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  • Public Health and Cost Benefits of Successful Reperfusion After Thrombectomy for Stroke
    Stroke (IF 6.046) Pub Date : 2020-01-22
    Wolfgang G. Kunz; Mohammed A. Almekhlafi; Bijoy K. Menon; Jeffrey L. Saver; Myriam G. Hunink; Diederik W.J. Dippel; Charles B.L.M. Majoie; David S. Liebeskind; Tudor G. Jovin; Antoni Davalos; Serge Bracard; Francis Guillemin; Bruce C.V. Campbell; Peter J. Mitchell; Philip White; Keith W. Muir; Scott Brown; Andrew M. Demchuk; Michael D. Hill; Mayank Goyal; for the HERMES Collaborators

    Background and Purpose—The benefit that endovascular thrombectomy offers to patients with stroke with large vessel occlusions depends strongly on reperfusion grade as defined by the expanded Thrombolysis in Cerebral Infarction (eTICI) scale. Our aim was to determine the lifetime health and cost consequences of the quality of reperfusion for patients, healthcare systems, and society.Methods—A Markov model estimated lifetime quality-adjusted life years (QALY) and lifetime costs of endovascular thrombectomy–treated patients with stroke based on eTICI grades. The analysis was performed over a lifetime horizon in a United States setting, adopting healthcare and societal perspectives. The reference case analysis was conducted for stroke at 65 years of age. National health and cost consequences of improved eTICI 2c/3 reperfusion rates were estimated. Input parameters were based on best available evidence.Results—Lifetime QALYs increased for every grade of improved reperfusion (median QALYs for eTICI 0/1: 2.62; eTICI 2a: 3.46; eTICI 2b: 5.42; eTICI 2c: 5.99; eTICI 3: 6.73). Achieving eTICI 3 over eTICI 2b reperfusion resulted on average in 1.31 incremental QALYs as well as healthcare and societal cost savings of $10 327 and $20 224 per patient. A 10% increase in the eTICI 2c/3 reperfusion rate of all annually endovascular thrombectomy–treated patients with stroke in the United States is estimated to yield additional 3656 QALYs and save $21.0 million and $36.8 million for the healthcare system and society, respectively.Conclusions—Improved reperfusion grants patients with stroke additional QALYs and leads to long-term cost savings. Procedural strategies to achieve complete reperfusion should be assessed for safety and feasibility, even when initial reperfusion seems to be adequate.

    更新日期:2020-01-23
  • Bypassing the Closest Stroke Center for Thrombectomy Candidates
    Stroke (IF 6.046) Pub Date : 2020-01-22
    Ludwig Schlemm; Matthias Endres; Christian H. Nolte

    Background and Purpose—Patients with acute ischemic stroke who have large vessel occlusion benefit from direct transport to a comprehensive stroke center (CSC) capable of endovascular therapy. To avoid harm for patients without large vessel occlusion from delayed access to intravenous thrombolysis (IVT), it has been suggested to only redirect patients with high likelihood of large vessel occlusion for whom the additional delay to intravenous thrombolysis (IVT) caused by transport to the CSC is below a certain threshold. However, which threshold achieves the greatest clinical benefit is unknown.Methods—We used mathematical modeling to calculate additional-delay-to-IVT thresholds associated with the greatest reduction in disability-adjusted life years in abstracted 2-stroke center and multiple-stroke center scenarios. Model parameters were extracted from recent meta-analyses or large prospective cohort studies. Uncertainty was quantified in probabilistic and 2-way univariate sensitivity analyses.Results—Assuming ideal treatment time performance metrics, transport to the nearest CSC was the preferred strategy irrespective of additional delay-to-IVT when the transfer time between primary stroke center and CSC was <40 minutes (95% credible interval: 25–66 minutes); otherwise, the optimal additional delay-to-IVT-threshold ranged from 28 to 139 minutes. In multiple-stroke center scenarios, optimal additional-delay-to-IVT thresholds were 30 to 54 minutes in urban and 49 to 141 minutes in rural settings; use of optimal thresholds as compared with a 15 minute-threshold saved 0 to 0.11 and 0 to 0.37 disability-adjusted life years per triage case, respectively. Assuming slower treatment times at primary stroke centers and CSCs yielded longer permissible additional delays.Conclusions—Our results suggest that patients with acute ischemic stroke with suspected large vessel occlusion should be redirected to a CSC if the additional delay to IVT is <30 minutes in urban and 50 minutes in rural settings.

    更新日期:2020-01-23
  • Early Initiation of Direct Oral Anticoagulants After Onset of Stroke and Short- and Long-Term Outcomes of Patients With Nonvalvular Atrial Fibrillation
    Stroke (IF 6.046) Pub Date : 2020-01-22
    Tadataka Mizoguchi; Kanta Tanaka; Kazunori Toyoda; Sohei Yoshimura; Ryo Itabashi; Masahito Takagi; Kenichi Todo; Masayuki Shiozawa; Yoshiki Yagita; Takeshi Yoshimoto; Tadashi Terasaki; Hiroshi Yamagami; Shunya Takizawa; Manabu Inoue; Kenji Kamiyama; Masafumi Ihara; Yasushi Okada; Takanari Kitazono; Masatoshi Koga; on behalf of the SAMURAI Study Investigators

    Background and Purpose—We aimed to compare outcomes of ischemic stroke patients with nonvalvular atrial fibrillation between earlier and later initiation of direct oral anticoagulants (DOACs) after stroke onset.Methods—From data for 1192 nonvalvular atrial fibrillation patients with acute ischemic stroke or transient ischemic attack in a prospective, multicenter, observational study, patients who started DOACs during acute hospitalization were included and divided into 2 groups according to a median day of DOAC initiation after onset. Outcomes included stroke or systemic embolism, major bleeding, and death at 3 months, as well as those at 2 years.Results—DOACs were initiated during acute hospitalization in 499 patients in median 4 (interquartile range, 2–7) days after onset. Thus, 223 patients (median age, 74 [interquartile range, 68–81] years; 78 women) were assigned to the early group (≤3 days) and 276 patients (median age, 75 [interquartile range, 69–82] years; 101 women) to the late (≥4 days) group. The early group had lower baseline National Institutes of Health Stroke Scale score and smaller infarcts than the late group. The rate at which DOAC administration persisted at 2 years was 85.2% overall, excluding patients who died or were lost to follow-up. Multivariable Cox shared frailty models showed comparable hazards between the groups at 2 years for stroke or systemic embolism (hazard ratio, 0.86 [95% CI, 0.47–1.57]), major bleeding (hazard ratio, 1.39 [95% CI, 0.42–4.60]), and death (hazard ratio, 0.61 [95% CI, 0.28–1.33]). Outcome risks at 3 months also did not significantly differ between the groups.Conclusions—Risks for events including stroke or systemic embolism, major bleeding, and death were comparable whether DOACs were started within 3 days or from 4 days or more after the onset of nonvalvular atrial fibrillation–associated ischemic stroke or transient ischemic attack.Registration—URL: https://www.clinicaltrials.gov. Unique identifier: NCT01581502.

    更新日期:2020-01-23
  • Stroke Outcome Prediction by Blood Pressure Variability, Heart Rate Variability, and Baroreflex Sensitivity
    Stroke (IF 6.046) Pub Date : 2020-01-22
    Shujin Tang; Li Xiong; Yuhua Fan; Vincent C.T. Mok; Ka Sing Wong; Thomas W. Leung

    Background and Purpose—Poststroke autonomic dysfunction portended an unfavorable prognosis. We investigated whether blood pressure variability (BPV), heart rate variability, and baroreflex sensitivity might predict stroke functional outcome.Methods—We calculated BPV, heart rate variability, baroreflex slope, and baroreflex effectiveness index from a 5-minute beat-to-beat blood pressure and heart rate monitoring within 7 days from the stroke onset. We compared the parameters between patients with a good outcome (modified Rankin Scale score, 0–2) and those with a poor outcome.Results—Among 142 patients (mean age, 63.9±10.2 years; 88.0% men), functional outcome was good in 112 (78.9%) and poor in 30 (21.1%). There were significant differences in admission National Institutes of Health Stroke Scale, prior stroke, high-frequency systolic BPV, low/high-frequency ratio of BPV, baroreflex sensitivity-up, and baroreflex sensitivity-total between the 2 groups (all P<0.05). In multivariate analysis, National Institutes of Health Stroke Scale (OR, 1.672 [95% CI, 1.316–2.125]; P<0.001), low/high-frequency ratio of systolic BPV (OR, 0.493 [95% CI, 0.250–0.973]; P=0.041), and baroreflex effectiveness index-down (OR, 0.958 [95% CI, 0.924–0.992]; P=0.017) independently predicted a poor functional outcome.Conclusions—A decreased low/high-frequency ratio of systolic BPV and impaired baroreflex sensitivity predicted an unfavorable stroke outcome, in addition to the established prognostic factor such as the National Institutes of Health Stroke Scale.

    更新日期:2020-01-23
  • Evaluating Hematoma Expansion Scores in Acute Spontaneous Intracerebral Hemorrhage
    Stroke (IF 6.046) Pub Date : 2020-01-22
    Vignan Yogendrakumar; Margaret Moores; Lindsey Sikora; Michel Shamy; Tim Ramsay; Dean Fergusson; Dar Dowlatshahi

    Background and Purpose—In acute spontaneous intracerebral hemorrhage, multiple hematoma expansion scores have been proposed for use in clinical trial environments. We performed a systematic scoping review to identify all existing hematoma expansion scores and describe their development, validation, and relative performance.Methods—Two reviewers searched MEDLINE, PUBMED, EMBASE, and CENTRAL (Cochrane Central Register of Controlled Trials) for studies that derived or validated a hematoma expansion prediction score in adults presenting with spontaneous intracerebral hemorrhage. A descriptive analysis of the extracted data was performed, focusing on score development techniques and predictive capabilities.Results—Of the 14 434 records retrieved, 15 studies met inclusion criteria and 10 prediction scores were identified. Validation analysis using independent samples was performed in 9 studies on 5 scores. All derivation studies reported high performance with C statistics ranging from 0.72 to 0.93. In validation, the C-statistic range was broader with studies reporting 0.62 to 0.77. For every score, the risk of expansion increased with each point increase, although patients with high scores were rare.Conclusions—At present, 10 hematoma expansion scores have been developed, of which 5 have been externally validated. Real-world performance in validation studies was lower than performance in derivation studies. Data from the current literature are insufficient to support a meaningful meta-analysis.

    更新日期:2020-01-23
  • Risk of Intracranial Aneurysm and Dissection and Fluoroquinolone Use
    Stroke (IF 6.046) Pub Date : 2020-01-22
    Sandy Maumus-Robert; Stéphanie Debette; Xavier Bérard; Yohann Mansiaux; Pascale Tubert-Bitter; Antoine Pariente

    Background and Purpose—Fluoroquinolone use is associated with an increased risk of aortic aneurysm and dissection. We investigated this risk of arterial wall injury on intracranial arteries, given the similar pathophysiological mechanisms for aneurysm and dissection in both types of arteries.Methods—A case-time-control study was conducted using French National Insurance databases covering >60 million inhabitants. Cases were aged ≥18 years with first ruptured intracranial aneurysm and dissection between 2010 and 2015. For each case, fluoroquinolone use was compared between the exposure-risk window (day 30–day 1 before the outcome) and matched control windows (day 120–day 91, day 150–day 121, and day 180–day 151) and adjusted for time-varying confounders; potential time-trend for exposure was controlled using an age- and sex-matched reference group. Amoxicillin use was studied similarly for indication bias controlling. The potential excess of risk conveyed by fluoroquinolones was assessed by the ratio of OR for fluoroquinolones to that for amoxicillin.Results—Of the 7443 identified cases, 75 had been exposed to fluoroquinolones in the prior 180 days, including 16 in the 30-day at-risk window (385/97 cases exposed to amoxicillin, respectively). The adjusted OR for fluoroquinolones was 1.26 (95%CI, 0.65–2.41) and that for amoxicillin of 1.36 (95% CI, 1.05–1.78). Ratio of OR for fluoroquinolones to that for amoxicillin was estimated at 0.92 (95% CI, 0.46–1.86). Result was similar when extending outcome definition to unruptured events (ratio of OR for fluoroquinolones to that for amoxicillin, 0.97 [95% CI, 0.61–1.53]).Conclusions—This study did not evidence an excess of risk of intracranial aneurysm or dissection with fluoroquinolone use.

