurons. SIK-2 expression was reduced after ICH. Exogenous SIK-2 aggravated post-ICH inflammation, leading to brain edema and the neurobehavioral deficits. SIK-2 inhibition attenuated post-ICH inflammation, reducing brain edema and ameliorating neurological dysfunctions. Bosutinib inhibited SIK-2–attenuating ICH-induced brain damage. Protective effects of Bosutinib were mediated, at least partly, by CRTC3 (cyclic amp-response element binding protein-regulated transcription coactivator 3)/cyclic amp-response element binding protein/NF-κB (nuclear factor-κB) pathway.Conclusions—SIK-2 participates in inflammation induction after ICH. SIK-2 inhibition via Bosutinib or small interfering RNA decreased inflammation, attenuating brain injury. SIK-2 effects are, at least partly, mediated by CRTC3-cyclic amp-response element binding protein-NF-κB signaling pathway.



Neuronal SIRT1 (Silent Information Regulator 2 Homologue 1) Regulates Glycolysis and Mediates Resveratrol-Induced Ischemic Tolerance [Basic Sciences]

2017-10-23T10:41:00-07:00

Background and Purpose—Resveratrol, at least in part via SIRT1 (silent information regulator 2 homologue 1) activation, protects against cerebral ischemia when administered 2 days before injury. However, it remains unclear if SIRT1 activation must occur, and in which brain cell types, for the induction of neuroprotection. We hypothesized that neuronal SIRT1 is essential for resveratrol-induced ischemic tolerance and sought to characterize the metabolic pathways regulated by neuronal Sirt1 at the cellular level in the brain.Methods—We assessed infarct size and functional outcome after transient 60 minute middle cerebral artery occlusion in control and inducible, neuronal-specific SIRT1 knockout mice. Nontargeted primary metabolomics analysis identified putative SIRT1-regulated pathways in brain. Glycolytic function was evaluated in acute brain slices from adult mice and primary neuronal-enriched cultures under ischemic penumbra-like conditions.Results—Resveratrol-induced neuroprotection from stroke was lost in neuronal Sirt1 knockout mice. Metabolomics analysis revealed alterations in glucose metabolism on deletion of neuronal Sirt1, accompanied by transcriptional changes in glucose metabolism machinery. Furthermore, glycolytic ATP production was impaired in acute brain slices from neuronal Sirt1 knockout mice. Conversely, resveratrol increased glycolytic rate in a SIRT1-dependent manner and under ischemic penumbra-like conditions in vitro.Conclusions—Our data demonstrate that resveratrol requires neuronal SIRT1 to elicit ischemic tolerance and identify a novel role for SIRT1 in the regulation of glycolytic function in brain. Identification of robust neuroprotective mechanisms that underlie ischemia tolerance and the metabolic adaptations mediated by SIRT1 in brain are crucial for the translation of therapies in cerebral ischemia and other neurological disorders.



Synergism of Short-Term Air Pollution Exposures and Neighborhood Disadvantage on Initial Stroke Severity [Brief Report]

2017-10-23T10:41:00-07:00

Background and Purpose—Little is known about the relation between environment and stroke severity. We investigated associations between environmental exposures, including neighborhood socioeconomic disadvantage and short-term exposure to airborne particulate matter <2.5 μm and ozone, and their interactions with initial stroke severity.Methods—First-ever ischemic stroke cases were identified from the Brain Attack Surveillance in Corpus Christi project (2000–2012). Associations between pollutants, disadvantage, and National Institutes of Health Stroke Scale were modeled using linear and logistic regression with adjustment for demographics and risk factors. Pollutants and disadvantage were modeled individually, jointly, and with interactions.Results—Higher disadvantage scores and previous-day ozone concentrations were associated with higher odds of severe stroke. Higher levels of particulate matter <2.5 μm were associated with higher odds of severe stroke among those in higher disadvantage areas (odds ratio, 1.24; 95% confidence interval, 1.00–1.55) but not in lower disadvantage areas (odds ratio, 0.82; 95% confidence interval, 0.56–1.22; P interaction =0.097).Conclusions—Air pollution exposures and neighborhood socioeconomic status may be important in understanding stroke severity. Future work should consider the multiple levels of influence on this important stroke outcome.



Safety of Pregnancy After Cerebral Venous Thrombosis [Brief Report]

2017-10-23T10:41:00-07:00

Background and Purpose—Pregnancy is associated with increased risk of venous thrombotic events, including cerebral venous thrombosis. We aimed to study the complications and outcome of subsequent pregnancies in women with previous cerebral venous thrombosis.Methods—Follow-up study of women with acute cerebral venous thrombosis at childbearing age included in a previously described cohort (International Study of Cerebral Vein and Dural Sinus Thrombosis). Patients were interviewed by local neurologists to assess rate of venous thrombotic events, pregnancy outcomes, and antithrombotic prophylaxis during subsequent pregnancies.Results—A total of 119 women were included, with a median follow-up of 14 years. Eighty-two new pregnancies occurred in 47 women. In 83% (68 of 82), some form of antithrombotic prophylaxis was given during at least 1 trimester of pregnancy or puerperium. Venous thrombotic events occurred in 3 pregnancies, including 1 recurrent cerebral venous thrombosis. Two of the 3 women were on prophylactic low-molecular-weight heparin at the time of the event. Outcomes of pregnancies were 51 full-term newborns, 9 preterm births, 2 stillbirths, and 20 abortions (14 spontaneous).Conclusions—In women with prior cerebral venous thrombosis, recurrent venous thrombotic events during subsequent pregnancies are infrequent.



