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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 <25 kg/m2) and 3 ideal health factors (untreated blood pressure <120/<80 mm Hg, untreated total cholesterol <200 mg/dL, and fasting blood glucose <100 mg/dL). In addition, in relation to maintenance of cognitive health, we recommend following previously published guidance from the AHA/American Stroke Association, Institute of Medicine, and Alzheimer’s Association that incorporates control of cardiovascular risks and suggest social engagement and other related strategies. We define optimal brain health but recognize that the truly ideal circumstance may be uncommon because there is a continuum of brain health as demonstrated by AHA’s Life’s Simple 7. Therefore, there is opportunity to improve brain health through primordial prevention and other interventions. Furthermore, although cardiovascular risks align well with brain health, we acknowledge that other factors differing from those related to cardiovascular health may drive cognitive health. Defining optimal brain health in adults and its maintenance is consistent with the AHA’s Strategic Impact Goal to improve cardiovascular health of all Americans by 20% and to reduce deaths resulting from cardiovascular disease and stroke by 20% by the year 2020. This work in defining optimal brain health in adults serves to provide the AHA/American Stroke Association with a foundation for a new strategic direction going forward in cardiovascular health promotion and disease prevention.














































































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 pooled results.Conclusions—In 3 large US cohorts, higher circulating levels of DHA were inversely associated with incident atherothrombotic stroke and DPA with cardioembolic stroke. These novel findings suggest differential pathways of benefit for DHA, DPA, and eicosapentaenoic acid.



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. These findings do not support our hypothesis that labetalol use improves outcomes relative to nicardipine in intracerebral hemorrhage.



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).Conclusions—STX-VCS was feasible and safe in patients with severe aneurysmal subarachnoid hemorrhage. Initial results indicate that DCI and mortality can be reduced, and neurological outcome may be improved with this method.



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 incident ICH, most clearly with ICH of nonlobar location. The results suggest that tumor necrosis factor–mediated inflammation could be associated with vascular changes preceding ICH.



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 (<6.8 cm2×10−9, median) had increased risk of ischemic stroke or transient ischemic attack (hazard ratio [HR], 6.55; 95% confidence interval [CI], 2.17–19.82) and major bleeds (HR, 10.65; 95% CI, 3.52–32.22). Patients with elevated Ks (≥6.8 cm2×10−9) had an increased rate of minor bleeding compared with the remainder (11.63% per year versus 3.55% per year; P<0.0001). The independent predictors of stroke or transient ischemic attack were low Ks (<6.8 cm2×10−9; HR, 7.24; 95% CI, 2.53–20.76), age (HR, 1.05; 95% CI, 1.01–1.10), and treatment with angiotensin-converting enzyme inhibitors (HR, 2.27; 95% CI, 1.08–4.77). Major bleeds were predicted by low Ks (<6.8 cm2×10−9; HR, 8.48; 95% CI, 2.99–24.1) and HAS-BLED score ≥3 (HR, 2.22; 95% CI, 1.12–4.38).Conclusions—This study is the first to show that unfavorable fibrin properties reflected by formation of denser fibrin networks determine, in part, the efficacy and safety of anticoagulation with vitamin K antagonists in patients with atrial fibrillation.



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 adjusting for age and pre-morbid mRS. Failure to account for sex differences in pre-morbid handicap could explain contradictory findings in previous studies. Properties of the mRS may also contribute to these inconsistencies.



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<0.0001). However, after adjusting for baseline ischemic core volume, the reperfused penumbral volume was a strong predictor of good functional outcome (area under the curve, 0.946; R2, 0.55; P<0.0001). For every 1% increase in penumbral reperfusion, the odds of achieving mRS 0 to 1 at day 90 increased by 7.4%. Improvement in acute 24-hour National Institutes of Health Stroke Scale was also significantly related to the degree of reperfused penumbra (R2, 0.31; P<0.0001). This association was again stronger after adjustment for baseline ischemic core volume (R2, 0.41; P<0.0001). For each 1% of penumbra that was reperfused, the 24-hour National Institutes of Health Stroke Scale decreased by 0.069 compared with baseline.Conclusions—In patients treated with alteplase, the extent of the penumbra that is reperfused is a powerful predictor of early and late clinical outcomes, particularly when baseline ischemic core is taken into account.



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, 3.45–19.5) were independent predictors for SR success. For predicting SR success, the area under the receiver operating characteristic curve value for CTA-determined branching-site occlusion (0.695) was significantly greater than atrial fibrillation (0.594; P=0.038) and hyperdense artery sign (0.603; P=0.023).Conclusions—CTA-determined branching-site occlusion was significantly associated with SR success. Furthermore, among the 3 rapidly- and readily-assessable pre-procedural findings, CTA-determined branching-site occlusion had the greatest predictive power for SR success.



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). The RR of all procedures was 0.10 (95% CI, 0.07–0.13) without differences in the RRs across procedures (P=0.29).Conclusions—One of 10 people with periprocedural RBIs during cardiac surgeries and invasive vascular diagnostic procedures resulted in strokes or transient ischemic attacks, which may serve as a potential surrogate marker of procedural proficiency and perhaps as a predictor of risk for periprocedural strokes.



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 hemorrhage. The median time from emergency medical services scene arrival to puncture was 152 minutes, and each hour delay in this interval was associated with a 5.5% absolute decline in the likelihood of achieving modified Rankin Scale score 0 to 2.Conclusions—This largest-to-date Solitaire registry documents that the results of the randomized trials can be reproduced in the community. The decrease of clinical benefit over time warrants optimization of the system of care.Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT02239640.



