The 50 most-cited articles in Stroke, 2018

Correction This article has two related Corrections: (10.1161/STR.0000000000000163) (10.1161/STR.0000000000000172)

Background and Purpose— In acute ischemic stroke, fast and complete recanalization of the occluded vessel is associated with improved outcomes. We describe a novel measure for newer generation devices: the first pass effect (FPE). FPE is defined as achieving a complete recanalization with a single thrombectomy device pass. Methods— The North American Solitaire Acute Stroke Registry database was used to identify a FPE subgroup. Their baseline features and clinical outcomes were compared with non-FPE patients. Clinical outcome measures included 90-days modified Rankin Scale score, National Institutes of Health Stroke Scale score, mortality, and symptomatic intracranial hemorrhage. Multivariate analyses were performed to determine whether FPE independently resulted in improved outcomes and to identify predictors of FPE. Results— A total of 354 acute ischemic stroke patients underwent thrombectomy in the North American Solitaire Acute Stroke registry. FPE was achieved in 89 out of 354 (25.1%). More middle cerebral artery occlusions (64% versus 52.5%) and fewer internal carotid artery…

BACKGROUND AND PURPOSE: Neutrophil Extracellular Traps (NETs) are DNA extracellular networks decorated with histones and granular proteins produced by activated neutrophils. NETs have been identified as major triggers and structural factors of thrombosis. A recent study designated extracellular DNA threads from NETs as a potential therapeutic target for improving tissue-type plasminogen activator (tPA)-induced thrombolysis in acute coronary syndrome. The aim of this study was to assess the presence of NETs in thrombi retrieved during endovascular therapy in patients with acute ischemic stroke (AIS) and their impact on tPA-induced thrombolysis. METHODS: We analyzed thrombi from 108 AIS patients treated with endovascular therapy. Thrombi were characterized by hematoxylin/eosin staining, immunostaining, and ex vivo enzymatic assay. Additionally, we assessed ex vivo the impact of deoxyribonuclease 1 (DNAse 1) on thrombolysis of AIS thrombi. RESULTS: Histological analysis revealed that NETs contributed to the composition of all AIS thrombi especially in their outer layers. Quantitative…

Background and Purpose- This ARISTOPHANES study (Anticoagulants for Reduction in Stroke: Observational Pooled Analysis on Health Outcomes and Experience of Patients) used multiple data sources to compare stroke/systemic embolism (SE) and major bleeding (MB) among a large number of nonvalvular atrial fibrillation patients on non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods- A retrospective observational study of nonvalvular atrial fibrillation patients initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015, was conducted pooling Centers for Medicare and Medicaid Services Medicare data and 4 US commercial claims databases. After 1:1 NOAC-warfarin and NOAC-NOAC propensity score matching in each database, the resulting patient records were pooled. Cox models were used to evaluate the risk of stroke/SE and MB across matched cohorts. Results- A total of 285 292 patients were included in the 6 matched cohorts: 57 929 apixaban-warfarin, 26 838 dabigatran-warfarin, 83 007 rivaroxaban-warfarin, 27 096 apixaban-dabigatran,…

INTRODUCTION: Endovascular thrombectomy is a highly efficacious treatment for large vessel occlusion (LVO). LVO prediction instruments, based on stroke signs and symptoms, have been proposed to identify stroke patients with LVO for rapid transport to endovascular thrombectomy-capable hospitals. This evidence review committee was commissioned by the American Heart Association/American Stroke Association to systematically review evidence for the accuracy of LVO prediction instruments. METHODS: Medline, Embase, and Cochrane databases were searched on October 27, 2016. Study quality was assessed with the Quality Assessment of Diagnostic Accuracy-2 tool. RESULTS: Thirty-six relevant studies were identified. Most studies (21 of 36) recruited patients with ischemic stroke, with few studies in the prehospital setting (4 of 36) and in populations that included hemorrhagic stroke or stroke mimics (12 of 36). The most frequently studied prediction instrument was the National Institutes of Health Stroke Scale. Most studies had either some risk of bias or unclear risk of bias. Reported…

Background and Purpose- Although there are a variety of risk factors and predictive models for stroke-associated pneumonia (SAP), more objective and easily accessible markers are still needed. In this study, we evaluated the relationship between the neutrophil-to-lymphocyte ratio (NLR) and SAP in patients with acute ischemic stroke. Methods- We assessed 1317 consecutive patients with acute ischemic stroke. SAP was defined according to the modified Centers for Disease Control and Prevention criteria. The severity of pneumonia was rated using scores from the Pneumonia Severity Index, the quick Sequential Organ Failure Assessment, and the Acute Physiology and Chronic Health Evaluation II. The NLR was calculated after dividing absolute neutrophil counts by absolute lymphocyte counts. Results- Among the total patients, SAP occurred in 112 (9.0%) patients. Using a multivariable analysis, the NLR (adjusted odds ratio=1.55; 95% confidence interval, 1.15-2.11; P=0.005) remained significant after adjusting for confounders. In addition, age, atrial fibrillation, previous stroke history,…