Carotid Web (Intimal Fibromuscular Dysplasia) Has High Stroke Recurrence Risk and Is Amenable to Stenting [Brief Report]

2017-10-23T10:41:00-07:00

Background and Purpose—Carotid webs have been increasingly recognized as a cause of recurrent stroke, but evidence remains scarce. We aim to report the clinical outcomes and first series of carotid stenting in a cohort of patients with strokes from symptomatic carotid webs.Methods—Prospective and consecutive data of patients <65 years old with cryptogenic stroke admitted within September 2014 to May 2017. Carotid web was defined by a shelf-like/linear filling defect in the posterior internal carotid artery bulb by computed tomographic angiography.Results—Twenty-four patients were identified (91.6% strokes/8.4% transient ischemic attacks [TIAs]). Median age was 46 (41–59) years, 61% were female, and 75% were black. Median National Institutes of Health Stroke Scale score was 10.5 (3.0–16.0) and ASPECTS (Alberta Stroke Program Early CT Score) was 8 (7–8). There were no parenchymal hemorrhages, and 96% of patients were independent at 3 months. All webs caused <50% stenosis. In patients with bilateral webs (58%), median ipsilateral web length was larger than contralateral (3.1 [3.0–4.5] mm versus 2.6 [1.85–2.9] mm; P=0.01), respectively. Twenty-nine percent of patients had thrombus superimposed on the symptomatic carotid web. A recurrent stroke/TIA involving the territory of the previously symptomatic web occurred in 7 (32%; 6 strokes/1 TIA) patients: 3 <1 week, 2 1 year of follow-up. Two recurrences occurred on dual antiplatelet therapy, 3 on antiplatelet monotherapy, 1 within 24 hours of thrombolysis, and 1 off antithrombotics. Median follow-up was 12.2 (8.0–18.0) months. Sixteen (66%) patients were stented at a median 12.2 (7.0–18.7) days after stroke with no periprocedural complications. No recurrent strokes/TIAs occurred in stented individuals (median follow-up of 4 [2.4–12.0] months).Conclusions—Carotid web is associated with high recurrent stroke/TIA risk, despite antithrombotic use, and is amenable to carotid stenting.



The Protective Effect of Middle Cerebral Artery Calcification on Symptomatic Middle Cerebral Artery Infarction [Brief Report]

2017-10-23T10:41:01-07:00

Background and Purpose—The presence of intracranial artery calcification is associated with an increased risk for stroke. However, calcified atherosclerotic plaques are also known to be less vulnerable to rupture. Given this discrepancy, we investigated whether the vulnerability of intracranial arterial atherosclerosis differed based on the presence or absence of calcification.Methods—We considered consecutive patients with acute stroke in the unilateral middle cerebral artery (MCA) territory. Patients with any stenotic MCAs were included in this study. Symptomatic MCA was defined as the occurrence of infarctions relevant to the stenotic MCA. The presence of calcification in the MCA was evaluated on noncontrast thin-section computed tomography images using a 3dimensional software package. Generalized estimating equations were used to compare the frequency of calcification between symptomatic and asymptomatic stenosis.Results—Of the 1066 MCAs examined in 533 patients, 645 MCAs were stenotic and were included in the study. Among the 645 stenotic MCAs, 406 MCAs (62.9%) were symptomatic. Calcification was observed in 36 MCAs (5.6%). Calcification in the MCA was more frequently observed in the asymptomatic group (7.9% versus 4.2%; P=0.032). On multivariable analysis, the presence of calcification in MCA atherosclerosis was less frequent in the symptomatic group (odds ratio, 0.46; 95% confidence interval, 0.23–0.92; P=0.027).Conclusions—This study showed that calcified atherosclerosis in the MCA was less frequently symptomatic.



Predicting Major Bleeding in Ischemic Stroke Patients With Atrial Fibrillation [Brief Report]

2017-10-23T10:41:01-07:00

Background and Purpose—Performance of risk scores for major bleeding in patients with atrial fibrillation and a previous transient ischemic attack or ischemic stroke is not well established. We aimed to validate risk scores for major bleeding in patients with atrial fibrillation treated with oral anticoagulants after cerebral ischemia and explore the net benefit of oral anticoagulants among bleeding risk categories.Methods—We analyzed 3623 patients with a history of transient ischemic attack or stroke included in the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). We assessed performance of HEMORR2HAGES (hepatic or renal disease, ethanol abuse, malignancy, older age, reduced platelet count or function, hypertension [uncontrolled], anemia, genetic factors, excessive fall risk, and stroke), Shireman, HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly), ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), and ORBIT scores (older age, reduced haemoglobin/haematocrit/history of anaemia, bleeding history, insufficient kidney function, and treatment with antiplatelet) with C statistics and calibration plots. Net benefit of oral anticoagulants was explored by comparing risk reduction in ischemic stroke with risk increase in major bleedings on warfarin.Results—During 6922 person-years of follow-up, 266 patients experienced a major bleed (3.8 per 100 person-years). C statistics ranged from 0.62 (Shireman) to 0.67 (ATRIA). Calibration was poor for ATRIA and moderate for other models. The reduction in recurrent ischemic strokes on warfarin was larger than the increase in major bleeding risk, irrespective of bleeding risk category.Conclusions—Performance of prediction models for major bleeding in patients with cerebral ischemia and atrial fibrillation is modest but comparable with performance in patients with only atrial fibrillation. Bleeding risk scores cannot guide treatment decisions for oral anticoagulants but may still be useful to identify modifiable risk factors for bleeding. Clinical usefulness may be best for ORBIT, which is based on a limited number of easily obtainable variables and showed reasonable performance.