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 at 30 days and 1 year, there was no evidence for a significant treatment-group effect although patients undergoing isolated CABG tended to have better outcomes.Conclusions—Although our results cannot rule out a treatment-group effect because of lack of power, a superiority of the synchronous combined carotid endarterectomy+CABG approach seems unlikely. Five-year follow-up of patients is still ongoing.Clinical Trial Registration—URL: https://www.controlled-trials.com. Unique identifier: ISRCTN13486906.



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<0.05). Shorter symptom-onset to recanalization times were also associated with WM− infarcts in univariate analysis, but not when adjusted for collateral grades. WM− infarcts were independently associated with good neurological outcome (adjusted odds ratio, 3.003; 95% confidence interval, 1.186–7.607; P=0.020) and good functional midterm outcome (adjusted odds ratio, 8.618; 95% confidence interval, 2.409–30.828; P=0.001) after correcting for potential confounders, including final infarct volume. Only 2.6% of WM− patients, but 20.5% of WM+ patients exhibited neurological worsening, and none versus 12.8% developed malignant swelling (P<0.001), contributing to lower mortality in this group (2.5% versus 10.3%; P=0.014).Conclusions—WM infarction commonly commences later than gray matter infarction after acute middle cerebral artery occlusion. Successful recanalization can therefore salvage completely the WM at risk in many patients even several hours after symptom onset. Preservation of the WM is associated with better neurological recovery, prevention of malignant swelling, and reduced mortality. This has important implications for neuroprotective strategies, and perfusion imaging-based patient selection, and provides a rationale for treating selected patients in extended time windows.



Anesthesia-Related Outcomes for Endovascular Stroke Revascularization [Clinical Sciences]

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

Background and Purpose—There is currently controversy on the ideal anesthesia strategy during mechanical thrombectomy for acute ischemic stroke. We performed a systematic review and meta-analysis of studies comparing clinical and angiographic outcomes of patients undergoing general anesthesia (GA group) and those receiving either local anesthesia or conscious sedation (non-GA group).Methods—A literature search on anesthesia and endovascular treatment of acute ischemic stroke was performed. Using random-effects meta-analysis, we evaluated the following outcomes: recanalization rate, good functional outcome at 90 days (modified Rankin Score≤2), symptomatic intracranial hemorrhage, death, vascular complications, respiratory complications, procedure time, and time to groin puncture.Results—Twenty-two studies (3 randomized controlled trials and 19 observational studies), including 4716 patients (1819 GA and 2897 non-GA) were included. In the nonadjusted analysis, patients in the GA group had higher odds of death (odds ratio [OR], 2.02; 95% confidence interval [CI], 1.66–2.45) and respiratory complications (OR, 1.70; 95% CI, 1.22–2.37) and lower odds of good functional outcome (OR, 0.58; 95% CI, 0.48–0.64) compared with the non-GA group. There was no difference in procedure time between the 2 primary comparison groups. When adjusting for baseline National Institutes of Health Stroke Scale, GA was still associated with lower odds of good functional outcome (OR, 0.59; 95% CI, 0.29–0.94). When considering studies performed in the stent-retriever/aspiration era, there was no significant difference in good neurological outcome rates (OR, 0.84; 95% CI, 0.67–1.06).Conclusions—Acute ischemic stroke patients undergoing intra-arterial therapy may have worse outcomes when treated with GA as compared with conscious sedation/local anesthesia. However, major limitations of current evidence (ie, retrospective studies and selection bias) indicate a need for adequately powered, multicenter randomized controlled trials to answer this question.



Spinal Arteriolosclerosis Is Common in Older Adults and Associated With Parkinsonism [Clinical Sciences]

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

Background and Purpose—There are few studies of spinal microvascular pathologies in older adults. We characterized spinal cord microvascular pathologies and examined their associations with other spinal and brain postmortem indices and parkinsonism in older adults.Methods—We documented 3 features of microvascular pathologies in spinal cord and brain specimens from 165 deceased older participants. We also measured spinal white matter pallor. Parkinsonian signs were assessed with a modified version of the motor section of the Unified Parkinson’s Disease Rating Scale. We examined the associations of spinal arteriolosclerosis with other spinal and brain postmortem indices and parkinsonism proximate to death using regression models which controlled for age and sex.Results—Microinfarcts and cerebral amyloid angiopathy were not observed within the spinal cord parenchyma. Spinal arteriolosclerosis was observed at all spinal levels (C7, T7, L4, S4) examined and was more severe posteriorly than anteriorly (posterior: 4.3, SD=0.72 versus anterior: 3.9, SD=0.74; t=14.58; P<0.001). Arteriolosclerosis was more severe in the spinal cord than in the brain (cord: 4.10, SD=0.70; brain: 3.5, SD=0.98; t=10.39; P<0.001). The severity of spinal arteriolosclerosis was associated with spinal white matter pallor (r=0.47; P<0.001). Spinal arteriolosclerosis accounted for ≈3% of the variation in parkinsonism in models controlling for age, sex, brain arteriolosclerosis, and cerebrovascular disease pathologies. Further models showed that the association of spinal arteriolosclerosis and parkinsonism was not mediated via spinal white matter pallor.Conclusions—Although the regional distribution of microvascular pathologies varies within the central nervous system, spinal arteriolosclerosis is common and may contribute to the severity of spinal white matter pallor and parkinsonism in older adults.