Background and Purpose— Treatment options for patients with acute ischemic stroke depend on the volume of salvageable tissue. This volume assessment is currently based on fixed thresholds and single imagine modalities, limiting accuracy. We wish to develop and validate a predictive model capable of automatically identifying and combining acute imaging features to accurately predict final lesion volume. Methods— Using acute magnetic resonance imaging, we developed and trained a deep convolutional neural network (CNN deep ) to predict final imaging outcome. A total of 222 patients were included, of which 187 were treated with rtPA (recombinant tissue-type plasminogen activator). The performance of CNN deep was compared with a shallow CNN based on the perfusion-weighted imaging biomarker Tmax (CNN Tmax ), a shallow CNN based on a combination of 9 different biomarkers (CNN shallow ), a generalized linear model, and thresholding of the diffusion-weighted imaging biomarker apparent diffusion coefficient (ADC) at 600×10 −6 mm 2 /s (ADC thres ). To assess whether CNN deep is capable of…

Background and Purpose— Although successful reperfusion is usually defined as a modified Thrombolysis in Cerebral Infarction (mTICI) 2B or 3 at the end of the procedure, studies have shown that mTICI 2B patients had poorer functional outcomes than TICI 3 patients. An mTICI 2C category has been recently introduced for patients with near-complete perfusion except for slow flow in a few distal cortical vessels or presence of small distal cortical emboli after mechanical thrombectomy. The purpose of this study was to evaluate the difference in functional outcome between patients achieving successful reperfusion (ie, mTICI 2B, mTICI 2C, and TICI 3 scores). Methods— Ancillary study from the ASTER (Contact Aspiration Versus Stent Retriever for Successful Revascularization) prospective multicenter blinded end point trial. Reperfusion results are reported as the mTICI score, including the mTICI 2C grade. Primary outcome was the percentage of patients with favorable outcome defined as a 90-day modified Rankin Scale score of 0 to 2. Results— Two hundred ninety patients with successful…

Background and Purpose- Minimally invasive surgery (MIS) for intracerebral hemorrhage (ICH) has been evaluated in numerous clinical trials. Although meta-analyses for this strategy have been performed in the past, recent trials add important information to results of the comparison and permit strategy-specific analyses, including evaluation of endoscopic evacuation and stereotactic thrombolysis. Methods- Major scientific databases including but not limited to Pubmed, the CENTRAL (Cochrane Central Register of Controlled Trials), Embase, Web of Science, Scopus, the ICTRP (International Clinical Trials Registry Platform), the Internet Stroke Center, and the CNKI (Chinese National Knowledge Infrastructure) were searched in October of 2017 for randomized controlled trials of MIS treatment of supratentorial spontaneous ICH. The primary outcome was defined as death or dependence at the end of follow-up, and the secondary outcome was defined as death. Results- The initial search yielded 958 reports, which were reduced to 15 high-quality randomized controlled trials involving 2152 patients.…

Background and Purpose— Preventive strategies, together with demographic and socioeconomic changes, might have modified the worldwide distribution of ischemic stroke (IS) subtypes. We investigated those changes by means of a systematic review and meta-analysis. Methods— We evaluated all population- and hospital-based studies reporting the distribution of IS etiologic subtypes according to the TOAST criteria (Trial of ORG 10172 in Acute Stroke Treatment). Studies were identified by searching articles indexed on PubMed and Scopus from January 1, 1993, to June 30, 2017. Two independent investigators extracted data and checked them for accuracy. Proportions of each etiologic subtype were pooled according to a random effect meta-analytic model weighted by study size; temporal trends were assessed using a mixed-effect meta-regression model. Results— Sixty-five studies including patients from 1993 to 2015 were finally included. Overall, ISs were attributed to cardioembolism (22%; 95% confidence interval [CI], 20–23); large artery atherosclerosis (23%; 95% CI, 21–25); small artery occlusion…

BACKGROUND AND PURPOSE: Chronic impairment of the arm and hand is a common consequence of stroke. Animal and human studies indicate that brief bursts of vagus nerve stimulation (VNS) in conjunction with rehabilitative training improve recovery of motor function after stroke. In this study, we tested whether VNS could promote generalization, long-lasting recovery, and structural plasticity in motor networks. METHODS: Rats were trained on a fully automated, quantitative task that measures forelimb supination. On task proficiency, unilateral cortical and subcortical ischemic lesions were administered. One week after ischemic lesion, rats were randomly assigned to receive 6 weeks of rehabilitative training on the supination task with or without VNS. Rats then underwent 4 weeks of testing on a task assessing forelimb strength to test generalization of recovery. Finally, the durability of VNS benefits was tested on the supination task 2 months after the cessation of VNS. After the conclusion of behavioral testing, viral tracing was performed to assess synaptic connectivity in motor…