    更新日期:2020-01-23
  • Is Anatomical Variations a Risk Factor for Cerebral Vasospasm in Anterior Communicating Complex Aneurysms Rupture?
    Stroke (IF 6.046) Pub Date : 2020-01-22
    Alice Jacquens; Eimad Shotar; Camille Bombled; Benjamin Glémain; Nader-Antoine Sourour; Aurélien Nouet; Kevin Premat; Stephanie Lenck; Vincent Degos; Frédéric Clarençon

    Background and Purpose—One-third of ruptured aneurysms are located on the anterior communicating complex with high prevalence of anatomic variations of this arterial segment. In this study, we hypothesized that anatomic variations of the anterior communicating complex increase the risk of angiographic vasospasm.Methods—Retrospective study of prospectively collected data from a monocentric subarachnoid hemorrhage cohort of patients admitted to neurointensive care between 2002 and 2018. Univariate followed by multivariate logistic regression analysis was used to identify factors associated with angiographic vasospasm.Results—One thousand three hundred seventy-four patients with aneurismal subarachnoid hemorrhage were admitted to our institution; 29.8% (n=410) were related to an anterior communicating complex aneurysm rupture; 9.2% (n=38) of them showed an anterior communicating artery variation. Angiographic vasospasm was diagnosed in 55.6% of this subgroup (vs 28.1%, P=0.003). In the multivariate analysis, external ventricular drain (2.2 [1.32–3.65], P=0.003) and anterior communicating artery variation (2.40 [1.2–4.9], P=0.04) were independently and significantly associated with angiographic vasospasm, while age above 60 years (0.3 [0.2–0.7]; P=0.002) was a protective factor. However, anterior communicating artery variation was not statistically associated with ischemic vasospasm or poor neurological outcome after anterior communicating artery aneurysm rupture.Conclusions—Anatomic variation of anterior communicating artery could be a new biomarker to identify patients at risk to develop angiographic vasospasm post-subarachnoid hemorrhage. External validation cohorts are necessary to confirm these results.

    更新日期:2020-01-23
  • Paramedic Global Impression of Change During Prehospital Evaluation and Transport for Acute Stroke
    Stroke (IF 6.046) Pub Date : 2020-01-20
    Kristina Shkirkova; Samuel Schuberg; Emma Balouzian; Sidney Starkman; Marc Eckstein; Samuel Stratton; Franklin D. Pratt; Scott Hamilton; Latisha Sharma; David S. Liebeskind; Robin Conwit; Jeffrey L. Saver; Nerses Sanossian; For the FAST-MAG Investigators and Coordinators

    Background and Purpose—The prehospital setting is a promising site for therapeutic intervention in stroke, but current stroke screening tools do not account for the evolution of neurological symptoms in this early period. We developed and validated the Paramedic Global Impression of Change (PGIC) Scale in a large, prospective, randomized trial.Methods—In the prehospital FAST-MAG (Field Administration of Stroke Therapy-Magnesium) randomized trial conducted from 2005 to 2013, EMS providers were asked to complete the PGIC Scale (5-point Likert scale values: 1-much improved, 2-mildly improved, 3-unchanged, 4-mildly worsened, 5-much worsened) for neurological symptom change during transport for consecutive patients transported by ambulance within 2 hours of onset. We analyzed PGIC concurrent validity (compared with change in Glasgow Coma Scale, Los Angeles Motor Scale), convergent validity (compared with National Institutes of Health Stroke Scale severity measure performed in the emergency department), and predictive validity (of neurological deterioration after hospital arrival and of final 90-day functional outcome). We used PGIC to characterize differential prehospital course among stroke subtypes.Results—Paramedics completed the PGIC in 1691 of 1700 subjects (99.5%), among whom 635 (37.5%) had neurological deficit evolution (32% improvement, 5.5% worsening) during a median prehospital care period of 33 (IQR, 27–39) minutes. Improvement was associated with diagnosis of cerebral ischemia rather than intracranial hemorrhage, milder stroke deficits on emergency department arrival, and more frequent nondisabled and independent 3-month outcomes. Conversely, worsening on the PGIC was associated with intracranial hemorrhage, more severe neurological deficits on emergency department arrival, more frequent treatment with thrombolytic therapy, and poor disability outcome at 3 months.Conclusions—The PGIC scale is a simple, validated measure of prehospital patient course that has the potential to provide information useful to emergency department decision-making.Registration—URL: https://www.clinicaltrials.gov. Unique identifier: NCT00059332.

    更新日期:2020-01-21
  • Perfusion Computed Tomography Accurately Quantifies Collateral Flow After Acute Ischemic Stroke
    Stroke (IF 6.046) Pub Date : 2020-01-17
    Longting Lin; Chushuang Chen; Huiqiao Tian; Andrew Bivard; Neil Spratt; Christopher R. Levi; Mark W. Parsons

    Background and Purpose—This study aimed to derive and validate an optimal collateral measurement on computed tomographic perfusion imaging for patients with acute ischemic stroke.Methods—In step 1 analysis of 22 patients, the parasagittal region of the ischemic hemisphere was divided into 6 pial arterial zones to derive the optimal collateral threshold by receiver operating characteristic analysis. The collateral threshold was then used to define the collateral index in step 2. In step 2 analysis of 156 patients, the computed tomographic perfusion collateral index was compared with collateral scores on dynamic computed tomographic angiography in predicting good clinical outcome by simple regression.Results—The optimal collateral threshold was delay time >6 s (sensitivity, 88%; specificity, 92%). The computed tomographic perfusion collateral index, defined by the ratio of delay time >6 s/delay time >2 s volume, showed a significant correlation with dynamic computed tomographic angiography collateral scores (correlation coefficient, 0.62; P<0.001), with an optimal cut point of 31.8% in predicting good collateral status (sensitivity of 83% and specificity of 86%). When predicting good clinical outcome, the delay time collateral index showed a similar predictive power to dynamic computed tomographic angiography collaterals (area under the curve, 0.78 [0.67–0.83] and 0.77 [0.69–0.84], respectively; P<0.001).Conclusions—Computed tomographic perfusion can accurately quantify collateral flow after acute ischemic stroke.

    更新日期:2020-01-17
  • A Risk Score Including Carotid Plaque Inflammation and Stenosis Severity Improves Identification of Recurrent Stroke
    Stroke (IF 6.046) Pub Date : 2020-01-17
    Peter J. Kelly; Pol Camps-Renom; Nicola Giannotti; Joan Martí-Fàbregas; Jonathan P. McNulty; Jean-Claude Baron; Mary Barry; Shelagh B. Coutts; Simon Cronin; Raquel Delgado-Mederos; Eamon Dolan; Alejandro Fernández-León; Shane Foley; Joseph Harbison; Gillian Horgan; Eoin Kavanagh; Michael Marnane; John McCabe; Ciaran McDonnell; Vijay K. Sharma; David J. Williams; Martin O’Connell; Sean Murphy

    Background and Purpose—In randomized trials of symptomatic carotid endarterectomy, only modest benefit occurred in patients with moderate stenosis and important subgroups experienced no benefit. Carotid plaque 18F-fluorodeoxyglucose uptake on positron emission tomography, reflecting inflammation, independently predicts recurrent stroke. We investigated if a risk score combining stenosis and plaque 18F-fluorodeoxyglucose would improve the identification of early recurrent stroke.Methods—We derived the score in a prospective cohort study of recent (<30 days) non-severe (modified Rankin Scale score ≤3) stroke/transient ischemic attack. We derived the SCAIL (symptomatic carotid atheroma inflammation lumen-stenosis) score (range, 0–5) including 18F-fluorodeoxyglucose standardized uptake values (SUVmax <2 g/mL, 0 points; SUVmax 2–2.99 g/mL, 1 point; SUVmax 3–3.99 g/mL, 2 points; SUVmax ≥4 g/mL, 3 points) and stenosis (<50%, 0 points; 50%–69%, 1 point; ≥70%, 2 points). We validated the score in an independent pooled cohort of 2 studies. In the pooled cohorts, we investigated the SCAIL score to discriminate recurrent stroke after the index stroke/transient ischemic attack, after positron emission tomography-imaging, and in mild or moderate stenosis.Results—In the derivation cohort (109 patients), recurrent stroke risk increased with increasing SCAIL score (P=0.002, C statistic 0.71 [95% CI, 0.56–0.86]). The adjusted (age, sex, smoking, hypertension, diabetes mellitus, antiplatelets, and statins) hazard ratio per 1-point SCAIL increase was 2.4 (95% CI, 1.2–4.5, P=0.01). Findings were confirmed in the validation cohort (87 patients, adjusted hazard ratio, 2.9 [95% CI, 1.9–5], P<0.001; C statistic 0.77 [95% CI, 0.67–0.87]). The SCAIL score independently predicted recurrent stroke after positron emission tomography-imaging (adjusted hazard ratio, 4.52 [95% CI, 1.58–12.93], P=0.005). Compared with stenosis severity (C statistic, 0.63 [95% CI, 0.46–0.80]), prediction of post-positron emission tomography stroke recurrence was improved with the SCAIL score (C statistic, 0.82 [95% CI, 0.66–0.97], P=0.04). Findings were confirmed in mild or moderate stenosis (adjusted hazard ratio, 2.74 [95% CI, 1.39–5.39], P=0.004).Conclusions—The SCAIL score improved the identification of early recurrent stroke. Randomized trials are needed to test if a combined stenosis-inflammation strategy improves selection for carotid revascularization where benefit is currently uncertain.

    更新日期:2020-01-17
  • Carotid Intima-Media Thickness and the Risk of First Stroke in Patients With Hypertension
    Stroke (IF 6.046) Pub Date : 2020-01-17
    Pengfei Sun; Lishun Liu; Chengzhang Liu; Yan Zhang; Ying Yang; Xianhui Qin; Jianping Li; Jingjing Cao; Yuanyuan Zhang; Ziyi Zhou; Xiping Xu; Yong Huo

    Background and Purpose—This study aimed to investigate the association between mean carotid intima-media thickness (cIMT) and the risk of first stroke and examine any possible effect modifiers in patients with hypertension.Methods—A total of 11 547 hypertensive participants without history of stroke from the CSPPT (China Stroke Primary Prevention Trial) were included in this analysis. The primary outcome was first stroke.Results—Over a median follow-up of 4.4 years, 726 first strokes were identified, of which 631 were ischemic, and 90 were hemorrhagic. A per SD increase in mean cIMT was positively associated with the risk of first stroke (hazard ratio [HR], 1.11 [95% CI, 1.03–1.20]), and first ischemic stroke (HR, 1.10 [95% CI, 1.01–1.20]). Moreover, when cIMT was categorized in quartiles, the higher risks of first stroke (HR, 1.31 [95% CI, 1.06–1.61]) and first hemorrhagic stroke (HR, 2.25 [95% CI, 1.11–4.58]) were found in participants in quartile 2 to 4 (≥0.66 mm), compared with those in quartile 1 (<0.66 mm). More importantly, the cIMT-first stroke association was significantly stronger in participants with higher mean arterial pressure (≥109.3 [quintile 5] versus <109.3 mm Hg, P-interaction=0.024) or diastolic blood pressure levels (≥90.7 [quintile 5] versus <90.7 mm Hg, P-interaction=0.009).Conclusions—There was a significant positive association between baseline cIMT and the risk of first stroke in patients with hypertension. This association was even stronger among those with higher mean arterial pressure or diastolic blood pressure levels.