Neuropathology of White Matter Lesions, Blood-Brain Barrier Dysfunction, and Dementia [Clinical Sciences]

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

Background and Purpose—We tested whether blood–brain barrier dysfunction in subcortical white matter is associated with white matter abnormalities or risk of clinical dementia in older people (n=126; mean age 86.4, SD: 7.7 years) in the MRC CFAS (Medical Research Council Cognitive Function and Ageing Study).Methods—Using digital pathology, we quantified blood–brain barrier dysfunction (defined by immunohistochemical labeling for the plasma marker fibrinogen). This was assessed within subcortical white matter tissue samples harvested from postmortem T2 magnetic resonance imaging (MRI)–detected white matter hyperintensities, from normal-appearing white matter (distant from coexistent MRI-defined hyperintensities), and from equivalent areas in MRI normal brains. Histopathologic lesions were defined using a marker for phagocytic microglia (CD68, clone PGM1).Results—Extent of fibrinogen labeling was not significantly associated with white matter abnormalities defined either by MRI (odds ratio, 0.90; 95% confidence interval, 0.79–1.03; P=0.130) or by histopathology (odds ratio, 0.93; 95% confidence interval, 0.77–1.12; P=0.452). Among participants with normal MRI (no detectable white matter hyperintensities), increased fibrinogen was significantly related to decreased risk of clinical dementia (odds ratio, 0.74; 95% confidence interval, 0.58–0.94; P=0.013). Among participants with histological lesions, increased fibrinogen was related to increased risk of dementia (odds ratio, 2.26; 95% confidence interval, 1.25–4.08; P=0.007).Conclusions—Our data suggest that some degree of blood–brain barrier dysfunction is common in older people and that this may be related to clinical dementia risk, additional to standard MRI biomarkers.



Interactions Between the Corticospinal Tract and Premotor-Motor Pathways for Residual Motor Output After Stroke [Clinical Sciences]

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

Background and Purpose—Brain imaging has continuously enhanced our understanding how different brain networks contribute to motor recovery after stroke. However, the present models are still incomplete and do not fit for every patient. The interaction between the degree of damage of the corticospinal tract (CST) and of corticocortical motor connections, that is, the influence of the microstructural state of one connection on the importance of another has been largely neglected.Methods—Applying diffusion–weighted imaging and probabilistic tractography, we investigated cross-network interactions between the integrity of ipsilesional CST and ipsilesional corticocortical motor pathways for variance in residual motor outcome in 53 patients with subacute stroke.Results—The main finding was a significant interaction between the CST and corticocortical connections between the primary motor and ventral premotor cortex in relation to residual motor output. More specifically, the data indicate that the microstructural state of the connection primary motor–ventral premotor cortex plays only a role in patients with significant damage to the CST. In patients with slightly affected CST, this connection did not explain a relevant amount of variance in motor outcome.Conclusions—The present data show that patients with stroke with different degree of CST disruption differ in their dependency on structural premotor–motor connections for residual motor output. This finding might have important implications for future research on recovery prediction models and on responses to treatment strategies.



Assessment Model to Identify Patients With Stroke With a High Possibility of Discharge to Home [Clinical Sciences]

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

Background and Purpose—Discharge planning for inpatients with acute stroke can enhance reasonable use of healthcare resources, as well as improve clinical outcomes and decrease financial burden of patients. Especially, prediction for discharge destination is crucial for discharge planning. This study aimed to develop an assessment model to identify patients with a high possibility of discharge to home after an acute stroke.Methods—We reviewed the electronic medical records of 3200 patients with acute stroke who were admitted to a stroke center in Japan between January 1, 2011, and December 31, 2015. The outcome variable was the discharge destination of postacute stroke patients. The predictive variables were identified through logistic regression analysis. Data were divided into 2 data sets: the learning data set (n=2240) for developing the instrument and the test data set (n=960) for evaluating the predictive capability of the model.Results—In all, 1548 (48%) patients were discharged to their homes. Multiple logistic regression analysis identified 5 predictive variables for discharge to home: living situation, type of stroke, functional independence measure motor score on admission, functional independence measure cognitive score on admission, and paresis. The assessment model showed a sensitivity of 85.0% and a specificity of 75.3% with an area under the curve equal to 0.88 (95% confidence interval, 0.86–0.89) when the cutoff point was 10. On evaluating the predictive capabilities, the model showed a sensitivity of 88.0% and a specificity of 68.7% with an area under the curve equal to 0.87 (95% confidence interval, 0.85–0.89).Conclusions—We have developed an assessment model for identifying patients with a high possibility of being discharged to their homes after an acute stroke. This model would be useful for health professionals to adequately plan patients’ discharge soon after their admission.



Burden of Intracranial Atherosclerosis Is Associated With Long-Term Vascular Outcome in Patients With Ischemic Stroke [Clinical Sciences]

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

Background and Purpose—Ischemic stroke patients often have intracranial atherosclerosis (ICAS), despite heterogeneity in the cause of stroke. We tested the hypothesis that ICAS burden can independently reflect the risk of long-term vascular outcome.Methods—This was a retrospective cohort study analyzing data from a prospective stroke registry enrolling consecutive patients with acute ischemic stroke or transient ischemic attack. A total of 1081 patients were categorized into no ICAS, single ICAS, and advanced ICAS (ICAS ≥2 different intracranial arteries) groups. Primary and secondary end points were time to occurrence of recurrent ischemic stroke and composite vascular outcome, respectively. Study end points by ICAS burden were compared using Cox proportional hazards models in overall and propensity-matched patients.Results—ICAS was present in 405 patients (37.3%). During a median 5-year follow-up, recurrent stroke and composite vascular outcome occurred in 6.8% and 16.8% of patients, respectively. As the number of ICAS increased, the risk for study end points increased after adjustment of potential covariates (hazard ratio per 1 increase in ICAS, 1.19; 95% confidence interval, 1.01–1.42 for recurrent ischemic stroke and hazard ratio, 1.18; 95% confidence interval, 1.05–1.33 for composite vascular outcome). The hazard ratios (95% confidence interval) for recurrent stroke and composite vascular outcome in patients with advanced ICAS compared with those without ICAS were 1.56 (0.88–2.74) and 1.72 (1.17–2.53), respectively, in the overall patients. The corresponding values in the propensity-matched patients were 1.28 (0.71–2.30) and 1.95 (1.27–2.99), respectively.Conclusions—ICAS burden was independently associated with the risk of subsequent composite vascular outcome in patients with ischemic stroke. These findings suggest that ICAS burden can reflect the risk of long-term vascular outcome.