BACKGROUND AND PURPOSE: Recent work from our group suggests that human neural stem cell-derived extracellular vesicle (NSC EV) treatment improves both tissue and sensorimotor function in a preclinical thromboembolic mouse model of stroke. In this study, NSC EVs were evaluated in a pig ischemic stroke model, where clinically relevant end points were used to assess recovery in a more translational large animal model. METHODS: Ischemic stroke was induced by permanent middle cerebral artery occlusion (MCAO), and either NSC EV or PBS treatment was administered intravenously at 2, 14, and 24 hours post-MCAO. NSC EV effects on tissue level recovery were evaluated via magnetic resonance imaging at 1 and 84 days post-MCAO. Effects on functional recovery were also assessed through longitudinal behavior and gait analysis testing. RESULTS: NSC EV treatment was neuroprotective and led to significant improvements at the tissue and functional levels in stroked pigs. NSC EV treatment eliminated intracranial hemorrhage in ischemic lesions in NSC EV pigs (0 of 7) versus control pigs (7 of 8). NSC…

Background and Purpose— Periodontal disease is independently associated with cardiovascular disease. Identification of periodontal disease as a risk factor for incident ischemic stroke raises the possibility that regular dental care utilization may reduce the stroke risk. Methods— In the ARIC (Atherosclerosis Risk in Communities) study, pattern of dental visits were classified as regular or episodic dental care users. In the ancillary dental ARIC study, selected subjects from ARIC underwent fullmouth periodontal measurements collected at 6 sites per tooth and classified into 7 periodontal profile classes (PPCs). Results— In the ARIC study 10 362 stroke-free participants, 584 participants had incident ischemic strokes over a 15-year period. In the dental ARIC study, 6736 dentate subjects were assessed for periodontal disease status using PPC with a total of 299 incident ischemic strokes over the 15-year period. The 7 levels of PPC showed a trend toward an increased stroke risk (χ 2 trend P <0.0001); the incidence rate for ischemic stroke/1000-person years was 1.29 for PPC-A (health),…

Background and Purpose— Longitudinal long-term prognostic data after stroke based on large cohorts are sparse. We report recent survival and functional outcome data on ischemic stroke (IS) and intracerebral hemorrhage (ICH) for up to 5 years poststroke from the Swedish Stroke Register (Riksstroke). Methods— Beyond Riksstroke’s regular follow-up surveys at 3 and 12 months, additional surveys were conducted in 2016 on 2 one-year cohorts with stroke 3 and 5 years earlier. Functional dependency was defined as modified Rankin Scale ≥3. Mortality data of the original cohorts were obtained from the Swedish Causes of Death Register. Multiple imputation was used to estimate functional status in nonresponders. Results— The study included 22 929 patients, 87.5% with IS and 12.5% with ICH. Loss to follow-up in the 4 surveys was 12.8% to 21.2%. Thirty-day mortality was higher for ICH than for IS (30.7% versus 11.1%; P <0.01), whereas for 30-day survivors, 5-year mortality did not differ significantly ( P =0.858). Functional outcome was less favorable for ICH at all follow-up points. At 5 years,…

Background and Purpose- Malignant brain edema after ischemic stroke has high mortality but limited treatment. Therefore, early prediction is important, and we systematically reviewed predictors and predictive models to identify reliable markers for the development of malignant edema. Methods- We searched Medline and Embase from inception to March 2018 and included studies assessing predictors or predictive models for malignant brain edema after ischemic stroke. Study quality was assessed by a 17-item tool. Odds ratios, mean differences, or standardized mean differences were pooled in random-effects modeling. Predictive models were descriptively analyzed. Results- We included 38 studies (3278 patients) with 24 clinical factors, 7 domains of imaging markers, 13 serum biomarkers, and 4 models. Generally, the included studies were small and showed potential publication bias. Malignant edema was associated with younger age (n=2075; mean difference, -4.42; 95% CI, -6.63 to -2.22), higher admission National Institutes of Health Stroke Scale scores (n=807, median 17-20 versus 5.5-15), and…

Background and Purpose- Carotid web (CW) is a rare form of focal fibromuscular dysplasia defined as an abnormal shelf-like projection of intimal fibrous tissue into the carotid bulb. It is theorized that CW leads to ischemic stroke secondary to blood flow stasis and subsequent embolization. The natural history and optimal management of CW are unclear. To address this knowledge gap, we performed a systematic literature review (SLR) of CW. Methods- Our librarians performed a SLR for CW and related terminology. Patient-level demographics, stroke risk factors, neuroimaging findings, stroke recurrence or stroke free-duration, and treatment modality were extracted. We used descriptive statistics to characterize our results. When specific patient-level metrics were not reported, the denominators for reporting percentage calculations were adjusted accordingly. Results- Our literature search produced 1150 articles. Thirty-seven articles including 158 patients (median age 46 years [range 16-85], 68% women, 76% symptomatic) met entry criteria and were included in our SLR. Of the symptomatic CW…