    更新日期:2020-01-17
  • Characteristics and Outcomes of Retinal Artery Occlusion
    Stroke (IF 6.046) Pub Date : 2020-01-17
    Emily M. Schorr; Kyle C. Rossi; Laura K. Stein; Brian L. Park; Stanley Tuhrim; Mandip S. Dhamoon

    Background and Purpose—There are few large studies examining comorbidities, outcomes, and acute interventions for patients with retinal artery occlusion (RAO). RAO shares pathophysiology with acute ischemic stroke (AIS); direct comparison may inform emergent treatment, evaluation, and secondary prevention.Methods—The National Readmissions Database contains data on ≈50% of US hospitalizations from 2013 to 2015. We used International Classification of Diseases, Ninth Revision, codes to identify and compare index RAO and AIS admissions, comorbidities, and interventions and Clinical Comorbidity Software codes to identify readmissions causes, using survey-weighted methods when possible. Cumulative risk of all-cause readmission after RAO ≤1 year was estimated by Kaplan-Meier analysis.Results—Among 4871 RAO and 1 239 963 AIS admissions, patients with RAO were less likely (P<0.0001) than patients with AIS to have diabetes mellitus (RAO, 24.3% versus AIS, 36.8%), congestive heart failure (9.1% versus 14.8%), atrial fibrillation (15.5% versus 25.2%), or hypertension (62.2% versus 67.6%) but more likely to have valvular disease (13.3% versus 10.5%) and tobacco usage (38.6% versus 32.9%). In RAO admissions, thrombolysis was administered in 2.9% (5.8% in central RAO subgroup, versus 8.0% of AIS), therapeutic anterior chamber paracentesis in 1.0%, thrombectomy in none; 1.4% received carotid endarterectomy during index admission, 1.6% within 30 days. Nearly 1 in 10 patients with RAO were readmitted within 30 days and were more than twice as likely as patients with AIS to be readmitted for dysrhythmia or endocarditis. Readmission for stroke after RAO was the highest within the first 150 days after index admission, and risk was higher in central RAO than in branch RAO.Conclusions—Patients with RAO had high prevalence of many stroke risk factors, particularly valvular disease and smoking, which can be addressed to minimize subsequent risk. Despite less baseline atrial fibrillation, RAO patients were more likely to be readmitted for atrial fibrillation/dysrhythmias. A variety of interventions was administered. AIS risk is the highest shortly after RAO, emphasizing the importance of urgent, thorough neurovascular evaluation.

    更新日期:2020-01-17
  • Safety and Outcomes of Intravenous Thrombolysis in Posterior Versus Anterior Circulation Stroke
    Stroke (IF 6.046) Pub Date : 2020-01-09
    Boris Keselman; Zuzana Gdovinová; Dalius Jatuzis; Teresa Pinho E. Melo; Aleksandras Vilionskis; Roberto Cavallo; Senta Frol; Lubomir Jurak; Bahar Koyuncu; Ana Paiva Nunes; Alfredo Petrone; Kennedy R. Lees; Michael V. Mazya

    Background and Purpose—Posterior circulation stroke (PCS) accounts for 5% to 19% of patients with acute stroke receiving intravenous thrombolysis. We aimed to compare safety and outcomes following intravenous thrombolysis between patients with PCS and anterior circulation stroke (ACS) and incorporate the results in a meta-analysis.Methods—We included patients in the Safe Implementation of Treatments in Stroke Thrombolysis Registry 2013 to 2017 with computed tomography/magnetic resonance angiographic occlusion data. Outcomes were parenchymal hematoma, symptomatic intracerebral hemorrhage (SICH) per SITS-MOST (Safe Implementation of Thrombolysis in Stroke Monitoring Study), ECASS II (Second European Co-operative Stroke Study) and NINDS (Neurological Disorders and Stroke definition), 3-month modified Rankin Scale score, and death. Adjustment for SICH risk factors (age, sex, National Institutes of Health Stroke Scale, blood pressure, glucose, and atrial fibrillation) and center was done using inverse probability treatment weighting, after which an average treatment effect (ATE) was calculated. Meta-analysis of 13 studies comparing outcomes in PCS versus ACS after intravenous thrombolysis was conducted.Results—Of 5146 patients, 753 had PCS (14.6%). Patients with PCS had lower median National Institutes of Health Stroke Scale: 7 (interquartile range, 4–13) versus 13 (7–18), P<0.001 and fewer cerebrovascular risk factors. In patients with PCS versus ACS, parenchymal hematoma occurred in 3.2% versus 7.9%, ATE (95% CI): −4.7% (−6.3% to 3.0%); SICH SITS-MOST in 0.6% versus 1.9%, ATE: −1.4% (−2.2% to −0.7%); SICH NINDS in 3.1% versus 7.8%, ATE: −3.0% (−6.3% to 0.3%); SICH ECASS II in 1.8% versus 5.4%, ATE: −2.3% (−5.3% to 0.7%). In PCS versus ACS, 3-month outcomes (70% data availability) were death 18.5% versus 20.5%, ATE: 6.0% (0.7%–11.4%); modified Rankin Scale score 0–1, 45.2% versus 37.5%, ATE: 1.7% (−6.6% to 3.2%); modified Rankin Scale score 0–2, 61.3% versus 49.4%, ATE: 2.4% (3.1%–7.9%). Meta-analysis showed relative risk for SICH in PCS versus ACS being 0.49 (95% CI, 0.32–0.75).Conclusions—The risk of bleeding complications after intravenous thrombolysis in PCS was half that of ACS, with similar functional outcomes and higher risk of death, acknowledging limitations of the National Institutes of Health Stroke Scale for stroke severity or infarct size adjustment.

    更新日期:2020-01-09
  • First-Ever Ischemic Stroke and Incident Major Adverse Cardiovascular Events in 93 627 Older Women and Men
    Stroke (IF 6.046) Pub Date : 2020-01-09
    Luciano A. Sposato; Melody Lam; Britney Allen; Salimah Z. Shariff; Gustavo Saposnik; on behalf of the PARADISE Study Group

    Background and Purpose—Stroke risk is sex-specific, but little is known about sex differences of poststroke major adverse cardiovascular events (MACEs). Stroke-related brain damage causes autonomic dysfunction and inflammation, sometimes resulting in cardiac complications. Sex-specific cardiovascular susceptibility to stroke without the confounding effect of preexisting heart disease constitutes an unexplored field because previous studies focusing on sex differences in poststroke MACE have not excluded patients with known cardiovascular comorbidities. We therefore investigated sex-specific risks of incident MACE in a heart disease-free population-based cohort of patients with first-ever ischemic stroke and propensity-matched individuals without stroke.Methods—We included Ontario residents ≥66 years, without known cardiovascular comorbidities, with first-ever ischemic stroke between 2002 and 2012 and propensity-matched individuals without stroke. We investigated the 1-year risk of incident MACE (acute coronary syndrome, myocardial infarction, incident coronary artery disease, coronary revascularization procedures, incident heart failure, or cardiovascular death) separately for females and males. For estimating cause-specific adjusted hazard ratios, we adjusted Cox models for variables with weighted standardized differences >0.10 or those known to influence MACE risk.Results—We included 93 627 subjects without known cardiovascular comorbidities; 21 931 with first-ever ischemic stroke and 71 696 propensity-matched subjects without stroke. Groups were well-balanced on propensity-matching variables. There were 53 476 women (12 421 with and 41 055 without ischemic stroke) and 40 151 men (9510 with and 30 641 without ischemic stroke). First-ever ischemic stroke was associated with increased risk of incident MACE in both sexes. The risk was time-dependent, highest within 30 days (women: adjusted hazard ratio, 25.1 [95% CI, 19.3–32.6]; men: aHR, 23.4 [95% CI, 17.2–31.9]) and decreasing but remaining significant between 31 and 90 days (women: aHR, 4.8 [95% CI, 3.8–6.0]; men: aHR, 4.2 [95% CI, 3.3–5.4]), and 91 to 365 days (aHR, 2.1 [95% CI, 1.8–2.3]; men: aHR, 2.0 [95% CI, 1.7–2.3]).Conclusions—In this large population-based study, ischemic stroke was independently associated with increased risk of incident MACE in both sexes.

    更新日期:2020-01-09
  • Brain Cleanup as a Potential Target for Poststroke Recovery
    Stroke (IF 6.046) Pub Date : 2020-01-09
    Shun-Ming Ting; Xiurong Zhao; Guanghua Sun; Lidiya Obertas; Mercedes Ricote; Jaroslaw Aronowski

    Background and Purpose—Phagocytic cells, such as microglia and blood-derived macrophages, are a key biological modality responsible for phagocytosis-mediated clearance of damaged, dead, or displaced cells that are compromised during senescence or pathological processes, including after stroke. This process of clearance is essential to eliminate the source of inflammation and to allow for optimal brain repair and functional recovery. Transcription factor, RXR (retinoic-X-receptor) is strongly implicated in phagocytic functions regulation, and as such could represent a novel target for brain recovery after stroke.Methods—Primary cultured microglia and bone marrow macrophages were used for phagocytic study. Mice with deleted RXR-α in myeloid phagocytes (Mac-RXR-α−/−) were subjected to transient middle cerebral artery occlusion to mimic ischemic stroke and then treated with RXR agonist bexarotene. RNA-sequencing and long-term recovery were evaluated.Results—Using cultured microglia, we demonstrated that the RXR-α promotes the phagocytic functions of microglia toward apoptotic neurons. Using mice with deleted RXR-α in myeloid phagocytes (Mac-RXR-α−/−), we have shown that despite behaving similarly to the control at early time points (up to 3 days, damage established histologically and behaviorally), these Mac-RXR-α−/− mice demonstrated worsened late functional recovery and developed brain atrophy that was larger in size than that seen in control mice. The RXR-α deficiency was associated with reduced expression of genes known to be under control of the prominent transcriptional RXR partner, PPAR (peroxisome proliferator-activated receptor)-γ, as well as genes encoding for scavenger receptors and genes that signify microglia/macrophages polarization to a reparative phenotype. Finally, we demonstrated that the RXR agonist, bexarotene, administered as late as 1 day after middle cerebral artery occlusion, improved neurological recovery, and reduced the atrophy volume as assessed 28 days after stroke. Bexarotene did not improve outcome in Mac-RXR-α−/− mice.Conclusions—Altogether, these data suggest that phagocytic cells control poststroke recovery and that RXR in these cells represents an attractive target with exceptionally long therapeutic window.

    更新日期:2020-01-09
  • Diastolic Blood Pressure Is Associated With Regional White Matter Lesion Load
    Stroke (IF 6.046) Pub Date : 2020-01-08
    Michelle R. Caunca; Marialaura Simonetto; Ying Kuen Cheung; Noam Alperin; Sang H. Lee; Mitchell S.V. Elkind; Ralph L. Sacco; Tatjana Rundek; Clinton B. Wright

    Background and Purpose—Few studies have examined the separate contributions of systolic blood pressure and diastolic blood pressures (DBP) on subclinical cerebrovascular disease, especially using the 2017 American College of Cardiology/American Heart Association Blood Pressure Guidelines. Furthermore, associations with region-specific white matter hyperintensity volume (WMHV) are underexplored.Methods—Using data from the NOMAS (Northern Manhattan Study), a prospective cohort study of stroke risk and cognitive aging, we examined associations between systolic blood pressure and DBP, defined by the 2017 American College of Cardiology/American Heart Association guidelines, with regional WMHV. We used a linear mixed model approach to account for the correlated nature of regional brain measures.Results—The analytic sample (N=1205; mean age 64±8 years) consisted of 61% women and 66% Hispanics/Latinos. DBP levels were significantly related to WMHV differentially across regions (P for interaction<0.05). Relative to those with DBP 90+ mm Hg, participants with DBP <80 mm Hg had 13% lower WMHV in the frontal lobe (95% CI, −21% to −3%), 11% lower WMHV in the parietal lobe (95% CI, −19% to −1%), 22% lower WMHV in the anterior periventricular region (95% CI, −30% to −14%), and 16% lower WMHV in the posterior periventricular region (95% CI, −24% to −6%). Participants with DBP 80 to 89 mm Hg also exhibited about 12% (95% CI, −20% to −3%) lower WMHV in the anterior periventricular region and 9% (95% CI, −18% to −0.4%) lower WMHV in the posterior periventricular region, relative to participants with DBP 90≥ mm Hg. Post hoc pairwise t tests showed that estimates for periventricular WMHV were significantly different from estimates for temporal WMHV (Holms stepdown–adjusted P<0.05). Systolic blood pressure was not strongly related to regional WMHV.Conclusions—Lower DBP levels, defined by the 2017 American College of Cardiology/American Heart Association guidelines, were related to lower white matter lesion load, especially in the periventricular regions relative to the temporal region.