Regional Evaluation of the Severity-Based Stroke Triage Algorithm for Emergency Medical Services Using Discrete Event Simulation [Clinical Sciences]

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

Background and Purpose—The Severity-Based Stroke Triage Algorithm for Emergency Medical Services endorses routing patients with suspected large vessel occlusion acute ischemic strokes directly to endovascular stroke centers (ESCs). We sought to evaluate different specifications of this algorithm within a region.Methods—We developed a discrete event simulation environment to model patients with suspected stroke transported according to algorithm specifications, which varied by stroke severity screen and permissible additional transport time for routing patients to ESCs. We simulated King County, Washington, and Mecklenburg County, North Carolina, distributing patients geographically into census tracts. Transport time to the nearest hospital and ESC was estimated using traffic-based travel times. We assessed undertriage, overtriage, transport time, and the number-needed-to-route, defined as the number of patients enduring additional transport to route one large vessel occlusion patient to an ESC.Results—Undertriage was higher and overtriage was lower in King County compared with Mecklenburg County for each specification. Overtriage variation was primarily driven by screen (eg, 13%–55% in Mecklenburg County and 10%–40% in King County). Transportation time specifications beyond 20 minutes increased overtriage and decreased undertriage in King County but not Mecklenburg County. A low- versus high-specificity screen routed 3.7× more patients to ESCs. Emergency medical services spent nearly twice the time routing patients to ESCs in King County compared with Mecklenburg County.Conclusions—Our results demonstrate how discrete event simulation can facilitate informed decision making to optimize emergency medical services stroke severity-based triage algorithms. This is the first step toward developing a mature simulation to predict patient outcomes.



Unexplained Variation for Hospitals’ Use of Inpatient Rehabilitation and Skilled Nursing Facilities After an Acute Ischemic Stroke [Clinical Sciences]

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

Background and Purpose—Rehabilitation is recommended after a stroke to enhance recovery and improve outcomes, but hospital’s use of inpatient rehabilitation facilities (IRFs) or skilled nursing facility (SNF) and the factors associated with referral are unknown.Methods—We analyzed clinical registry and claims data for 31 775 Medicare beneficiaries presenting with acute ischemic stroke from 918 Get With The Guidelines-Stroke hospitals who were discharged to either IRF or SNF between 2006 and 2008. Using a multilevel logistic regression model, we evaluated patient and hospital characteristics, as well as geographic availability, in relation to discharge to either IRF or SNF. After accounting for observed factors, the median odds ratio was reported to quantify hospital-level variation in the use of IRF versus SNF.Results—Of 31 775 patients, 17 662 (55.6%) were discharged to IRF and 14 113 (44.4%) were discharged to SNF. Compared with SNF patients, IRF patients were younger, more were men, had less health-service use 6 months prestroke, and had fewer comorbid conditions and in-hospital complications. Use of IRF or SNF varied significantly across hospitals (median IRF use, 55.8%; interquartile range, 34.8%–75.0%; unadjusted median odds ratio, 2.59; 95% confidence interval, 2.44–2.77). Hospital-level variation in discharge rates to IRF or SNF persisted after adjustment for patient, clinical, and geographic variables (adjusted median odds ratio, 2.87; 95% confidence interval, 2.68–3.11).Conclusions—There is marked unexplained variation among hospitals in their use of IRF versus SNF poststroke even after accounting for clinical characteristics and geographic availability.Clinical Trial Registration—URL: https://clinicaltrials.gov. Unique identifier: NCT02284165.



Cost-Effectiveness of Thrombectomy in Patients With Acute Ischemic Stroke [Clinical Sciences]

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

Background and Purpose—The benefit of mechanical thrombectomy added to intravenous thrombolysis (IVT) in patients with acute ischemic stroke has been largely demonstrated. However, evidence of the economic incentive of this strategy is still limited, especially in the context of a randomized controlled trial. We aimed to analyze whether mechanical thrombectomy combined with IVT (IVMT) is cost-effective when compared with IVT alone.Methods—Individual-level cost and outcome data were collected in the THRACE randomized controlled trial (Thrombectomie des Artères Cerébrales) including patients with acute ischemic stroke. Patients were assigned to receive IVT or IVMT. The primary outcomes were modified Rankin Scale score of functional independence at 90 days (score 0–2) and the EuroQol-5D quality-of-life score at 1 year.Results—Treating acute ischemic stroke with IVMT (n=200) versus IVT (n=202) increased the rate of functional independence by 10.9% (53.0% versus 42.1%; P=0.028), at an increased cost of $2116 (€1909), with no significant difference in mortality (12% versus 13%; P=0.70) or symptomatic intracranial hemorrhage (2% versus 2%; P=0.71). The cost per one averted case of disability was estimated at $19 379 (€17 480). The incremental cost per one quality-adjusted life year gained was $14 881 (€13 423). On sensitivity analysis, the probability of cost-effectiveness with IVMT was 84.1% in terms of cases of averted disability and 92.2% in terms of quality-adjusted life years.Conclusions—Based on randomized trial data, this study demonstrates that IVMT used to treat acute ischemic stroke is cost-effective when compared with IVT alone.Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01062698.