Background and Purpose— The proinflammatory cytokine IL-1 (interleukin-1) has a deleterious role in cerebral ischemia, which is attenuated by IL-1 receptor antagonist (IL-1Ra). IL-1 induces peripheral inflammatory mediators, such as interleukin-6, which are associated with worse prognosis after ischemic stroke. We investigated whether subcutaneous IL-1Ra reduces the peripheral inflammatory response in acute ischemic stroke. Methods— SCIL-STROKE (Subcutaneous Interleukin-1 Receptor Antagonist in Ischemic Stroke) was a single-center, double-blind, randomized, placebo-controlled phase 2 trial of subcutaneous IL-1Ra (100 mg administered twice daily for 3 days) in patients presenting within 5 hours of ischemic stroke onset. Randomization was stratified for baseline National Institutes of Health Stroke Scale score and thrombolysis. Measurement of plasma interleukin-6 and other peripheral inflammatory markers was undertaken at 5 time points. The primary outcome was difference in concentration of log(interleukin-6) as area under the curve to day 3. Secondary outcomes included exploratory…

Background and Purpose- We assessed safety, feasibility, and potential effects of vagus nerve stimulation (VNS) paired with rehabilitation for improving arm function after chronic stroke. Methods- We performed a randomized, multisite, double-blinded, sham-controlled pilot study. All participants were implanted with a VNS device and received 6-week in-clinic rehabilitation followed by a home exercise program. Randomization was to active VNS (n=8) or control VNS (n=9) paired with rehabilitation. Outcomes were assessed at days 1, 30, and 90 post-completion of in-clinic therapy. Results- All participants completed the course of therapy. There were 3 serious adverse events related to surgery. Average FMA-UE scores increased 7.6 with active VNS and 5.3 points with control at day 1 post-in-clinic therapy (difference, 2.3 points; CI, -1.8 to 6.4; P=0.20). At day 90, mean scores increased 9.5 points from baseline with active VNS, and the control scores improved by 3.8 (difference, 5.7 points; CI, -1.4 to 11.5; P=0.055). The clinically meaningful response rate of FMA-UE at day 90 was 88% with…

Background and Purpose- We aimed to determine whether low-frequency electric field navigated repetitive transcranial magnetic stimulation to noninjured motor cortex versus sham repetitive transcranial magnetic stimulation avoiding motor cortex could improve arm motor function in hemiplegic stroke patients when combined with motor training. Methods- Twelve outpatient US rehabilitation centers enrolled participants between May 2014 and December 2015. We delivered 1 Hz active or sham repetitive transcranial magnetic stimulation to noninjured motor cortex before each of eighteen 60-minute therapy sessions over a 6-week period, with outcomes measured at 1 week and 1, 3, and 6 months after end of treatment. The primary end point was the percentage of participants improving ≥5 points on upper extremity Fugl-Meyer score 6 months after end of treatment. Secondary analyses assessed changes on the upper extremity Fugl-Meyer and Action Research Arm Test and Wolf Motor Function Test and safety. Results- Of 199 participants, 167 completed treatment and follow-up because of early discontinuation…

BACKGROUND AND PURPOSE: Statin therapy is associated with a lower risk of ischemic stroke supporting a causal role of low-density lipoprotein (LDL) cholesterol. However, more evidence is needed to answer the question whether LDL cholesterol plays a causal role in ischemic stroke subtypes. In addition, it is unknown whether high-density lipoprotein cholesterol and triglycerides have a causal relationship to ischemic stroke and its subtypes. Our aim was to investigate the causal role of LDL cholesterol, high-density lipoprotein cholesterol, and triglycerides in ischemic stroke and its subtypes through Mendelian randomization (MR). METHODS: Summary data on 185 genome-wide lipids-associated single nucleotide polymorphisms were obtained from the Global Lipids Genetics Consortium and the Stroke Genetics Network for their association with ischemic stroke (n=16 851 cases and 32 473 controls) and its subtypes, including large artery atherosclerosis (n=2410), small artery occlusion (n=3186), and cardioembolic (n=3427) stroke. Inverse-variance-weighted MR was used to obtain the causal…

Background and Purpose— To identify predictors of in-hospital mortality in patients with aneurysmal subarachnoid hemorrhage and to estimate their impact. Methods— Retrospective analysis of prospective data from a nationwide multicenter registry on all aneurysmal subarachnoid hemorrhage cases admitted to a tertiary neurosurgical department in Switzerland (Swiss SOS [Swiss Study on Aneurysmal Subarachnoid Hemorrhage]; 2009–2015). Both clinical and radiological independent predictors of in-hospital mortality were identified, and their effect size was determined by calculating adjusted odds ratios (aORs) using multivariate logistic regression. Survival was displayed using Kaplan–Meier curves. Results— Data of n=1866 aneurysmal subarachnoid hemorrhage patients in the Swiss SOS database were available. In-hospital mortality was 20% (n=373). In n=197 patients (10.6%), active treatment was discontinued after hospital admission (no aneurysm occlusion attempted), and this cohort was excluded from analysis of the main statistical model. In the remaining n=1669 patients, the rate of in-hospital…