    更新日期:2020-01-08
  • Liver Fibrosis Indices and Outcomes After Primary Intracerebral Hemorrhage
    Stroke (IF 6.046) Pub Date : 2020-01-07
    Neal S. Parikh; Hooman Kamel; Babak B. Navi; Costantino Iadecola; Alexander E. Merkler; Arun Jesudian; Jesse Dawson; Guido J. Falcone; Kevin N. Sheth; David J. Roh; Mitchell S.V. Elkind; Daniel F. Hanley; Wendy C. Ziai; Santosh B. Murthy

    Background and Purpose—Cirrhosis—clinically overt, advanced liver disease—is associated with an increased risk of hemorrhagic stroke and poor stroke outcomes. We sought to investigate whether subclinical liver disease, specifically liver fibrosis, is associated with clinical and radiological outcomes in patients with primary intracerebral hemorrhage.Methods—We performed a retrospective cohort study using data from the Virtual International Stroke Trials Archive–Intracerebral Hemorrhage. We included adult patients with primary intracerebral hemorrhage presenting within 6 hours of symptom onset. We calculated 3 validated fibrosis indices—Aspartate Aminotransferase–Platelet Ratio Index, Fibrosis-4 score, and Nonalcoholic Fatty Liver Disease Fibrosis Score—and modeled them as continuous exposure variables. Primary outcomes were admission hematoma volume and hematoma expansion. Secondary outcomes were mortality, and the composite of major disability or death, at 90 days. We used linear and logistic regression models adjusted for previously established risk factors.Results—Among 432 patients with intracerebral hemorrhage, the mean Aspartate Aminotransferase–Platelet Ratio Index, Fibrosis-4, and Nonalcoholic Fatty Liver Disease Fibrosis Score values on admission reflected intermediate probabilities of fibrosis, whereas standard hepatic assays and coagulation parameters were largely normal. After adjusting for potential confounders, Aspartate Aminotransferase–Platelet Ratio Index was associated with hematoma volume (β, 0.20 [95% CI, 0.04–0.36]), hematoma expansion (odds ratio, 1.6 [95% CI, 1.1–2.3]), and mortality (odds ratio, 1.8 [95% CI, 1.1–2.7]). Fibrosis-4 was also associated with hematoma volume (β, 0.27 [95% CI, 0.07–0.47]), hematoma expansion (odds ratio, 1.9 [95% CI, 1.2–3.0]), and mortality (odds ratio, 2.0 [95% CI, 1.1–3.6]). Nonalcoholic Fatty Liver Disease Fibrosis Score was not associated with any outcome. Indices were not associated with the composite of major disability or death.Conclusions—In patients with largely normal liver chemistries, 2 liver fibrosis indices were associated with admission hematoma volume, hematoma expansion, and mortality after intracerebral hemorrhage.

    更新日期:2020-01-07
  • Recovery and Prediction of Dynamic Precision Grip Force Control After Stroke
    Stroke (IF 6.046) Pub Date : 2020-01-07
    Gaia Valentina Pennati; Jeanette Plantin; Loïc Carment; Pauline Roca; Jean-Claude Baron; Elena Pavlova; Jörgen Borg; Påvel G. Lindberg

    Background and Purpose—Dexterous object manipulation, requiring generation and control of finger forces, is often impaired after stroke. This study aimed to describe recovery of precision grip force control after stroke and to determine clinical and imaging predictors of 6-month performance.Methods—Eighty first-ever stroke patients with varying degrees of upper limb weakness were evaluated at 3 weeks, 3 months, and 6 months after stroke. Twenty-three healthy individuals of comparable age were also studied. The Strength-Dexterity test was used to quantify index finger and thumb forces during compression of springs of varying length in a precision grip. The coordination between finger forces (CorrForce), along with Dexterity-score and Repeatability-score, was calculated. Anatomical magnetic resonance imaging was used to calculate weighted corticospinal tract lesion load (wCST-LL).Results—CorrForce, Dexterity-score, and Repeatability-score in the affected hand were dramatically lower at each time point compared with the less-affected hand and the control group, even in patients with mild motor impairment according to Fugl-Meyer assessment. Improved performance over time occurred in CorrForce and Dexterity-score but not in Repeatability-score. The Fugl-Meyer assessment hand subscale, sensory function, and wCST-LL best predicted CorrForce and Dexterity-score status at 6 months (R2=0.56 and 0.87, respectively). wCST-LL explained substantial variance in CorrForce (R2=0.34) and Dexterity-score (R2=0.50) at 6 months; two-point discrimination and Fugl-Meyer score accounted for considerable additional variance. Absence of recovery in CorrForce was predicted by wCST-LL >4 cc and in Dexterity-score by wCST-LL >6 cc.Conclusions—Findings highlight persisting deficits in the ability to grasp and control finger forces after stroke. wCST-LL was the strongest predictor of performance at 6 months, but early two-point discrimination and Fugl-Meyer score had substantial additional predictive value.Clinical Trial Registration—URL: https://www.clinicaltrials.gov. Unique identifier: NCT02878304.

    更新日期:2020-01-07
  • Normal-Appearing White Matter Integrity Is a Predictor of Outcome After Ischemic Stroke
    Stroke (IF 6.046) Pub Date : 2020-01-07
    Sharmila Sagnier; Gwenaëlle Catheline; Bixente Dilharreguy; Pierre-Antoine Linck; Pierrick Coupé; Fanny Munsch; Antoine Bigourdan; Sabrina Debruxelles; Mathilde Poli; Stéphane Olindo; Pauline Renou; François Rouanet; Vincent Dousset; Sylvie Berthoz; Thomas Tourdias; Igor Sibon

    Background and Purpose—The aim of the present study was to evaluate the relationship between normal-appearing white matter (NAWM) integrity and postischemic stroke recovery in 4 main domains including cognition, mood, gait, and dependency.Methods—A prospective study was conducted, including patients diagnosed for an ischemic supratentorial stroke on a 3T brain MRI performed 24 to 72 hours after symptom onset. Clinical assessment 1 year after stroke included a Montreal Cognitive Assessment, an Isaacs set test, a Zazzo cancelation task, a Hospital Anxiety and Depression scale, a 10-meter walking test, and a modified Rankin Scale (mRS). Diffusion tensor imaging parameters in the NAWM were computed using FMRIB (Functional Magnetic Resonance Imaging of the Brain) Diffusion Toolbox. The relationships between mean NAWM diffusion tensor imaging parameters and the clinical scores were assessed using linear and ordinal regression analyses, including the volumes of white matter hyperintensities, gray matter, and ischemic stroke as radiological covariates.Results—Two hundred seven subjects were included (66±13 years old; 67% men; median National Institutes of Health Stroke Scale score, 3; interquartile range, 2–6). In the models including only radiological variables, NAWM fractional anisotropy was associated with the mRS and the cognitive scores. After adjusting for demographic confounders, NAWM fractional anisotropy remained a significant predictor of mRS (β=−0.24; P=0.04). Additional path analysis showed that NAWM fractional anisotropy had a direct effect on mRS (β=−0.241; P=0.001) and a less important indirect effect mediating white matter hyperintensity burden. Similar results were found with mean diffusivity, axial diffusivity, and radial diffusivity. In further subgroup analyses, a relationship between NAWM integrity in widespread white matter tracts, mRS, and Isaacs set test was found in right hemispheric strokes.Conclusions—NAWM diffusion tensor imaging parameters measured early after an ischemic stroke are independent predictors of functional outcome and may be additional markers to include in studies evaluating poststroke recovery.

    更新日期:2020-01-07
  • Characterization of Carotid Atherosclerotic Plaques Using 3-Dimensional MERGE Magnetic Resonance Imaging and Correlation With Stroke Risk Factors
    Stroke (IF 6.046) Pub Date : 2020-01-06
    Kiyoko Murata; Nozomu Murata; Baocheng Chu; Hiroko Watase; Daniel S. Hippe; Niranjan Balu; Jie Sun; Xihai Zhao; Thomas S. Hatsukami; Chun Yuan; on behalf of the CARE-II Study Collaborators

    Background and Purpose—High-resolution magnetic resonance imaging is capable of characterizing carotid atherosclerotic plaque morphology and composition. Most reported carotid plaque imaging techniques are 2-dimensional (2D) based with limited longitudinal coverage of ≈30 mm, which may be insufficient for complete visualization of extracranial carotid atheroma. A 3D black-blood imaging technique, motion-sensitized driven equilibrium prepared rapid gradient echo technique (3D-MERGE) can provide larger coverage. We sought to use 3D-MERGE to investigate carotid atherosclerosis plaque distribution and to analyze their correlation with clinical information and stroke risk factors.Methods—From 5 hospitals in China, 97 subjects suspected of recent stroke or transient ischemic attack were imaged with 3D-MERGE within 2 weeks of symptoms using 3T magnetic resonance imaging. Images were analyzed by 2 reviewers. Plaque length was calculated and categorized as plaques within, partially outside, or completely outside of typical 2D magnetic resonance imaging coverage. Associations between plaque features and clinical information, stroke risk factors were assessed.Results—Ninety-seven subjects with 194 carotid arteries (70 men and 27 women, mean age 60 years) were analyzed. Of the 136 plaques identified, 68 (50%) were within, 46 (33.8%) were partially outside, and 22 (16.2%) were completely outside of 2D magnetic resonance imaging coverage. Total plaque length was significantly positively associated with male sex (P<0.001), hypertension (P=0.011), and history of smoking (P<0.001). Hypertensive subjects were more likely to have at least one plaque completely outside the 2D magnetic resonance imaging coverage than nonhypertensive subjects (P=0.007).Conclusions—The 3D-MERGE allows for the identification of substantially more carotid plaques than 2D black-blood techniques. The extent and distribution of plaque, identified by the larger coverage afforded by 3D-MERGE, were found to correlate significantly with male sex and risk factors that are common among patients with stroke, including hypertension and history of cigarette smoking.

    更新日期:2020-01-06
  • Smoking Status and Functional Outcomes After Acute Ischemic Stroke
    Stroke (IF 6.046) Pub Date : 2020-01-03
    Ryu Matsuo; Tetsuro Ago; Fumi Kiyuna; Noriko Sato; Kuniyuki Nakamura; Junya Kuroda; Yoshinobu Wakisaka; Takanari Kitazono

    Background and Purpose—Smoking is an established risk factor for stroke; however, it is uncertain whether prestroke smoking status affects clinical outcomes of acute ischemic stroke. This study aimed to elucidate the association between smoking status and functional outcomes after acute ischemic stroke.Methods—Using a multicenter hospital-based stroke registry in Japan, we investigated 10 825 patients with acute ischemic stroke hospitalized between July 2007 and December 2017 who had been independent before stroke onset. Smoking status was categorized into those who had never smoked (nonsmokers), former smokers, and current smokers. Clinical outcomes included poor functional outcome (modified Rankin Scale score ≥2) and functional dependence (modified Rankin Scale score 2–5) at 3 months. We adjusted for potential confounding factors using a logistic regression analysis.Results—The mean age of patients was 70.2±12.2 years, and 37.0% were women. There were 4396 (42.7%) nonsmokers, 3328 (32.4%) former smokers, and 2561 (24.9%) current smokers. The odds ratio (95% CI) for poor functional outcome after adjusting for confounders increased in current smokers (1.29 [1.11–1.49] versus nonsmokers) but not in former smokers (1.05 [0.92–1.21] versus nonsmokers). However, among the former smokers, the odds ratio of poor functional outcome was higher in those who quit smoking within 2 years of stroke onset (1.75 [1.15–2.66] versus nonsmokers). The risk of poor functional outcome tended to increase as the number of daily cigarettes increased in current smokers (P for trend=0.002). All these associations were maintained for functional dependence.Conclusions—Current and recent smoking is associated with an increased risk of unfavorable functional outcomes at 3 months after acute ischemic stroke.Clinical Trial Registration—URL: http://www.fukuoka-stroke.net/english/index.html. Unique identifier: 000000800.