Normobaric Hyperoxia Reduces Blood Occludin Fragments in Rats and Patients With Acute Ischemic Stroke [Basic Sciences]

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

Background and Purpose—Damage of the blood–brain barrier (BBB) increases the incidence of neurovascular complications, especially for cerebral hemorrhage after tPA (tissue-type plasminogen activator) therapy. Currently, there is no effective method to evaluate the extent of BBB damage to guide tPA use. Herein, we investigated whether blood levels of tight junction proteins could serve as biomarker of BBB damages in acute ischemic stroke (AIS) in both rats and patients. We examined whether this biomarker could reflect the extent of BBB permeability during cerebral ischemia/reperfusion and the effects of normobaric hyperoxia (NBO) on BBB damage.Methods—Rats were exposed to NBO (100% O2) or normoxia (21% O2) during middle cerebral artery occlusion. BBB permeability was determined. Occludin and claudin-5 in blood and cerebromicrovessels were measured. Patients with AIS were assigned to oxygen therapy or room air for 4 hours, and blood occludin and claudin-5 were measured at different time points after stroke.Results—Cerebral ischemia/reperfusion resulted in the degradation of occludin and claudin-5 in microvessels, leading to increased BBB permeability in rats. In blood samples, occludin increased with 4-hour ischemia and remained elevated during reperfusion, correlating well with its loss from ischemic cerebral microvessels. NBO treatment both prevented occludin degradation in microvessels and reduced occludin levels in blood, leading to improved neurological functions in rats. In patients with AIS receiving intravenous tPA thrombolysis, the blood occludin was already elevated when patients arrived at hospital (within 4.5 hours since symptoms appeared) and remained at a high level for 72 hours. NBO significantly lowered the level of blood occludin and improved neurological functions in patients with AIS.Conclusions—Blood occludin may be a clinically viable biomarker for evaluating BBB damage during ischemia/reperfusion. NBO therapy has the potential to reduce blood occludin, protect BBB, and improve outcome in AIS patients with intravenous tPA thrombolysis.Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT02974283.



Effects of High- Versus Moderate-Intensity Training on Neuroplasticity and Functional Recovery After Focal Ischemia [Basic Sciences]

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

Background and Purpose—This study was designed to compare the effects of high-intensity interval training (HIT) and moderate-intensity aerobic training (MOD) on functional recovery and cerebral plasticity during the first 2 weeks after cerebral ischemia.Methods—Rats were randomized as follows: control (n=15), SHAM (n=9), middle cerebral artery occlusion (n=13), middle cerebral artery occlusion at day 1 (n=7), MOD (n=13), and HIT (n=13). Incremental tests were performed at day 1 (D1) and 14 (D14) to identify the running speed associated with the lactate threshold (SLT) and the maximal speed (Smax). Functional tests were performed at D1, D7, and D14. Microglia form, cytokines, p75NTR (pan-neurotrophin receptor p75), potassium–chloride cotransporter type 2, and sodium–potassium–chloride cotransporter type 1 expression were made at D15.Results—HIT was more effective to improve the endurance performance than MOD and induced a fast recovery of the impaired forelimb grip force. The ionized calcium binding adaptor molecule 1 (Iba-1)–positive cells with amoeboid form and the pro- and anti-inflammatory cytokine expression were lower in HIT group, mainly in the ipsilesional hemisphere. A p75NTR overexpression is observed on the ipsilesional side together with a restored sodium–potassium–chloride cotransporter type 1/potassium–chloride cotransporter type 2 ratio on the contralesional side.Conclusions—Low-volume HIT based on lactate threshold seems to be more effective after cerebral ischemia than work-matched MOD to improve aerobic fitness and grip strength and might promote cerebral plasticity.



Hemorrhagic Transformation After Large Cerebral Infarction in Rats Pretreated With Dabigatran or Warfarin [Basic Sciences]

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

Background and Purpose—It is uncertain whether hemorrhagic transformation (HT) after large cerebral infarction is less frequent in dabigatran users than warfarin users. We compared the occurrence of HT after large cerebral infarction among rats pretreated with dabigatran, warfarin, or placebo.Methods—This was a triple-blind, randomized, and placebo-controlled experiment. After treatment with warfarin (0.2 mg/kg), dabigatran (20 mg/kg), or saline for 7 days, Wistar rats were subjected to transient middle cerebral artery occlusion. As the primary outcome, HT was determined by gradient-recalled echo imaging. For the secondary outcome, intracranial hemorrhage was assessed via gradient-recalled echo imaging in surviving rats and via autopsy for dead rats.Results—Of 62 rats, there were 33 deaths (53.2%, 17 technical reasons). Of the intention-to-treat population, 33 rats underwent brain imaging. HT was less frequent in the dabigatran group than the warfarin group (placebo 2/14 [14%], dabigatran 0/10 [0%], and warfarin 9/9 [100%]; dabigatran versus warfarin; P<0.001). In all 62 rats, compared with the placebo (2/14 [14.3%]), the incidence of intracranial hemorrhage was significantly higher in the warfarin group (19/29 [65.5%]; P=0.003), but not in the dabigatran group (6/19 [31.6%]; P=0.420). Mortality was significantly higher in the warfarin group than the dabigatran group (79.3% versus 47.4%; P=0.022), but not related to the hemorrhage frequency.Conclusions—The risk of HT after a large cerebral infarction was significantly increased in rats pretreated with warfarin than those with dabigatran. However, the results here may not have an exact clinical translation.