Thrombectomy in Acute Stroke With Tandem Occlusions From Dissection Versus Atherosclerotic Cause [Brief Report]

2017-10-23T10:41:01-07:00

Background and Purpose—Tandem steno-occlusive lesions were poorly represented in randomized trials and represent a major challenge for endovascular thrombectomy in acute anterior circulation strokes. The impact of the cervical carotid lesion cause (ie, atherosclerotic versus dissection) on outcome of tandem patients endovascularly treated remains to be assessed.Methods—We retrospectively analyzed individual data of prospectively collected consecutive tandem patients treated with endovascular thrombectomy. The primary outcome was favorable outcome at 90 days (modified Rankin Scale score of 0–2). Secondary efficacy outcomes included successful reperfusion (modified Thrombolysis in Cerebrovascular Infarction scores of 2b-3), time to reperfusion, and safety outcomes encompassed procedural complications, symptomatic intracerebral hemorrhage, and 90-day mortality.Results—Among the 295 included patients, 65 had cervical carotid dissection and 230 had cervical carotid atherosclerotic cause. The rate of favorable outcome was 56.3% in the dissection group versus 47.6% in the atherosclerotic arm (center-, age-, and admission National Institutes of Health Stroke Scale–adjusted odds ratio, 1.08; 95% confidence interval, 0.50–2.30; P=0.85). No significant differences were observed in secondary outcomes. The rates of successful reperfusion, symptomatic intracerebral hemorrhage, and 90-day mortality were 78.5% versus 74.5% (P=0.13), 4.6% versus 5.2% (P=1.0), and 7.8% versus 15.3% (P=0.94) in the dissection versus atherosclerotic groups, respectively. The median procedural time was 76 minutes (interquartile range, 52–95 minutes) in the dissection group and 67 minutes (interquartile range, 45–98 minutes) in the atherosclerotic group (P=0.24).Conclusions—We found no differences in the outcomes of patients with anterior circulation tandem atherosclerotic and dissection lesions treated with endovascular thrombectomy. Further studies are warranted.



Mechanical Thrombectomy in Perioperative Strokes [Brief Report]

2017-10-23T10:41:01-07:00

Background and Purpose—Perioperative strokes (POS) are rare but serious complications for which mechanical thrombectomy could be beneficial. We aimed to compare the technical results and patients outcomes in a population of POS versus non-POS (nPOS) treated by mechanical thrombectomy.Methods—From 2010 to 2017, 25 patients with POS (ie, acute ischemic stroke occurring during or within 30 days after a procedure) who underwent mechanical thrombectomy (POS group) were enrolled and paired with 50 consecutive patients with nPOS (control group), based on the occlusion’s site, National Institute of Health Stroke Scale, and age.Results—Respectively, mean age was 68.3±16.6 versus 67.2±16.6 years (P=0.70), and median National Institute of Health Stroke Scale score at admission was 20 (interquartile range, 15–25) versus 19 (interquartile range, 17–25; P=0.79). Good clinical outcome (modified Rankin Scale score of 0–2 at 3 months) was achieved by 33.3% (POS) versus 56.5% (nPOS) of patients (P=0.055). Successful reperfusion (modified Thrombolysis In Cerebral Infarction score of ≥2b) was obtained in 76% (POS) versus 86% (nPOS) of cases (P=0.22). Mortality at 3 months was 33.3% in the POS group versus 4.2% (nPOS) (P=0.002). The rate of major procedural complications was 4% (POS) versus 6% (nPOS); none were lethal. Average time from symptoms’ onset to reperfusion was 4.9 hours (±2.0) in POS versus 5.2 hours (±2.6).Conclusions—Successful reperfusion seems accessible in POS within a reasonable amount of time and with a good level of safety. However, favorable outcome was achieved with a lower rate than in nPOS, owing to a higher mortality rate.



One-Stop Management of Acute Stroke Patients [Brief Report]

2017-10-23T10:41:01-07:00

Background and Purpose—Intrahospital time delays significantly affect the neurological outcome of stroke patients with large-vessel occlusion. This study was conducted to determine whether a one-stop management can reduce intrahospital times of patients with acute large-vessel occlusion.Methods—In this observational study, we report the first 30 consecutive stroke patients imaged and treated in the same room. As part of our protocol, we transported patients with a National Institutes of Health Stroke Scale score of ≥10 directly to the angio suite, bypassing multidetector computed tomography (CT). Preinterventional imaging consisted of noncontrast flat detector CT and flat detector CT angiography, acquired with an angiography system. Patients with large-vessel occlusions remained on the angio table and were treated with mechanical thrombectomy; patients with small artery occlusions were treated with intravenous thrombolysis, whereas patients with an intracranial hemorrhage and stroke mimics were treated as per guidelines. Door-to-groin puncture times were recorded and compared with our past results.Results—Thirty patients were transferred directly to our angio suite from June to December 2016. The time from symptom onset to admission was 105 minutes. Ischemic stroke was diagnosed in 22 of 30 (73%) patients, 4 of 30 (13.5%) had an intracranial hemorrhage, and 4 of 30 (13.5) were diagnosed with a Todd’s paresis. Time from admission to groin puncture was 20.5 minutes. Compared with 44 patients imaged with multidetector CT in the first 6 months of 2016, door-to-groin times were significantly reduced (54.5 minutes [95% confidence interval, 47–61] versus 20.5 minutes [95% confidence interval, 17–26]).Conclusions—In this small series, a one-stop management protocol of selected stroke patients using latest generation flat detector CT led to a significant reduction of intrahospital times.