    更新日期:2020-01-04
  • Computed Tomography Perfusion Identifies Patients With Stroke With Impaired Cardiac Function
    Stroke (IF 6.046) Pub Date : 2020-01-03
    Carlos Garcia-Esperon; Neil J. Spratt; Shyam Gangadharan; Ferdinand Miteff; Andrew Bivard; Thomas Lillicrap; Shinya Tomari; Christopher R. Levi; Mark W. Parsons

    Background and Purpose—Low left ventricular ejection fraction (LVEF) leads to worse outcomes after stroke. We hypothesized that the arterial input function (AIF) variability on perfusion computed tomography, especially the time between scan onset and end of AIF (SO-EndAIF), would reflect reduction of cardiac output.Methods—Retrospective analysis of consecutive stroke patients, who underwent computed tomography between January 2013 and September 2018, was performed in 2 parts. (1) To determine the correlation between SO-EndAIF and LVEF, all patients with a transthoracic echocardiogram performed ±6 months from the time of stroke were included. LVEF was dichotomized as either normal (≥50%) or decreased (<50%). (2) AIF was compared with hypoperfusion volume, defined as delay time >3 seconds and with clinical outcome measured using 3-month modified Rankin Scale.Results—A total of 732 ischemic stroke patients underwent computed tomography, 231 with transthoracic echocardiogram were included in part (1), 393 with outcome data were included in part (2). In part (1), 193/231 (83.5%) had normal LVEF (median 61%) and 38/231 (16.5%) decreased LVEF (median 39%). The low-LVEF group had significantly prolonged SO-EndAIF compared with normal-LVEF group (mean of 39.7 versus 26 second; P<0.001), and larger hypoperfusion lesions (94.9 versus 37.6 mL; P<0.001). SO-EndAIF time was strongly associated with EF, with an area under the curve of 0.86. Twenty nine seconds was the best threshold to distinguish between normal and impaired EF (area under the curve, 0.77). In part (2), the SO-EndAIF ≥29 second group had larger hypoperfusion volumes (21.8 versus 89.7 mL; P<0.001) and infarct core (12.2 versus 2.3 mL; P<0.0001) and patients with SO-EndAIF ≥29 seconds had fewer excellent or good clinical outcomes (modified Rankin Scale score 0–1; 40% versus 22%; OR, 2.79; P<0.001, modified Rankin Scale score 0–2; 65% versus 35%; OR, 1.41; P=0.033).Conclusions—AIF width correlates with ejection fraction in acute ischemic stroke. A 29-second threshold from scan onset to end of AIF accurately predicts reduced LVEF and identifies patients more likely to have worse outcomes after stroke.

    更新日期:2020-01-04
  • MRI Vessel Wall Enhancement and Other Imaging Biomarkers in Pediatric Focal Cerebral Arteriopathy-Inflammatory Subtype
    Stroke (IF 6.046) Pub Date : 2020-01-02
    Francisco A. Perez; Gabriela Oesch; Catherine M. Amlie-Lefond

    Background and Purpose—Focal cerebral arteriopathy-inflammatory type (FCA-i) is a common cause of pediatric arterial ischemic stroke characterized angiographically by unifocal and unilateral stenosis/irregularity of the large anterior circulation arteries with a presumed inflammatory cause. Arterial vessel wall enhancement (VWE) on vessel wall magnetic resonance imaging is a potential biomarker of inflammation that may improve diagnosis, guide treatment, and predict outcomes in patients with FCA-i. We hypothesized that patients with FCA-i with more severe or extensive VWE would have worse arteriopathy, larger infarcts, worse clinical outcome, and increased risk for infarct progression/recurrence.Methods—Pediatric patients with arterial ischemic stroke, classified as FCA-i, and who underwent vessel wall imaging were retrospectively identified at our institution. Clinical data were reviewed and the Pediatric Stroke Outcome Measure at 1 year was determined as the primary clinical end point. Neuroimaging studies were assessed for infarct size, arteriopathy severity (Focal Cerebral Arteriopathy Severity Score), and VWE.Results—Nine cases of FCA-i with vessel wall imaging were evaluated, and there was a strong correlation between clinical outcome at 1-year with initial infarct volume (Spearman correlation coefficient rho=0.84; P<0.01) and arteriopathy severity (Focal Cerebral Arteriopathy Severity Score; rho=0.85; P<0.01). Patients with infarct progression/recurrence had worse Focal Cerebral Arteriopathy Severity Score at presentation compared with those without progression/recurrence (median [IQR]; 9.0 [8.0–11.8] and 5.0 [4.0–7.0], respectively; P<0.05). On the contrary, measures of VWE were not correlated with arteriopathy severity, infarct size, clinical outcome, or risk of infarct progression/recurrence. Moreover, not all patients with FCA-i demonstrated VWE.Conclusions—VWE may not be a reliable biomarker for the diagnosis or assessment of FCA-i, and future work is needed to assess the utility of vessel wall imaging in pediatric arterial ischemic stroke and FCA-i.

    更新日期:2020-01-02
  • Atrial Cardiopathy and Nonstenosing Large Artery Plaque in Patients With Embolic Stroke of Undetermined Source
    Stroke (IF 6.046) Pub Date : 2020-01-02
    Hooman Kamel; Lesly A. Pearce; George Ntaios; David J. Gladstone; Kanjana Perera; Risto O. Roine; Elena Meseguer; Ashkan Shoamanesh; Scott D. Berkowitz; Hardi Mundl; Mukul Sharma; Stuart J. Connolly; Robert G. Hart; Jeff S. Healey

    Background and Purpose—Atrial cardiopathy and atherosclerotic plaque are two potential mechanisms underlying embolic strokes of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear. A better understanding of their association may inform targeted secondary prevention strategies.Methods—We examined the association between atrial cardiopathy and atherosclerotic plaque in the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), which enrolled 7213 patients with recent ESUS during 2014 to 2017. For this analysis, we included patients with data on left atrial dimension, location of brain infarction, and cervical large artery plaque. The variables of primary interest were left atrial diameter and cervical plaque ipsilateral to brain infarction. Secondary markers of atrial cardiopathy were premature atrial contractions on Holter monitoring and newly diagnosed atrial fibrillation. For descriptive purposes, left atrial enlargement was defined as ≥4.7 cm. Multivariable logistic regression was used to examine the association between atrial cardiopathy markers and ipsilateral plaque after adjustment for age, sex, body mass index, hypertension, diabetes mellitus, current smoking, and hyperlipidemia.Results—Among 3983 eligible patients, 235 (5.9%) had left atrial enlargement, 939 (23.6%) had ipsilateral plaque, and 94 (2.4%) had both. Shared risk factors for left atrial enlargement and ipsilateral plaque were male sex, white race, hypertension, tobacco use, and coronary artery disease. Despite shared risk factors, increasing left atrial dimension was not associated with ipsilateral plaque after adjustment for covariates (odds ratio per cm, 1.1 [95% CI, 1.0–1.2]; P=0.08). We found no consistent associations between secondary markers of atrial cardiopathy and ipsilateral plaque.Conclusions—In a large population of patients with ESUS, we did not observe a notable association between atrial cardiopathy and atherosclerotic plaque, and few patients had both conditions. These findings suggest that atrial cardiopathy and atherosclerotic plaque may be distinct, nonoverlapping risk factors for stroke among ESUS patients.

    更新日期:2020-01-02
  • Risks of Stroke and Mortality in Atrial Fibrillation Patients Treated With Rivaroxaban and Warfarin
    Stroke (IF 6.046) Pub Date : 
    Mark Alberts; Yen-Wen Chen; Jennifer H. Lin; Emily Kogan; Kathryn Twyman; Dejan Milentijevic

    Background and Purpose—Oral anticoagulation therapy is standard of care for patients with nonvalvular atrial fibrillation to prevent stroke. This study compared rivaroxaban and warfarin for stroke and all-cause mortality risk reduction in a real-world setting.Methods—This retrospective cohort study (2011–2017) included de-identified patients from the Optum Clinformatics Database who started treatment with rivaroxaban or warfarin within 30 days following initial diagnosis of nonvalvular atrial fibrillation. Before nonvalvular atrial fibrillation diagnosis, patients had 6 months of continuous health plan enrollment and CHA2DS2-VASc score ≥2. Stroke severity was determined by the National Institutes of Health Stroke Scale, imputed based on machine learning algorithms. Stroke and all-cause mortality risks were compared by treatment using Cox proportional hazard regression, with inverse probability of treatment weighting to balance cohorts for baseline risk factors. Stratified analysis by treatment duration was also performed.Results—During a mean follow-up of 27 months, 175 (1.33/100 patient-years [PY]) rivaroxaban-treated and 536 (1.66/100 PY) warfarin-treated patients developed stroke. The inverse probability of treatment weighting model showed that rivaroxaban reduced stroke risk by 19% (hazard ratio [HR], 0.81 [95% CI, 0.73–0.91]). Analysis by stroke severity revealed risk reductions by rivaroxaban of 48% for severe stroke (National Institutes of Health Stroke Scale score, 16–42; HR, 0.52 [95% CI, 0.33–0.82]) and 19% for minor stroke (National Institutes of Health Stroke Scale score, 1 to <5; HR, 0.81 [95% CI, 0.68–0.96]), but no difference for moderate stroke (National Institutes of Health Stroke Scale score, 5 to <16; HR, 0.93 [95% CI, 0.78–1.10]). A total of 41 (0.31/100 PY) rivaroxaban-treated and 147 (0.44/100 PY) warfarin-treated patients died poststroke, 12 (0.09/100 PY) and 67 (0.20/100 PY) of whom died within 30 days, representing mortality risk reductions by rivaroxaban of 24% (HR, 0.76 [95% CI, 0.61–0.95]) poststroke and 59% (HR, 0.41 [95% CI, 0.28–0.60]) within 30 days.Conclusions—After the initial diagnosis of atrial fibrillation, patients treated with rivaroxaban versus warfarin had significant risk reduction for stroke, especially severe stroke, and all-cause mortality after a stroke. Findings from this observational study may help inform anticoagulant choice for stroke prevention in patients with nonvalvular atrial fibrillation.

    更新日期:2019-12-31
  • Deep Learning Detection of Penumbral Tissue on Arterial Spin Labeling in Stroke
    Stroke (IF 6.046) Pub Date : 2019-12-30
    Kai Wang; Qinyang Shou; Samantha J. Ma; David Liebeskind; Xin J. Qiao; Jeffrey Saver; Noriko Salamon; Hosung Kim; Yannan Yu; Yuan Xie; Greg Zaharchuk; Fabien Scalzo; Danny J.J. Wang

    Background and Purpose—Selection of patients with acute ischemic stroke for endovascular treatment generally relies on dynamic susceptibility contrast magnetic resonance imaging or computed tomography perfusion. Dynamic susceptibility contrast magnetic resonance imaging requires injection of contrast, whereas computed tomography perfusion requires high doses of ionizing radiation. The purpose of this work was to develop and evaluate a deep learning (DL)–based algorithm for assisting the selection of suitable patients with acute ischemic stroke for endovascular treatment based on 3-dimensional pseudo-continuous arterial spin labeling (pCASL).Methods—A total of 167 image sets of 3-dimensional pCASL data from 137 patients with acute ischemic stroke scanned on 1.5T and 3.0T Siemens MR systems were included for neural network training. The concurrently acquired dynamic susceptibility contrast magnetic resonance imaging was used to produce labels of hypoperfused brain regions, analyzed using commercial software. The DL and 6 machine learning (ML) algorithms were trained with 10-fold cross-validation. The eligibility for endovascular treatment was determined retrospectively based on the criteria of perfusion/diffusion mismatch in the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). The trained DL algorithm was further applied on twelve 3-dimensional pCASL data sets acquired on 1.5T and 3T General Electric MR systems, without fine-tuning of parameters.Results—The DL algorithm can predict the dynamic susceptibility contrast–defined hypoperfusion region in pCASL with a voxel-wise area under the curve of 0.958, while the 6 ML algorithms ranged from 0.897 to 0.933. For retrospective determination for subject-level endovascular treatment eligibility, the DL algorithm achieved an accuracy of 92%, with a sensitivity of 0.89 and specificity of 0.95. When applied to the GE pCASL data, the DL algorithm achieved a voxel-wise area under the curve of 0.94 and a subject-level accuracy of 92% for endovascular treatment eligibility.Conclusions—pCASL perfusion magnetic resonance imaging in conjunction with the DL algorithm provides a promising approach for assisting decision-making for endovascular treatment in patients with acute ischemic stroke.