BACKGROUND AND PURPOSE: Endovascular therapy is the standard of care for the treatment of proximal large vessel occlusion strokes. Its safety and efficacy in the treatment of distal intracranial occlusions has not been well studied. METHODS: The data that support the findings of this study are available from the corresponding author on reasonable request. Retrospective review of a prospectively collected endovascular database (2010-2015, n=949) for all patients with distal intracranial occlusions treated endovascularly. Distal occlusions were defined as any segment of the anterior cerebral artery (ACA), posterior cerebral artery, or occlusion at or distal to the middle cerebral artery (MCA)-M3 opercular segment. RESULTS: Distal occlusions were treated in 69 patients. The mean age was 66.7±15.8 and 57% were male. Patients (29 [42%]) received intravenous tPA (tissue-type plasminogen activator). The median preprocedure National Institutes of Health Stroke Scale score was 18 (interquartile range, 13-23). The distal occlusion was the primary treatment location in 45 patients, in 23…

Public Health ConcernDizziness and vertigo are responsible for an estimated 4.4 million emergency department (ED) visits in the United States each year and account for 4% of chief symptoms in the ED. 1 Strokes are the underlying cause of ≈3% to 5% of such visits (130 000-220 000). 2 These visits are associated with a high cost, estimated now to exceed $10 billion per year in the United States.3 This results from neuroimaging obtained in roughly half the patients 1 and admissions for nearly 20%. 4 ED physicians worldwide rank vertigo a top priority for developing better diagnostic tools.5 An evidence-based, cost-effective approach to diagnosing acute dizziness and vertigo is needed.

Background and Purpose— Anxiety after stroke is common and disabling. Stroke trialists have treated anxiety as a homogenous condition, and intervention studies have followed suit, neglecting the different treatment approaches for phobic and generalized anxiety. Using diagnostic psychiatric interviews, we aimed to report the frequency of phobic and generalized anxiety, phobic avoidance, predictors of anxiety, and patient outcomes at 3 months poststroke/transient ischemic attack. Methods— We followed prospectively a cohort of new diagnosis of stroke/transient ischemic attack at 3 months with a telephone semistructured psychiatric interview, Fear Questionnaire, modified Rankin Scale, EuroQol-5D5L, and Work and Social Adjustment Scale. Results— Anxiety disorder was common (any anxiety disorder, 38 of 175 [22%]). Phobic disorder was the predominant anxiety subtype: phobic disorder only, 18 of 175 (10%); phobic and generalized anxiety disorder, 13 of 175 (7%); and generalized anxiety disorder only, 7 of 175 (4%). Participants with anxiety disorder reported higher level of phobic avoidance…

Background and Purpose— Although perfusion abnormality is an increasingly important therapeutic target, the natural history of tissue at risk without reperfusion treatment is understudied. Our objective was to determine how time affects penumbral salvage and infarct growth in untreated acute ischemic stroke patients and whether collateral status affects this relationship. Methods— We used a prospectively collected, multicenter acute stroke registry to assess acute stroke patients who were not treated with intravenous thrombolysis or endovascular treatment. We analyzed baseline computed tomography angiogram and computed tomography perfusion within 24 hours of stroke onset along with follow-up imaging and assessed time from stroke onset to baseline imaging, ASPECTS (Alberta Stroke Program Early CT Score), vessel occlusion, collaterals, ischemic core, and penumbra. Penumbral salvage and infarct growth were calculated. Correlations between time and penumbral salvage and infarct growth were evaluated with Spearman correlation. Penumbral salvage and infarct growth were compared between…

Background and Purpose— Emerging evidence suggests that an underlying atrial cardiopathy may result in thromboembolism before atrial fibrillation (AF) develops. We examined the association between various markers of atrial cardiopathy and the risk of ischemic stroke. Methods— The CHS (Cardiovascular Health Study) prospectively enrolled community-dwelling adults ≥65 years of age. For this study, we excluded participants diagnosed with stroke or AF before baseline. Exposures were several markers of atrial cardiopathy: baseline P-wave terminal force in ECG lead V 1 , left atrial dimension on echocardiogram, and N terminal pro B type natriuretic peptide (NT-proBNP), as well as incident AF. Incident AF was ascertained from 12-lead electrocardiograms at annual study visits for the first decade after study enrollment and from inpatient and outpatient Medicare data throughout follow-up. The primary outcome was incident ischemic stroke. We used Cox proportional hazards models that included all 4 atrial cardiopathy markers along with adjustment for demographic characteristics and established…