Utilization of a Smartphone Platform for Electronic Informed Consent in Acute Stroke Trials [Brief Report]

2017-10-23T10:41:01-07:00

Background and Purpose—The informed consent process is a major limitation for enrollment in acute stroke clinical investigations. We aim to describe the novel application of smartphone electronic informed consenting (e-Consent) in trials of cerebral thrombectomy.Methods—The e-Consent tool consists of a secure/Health Insurance Portability and Accountability Act compliant smartphone platform based on REDCap (Research Electronic Data Capture; Vanderbilt University, TN) that uses a survey project located on a static webpage. A link to the webpage is sent via text message or email to the legally authorized representative. The e-Consent form is filled and a freehand electronic signature added in the smartphone browser; a record ID and an e-Consent Process Attestation form are automatically generated. The e-Consent application was piloted in a randomized trial comparing endovascular versus medical therapy in late presenting patients (DAWN [Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo]). Trial enrollment began in January 2015; e-Consent was approved by the local institutional review board in December 2016, and the study was stopped in February 2017.Results—During the trial period, Grady Memorial Hospital performed 273 thrombectomies with 47 patients being consented and 38 patients enrolled in the DAWN trial. Of the randomized patients, 29 (76%) were transferred from outside hospitals. A total of 6 surrogates were e-Consented, with 2 patients being screen failures. Enrolled e-Consented patients (n=4) had similar age (73±14 versus 69±12 years; P=0.65) and National Institutes of Health Stroke Scale (16±5 versus 16±5; P=0.88) as compared with conventionally consented (n=25). Time from door-to-randomization was decreased with e-Consenting (28±9 versus 57±24 minutes; P=0.002).Conclusions—e-Consenting streamlined the consenting process in a randomized trial of patients with emergent large vessel occlusion strokes.



For-Profit Hospital Status and Carotid Artery Stent Utilization in US Hospitals Performing Carotid Revascularization [Brief Report]

2017-10-23T10:41:01-07:00

Background and Purpose—Carotid artery stenting may be an economically attractive procedure for hospitals and physicians. We sought to identify the association of hospital ownership (nonprofit versus for-profit) on carotid artery stenting (CAS) versus carotid endarterectomy utilization in US hospitals.Methods—Using the Nationwide Inpatient Sample admissions for cerebrovascular disease from 2008 to 2011, we identified all private, nonfederal US hospitals performing at least 20 carotid revascularization procedures annually, including carotid artery stenting (International Classification of Diseases-Ninth Revision 00.63) or carotid endarterectomy (International Classification of Diseases-Ninth Revision 38.12). We used a multilevel multivariable logistic regression controlling for patient demographics, comorbidities, and hospital characteristics, to assess the effect of hospital ownership on CAS use.Results—Across 723 hospitals (600 nonprofit, 123 for-profit), 66 731 carotid revascularization admissions were identified. Approximately 1 in 5 (n=11 641; 17.4%) revascularizations received CAS. The mean CAS rate among nonprofit hospitals was 17.5 per 100 revascularizations (median, 11.5; interquartile range, 5.2–24.5), and the mean CAS rate among for-profit hospitals was 24.2 per 100 revascularizations (median, 16.0; interquartile range, 6.7–33.3; P<0.001). Adjusting for patient and hospital characteristics, for-profit hospital designation was associated with greater odds of CAS (adjusted odds ratio, 1.45; 95% confidence interval, 1.07–1.98).Conclusions—For-profit hospital ownership is associated with a higher rate of CAS compared to nonprofit hospitals in those receiving carotid revascularization. Further research is needed to understand the individual- and system-level factors driving this difference.
























Defining Optimal Brain Health in Adults: A Presidential Advisory From the American Heart Association/American Stroke Association [AHA/ASA Presidential Advisory]

2017-09-25T12:45:00-07:00

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 [...]














































































Omega-3 Fatty Acids and Incident Ischemic Stroke and Its Atherothrombotic and Cardioembolic Subtypes in 3 US Cohorts [Clinical Sciences]

2017-09-25T12:45:00-07:00

Background and Purpose—The associations of individual long-chain n-3 polyunsaturated fatty acids with incident ischemic stroke and its main subtypes are not well established. We aimed to investigate prospectively the relationship of circulating eicosapentaenoic acid, docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with risk of total ischemic, atherothrombotic, and cardioembolic stroke.Methods—We measured circulating phospholipid fatty acids at baseline in 3 separate US cohorts: CHS (Cardiovascular Health Study), NHS (Nurses’ Health Study), and HPFS (Health Professionals Follow-Up Study). Ischemic strokes were prospectively adjudicated and classified into atherothrombotic (large- and small-vessel infarctions) or cardioembolic by imaging studies and medical records. Risk according to fatty acid levels was assessed using Cox proportional hazards (CHS) or conditional logistic regression (NHS, HPFS) according to study design. Cohort findings were pooled using fixed-effects meta-analysis.Results—A total of 953 incident ischemic strokes were identified (408 atherothrombotic, 256 cardioembolic, and 289 undetermined subtypes) during median follow-up of 11.2 years (CHS) and 8.3 years (pooled, NHS and HPFS). After multivariable adjustment, lower risk of total ischemic stroke was seen with higher DPA (highest versus lowest quartiles; pooled hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.58–0.92) and DHA (HR, 0.80; 95% CI, 0.64–1.00) but not eicosapentaenoic acid (HR, 0.94; 95% CI, 0.77–1.19). DHA was associated with lower risk of atherothrombotic stroke (HR, 0.53; 95% CI, 0.34–0.83) and DPA with lower risk of cardioembolic stroke (HR, 0.58; 95% CI, 0.37–0.92). Findings in each individual cohort were consistent with p[...]