    更新日期:2019-12-30
  • Development of a Novel Prognostic Model to Predict 6-Month Swallowing Recovery After Ischemic Stroke
    Stroke (IF 6.046) Pub Date : 2019-12-30
    Woo Hyung Lee; Min Hyuk Lim; Han Gil Seo; Min Yong Seong; Byung-Mo Oh; Sungwan Kim

    Background and Purpose—The aim of this study was to explore clinical and radiological prognostic factors for long-term swallowing recovery in patients with poststroke dysphagia and to develop and validate a prognostic model using a machine learning algorithm.Methods—Consecutive patients (N=137) with acute ischemic stroke referred for swallowing examinations were retrospectively reviewed. Dysphagia was monitored in the 6 months poststroke period and then analyzed using the Kaplan-Meier method and Cox regression model for clinical and radiological factors. Bayesian network models were developed using potential prognostic factors to classify patients into those with good (no need for tube feeding or diet modification for 6 months) and poor (tube feeding or diet modification for 6 months) recovery of swallowing function.Results—Twenty-four (17.5%) patients showed persistent dysphagia for the first 6 months with a mean duration of 65.6 days. The time duration of poststroke dysphagia significantly differed by tube feeding status, clinical dysphagia scale, sex, severe white matter hyperintensities, and bilateral lesions at the corona radiata, basal ganglia, or internal capsule (CR/BG/IC). Among these factors, tube feeding status (P<0.001), bilateral lesions at CR/BG/IC (P=0.001), and clinical dysphagia scale (P=0.042) were significant prognostic factors in a multivariate analysis using Cox regression models. The tree-augmented network classifier, based on 10 factors (sex, lesions at CR, BG/IC, and insula, laterality, anterolateral territory of the brain stem, bilateral lesions at CR/BG/IC, severe white matter hyperintensities, clinical dysphagia scale, and tube feeding status), performed better than other benchmarking classifiers developed in this study.Conclusions—Initial dysphagia severity and bilateral lesions at CR/BG/IC are revealed to be significant prognostic factors for 6-month swallowing recovery. The prediction of 6-month swallowing recovery was feasible based on clinical and radiological factors using the Bayesian network model. We emphasize the importance of bilateral subcortical lesions as prognostic factors that can be utilized to develop prediction models for long-term swallowing recovery.

    更新日期:2019-12-30
  • Safety of Intravenous Thrombolysis Among Patients Taking Direct Oral Anticoagulants
    Stroke (IF 6.046) Pub Date : 2019-12-30
    Shima Shahjouei; Georgios Tsivgoulis; Nitin Goyal; Alireza Sadighi; Ashkan Mowla; Ming Wang; David J. Seiffge; Ramin Zand

    Background and Purpose—There are scarce data regarding the safety of intravenous thrombolysis (IVT) in acute ischemic stroke among patients on direct oral anticoagulants (DOACs).Methods—We performed a systematic review and meta-analysis of the current literature. Data regarding all adult patients pretreated with DOAC who received IVT for acute ischemic stroke were recorded. Meta-analysis was performed by comparing the rate of symptomatic intracerebral hemorrhage in these patients with (1) stroke patients without prior anticoagulation therapy and (2) patients on warfarin with international normalized ratio <1.7. Meta-analyses were further conducted in subgroups as follows: (1) administration of DOAC within 48 hours versus an unknown interval before IVT, (2) consideration of symptomatic intracerebral hemorrhage outcome according to the National Institute of Neurological Disorders (NINDS) versus the European Cooperative Acute Stroke Study II (ECASS-II) criteria.Results—After reviewing 13 392 reports and communicating with certain authors of 12 published studies, a total of 52 823 acute ischemic stroke patients from 6 studies were enrolled in the present meta-analysis: DOACs: 366, warfarin: 2133, and 503 241 patients without prior anticoagulation. We detected no additional risk of symptomatic intracerebral hemorrhage following IVT among patients taking DOACs within 48 hours—DOACs-warfarin: NINDS (odds ratio [OR], 0.55 [95% CI, 0.19–1.59]), ECASS-II (OR, 0.77 [95% CI, 0.28–2.16]); DOACs-no-anticoagulation: NINDS (OR, 1.23 [95% CI, 0.46–3.31]), ECASS-II (OR, 0.87 [95% CI, 0.32–2.41]). Similarly, no additional risk was detected with no time limit between last DOAC intake—DOACs warfarin: NINDS (OR, 0.85 [95% CI, 0.49–1.45]), ECASS-II (OR, 1.11 [95% CI, 0.67–1.85]); DOACs-no-anticoagulation: NINDS (OR, 1.17 [95% CI, 0.43–3.15]), ECASS-II (OR, 0.87 [95% CI, 0.33–2.41]). There was no evidence of heterogeneity across included studies (I2=0%). We also provided the details of 123 individual cases with or without reversal agents before IVT. There was no significant increase in the risk of hemorrhagic transformation (OR, 1.48 [95% CI, 0.50–4.38]), symptomatic hemorrhagic transformation (OR, 0.47 [95% CI, 0.09–2.55]), or early mortality (OR, 0.60 [95% CI, 0.11–3.43]) between cohorts who did or did not receive prethrombolysis idarucizumab.Conclusions—The results of our study indicated that prior intake of DOAC appears not to increase the risk of symptomatic intracerebral hemorrhage in selected AIS patients treated with IVT.

    更新日期:2019-12-30
  • Confounding of Cerebral Blood Flow Velocity by Blood Pressure During Breath Holding or Hyperventilation in Transient Ischemic Attack or Stroke
    Stroke (IF 6.046) Pub Date : 2019-12-30
    Alastair J.S. Webb; Matteo Paolucci; Sara Mazzucco; Linxin Li; Peter M. Rothwell

    Background and Purpose—Breath holding (BH) and hyperventilation are used to assess abnormal cerebrovascular reactivity, often in relation to severity of small vessel disease and risk of stroke with carotid stenosis, but responses may be confounded by blood pressure (BP) changes. We compared effects of BP and end-tidal carbon dioxide (etCO2) on middle cerebral artery mean flow velocity (MFV) in consecutive transient ischemic attack and minor stroke patients.Methods—In the population-based, prospective OXVASC (Oxford Vascular Study) phenotyped cohort, change in MFV on transcranial Doppler ultrasound (ΔMFV, DWL-DopplerBox), beat-to-beat BP (Finometer), and etCO2 was measured during 30 seconds of BH or hyperventilation. Two blinded reviewers independently assessed recording quality. Dependence of ΔMFV on ΔBP and ΔetCO2 was determined by general linear models, stratified by quartiles.Results—Four hundred eighty-eight of 602 (81%) patients with adequate bone windows had high-quality recordings, more often in younger participants (64.6 versus 68.7 years; P<0.01), whereas 426 had hyperventilation tests (70.7%). During BH, ΔMFV was correlated with a rise in mean blood pressure (MBP; r2=0.15, P<0.001) but not ΔCO2 (r2=0.002, P=0.32), except in patients with ΔMBP <10% (r2=0.13, P<0.001). In contrast during hyperventilation, the fall in MFV was similarly correlated with reduction in CO2 and reduction in MBP (ΔCO2: r2=0.13, P<0.001; ΔMBP: r2=0.12, P<0.001), with a slightly greater effect of ΔCO2 when ΔMBP was <10% (r2=0.15). Stratifying by quartile, MFV increased linearly during BH across quartiles of ΔMBP, with no increase with ΔetCO2. In contrast, during hyperventilation, MFV decreased linearly with ΔetCO2, independent of ΔMBP.Conclusions—In older patients with recent transient ischemic attack or minor stroke, cerebral blood flow responses to BH were confounded by BP changes but reflected etCO2 change during hyperventilation. Correct interpretation of cerebrovascular reactivity responses to etCO2, including in small vessel disease and carotid stenosis, requires concurrent BP measurement.

    更新日期:2019-12-30
  • New Endovascular Approach for Hypothermia With Intrajugular Cooling and Neuroprotective Effect in Ischemic Stroke
    Stroke (IF 6.046) Pub Date : 2019-12-30
    Yunxia Duan; Di Wu; Mitchell Huber; Jingfei Shi; Hong An; Wenjing Wei; Xiaoduo He; Yuchuan Ding; Xunming Ji

    Background and Purpose—Induction of hypothermia as a stroke therapy has been limited by logistical challenges. This study was designed to determine the hypothermic and neuroprotective efficacy of infusing cold saline directly into the internal jugular (IJ) vein and compare the effects of IJ hypothermia to those achieved by intracarotid artery hypothermia in an ischemic stroke model.Methods—The right middle cerebral artery was occluded in rats using an intraluminal filament. Immediately following reperfusion, hypothermia was achieved by infusing isotonic saline through microcatheter into the right IJ or right intracarotid over 30 minutes. Infarct sizes, neurological deficits, blood-brain barrier damage, edema volume, blood-brain barrier associated molecules (MMP-9 [matrix metallopeptidase 9] and AQP-4 [aquaporin 4]), and apoptosis-associated proteins (Bcl-2 and cleaved Caspase-3) were measured.Results—We found that both IJ- and intracarotid-based infusion cooled the brain robustly with a minimal effect on rectal temperatures. This brain cooling led to significantly reduced infarct volumes at 24 hours after reperfusion, as well as decreased expression of the proapoptotic protein cleaved Caspase-3 and increased expression of the antiapoptotic protein Bcl-2. Intracarotid and IJ cooling also aided in blood-brain barrier maintenance, as shown by decreased edema volumes, reduced Evans Blue leakage, and decreased expression of edema-facilitating proteins (MMP-9 and AQP-4). Both cooling methods then translated to preserved neurological function as determined by multiple functional tests over a 28-day observation period. Most importantly, the cooling and neuroprotective efficacy of IJ cooling was comparable to intracarotid cooling by almost every metric evaluated.Conclusions—Compared with intracarotid infusion, IJ infusion conferred a similar degree of hypothermia and neuroprotection following ischemic stroke. Given the ease of establishing vascular access via the internal jugular vein and the powerful neuroprotection that hypothermia provides, IJ brain cooling could be used as a promising hypothermia-induction modality going forward.

    更新日期:2019-12-30
  • Implementation of High-Intensity Stepping Training During Inpatient Stroke Rehabilitation Improves Functional Outcomes
    Stroke (IF 6.046) Pub Date : 2019-12-30
    Jennifer L. Moore; Jan E. Nordvik; Anne Erichsen; Ingvild Rosseland; Elisabeth Bø; T. George Hornby

    Background and Purpose—Therapeutic strategies that capitalize on the intrinsic capacity for neurological recovery early poststroke to improve locomotion are uncertain. Emerging data suggest that task-specific stepping practice provided at higher cardiovascular intensities may be critical dosage parameters that could maximize locomotor recovery. The purpose of this investigation was to determine the comparative effectiveness of providing high-intensity training on locomotor capacity early poststroke as compared with usual care.Methods—A quasi-experimental design was used to compare changes in stepping activity (StepWatch), walking, and balance outcomes during usual care (n=56) versus high-intensity stepping intervention (n=54) in inpatient stroke patients. Primary outcomes assessed weekly included self-selected and fastest gait speed, 6-minute walk test, and the Berg Balance Scale, with secondary outcomes of Swedish Postural Assessment Scale for Stroke-Norwegian version, Functional Ambulation Category, 30-s sit-to-stand, strength (average manual muscle testing), and Barthel Index. Regression analyses identified relationships between demographics, baseline function, and training activities (steps per day; duration achieved, 70%–85% maximum heart rates) and primary outcomes at discharge.Results—Following implementation of high-intensity stepping, average steps per day (5777±2784) were significantly greater than during usual care (3917±2656; P<0.001). Statistically different and clinically meaningful changes in self-selected speed (0.39±0.28 versus 0.16±0.26 m/s) and fastest gait speed (0.47±0.41 versus 0.17±0.38 m/s; both P<0.001) were observed following high-intensity interventions versus usual care and at every assessment throughout the length of stay. Changes in Berg Balance Scale and 6-minute walk test were also statistically and clinically different between groups, while secondary measures of Functional Ambulation Category and strength were also different at discharge. Primary predictors of improved walking capacity were steps per day, baseline impairments, and age.Conclusions—Provision of high-intensity stepping training applied during inpatient rehabilitation resulted in significantly greater walking and balance outcomes. This training paradigm should be further tested in other contexts to determine the generalizability to real-world and community settings.