Background and Purpose- Endovascular treatment for acute intracranial atherosclerosis-related large vessel occlusion (ICAS [+]-LVO) is one of the challenging issues in modern mechanical thrombectomy era. We evaluated procedural and clinical outcomes of endovascular treatment for the ICAS (+)-LVO. We also compared their outcomes with those of large vessel occlusion not associated with intracranial atherosclerosis (ICAS [-]-LVO). Methods- We retrospectively reviewed consecutive patients with acute stroke who underwent endovascular treatment for LVO. Patients were assigned to the ICAS (+)-LVO group or the ICAS (-)-LVO group primarily based on catheter angiogram. Procedural and clinical outcomes were compared between the ICAS (+)-LVO and ICAS (-)-LVO groups. Results- The present study included 318 patients. Fifty-six patients (17.6%) had an ICAS (+)-LVO. Recanalization was achieved in 45 patients in the ICAS (+)-LVO group (80.4%), which was comparable with the ICAS (-)-LVO group (88.5%; P=0.097). However, recanalization using a stent retriever was less successful in the ICAS (+)-LVO…

Background and Purpose- Trimethylamine N-oxide (TMAO)-a gut derived metabolite-has been shown to be atherogenic. It remains unknown whether TMAO is associated with the risk of first stroke. We aimed to determine the association between serum TMAO levels and first stroke in hypertensive patients without major cardiovascular diseases and examine any possible effect modifiers. Methods- We used a nested case-control design, using data from the CSPPT (China Stroke Primary Prevention Trial), including 622 patients with first stroke and 622 matched controls. The study was conducted from May 2008 to August 2013. The primary outcome was a first stroke. Results- After adjusting for choline, L-carnitine, and other important covariates, including baseline systolic blood pressure and time-averaged systolic blood pressure, during the treatment period, the risk of first stroke increased with each increment of TMAO level (per natural log [TMAO] increment: odds ratio, 1.22; 95% CI, 1.02-1.46). Consistently, compared with participants in the lowest tertile (<1.79 μmol/L) of serum TMAO levels, a…

Background and Purpose— Effective rescue treatment has not yet been suggested in patients with mechanical thrombectomy (MT) failure. This study aimed to test whether rescue stenting (RS) improved clinical outcomes in MT-failed patients. Methods— This is a retrospective analysis of the cohorts of the 16 comprehensive stroke centers between September 2010 and December 2015. We identified the patients who underwent MT but failed to recanalize intracranial internal carotid artery or middle cerebral artery M1 occlusion. Patients were dichotomized into 2 groups: patients with RS and without RS after MT failure. Clinical and laboratory findings and outcomes were compared between the 2 groups. It was tested whether RS is associated with functional outcome. Results— MT failed in 148 (25.0%) of the 591 patients with internal carotid artery or middle cerebral artery M1 occlusion. Of these 148 patients, 48 received RS (RS group) and 100 were left without further treatment (no stenting group). Recanalization was successful in 64.6% (31 of 48 patients) of RS group. Compared with no stenting…

BACKGROUND AND PURPOSE: Stroke in lower and middle-income countries affects a young and productive age group. Data on factors associated with stroke in the young are sorely lacking from lower and middle-income countries. Our objective is to characterize the nature of stroke and its risk factors among young West Africans aged <50 years old. METHODS: The SIREN (Stroke Investigative Research and Educational Network) is a multicenter, case-control study involving 15 sites in Nigeria and Ghana. Cases included adults aged ≥18 years with computed tomography/magnetic resonance imaging-confirmed stroke. Controls were age-and gender-matched stroke-free adults recruited from the communities in catchment areas of cases. Comprehensive evaluation for vascular, lifestyle, and psychosocial factors was performed. We used conditional logistic regression to estimate odds ratios and population attributable risks with 95% confidence intervals. RESULTS: Five hundred fifteen (24.3%) out of 2118 cases enrolled were <50 years old. Among subjects <50 years old, hemorrhagic stroke proportion was 270 (52.5%)…

BACKGROUND AND PURPOSE: EmboTrap is a novel stent retriever designed to achieve rapid and substantial flow restoration in acute ischemic stroke secondary to large-vessel occlusions. Here, we evaluated EmboTrap's safety and efficacy compared with established stent retrievers. METHODS: ARISE II (Analysis of Revascularization in Ischemic Stroke With EmboTrap) was a single-arm, prospective, multicenter study, comparing the EmboTrap device to a composite performance goal criterion derived using a Bayesian meta-analysis from the pivotal SWIFT (Solitaire device) and TREVO 2 (Trevo device) trials. Patients at 11 US and 8 European sites were eligible for inclusion if they had large-vessel occlusions and moderate-to-severe neurological deficits within 8 hours of symptom onset. The primary efficacy end point was achievement of modified Thrombolysis in Cerebral Ischemia (mTICI) reperfusion scores of ≥2b within 3 EmboTrap passes as adjudicated by the core laboratory. The primary safety end point was a composite of symptomatic intracerebral hemorrhage and serious adverse device effects. Secondary…