Eosinophil Cationic Protein, Carotid Plaque, and Incidence of Stroke [Clinical Sciences]

2017-09-25T12:45:00-07:00

Background and Purpose—ECP (eosinophil cationic protein) is a marker of eosinophil activity and degranulation, which has been linked to atherosclerosis and cardiovascular disease. We examined the relationship between ECP, carotid plaque, and incidence of stroke in a prospective population-based cohort.Methods—The subjects participated in the Malmö Diet and Cancer Study between 1991 and 1994. A total of 4706 subjects with no history of stroke were included (40% men; mean age, 57.5 years). Carotid plaque was determined by B-mode ultrasound of the right carotid artery. Incidence of stroke was followed up during a mean period of 16.5 years in relation to plasma ECP levels.Results—Subjects in the third tertile (versus first tertile) of ECP tended to have higher prevalence of carotid plaque (odds ratio: 1.18; 95% confidence interval: 1.003–1.39; P=0.044 after multivariate adjustments). A total of 258 subjects were diagnosed with ischemic stroke (IS) during follow-up. ECP was associated with increased incidence of IS after risk factor adjustment (hazard ratio, 1.57; 95% confidence interval: 1.13–2.18; for third versus first tertile; P=0.007). High ECP was associated with increased risk of IS in subjects with carotid plaque. The risk factor–adjusted hazard ratio for IS was 1.86 (95% confidence interval: 1.32–2.63) in subjects with carotid plaque and ECP in the top tertile, compared with those without plaque and ECP in the first or second tertiles.Conclusions—High ECP is associated with increased incidence of IS. The association between ECP and IS was also present in the subgroup with carotid plaque.



Labetalol Use Is Associated With Increased In-Hospital Infection Compared With Nicardipine Use in Intracerebral Hemorrhage [Clinical Sciences]

2017-09-25T12:45:00-07:00

Background and Purpose—Increased sympathetic tone causes hypertension after intracerebral hemorrhage, and blood pressure reduction has been studied as a way to decrease hemorrhage growth and improve outcomes. It is unknown if the antihypertensive used to achieve blood pressure goals influences either. Because sympatholytic drugs reduce death and infection in animal models, we hypothesized that labetalol would improve outcomes compared with nicardipine.Methods—Prospective data from a single center were retrospectively reviewed. Patients receiving labetalol, nicardipine, or both during their first 3 days of hospitalization were included. Outcomes included in-hospital death; discharge modified Rankin Score >2; and in-hospital urinary tract infection, pneumonia, or bacteremia. Patients were compared with propensity scoring and analyzed with linear models adjusted for significant confounders.Results—Of 1066 admissions, 525 were treated with labetalol or nicardipine and are included; 229 (43.6%) received labetalol, 107 (20.4%) received nicardipine, and 189 (36.0%) received both. Mortality and infection rates were 40.2% and 15.8%, respectively, 77.2% had a modified Rankin Score >2. After adjustment, compared with nicardipine alone, labetalol alone was associated with infection (odds ratio, 3.12; confidence interval, 1.27–7.64; P=0.013) but not when combined with nicardipine (odds ratio, 2.44; confidence interval, 0.98–6.07; P=0.055). Labetalol, with or without nicardipine, was not associated with death or discharge modified Rankin Score >2.Conclusions—Compared with nicardipine, labetalol was associated with increased in-hospital infections, but not mortality or modified Rankin Score >2.[...]



Cerebral Microbleeds and the Risk of Incident Ischemic Stroke in CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy) [Clinical Sciences]

2017-09-25T12:45:00-07:00

Background and Purpose—Cerebral microbleeds are associated with an increased risk of intracerebral hemorrhage. Recent data suggest that microbleeds may also predict the risk of incident ischemic stroke. However, these results were observed in elderly individuals undertaking various medications and for whom causes of microbleeds and ischemic stroke may differ. We aimed to test the relationship between the presence of microbleeds and incident stroke in CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy)—a severe monogenic small vessel disease known to be responsible for both highly prevalent microbleeds and a high incidence of ischemic stroke in young patients.Methods—We assessed microbleeds on baseline MRI in all 378 patients from the Paris–Munich cohort study. Incident ischemic strokes were recorded during 54 months. Survival analyses were used to test the relationship between microbleeds and incident ischemic stroke.Results—Three hundred sixty-nine patients (mean age, 51.4±11.4 years) were followed-up during a median time of 39 months (interquartile range, 19 months). The risk of incident ischemic stroke was higher in patients with microbleeds than in patients without (35.8% versus 19.6%, hazard ratio, 1.87; 95% confidence interval, 1.16–3.01; P=0.009). These results persisted after adjustment for history of ischemic stroke, age, sex, vascular risk factors, and antiplatelet agents use (hazard ratio, 1.89; 95% confidence interval, 1.10–3.26; P=0.02).Conclusions—The presence of microbleeds is an independent risk marker of incident ischemic stroke in CADASIL, emphasizing the need to carefully interpret MRI data.