Impact of Stroke Risk Factors on Ethnic Stroke Disparities Among Midlife Mexican Americans and Non-Hispanic Whites [Brief Report]

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

Background and Purpose—We examined the contribution of stroke risk factors to midlife (age 45–59 years) Mexican American and non-Hispanic White ischemic stroke (IS) rate disparities from 2000 to 2010.Methods—Incident IS cases (n=707) and risk factors were identified from the Brain Attack Surveillance in Corpus Christi Project, Nueces County, TX (2000–2010). US Census data (2000–2010) were used to estimate the population at-risk for IS, and the Behavioral Risk Factor Surveillance System (2000–2010) was used to estimate risk factor prevalence in the stroke-free population. Poisson regression models combined IS counts (numerator) and population at-risk counts (denominator) classified by ethnicity and risk factor status to estimate unadjusted and risk factor–adjusted associations between ethnicity and IS rates. Separate models were run for each risk factor and extended to include an interaction term between ethnicity and risk factor.Results—The crude rate ratio (RR) for ethnicity (Mexican American versus non-Hispanic White) was 2.01 (95% confidence interval [CI], 1.71–2.36) and was attenuated in models that adjusted for diabetes mellitus (RR: 1.50; 95% CI, 1.26–1.78) and hypertension (RR: 1.84; 95% CI, 1.50–2.26). In addition, diabetes mellitus had a stronger association with IS rates among Mexican Americans (RR: 6.42; 95% CI, 5.31–7.76) compared with non-Hispanic Whites (RR: 4.07; 95% CI, 3.68–4.51).Conclusions—The higher prevalence of diabetes mellitus and hypertension and stronger association of diabetes mellitus with IS among midlife Mexican Americans likely contribute to persistent midlife ethnic stroke disparities.



Parvovirus B19 Infection in Children With Arterial Ischemic Stroke [Brief Report]

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

Background and Purpose—Case–control studies suggest that acute infection transiently increases the risk of childhood arterial ischemic stroke. We hypothesized that an unbiased pathogen discovery approach utilizing MassTag–polymerase chain reaction would identify pathogens in the blood of childhood arterial ischemic stroke cases.Methods—The multicenter international VIPS study (Vascular Effects of Infection in Pediatric Stroke) enrolled arterial ischemic stroke cases, and stroke-free controls, aged 29 days through 18 years. Parental interview included questions on recent infections. In this pilot study, we used MassTag–polymerase chain reaction to test the plasma of the first 161 cases and 34 controls enrolled for a panel of 28 common bacterial and viral pathogens.Results—Pathogen DNA was detected in no controls and 14 cases (8.7%): parvovirus B19 (n=10), herpesvirus 6 (n=2), adenovirus (n=1), and rhinovirus 6C (n=1). Parvovirus B19 infection was confirmed by serologies in all 10; infection was subclinical in 8. Four cases with parvovirus B19 had underlying congenital heart disease, whereas another 5 had a distinct arteriopathy involving a long-segment stenosis of the distal internal carotid and proximal middle cerebral arteries.Conclusions—Using MassTag–polymerase chain reaction, we detected parvovirus B19—a virus known to infect erythrocytes and endothelial cells—in some cases of childhood arterial ischemic stroke. This approach can generate new, testable hypotheses about childhood stroke pathogenesis.



Relationship of Preexisting Cardiovascular Comorbidities to Newly Diagnosed Atrial Fibrillation After Ischemic Stroke [Brief Report]

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

Background and Purpose—There remains uncertainty as whether newly diagnosed atrial fibrillation (AF) after ischemic stroke reflects underlying heart disease and represents an increased risk of cardioembolic stroke, or whether it is triggered by neurogenic mechanisms. We aimed to determine whether cardiovascular comorbidities in patients with new AF after ischemic stroke differ from patients with previous known AF or without AF.Methods—This French longitudinal cohort study was based on the database covering hospital care from 2009 to 2012 for the entire population.Results—Of 336 291 patients with ischemic stroke, 240 459 (71.5%) had no AF and 95 832 (28.5%) had previously known AF at baseline. Patients without previous AF had a mean CHA2DS2-VASc score of 4.98±1.63 SD. During a mean follow-up of 7.9±11.5 months, 14 095 (5.9%) of these patients had incident AF, representing an annual incidence of AF after ischemic stroke of 8.9 per 100 person-years (95% confidence interval, 8.8–9.0). New AF patients had higher CHA2DS2-VASc score, more likely comorbidities, and more frequent history of previous transient ischemic attack than patients with previous known AF or without AF.Conclusions—Preexisting cardiovascular comorbidities underlie AF newly diagnosed after stroke. Consequently, these high-risk patients should be closely monitored for incident AF to facilitate an earlier diagnosis of AF and avoid stroke with appropriate thromboprophylaxis.