Background and Purpose- Early selection of patients with acute middle cerebral artery infarction at risk for malignant edema is critical to initiate timely decompressive surgery. Net water uptake (NWU) per brain volume is a quantitative imaging biomarker of space-occupying ischemic edema which can be measured in computed tomography. We hypothesize that NWU in early infarct lesions can predict development of malignant edema. The aim was to compare NWU in acute brain infarct against other common predictors of malignant edema. Methods- After consecutive screening of single-center registry data, 153 patients with acute proximal middle cerebral artery occlusion fulfilled the inclusion criteria. A total of 29 (18.2%) patients developed malignant edema defined as end point in follow-up imaging leading to decompressive surgery and death as a direct implication of mass effect. Early infarct lesion volume and NWU were quantified in multimodal admission computed tomography; time from symptom onset to admission imaging was recorded. Results- Mean time from onset to admission imaging was…

Background and Purpose- The purpose of this study is to evaluate the relationship between neutrophil-to-lymphocyte ratio (NLR) at admission with safety and efficacy outcomes in acute stroke patients with large vessel occlusion after mechanical thrombectomy. Methods- Consecutive large vessel occlusion patients treated with mechanical thrombectomy during a 4-year period were evaluated. Outcome measures included symptomatic intracranial hemorrhage, 3-month mortality, successful reperfusion (modified Thrombolysis in Cerebral Infarction score of 2b/3), and 3-month functional independence (modified Rankin Scale scores of 0-2). Results- A total of 293 large vessel occlusion patients underwent mechanical thrombectomy (median admission NLR, 3.5; interquartile range [IQR], 1.7-6.8). In initial univariable analyses, higher median admission NLR values were documented in patients with symptomatic intracranial hemorrhage (8.5; IQR, 4.7-11.3) versus (3.9; IQR, 1.9-6.5); P<0.001 and individuals who were dead at 3-months (5.4; IQR, 2.8-9.6) versus (4.0; IQR, 1.8-6.4); P=0.004. Lower NLR values were…

BACKGROUND AND PURPOSE: Although the computed tomographic angiography spot sign performs well as a biomarker for hematoma expansion (HE), computed tomographic angiography is not routinely performed in the emergency setting. We developed and validated a score to predict HE-based on noncontrast computed tomography (NCCT) findings in spontaneous acute intracerebral hemorrhage. METHODS: After developing the score in a single-center cohort of patients with intracerebral hemorrhage (n=344), we validated it in a large clinical trial population (n=954) and in a multicenter intracerebral hemorrhage cohort (n=241). The following NCCT markers of HE were analyzed: hypodensities, blend sign, hematoma shape and density, and fluid level. HE was defined as hematoma growth >6 mL or >33%. The score was created using the estimates from multivariable logistic regression after final predictors were selected from bootstrap samples. RESULTS: =0.0002) were predictors of HE. A 5-point score was created (BAT score: 1 point for blend sign, 2 points for any hypodensity, and 2 points for timing of NCCT <2.5…

Background and Purpose— Although aggressive medical therapy was superior to stenting in the SAMMPRIS trial (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis), the stroke rate in the medical arm was still high. The aim of this study was to determine the association between hemodynamic markers (borderzone infarct pattern and impaired collateral flow on baseline imaging) and rates of recurrent stroke in patients treated medically in SAMMPRIS. Methods— This was a post hoc analysis of patients whose qualifying event for SAMMPRIS was an infarct in the territory of a stenotic middle cerebral artery or intracranial carotid artery. Infarcts were adjudicated as involving primarily internal or cortical borderzone territories, the core middle cerebral artery territory, or perforator territories, and collateral flow was assessed according to a standard scale (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology). Log-rank tests and χ 2 tests were performed to assess associations of infarct…

Background and Purpose— Poststroke cognitive decline causes disability. Risk factors for poststroke cognitive decline independent of survivors’ prestroke cognitive trajectories are uncertain. Methods— Among 22 875 participants aged ≥45 years without baseline cognitive impairment from the REGARDS cohort (Reasons for Geographic and Racial Differences in Stroke), enrolled from 2003 to 2007 and followed through September 2015, we measured the effect of incident stroke (n=694) on changes in cognitive functions and cognitive impairment (Six-Item Screener score <5) and tested whether patient factors modified the effect. Median follow-up was 8.2 years. Results— Incident stroke was associated with acute declines in global cognition, new learning, verbal memory, and executive function. Acute declines in global cognition after stroke were greater in survivors who were black ( P =0.04), men ( P =0.04), and had cardioembolic ( P =0.001) or large artery stroke ( P =0.001). Acute declines in executive function after stroke were greater in survivors who had P =0.01). Incident stroke was associated…