Stereotactic Catheter Ventriculocisternostomy for Clearance of Subarachnoid Hemorrhage [Clinical Sciences]

2017-09-25T12:45:00-07:00

Background and Purpose—Delayed cerebral infarction (DCI) is a major source of morbidity and mortality after aneurysmal subarachnoid hemorrhage. We report a novel intervention—stereotactic catheter ventriculocisternostomy (STX-VCS) and fibrinolytic/spasmolytic lavage therapy—for DCI prevention. Outcomes of 20 consecutive patients are compared with 60 matched controls.Methods—On the basis of individual treatment decisions, STX-VCS was performed in 20 high-risk aneurysmal subarachnoid hemorrhage patients admitted to our department between September 2015 and October 2016. Three controls matched for age, sex, aneurysm treatment method, and admission Hunt and Hess grade were assigned to each case treated by STX-VCS. DCI was the primary outcome. Mortality and mRS at rehabilitation discharge were secondary outcome parameters. The association between STX-VCS and DCI, mortality, and mRS was assessed by conditional logistic regression.Results—Stereotactic procedures were performed without surgical complications. Continuous cisternal lavage was feasible in 17 of 20 patients (85%). One adverse event because of cisternal lavage was without sequelae. DCI occurred in 25 of 60 (42%) controls and 3 of 20 (15%) patients with STX-VCS (odds ratio, 0.15; 95% confidence interval, 0.04–0.64). Mortality occurred in 20 of 60 (33%) controls and 1 of 20 (5%) patients with STX-VCS, respectively (odds ratio, 0.08; 95% confidence interval, 0.01 – 0.66). Favorable outcome (mRS≤3) at rehabilitation discharge was observed in 12 of 20 patients with STX-VCS (60%) versus 21 of 60 (35%) matched controls (odds ratio, 0.26; 95% confidence interval, 0.8–0.86).[...]



Tumor Necrosis Factor Receptor 1 and 2 Are Associated With Risk of Intracerebral Hemorrhage [Clinical Sciences]

2017-09-25T12:45:00-07:00

Background and Purpose—Raised plasma concentrations of tumor necrosis factor receptors (TNFR) have been linked to arterial stiffness, cerebral microbleeds, and vascular events. The aim of this study was to investigate the association of circulating levels of TNFR1 and TNFR2 with risk for future intracerebral hemorrhage (ICH).Methods—The population-based MDCS cohort (Malmö Diet and Cancer Study; n=28 449) was conducted in 1991 to 1996. A nested case–control study was performed in the MDCS, including 220 cases who experienced ICH during the follow-up period (mean age at inclusion 62 years, 48% men) and 244 matched controls. Of the 220 ICH cases, 68 died within 28 days. Conditional logistic regression was used to study the association between plasma levels of TNFR1 and TNFR2 and incident ICH, adjusting for known ICH risk factors.Results—Concentrations of both TNFR1 and TNFR2 were significantly higher in subjects who developed ICH during the follow-up. The associations remained after adjustment for ICH risk factors (TNFR1: odds ratio [OR], 2.28; 95% confidence interval [CI], 1.26–4.11; P=0.006; TNFR2: OR, 1.77; CI, 1.16–2.70; P=0.008). ORs were somewhat higher for nonlobar ICH (3.04; CI, 1.29–7.14 and 2.39; CI, 1.32–4.32, respectively) than for lobar ICH (2.03; CI, 0.93–4.41 and 1.35; CI, 0.78–2.37, respectively). TNFR1 and TNFR2 were also associated with increased risk of fatal ICH (TNFR1: OR, 4.42; CI, 1.67–11.6; TNFR2: OR, 2.90; CI, 1.50–5.58) and with poor functional outcome according to the modified Rankin Scale.Conclusions—High plasma levels of TNFR1 and TNFR2 were associated with[...]



Fibrin Clot Permeability as a Predictor of Stroke and Bleeding in Anticoagulated Patients With Atrial Fibrillation [Clinical Sciences]

2017-09-25T12:45:00-07:00

Background and Purpose—Formation of denser fiber networks has been reported in atrial fibrillation and ischemic stroke. In this longitudinal cohort study, we evaluated whether fibrin clot density may predict thromboembolic and bleeding risk in patients with atrial fibrillation on vitamin K antagonists.Methods—In 236 patients with atrial fibrillation receiving vitamin K antagonists treatment, we measured ex vivo plasma clot permeability (Ks), a measure of the pore size in fibrin networks.Results—During a median follow-up of 4.3 (interquartile range, 3.7–4.8) years, annual rates of ischemic stroke or transient ischemic attack and major bleeds were 2.96% and 3.45%, respectively. In multivariate Cox regression analysis, patients with lower Ks ([...]