Higher Flow Is Present in Unruptured Arteriovenous Malformations With Silent Intralesional Microhemorrhages [Brief Report]

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

Background and Purpose—Silent microhemorrhage (hemosiderin) has been observed in resected brain arteriovenous malformations (bAVM) tissue and may represent a subgroup at increased risk for clinical hemorrhage. Previous studies suggest that ruptured bAVMs have faster flow and shorter mean transit time of contrast in blood vessels than unruptured bAVMs. We hypothesized that flow would be faster in unruptured AVMs with hemosiderin compared with those without hemosiderin.Methods—We selected unruptured, supratentorial bAVMs >3.5 cc with pathology specimens. Hemodynamic features were evaluated using color-coding angiography, including contrast mean transit time of AVM nidus, time to peak (TTP) of feeding artery (FA) and draining vein (DV), and the ratio (TTP DV/FA). Characteristics of 9 cases with hemosiderin and 16 without hemosiderin were compared using 2-sample t tests and Fisher exact tests.Results—No difference in FA TTP and DV TTP was observed between groups. However, cases with hemosiderin had significantly shorter mean transit time compared with those without hemosiderin (1.11±0.28 versus 1.64±0.55 seconds; P=0.013) and a lower ratio of DV TTP/FA TTP (1.48±0.32 versus 1.94±0.61; P=0.045). Presence of venous varix was significantly associated with hemosiderin (P=0.003). No other clinical or angioarchitectural factors were associated with hemosiderin.Conclusions—Shorter mean transit time through the AVM nidus, lower DV TTP/FA TTP, and the high prevalence of venous varices suggests that high flow is an important feature of unruptured bAVMs with hemosiderin.



Minocycline in Acute Cerebral Hemorrhage [Brief Report]

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

Background and Purpose—Minocycline is under investigation as a neurovascular protective agent for stroke. This study evaluated the pharmacokinetic, anti-inflammatory, and safety profile of minocycline after intracerebral hemorrhage.Methods—This study was a single-site, randomized controlled trial of minocycline conducted from 2013 to 2016. Adults ≥18 years with primary intracerebral hemorrhage who could have study drug administered within 24 hours of onset were included. Patients received 400 mg of intravenous minocycline, followed by 400 mg minocycline oral daily for 4 days. Serum concentrations of minocycline after the last oral dose and biomarkers were sampled to determine the peak concentration, half-life, and anti-inflammatory profile.Results—A total of 16 consecutive eligible patients were enrolled, with 8 randomized to minocycline. Although the literature supports a time to peak concentration (Tmax) of 1 hour for oral minocycline, the Tmax was estimated to be at least 6 hours in this cohort. The elimination half-life (available on 7 patients) was 17.5 hours (SD±3.5). No differences were observed in inflammatory biomarkers, hematoma volume, or perihematomal edema. Concentrations remained at neuroprotective levels (>3 mg/L) throughout the dosing interval in 5 of 7 patients.Conclusions—In intracerebral hemorrhage, a 400 mg dose of minocycline was safe and achieved neuroprotective serum concentrations. However, oral administration led to delayed absorption in these critically ill patients and should not be used when rapid, high concentrations are desired. Given the safety and pharmacokinetic profile of minocycline in intracerebral hemorrhage and promising data in the treatment of ischemic stroke, intravenous minocycline is an excellent candidate for a prehospital treatment trial.Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01805895.



{gamma}-Glutamyl Transferase as a Risk Factor for All-Cause or Cardiovascular Disease Mortality Among 5912 Ischemic Stroke [Brief Report]

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

Background and Purpose—The aim of the study was to evaluate the association of the measurement of serum γ-glutamyl transferase (GGT) concentrations at admission with 1-year all-cause or cardiovascular disease (CVD) mortality in patients with acute ischemic stroke.Methods—This prospective, multicenter cohort study was conducted in 4 stroke centers in China. Baseline GGT measurements were tested. The relationship of GGT to the risk of death from all-cause or CVD was examined among 1-year follow-up patients.Results—We recorded results from 5912 patients with stroke. In those patients, 51.0% were men, and the median age was 61 years. In both men and women, high GGT was significantly associated with total mortality from all-cause or CVD (P<0.001). The elevated GGT revealed adjusted hazard ratios (95% confidence interval) of 3.03 (1.99–4.54) and 3.24 (2.14–4.92) for mortality from all-cause and CVD, respectively. With an area under the curve of 0.69 (95% confidence interval, 0.66–0.73), GGT showed a significantly greater discriminatory ability to predict all-cause mortality as compared with others factors. GGT improved the National Institutes of Health Stroke Scale score (area under the curve of the combined model, 0.75 [95% confidence interval, 0.73–0.78]; P<0.01).Conclusions—This study demonstrates that GGT is independently associated with all-cause and CVD mortality in patients with ischemic stroke.



White Matter Hyperintensity Volume and Outcome of Mechanical Thrombectomy With Stentriever in Acute Ischemic Stroke [Brief Report]

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

Background and Purpose—Finding of white matter hyperintensity (WMH) has been associated with an increased risk of parenchymal hematoma and poor clinical outcomes after mechanical thrombectomy using old-generation endovascular devices. Currently, no data exist with regard to the risk of mechanical thrombectomy using stentriever devices in patients with significant WMH. We hypothesized that WMH volume will not affect the hemorrhagic and clinical outcome in patients with acute ischemic stroke undergoing thrombectomy using new-generation devices.Methods—A retrospective cohort of consecutive acute ischemic stroke patients >18-year-old receiving mechanical thrombectomy with stentriever devices at a single academic center was examined. WMH volume was assessed by a semiautomated volumetric analysis on T2 fluid attenuated inversion recovery–magnetic resonance imaging. Outcomes included the rate of any intracerebral hemorrhage, 90-day modified Rankin Score (mRS), the rate of good outcome (discharge mRS ≤2), and the rate of successful reperfusion (thrombolysis in cerebral ischemia score 2b or 3).Results—Between June 2012 and December 2015, 56 patients with acute ischemic stroke met the study criteria. Median WMH volume was 6.76 cm3 (4.84–16.09 cm3). Increasing WMH volume did not significantly affect the odds of good outcome (odds ratio [OR], 0.811; 95% confidence interval [CI], 0.456–1.442), intracerebral hemorrhage (OR, 1.055; 95% CI, 0.595–1.871), parenchymal hematoma (OR, 0.353; 95% CI, 0.061–2.057), successful recanalization (OR, 1.295; 95% CI, 0.704–2.383), or death (OR, 1.583; 95% CI, 0.84–2.98).Conclusions—Mechanical thrombectomy using stentrievers seems to be safe in selected patients with acute ischemic stroke with large vessel occlusion, nonwithstanding the severity of WMH burden in this population. Larger prospective studies are warranted to validate these findings.