    更新日期:2019-12-30
  • Right Hemispheric Homologous Language Pathways Negatively Predicts Poststroke Naming Recovery
    Stroke (IF 6.046) Pub Date : 2019-12-30
    Zafer Keser; Rajani Sebastian; Khader M. Hasan; Argye E. Hillis

    Background and Purpose—Stroke is the leading cause of disability in United States, and aphasia is a common sequela after a left hemisphere stroke. Functional imaging and brain stimulation studies show that right hemisphere structures are detrimental to aphasia recovery but evidence from diffusion tensor imaging is lacking. We investigated the role of homologous language pathways in naming recovery after left hemispheric stroke.Methods—Patients with aphasia after a left hemispheric stroke underwent naming assessment using the Boston Naming Test and diffusion tensor imaging at the acute and chronic time points. We analyzed diffusion tensor imaging of right arcuate fasciculus and frontal aslant tracts. We used Wilcoxon rank-sum test to evaluate structural lateralization patterns and partial Spearman correlation/multivariate generalized linear model to determine the role of right arcuate fasciculus and frontal aslant tracts in naming recovery after controlling for confounders. Results were corrected for multiple comparisons.Results—On average, the structural integrity of left language pathways deteriorated more than their right homologs, such that there was rightward lateralization in the chronic stage. Regression/correlation analyses showed that greater preservation of tract integrity of right arcuate fasciculus was associated with poorer naming recovery.Conclusions—Our study provides preliminary evidence that preservation of right homologs of language pathways is associated with poor recovery of naming after a left hemispheric stroke, consistent with previous evidence that maintaining greater reliance on left hemisphere structures is associated with better language recovery.

    更新日期:2019-12-30
  • Covert Brain Infarcts
    Stroke (IF 6.046) Pub Date : 2019-11-26
    Hugues Chabriat

    See related article, p 90 Covert brain infarcts (CBI) are predominantly small ischemic cerebral lesions that are detected on magnetic resonance imaging (MRI) in the absence of stroke events.1 They have been repeatedly reported using MRI in large population-based cohorts as well as in stroke patients in association with symptomatic ischemic or hemorrhagic lesions. Their prevalence increases considerably with aging. Previous reports suggest that the lack of acute clinical manifestations in CBI might be related to their location in the brain,2 associated lesions, or sex2,3 but not to the underlying lesion type itself or cause. CBI were initially described as silent infarcts in the literature, but the term silent was rapidly challenged and is progressively abandoned after subtle but true clinical effects were depicted at their occurrence.1,4 In the most severe forms of cerebral small vessel disease, accumulation of CBI has been shown to participate in cognitive and motor decline of progressive appearance.5 Therefore, there is no doubt that CBIs should not be considered as benign MRI markers but are true focal tissue injuries with serious potential consequences. The risk factors associated with CBIs appear very similar to those associated with stroke events.6 In previous large population-based studies, their presence or number on MRI are found strongly associated with an increased risk of incident stroke, cognitive decline, or dementia.7 Covert cerebral infarcts are also associated with a higher risk of incident cerebral lesions accumulating in the brain along aging.6 Accumulating evidence suggests that these different risks could be modulated by the number or severity of vascular risk factors and by their control.8,9 However, in clinical practice, the fact remains that no strong recommendation can be proposed today to an individual with an isolated covert infarct, whereas the same lesion associated with acute neurological manifestations will lead to a large etiological work-up and strong therapeutic recommendations. To date, there is not a single preventive trial in stroke-free patients who present only with covert cerebral infarcts on their MRI. In our aging countries, these questions are, however, crucial for preventing stroke, disability, and dementia. The number of individuals asking for an advice after the discovery of CBIs is increasing with improving access to MRI investigations, particularly in elderly people. Numerous practical questions are often raised by these incidental findings. Should we perform MRI in patients at risk of developing CBI? Should we follow them and control all their potential risk factors? Which preventive strategy should we adopt in presence of 1, 2, or several CBIs? Should we use statins, antiplatelets, or antihypertensive agents? We have not yet the answers to these questions. However, we learned from the literature that the risk associated with CBI considerably varies according to the population, age, risk factors, severity of associated cerebral lesions, and the underlying pathology. It is, therefore, crucial to delineate the group of individuals with the highest risk for testing innovative preventive strategies and treatments in the next future. In the NOMAS (Northern Manhattan Study), a population-based cohort study of stroke-free individuals aged >40 years, 1287 stroke-free subjects of median age 70 years participated in a large MRI substudy. Wright et al10 already showed that the NOMAS participants with subclinical cerebral infarcts on MRI had a greater risk of all stroke types (hazard ratio, 1.9 [95% CI, 1.1–3.3]). The highest risk corresponded to the occurrence of lacunar strokes (hazard ratio, 4.0 [95% CI, 1.3–12.3]) or of cryptogenic strokes (hazard ratio 3.6 [95% CI, 1.0–12.7]). An increased risk of mortality among Hispanic participants harboring CBI was also detected (hazard ratio 2.9 [95% CI, 1.4–5.8]).10 Interestingly, Wright et al10 showed that covert ischemic lesions with cavitation between 3 and 15 mm in diameter actually increased the risk of incident stroke but not the other small cerebral cavities observed on MRI. Their data emphasized the risk related to CBI may vary according to different cerebral small vessel lesions subtypes and ethnicity.10 In the present study of Gutierez et al11 in the journal Stroke, also obtained in the NOMAS cohort, special efforts were first made to improve the diagnosis of CBIs and to segregate them from perivascular spaces on MRI.12 Thus, voids in the brain stem were considered as covert infarcts whatever their aspects but the presence of an hyperintense rim was needed for defining covert infarcts in the subinsular cortex, infraputaminal regions, or in the cerebellum. Gutierez et al11 showed that CBIs thus defined were more frequent in the right hemisphere and smaller than lesions related to clinical stroke. They also confirmed that the presence of CBI is associated with an increased risk of any stroke, myocardial infarction, and death. But their main findings is that these different risks largely vary among subjects with CBI according to the following categorization: (1) a positive history of atrial fibrillation, congestive heart failure, or valvulopathy; (2) the presence of a stenosis of the ipsilateral extracranial or intracranial large artery; (3) irregularities or stenosis of the corresponding penetrating intracranial artery; (4) the total absence of all these potential sources of embolism.11 The risk of ischemic stroke, myocardial infarction, and that of death increased particularly in patients with either a significant stenosis of extracranial or intracranial artery or in the absence of any detectable source of embolism. The highest risk was clearly driven by the presence of stenosis of the ipsilateral extra or intracranial arteries (>50%) associated with a crude incidence rate of about 2.2%/y for stroke events, 3.2% for myocardial infarction, and 6.9% for death.11 These results are important. They further confirm that CBIs are not benign lesions. They suggest that a work-up as performed in stroke patients may help to select individuals exposed to the highest risk of stroke, myocardial infarction, or death. They indicate that individuals with CBIs and significant stenosis of extra or intracranial arteries are at increased risk of stroke, myocardial infarction, or death. Finally, these findings will certainly help determining the best population of individuals with CBI for testing future preventive strategies. The status of the cerebrovascular network clearly matters for estimating the risk associated with CBIs. Thus, look at magnetic resonance angiography when MRI shows such lesions. The research of Dr Chabriat on imaging biomarkers in cerebral small vessel disease is funded by ANR - RHU TRT_cSVEV. Dr Chabriat declares to have received fees from Servier and Hovid Companies for participating in a steering committee during the past 5 years. This work was unrelated to the content of the present article. The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. Guest Editor for this article was Emmanuel Touzé, PhD.

    更新日期:2019-12-25
  • Cerebellar Microbleed Patterns
    Stroke (IF 6.046) Pub Date : 2019-11-15
    Eric E. Smith; Frank A. Wollenweber

    See related article, p 202 After excluding rare causes, the diagnostic question in a patient with primary intracerebral hemorrhage (ICH) is whether it was caused by arteriolosclerosis due to aging, hypertension and other vascular risk factors (sometimes simply called hypertensive ICH), or cerebral amyloid angiopathy (CAA). These 2 small vessel diseases have different risk factors and prognoses. The risk for recurrence is >6-fold higher for CAA-related ICH compared with hypertensive ICH.1 For many years, the Boston criteria have served as a useful research and clinical tool for assigning the probability that a primary ICH was caused by CAA.2 Taking advantage of the fact that CAA does not affect the vessels of the basal ganglia and brain stem to the same extent as non-CAA–related arteriolosclerosis does, a diagnosis of probable or possible CAA can be made based on the pattern of hemorrhages. When 2 or more hemorrhages, including microbleeds, are restricted to the cerebral cortical surface, cerebral cortex, or subcortical white matter, without affecting the basal ganglia or brain stem, then CAA is very likely to be present. The criteria were modified in 2010 to include cortical superficial siderosis as another sign of CAA.3 Until recently, the cerebellum was a neutral territory in CAA diagnosis. It has been assumed that most cerebellar hemorrhages are caused by hypertension and not CAA. However, a case series of cerebellar hematoma resections reported that CAA was the cause in a minority (14%).4 In light of the fact that CAA can cause cerebellar hemorrhages, the Boston criteria state that “cerebellar hemorrhage [is] allowed” when making a diagnosis of probable CAA. The intent was that cerebellar hemorrhages should not disqualify a patient from a diagnosis of probable CAA if there are lobar hemorrhages or cortical superficial siderosis without deep hemorrhages (personal communication, Dr Steven Greenberg). For example, a patient with an occipital lobar ICH, one or more lobar microbleeds (or a microbleed and cortical superficial siderosis), and additionally one or more cerebellar microbleeds would be classified as probable CAA. A patient with an occipital ICH and one or more cerebellar microbleeds, without lobar microbleeds or cortical superficial siderosis, would instead be classified as possible CAA. A patient with a primary cerebellar ICH and two or more microbleeds or one microbleed and cortical superficial siderosis would be classified as probable CAA. Now, emerging evidence is showing that cerebellar hemorrhages and microbleeds can be classified as lobar (also termed superficial; ie, centered in the cerebellar cortex or underlying white matter) versus deep (ie, affecting the subcortical dentate nucleus), analogous to the classification of supratentorial microbleeds, and that the superficial and deep patterns are potentially related to the presence of CAA.5–8 However, validation against neuropathologic evidence of β-amyloid, or validated in vivo surrogates, is still lacking. This gap in knowledge is addressed by an article in this issue of Stroke, in which the authors used positron emission tomography with Pittsburgh compound B—a validated biomarker of β-amyloid—to investigate its association with deep and lobar cerebellar microbleeds.9 The authors retrospectively analyzed 257 patients with primary ICH who were categorized by modified Boston criteria as CAA-ICH (36), hypertensive ICH (100), or mixed ICH (with both deep and lobar hemorrhages or microbleeds; 121). Cerebellar microbleeds were common, being present in 85 patients (33.1%) of whom 37 harbored superficial microbleeds while 48 had either deep or mixed cerebellar microbleeds. Patients with superficial cerebellar microbleeds were more likely to have CAA-related ICH by the modified Boston criteria (assigned independently of the cerebellar microbleeds) and to exhibit other CAA-related neuroimaging markers including cortical superficial siderosis and a higher number of visible centrum semiovale perivascular spaces. Conversely, deep cerebellar microbleeds were associated with a history of hypertension and supratentorial deep microbleeds. Pittsburgh compound B positron emission tomography amyloid imaging was done in a subgroup of 33 patients with cerebellar microbleeds including 16 patients with strictly superficial cerebellar microbleeds. Cerebellar amyloid signal was significantly higher in patients with CAA-related ICH by modified Boston criteria compared with non-CAA ICH and in patients with superficial cerebellar microbleeds compared with deep or mixed cerebellar microbleeds. This study, although limited by relatively small sample size, suggests that superficial cerebellar microbleeds are associated with a highly specific pathologically validated biomarker of β-amyloid. This makes it likely that the presence or absence of superficial and deep cerebellar microbleeds will be included in future iterations of the Boston criteria. However, several important aspects of validation remain for future research. Direct pathological correlation, in hematoma resection specimens or full autopsies, is needed. The positron emission tomography ligand Pittsburgh compound B binds nonspecifically to parenchymal β-amyloid, as well as vascular β-amyloid10; so data are needed on the extent to which the positive Pittsburgh compound B signal is related to β-amyloid in either compartment. Studies with pathological confirmation will also be needed to determine how much cerebellar microbleeds add to the accuracy of CAA classification. In the present study, 1 of 36 (2.7%) patients with CAA-related ICH would have been reclassified as mixed ICH based on the presence of deep or mixed cerebellar microbleeds. The extent to which the presence or number of superficial cerebellar microbleeds increases the certainty that CAA is present is not clear. Many patients with deep or mixed ICH also had superficial cerebellar microbleeds (25/221, 11.3%). So it appears that CAA is not the exclusive cause of cerebellar superficial hemorrhages, just as it is not the exclusive cause of supratentorial lobar hemorrhages either. Whether cerebellar microbleed location, superficial versus deep, can be classified as reliably in routine radiological practice as in research studies is uncertain and warrants investigation. More studies are needed on patients with cerebellar ICH, who were excluded from the present study. Finally, prospective longitudinal studies are needed to determine whether ICH recurrence rates differ for superficial compared with deep cerebellar hemorrhages, as they do for supratentorial superficial and deep ICHs. Cerebellar microbleed location is only one of a plethora of new markers of CAA that have been discovered since the original Boston criteria were derived. Other new markers include cortical superficial siderosis, centrum semiovale lacunes and perivascular spaces, acute diffusion-weighted imaging lesions, microinfarcts, abnormal white matter diffusion, cerebral atrophy, positive β-amyloid imaging, and low cerebrospinal fluid β-amyloid.11 An international multicenter consensus effort is underway to correlate these new markers with CAA pathology, to produce a revised and recalibrated Boston criteria, version 2.0.12 This effort should provide the pathological validation of cerebellar hemorrhage location with CAA and the added discriminative value compared with other CAA markers. Dr Smith reports consulting fees from Alnylam Pharmaceuticals and Portola Pharmaceuticals and royalties from UpToDate. Dr Wollenweber reports receiving speakers fees and travel compensation from Bayer, Boehringer-Ingelheim, Bristol-Meyers Squibb, and Portola. The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. Guest Editor for this article was Jean-Claude Baron, MD, ScD.