Effects of Statin Intensity and Adherence on the Long-Term Prognosis After Acute Ischemic Stroke [Clinical Sciences]

2017-09-25T12:45:00-07:00

Background and Purpose—Statin is an established treatment for secondary prevention after ischemic stroke. However, the effects of statin intensity and adherence on the long-term prognosis after acute stroke are not well known.Methods—This retrospective cohort study using a nationwide health insurance claim data in South Korea included patients admitted with acute ischemic stroke between 2002 and 2012. Statin adherence and intensity were determined from the prescription data for a period of 1 year after the index stroke. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause mortality. We performed multivariate Cox proportional regression analyses.Results—We included 8001 patients with acute ischemic stroke. During the mean follow-up period of 4.69±2.72 years, 2284 patients developed a primary outcome. Compared with patients with no statin, adjusted hazard ratios (95% confidence interval) were 0.74 (0.64–0.84) for good adherence, 0.93 (0.79–1.09) for intermediate adherence, and 1.07 (0.95–1.20) for poor adherence to statin. Among the 1712 patients with good adherence, risk of adverse events was lower in patients with high-intensity statin (adjusted hazard ratio [95% confidence interval], 0.48 [0.24–0.96]) compared with those with low-intensity statin. Neither good adherence nor high intensity of statin was associated with an increased risk of hemorrhagic stroke.Conclusions—After acute ischemic stroke, high-intensity statin therapy with good adherence was significantly associated with a lower risk of adverse events.



Confounding by Pre-Morbid Functional Status in Studies of Apparent Sex Differences in Severity and Outcome of Stroke [Clinical Sciences]

2017-09-25T12:45:00-07:00

Background and Purpose—Several studies have reported unexplained worse outcomes after stroke in women but none included the full spectrum of symptomatic ischemic cerebrovascular events while adjusting for prior handicap.Methods—Using a prospective population-based incident cohort of all transient ischemic attack/stroke (OXVASC [Oxford Vascular Study]) recruited between April 2002 and March 2014, we compared pre-morbid and post-event modified Rankin Scale score (mRS) in women and men and change in mRS score 1 month, 6 months, 1 year, and 5 years after stroke. Baseline stroke-related neurological impairment was measured with the National Institutes of Health Stroke Scale.Results—Among 2553 patients (50.6% women) with a first transient ischemic attack/ischemic stroke, women had a worse handicap 1 month after ischemic stroke (age-adjusted odds ratio for mRS score, 1.35; 95% confidence interval, 1.12–1.63). However, women also had a higher pre-morbid mRS score compared with men (age-adjusted odds ratio, 1.58; 95% confidence interval, 1.36–1.84). There was no difference in stroke severity when adjusting for age and pre-morbid mRS (odds ratio, 1.10; 95% confidence interval, 0.90–1.35) and no difference in the pre-/poststroke change in mRS at 1 month (age-adjusted odds ratio, 1.00; 95% confidence interval, 0.82–1.21), 6 months, 1 year, and 5 years. Women had a lower mortality rate, and there was no sex difference in risk of recurrent stroke.Conclusions—We found no evidence of a worse outcome of stroke in women when adjusti[...]



Influence of Penumbral Reperfusion on Clinical Outcome Depends on Baseline Ischemic Core Volume [Clinical Sciences]

2017-09-25T12:45:00-07:00

Background and Purpose—In alteplase-treated patients with acute ischemic stroke, we investigated the relationship between penumbral reperfusion at 24 hours and clinical outcomes, with and without adjustment for baseline ischemic core volume.Methods—Data were collected from consecutive acute ischemic stroke patients with baseline and follow-up perfusion imaging presenting to hospital within 4.5 hours of symptom onset at 7 hospitals. Logistic regression models were used for predicting the effect of the reperfused penumbral volume on the dichotomized modified Rankin Scale (mRS) at 90 days and improvement of National Institutes of Health Stroke Scale at 24 hours, both adjusted for baseline ischemic core volume.Results—This study included 1507 patients. Reperfused penumbral volume had moderate ability to predict 90-day mRS 0 to 1 (area under the curve, 0.77; R2, 0.28; P[...]



Predictive Value of Computed Tomography Angiography-Determined Occlusion Type in Stent Retriever Thrombectomy [Clinical Sciences]

2017-09-25T12:45:00-07:00

Background and Purpose—We investigated whether occlusion type identified with computed tomography angiography (CTA-determined occlusion type) could predict endovascular treatment success using stent retriever (SR) thrombectomy.Methods—Consecutive patients with stroke who underwent CTA and then endovascular treatment for intracranial large artery occlusion were retrospectively reviewed. CTA-determined occlusion type was classified into truncal-type occlusion or branching-site occlusion and compared with digital subtraction angiography–determined occlusion type during endovascular treatment. Three rapidly- and readily-assessable pre-procedural findings (CTA-determined occlusion type, atrial fibrillation, and hyperdense artery sign), which may infer occlusion pathomechanism (embolic versus nonembolic) before endovascular treatment, were evaluated for association with SR success along with stroke risk factors and laboratory results. In addition, the predictive power of the 3 pre-procedural findings for SR success was compared with receiver operating characteristic curve analyses.Results—A total of 238 patients (mean age, 70.0 years; male patients, 52.9%) were included in this study. CTA-determined occlusion type corresponded adequately with digital subtraction angiography–determined occlusion type (P=0.453). Atrial fibrillation (odds ratio, 2.66; 95% confidence interval, 1.25–5.66) and CTA-determined branching-site occlusion (odds ratio, 8.20; confidence interval, 3.45[...]