Background and Purpose— The relationship between type 2 diabetes mellitus (T2D) and cerebral small vessel disease (CSVD) is unclear. We aimed to examine the causal effect of T2D, fasting glucose levels, and higher insulin resistance on CSVD using Mendelian randomization. Methods— Five CSVD phenotypes were studied; 2 were clinical outcomes associated with CSVD (lacunar stroke: n=2191/27 297 and intracerebral hemorrhage [ICH]: n=2254/8195 [deep and lobar ICH]), whereas 3 were radiological markers of CSVD (white matter hyperintensities: n=8429; fractional anisotropy [FA]: n=8357; and mean diffusivity: n=8357). We applied 2 complementary analyses to evaluate the association of T2D with CSVD. First, we used summarized data from genome-wide association study to calculate the effects of T2D-related variants on CSVD with inverse-variance weighted and weighted median approaches. Second, we performed a genetic risk score approach to test the effects of T2D-associated variants on white matter hyperintensities, FA, and mean diffusivity using individual-level data in UK Biobank. Results— T2D was…

BACKGROUND AND PURPOSE: There is a strong dose-response relationship between smoking and risk of ischemic stroke in young women, but there are few data examining this association in young men. We examined the dose-response relationship between the quantity of cigarettes smoked and the odds of developing an ischemic stroke in men under age 50 years. METHODS: test was used to test categorical comparisons. Logistic regression models were used to calculate the odds ratio for ischemic stroke occurrence comparing current and former smokers to never smokers. In the first model, we adjusted solely for age. In the second model, we adjusted for potential confounding factors, including age, race, education, hypertension, myocardial infarction, angina, diabetes mellitus, and body mass index. RESULTS: The study population consisted of 615 cases and 530 controls. The odds ratio for the current smoking group compared with never smokers was 1.88. Furthermore, when the current smoking group was stratified by number of cigarettes smoked, there was a dose-response relationship for the odds ratio,…

Background and Purpose- The clinical significance of vessel wall imaging (VWI) remains unclear in patients with unruptured intracranial aneurysms. This study was performed to investigate the correlations between aneurysm wall imaging findings and histopathologic aneurysm wall architectures. Methods- A total of 9 aneurysms was evaluated by VWI and subsequently characterized with histopathology. We used VWI to visualize the aneurysm wall and determine if there was aneurysm wall enhancement after gadolinium contrast administration. Results- Aneurysm wall structures were identified in 6 of 9 unruptured intracranial aneurysms by native VWI, and wall enhancement was identified in 5 of these 6 aneurysms. Histopathologic studies revealed that wall thickening accompanied by atherosclerosis, neovascularization, and macrophage infiltration corresponded to visualization of the aneurysm wall by native VWI and to aneurysm wall enhancement. Conclusions- VWI can visualize thickening of the aneurysm wall, and wall enhancement corresponded to histologically confirmed degenerative changes accompanied…

Background and Purpose- We aimed to describe the safety and efficacy of immediate mechanical thrombectomy (MT) in patients with large vessel occlusions and low National Institutes of Health Stroke Scale (NIHSS) versus best medical management. Methods- Patients from prospectively collected databases of 6 international comprehensive stroke centers with large vessel occlusions (distal intracranial internal carotid, middle cerebral artery-M1 and M2 segments, or basilar artery with or without tandem occlusions) and NIHSS 0 to 5 were identified and divided into 2 groups for analysis: immediate MT or initial best medical management which included rescue MT after neurological deterioration (best medical management-MT). Uni- and multivariate analyses and patient-level matching for age, baseline NIHSS, and occlusion site were performed to compare baseline and outcome variables across the 2 groups. The primary outcome was defined as good outcome (modified Rankin Scale score, 0-2) at day 90. Safety outcome was symptomatic intracranial hemorrhage as defined by the ECASS (European Cooperative…

Background and Purpose- Endovascular thrombectomy (EVT) is effective for acute ischemic stroke with large vessel occlusion and National Institutes of Health Stroke Scale (NIHSS) ≥6. However, EVT benefit for mild deficits large vessel occlusions (NIHSS, <6) is uncertain. We evaluated EVT efficacy and safety in mild strokes with large vessel occlusion. Methods- A retrospective cohort of patients with anterior circulation large vessel occlusion and NIHSS <6 presenting within 24 hours from last seen normal were pooled. Patients were divided into 2 groups: EVT or medical management. Ninety-day mRS of 0 to 1 was the primary outcome, mRS of 0 to 2 was the secondary. Symptomatic intracerebral hemorrhage was the safety outcome. Clinical outcomes were compared through a multivariable logistic regression after adjusting for age, presentation NIHSS, time last seen normal to presentation, center, IV alteplase, Alberta Stroke Program early computed tomographic score, and thrombus location. We then performed propensity score matching as a sensitivity analysis. Results were also stratified by…