Integrin {alpha}4 Overexpression on Rat Mesenchymal Stem Cells Enhances Transmigration and Reduces Cerebral Embolism After Intracarotid Inȷection [Brief Report]

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

Background and Purpose—Very late antigen-4 (integrin α4β1)/vascular cell adhesion molecule-1 mediates leukocyte trafficking and transendothelial migration after stroke. Mesenchymal stem cells (MSCs) typically express integrin β1 but insufficient ITGA4 (integrin α4), which limits their homing after intravascular transplantation. We tested whether ITGA4 overexpression on MSCs increases cerebral homing after intracarotid transplantation and reduces MSC-borne cerebral embolism.Methods—Rat MSCs were lentivirally transduced to overexpress ITGA4. In vitro transendothelial migration was assessed using a Boyden chamber assay. Male Wistar rats intracarotidly received 0.5×106 control or modified MSCs 24 hours after sham or stroke surgery. In vivo behavior of MSCs in the cerebral vasculature was observed by intravital microscopy and single-photon emission computed tomography for up to 72 hours.Results—Transendothelial migration of ITGA4-overexpressing MSCs was increased in vitro. MSCs were passively entrapped in microvessels in vivo and occasionally formed large cell aggregates causing local blood flow interruptions. MSCs were rarely found in perivascular niches or parenchyma at 72 hours post-transplantation, but ITGA4 overexpression significantly decreased cell aggregation and ameliorated the evoked cerebral embolism in stroke rats.Conclusions—ITGA4 overexpression on MSCs enhances transendothelial migration in vitro, but not in vivo, although it improves safety after intracarotid transplantation into stroke rats.





















Identifying the Right Mentor [InterSECT]

2017-08-28T12:44:44-07:00


















































































Trajectories in Leisure-Time Physical Activity and Risk of Stroke in Women in the California Teachers Study [Clinical Sciences]

2017-08-28T12:44:43-07:00

Background and Purpose—Whether changes in leisure-time physical activity (LTPA) over time are associated with lower risk of stroke is not well established. We examined the association between changes in self-reported LTPA 10 years apart, with risk of incident stroke in the CTS (California Teachers Study). We hypothesized that the risk of stroke would be lowest among those who remained active.Methods—Sixty-one thousand two hundred and fifty-six CTS participants reported LTPA at 2 intensity levels (moderate and strenuous activity) at 2 time points (baseline 1995–96; 10-year follow-up 2005–2006). LTPA at each intensity level was categorized based on American Heart Association (AHA) recommendations (moderate, >150 minutes/week; strenuous, >75 minutes/week). Changes in LTPA were summarized as follows: (1) not meeting recommendations at both time points; (2) meeting recommendations only at follow-up; (3) meeting recommendations only at baseline; and (4) meeting recommendations at both time points. Incident strokes were identified through California state hospitalization records. Using multivariable Cox models, we examined the associations between changes in LTPA with incident stroke.Results—Nine hundred and eighty-seven women were diagnosed with stroke who completed both questionnaires. Meeting AHA recommendations at both the time points was associated with a lower risk of all stroke (adjusted hazard ratio, 0.84; 95% co[...]



Incidence of Brain Infarcts, Cognitive Change, and Risk of Dementia in the General Population [Clinical Sciences]

2017-08-28T12:44:43-07:00

Background and Purpose—The differentiation of brain infarcts by region is important because their cause and clinical implications may differ. Information on the incidence of these lesions and association with cognition and dementia from longitudinal population studies is scarce. We investigated the incidence of infarcts in cortical, subcortical, cerebellar, and overall brain regions and how prevalent and incident infarcts associate with cognitive change and incident dementia.Methods—Participants (n=2612, 41% men, mean age 74.6±4.8) underwent brain magnetic resonance imaging for the assessment of infarcts and cognitive testing at baseline and on average 5.2 years later. Incident dementia was assessed according to the international guidelines.Results—Twenty-one percent of the study participants developed new infarcts. The risk of incident infarcts in men was higher than the risk in women (1.8; 95% confidence interval, 1.5–2.3). Persons with both incident and prevalent infarcts showed steeper cognitive decline and had almost double relative risk of incident dementia (1.7; 95% confidence interval, 1.3–2.2) compared with those without infarcts. Persons with new subcortical infarcts had the highest risk of incident dementia compared with those without infarcts (2.6; 95% confidence interval, 1.9–3.4).Conclusions—Men are at greater risk of developing incident brain infarcts than women. Per[...]



Dolichoectasia and Small Vessel Disease in Young Patients With Transient Ischemic Attack and Stroke [Clinical Sciences]

2017-08-28T12:44:43-07:00

Background and Purpose—We evaluated whether basilar dolichoectasia is associated with markers of cerebral small vessel disease in younger transient ischemic attack and ischemic stroke patients.Methods—We used data from the SIFAP1 study (Stroke in Young Fabry Patients), a large prospective, hospital-based, screening study for Fabry disease in young ([...]