Radiographic and Clinical Brain Infarcts in Cardiac and Diagnostic Procedures [Clinical Sciences]

2017-09-25T12:45:00-07:00

Background and Purpose—The incidence of periprocedural brain infarcts varies among cardiovascular procedures. In a systematic review, we compared the ratio of radiographic brain infarcts (RBI) to strokes and transient ischemic attacks across cardiac and vascular procedures.Methods—We searched MEDLINE and 5 other databases for brain infarcts in aortic valve replacement, coronary artery bypass grafting, cardiac catheterization, and cerebral angiogram through September 2015. We followed the PRISMA (preferred reporting items for systematic reviews and meta-analyses) recommendations. We defined symptomatic rate ratio (RR) as ratio of stroke plus transient ischemic attack rate to RBI rate.Results—Twenty-nine studies involving 2124 subjects met the inclusion criteria. In meta-analysis of aortic valve replacements with 494 people, 69.4% (95% confidence interval (CI), 57.6%–81.4%) had RBIs, whereas 3.6% (95% CI, 2.0%–5.2%) had clinical events (RR, 0.08; 95% CI, 0.05–0.12). Coronary artery bypass grafting among 204 patients had 27.4% (95% CI, 6.0%–48.8%) RBIs and 2.4% (95% CI, 0.3%–4.5%) clinical events (RR, 0.11; 95% CI, 0.05–0.26). Cardiac catheterization among 833 people had 8.0% (95% CI, 4.1%–12.0%) RBIs, and 0.6% (95% CI, 0.1%–1.1%) had clinical events (RR, 0.16; 95% CI, 0.08–0.31). Cerebral angiogram among 593 people had 12.8% (95% CI, 6.6–19.0) RBIs and 0.6% (95% CI, 0%–13%) clinical events (RR, 0.10; 95% CI, 0.04–0.27). Th[...]



Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke [Clinical Sciences]

2017-09-25T12:45:00-07:00

Background and Purpose—Mechanical thrombectomy with stent retrievers has become standard of care for treatment of acute ischemic stroke patients because of large vessel occlusion. The STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) aimed to assess whether similar process timelines, technical, and functional outcomes could be achieved in a large real world cohort as in the randomized trials.Methods—STRATIS was designed to prospectively enroll patients treated in the United States with a Solitaire Revascularization Device and Mindframe Capture Low Profile Revascularization Device within 8 hours from symptom onset. The STRATIS cohort was compared with the interventional cohort of a previously published SEER patient-level meta-analysis.Results—A total of 984 patients treated at 55 sites were analyzed. The mean National Institutes of Health Stroke Scale score was 17.3. Intravenous tissue-type plasminogen activator was administered in 64.0%. The median time from onset to arrival in the enrolling hospital, door to puncture, and puncture to reperfusion were 138, 72, and 36 minutes, respectively. The Core lab–adjudicated modified Thrombolysis in Cerebral Infarction ≥2b was achieved in 87.9% of patients. At 90 days, 56.5% achieved a modified Rankin Scale score of 0 to 2, all-cause mortality was 14.4%, and 1.4% suffered a symptomatic intracranial hemorrhag[...]



Safety of Simultaneous Coronary Artery Bypass Grafting and Carotid Endarterectomy Versus Isolated Coronary Artery Bypass Grafting [Clinical Sciences]

2017-09-25T12:45:00-07:00

Background and Purpose—The optimal operative strategy in patients with severe carotid artery disease undergoing coronary artery bypass grafting (CABG) is unknown. We sought to investigate the safety and efficacy of synchronous combined carotid endarterectomy and CABG as compared with isolated CABG.Methods—Patients with asymptomatic high-grade carotid artery stenosis ≥80% according to ECST (European Carotid Surgery Trial) ultrasound criteria (corresponding to ≥70% NASCET [North American Symptomatic Carotid Endarterectomy Trial]) who required CABG surgery were randomly assigned to synchronous carotid endarterectomy+CABG or isolated CABG. To avoid unbalanced prognostic factor distributions, randomization was stratified by center, age, sex, and modified Rankin Scale. The primary composite end point was the rate of stroke or death at 30 days.Results—From 2010 to 2014, a total of 129 patients were enrolled at 17 centers in Germany and the Czech Republic. Because of withdrawal of funding after insufficient recruitment, enrolment was terminated early. At 30 days, the rate of any stroke or death in the intention-to-treat population was 12/65 (18.5%) in patients receiving synchronous carotid endarterectomy+CABG as compared with 6/62 (9.7%) in patients receiving isolated CABG (absolute risk reduction, 8.8%; 95% confidence interval, −3.2% to 20.8%; PWALD=0.12). Also for all secondary end points a[...]



Tissue-Selective Salvage of the White Matter by Successful Endovascular Stroke Therapy [Clinical Sciences]

2017-09-25T12:45:00-07:00

Background and Purpose—White matter (WM) is less vulnerable to ischemia than gray matter. In ischemic stroke caused by acute large-vessel occlusion, successful recanalization might therefore sometimes selectively salvage the WM, leading to infarct patterns confined to gray matter. This study examines occurrence, determinants, and clinical significance of such effects.Methods—Three hundred twenty-two patients with acute middle cerebral artery occlusion subjected to mechanical thrombectomy were included. Infarct patterns were categorized into WM− (sparing the WM) and WM+ (involving WM). National Institutes of Health Stroke Scale–based measures of neurological outcome, including National Institutes of Health Stroke Scale improvement or National Institutes of Health Stroke Scale worsening, good functional midterm outcome (day 90-modified Rankin Scale score of ≤2), the occurrence of malignant swelling, and in-hospital mortality were predefined outcome measures.Results—WM− infarcts occurred in 118 of 322 patients and were associated with successful recanalization and better collateral grades (P[...]