    更新日期:2019-12-25
  • Checklists for Authors Improve the Reporting of Basic Science Research
    Stroke (IF 6.046) Pub Date : 2019-11-13
    Jens Minnerup; Ulrich Dirnagl; Wolf-Rüdiger Schäbitz

    See related article, p 291 New treatments are usually tested in animal studies to inform clinical trials. However, the value of animal experiments in predicting the effectiveness of a drug in patients has remained controversial.1 The disparity between results of experimental and clinical studies affects many research areas, for example, stroke, neurodegenerative disorders, and sepsis. Shortcomings in the design, conduct, analysis, and reporting of animal experiments contribute to translational failure.2 For example, omitting blinding and randomization in animal studies demonstrably leads to false positives and major overstatement of efficacy. Pioneered by Stroke, some journals and publishers introduced checklists for submitted manuscripts on experimental studies to prompt authors to disclose information about study design elements. In a recent article, Ramirez et al3 systematically reviewed 3 journals (Nature Medicine, Science Translational Medicine, Stroke) with and 2 control journals without such a checklist to evaluate its effect on the quality of published experimental studies. Overall, >4000 articles published over a period between 9 and 18 years were included in the analysis. In summary, marked increases in reporting on randomization, blinding, and sample size estimation were observed after implementation of checklists. Reassuringly, articles published in journals using checklists achieved relatively high reporting levels. Surprisingly and yet unexplained, however, quite a few studies reporting on randomization, blinding, or sample size calculations in Nature Medicine and Science Translational Medicine have apparently not applied them. Studies published in Stroke lack such a discrepancy, suggesting greater robustness and methodological rigor of basic science articles published in this journal. Conversely, reporting of study design elements of articles published in control journals without checklists did not change over time: Randomization and blinding procedures were reported only in approximately one-third of the articles, whereas sample size calculations were reported in <10% of the studies. A positive effect of guidelines or checklists on reporting practice has also recently been demonstrated by others (The NPQIP Collaborative Group 2019),4 in addition to a general improvement in the reporting of study design elements in the field of focal cerebral ischemia research.5 A randomized controlled trial found no effect of implementing a checklist on the compliance with the ARRIVE (Animal Research: Reporting of In Vivo Experiments) reporting guidelines at the multidiciplinary journal PLOS ONE.6 Together with the findings of the Ramirez study, the available literature points to field specific effects, and more specifically indicates that preclinical cerebrovascular research may be a leader in the quest to improve the quality of published studies. Although there is clearly still room for improvement (eg, higher prevalence of important measures to prevent bias, such as randomization or blinding, as well as sample size calculations; inclusion of both sexes in studies), these data demonstrate that journals, editorial teams, and reviewers have an important and we think ethical mandate in scientific publishing and evidence generation.7 We posit that every journal publishing basic science articles should assess study quality. This, however, clearly increases work load of investigators and authors but also editors and reviewers and may be more difficult to implement in small journals and in the lower tiers of journal rankings. The findings of Ramirez and colleagues are reassuring from the perspective of the journal Stroke. Basic science articles published in Stroke are not only selected by innovation and translational importance but also by methodological rigor. In now almost 50 years of publishing, Stroke journal and editorial team should continue its policy of publication of innovative and translationally important experimental studies of high methodological quality contributing to better diagnosis and treatment of our patients. Dr Schäbitz is associate editor for the journal Stroke. Dr Dirnagl received funding from Berlin Institute of Health. The other author reports no conflicts. The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.

    更新日期:2019-12-25
  • Depressive Symptoms After Ischemic Stroke
    Stroke (IF 6.046) Pub Date : 2019-12-10
    David L. Roth; William E. Haley; Orla C. Sheehan; Chelsea Liu; Olivio J. Clay; J. David Rhodes; Suzanne E. Judd; Mandip Dhamoon

    Background and Purpose—Persistent depression after ischemic stroke is common in stroke survivors and may be even higher in family caregivers, but few studies have examined depressive symptom levels and their predictors in patient and caregiver groups simultaneously.Methods—Stroke survivors and their family caregivers (205 dyads) were enrolled from the national REGARDS study (Reasons for Geographic and Racial Differences in Stroke) into the CARES study (Caring for Adults Recovering from the Effects of Stroke) ≈9 months after a first-time ischemic stroke. Demographically matched stroke-free dyads (N=205) were also enrolled. Participants were interviewed by telephone, and depressive symptoms were assessed with the 20-item Center for Epidemiological Studies-Depression scale.Results—Significant elevations in depressive symptoms (Ps<0.03) were observed for stroke survivors (M=8.38) and for their family caregivers (M=6.42) relative to their matched controls (Ms=5.18 and 4.62, respectively). Stroke survivors reported more symptoms of depression than their caregivers (P=0.008). No race or sex differences were found, but differential prediction of depressive symptom levels was found across patients and caregivers. Younger age and having an older caregiver were associated with more depressive symptoms in stroke survivors while being a spouse caregiver and reporting fewer positive aspects of caregiving were associated with more depressive symptoms in caregivers. The percentage of caregivers at risk for clinically significant depression was lower in this population-based sample (12%) than in previous studies of caregivers from convenience or clinical samples.Conclusions—High depressive symptom levels are common 9 months after first-time ischemic strokes for stroke survivors and family caregivers, but rates of depressive symptoms at risk for clinical depression were lower for caregivers than previously reported. Predictors of depression differ for patients and caregivers, and standards of care should incorporate family caregiving factors.

    更新日期:2019-12-25
  • Increased Incidence of Ischemic Cerebrovascular Events in Cardiovascular Patients With Elevated Apolipoprotein CIII
    Stroke (IF 6.046) Pub Date : 2019-12-04
    Oliviero Olivieri; Manuel Cappellari; Gianni Turcato; Bruno Bonetti; Domenico Girelli; Francesca Pizzolo; Simonetta Friso; Antonella Bassi; Annalisa Castagna; Nicola Martinelli

    Background and Purpose—Apo CIII (apolipoprotein CIII), a crucial regulator of lipoprotein metabolism, has been associated with increased activity of coagulation factors and thrombin generation and, in turn, with an increased risk of thromboembolic events in both arterial and venous districts. Thus, we hypothesized that it may affect the risk of acute ischemic cerebrovascular events in cardiovascular patients.Methods—We systematically checked medical records and quantified cerebral ischemic events in a cohort of 950 subjects (median age 65 with interquartile range, 55–79 years; 30.7% females) with or without angiographically defined coronary artery disease (CAD: 774 CAD and 176 CAD-free, respectively). All the subjects, enrolled between May 1999 and December 2006, were prospectively followed until death or July 31, 2018. Assessments of complete plasma lipid and apolipoprotein profiles, including Apo A-I, B, CIII, and E, were available for all subjects at enrollment.Results—After a median follow-up of 130 months (interquartile range, 69–189), 95 subjects (10%) suffered ischemic stroke/transient ischemic attack (TIA) events. Stroke/TIA subjects had higher Apo CIII plasma concentration (11.4; interquartile range: 9.3–14.4 mg/dL) at enrollment than those without stroke/TIA (10.4, interquartile range: 8.7–13.0 mg/dL). Subjects with Apo CIII levels above the median value (10.6 mg/dL) exhibited an ≈2-fold increased risk of stroke/TIA, even after adjustment for potential confounders, including sex, age, CAD diagnosis, hypertension, atrial fibrillation, oral anticoagulant treatment, and all plasma lipid parameters (hazard ratio: 2.23 [95% CI, 1.21–4.13]). This result was confirmed in CAD and CAD-free populations, separately, and even by a propensity score matching method, in which 98 CAD and 98 CAD-free subjects were one-to-one matched for all clinical and laboratory characteristics.Conclusions—These findings suggest that a high Apo CIII plasma concentration may predict an increased risk of ischemic stroke/TIA in cardiovascular patients.

    更新日期:2019-12-25
  • Cholesterol Variability and Cranial Magnetic Resonance Imaging Findings in Older Adults
    Stroke (IF 6.046) Pub Date : 2019-12-17
    Rizwan Kalani; Traci M. Bartz; Astrid Suchy-Dicey; Mitchell S.V. Elkind; Bruce M. Psaty; Lester Y. Leung; Kenneth Rice; David Tirschwell; W.T. Longstreth Jr

    Background and Purpose—Serum cholesterol variability, independent of mean, has been associated with stroke, white matter hyperintensities on cranial magnetic resonance imaging (MRI), and other cardiovascular events. We sought to assess the relationship between total serum cholesterol (TC) variability and cranial MRI findings of subclinical or covert vascular brain injury in a longitudinal, population-based cohort study of older adults.Methods—In the Cardiovascular Health Study, we assessed associations between intraindividual TC mean, trend, and variability over ≈5 years with covert brain infarction (CBI) and white matter grade (WMG) on cranial MRI. Mean TC was calculated for each study participant from 4 annual TC measurements between 2 MRI scans. TC trend was calculated as the slope of the linear regression of the TC measurements, and TC variability was calculated as the SD of the residuals from the linear regression. We evaluated the association of intraindividual TC variability with incident CBI and worsening WMG between 2 MRI scans in primary analyses and with prevalent CBI number and WMG on the follow-up MRI scan in secondary analyses.Results—Among participants who were eligible for the study and free of clinical stroke before the follow-up MRI, 17.9% of 1098 had incident CBI, and 27.8% of 1351 had worsening WMG on the follow-up MRI. Mean, trend, and variability of TC were not associated with these outcomes. TC variability, independent of mean and trend, was significantly associated with the number of CBI (β=0.009 [95% CI, 0.003–0.016] P=0.004; N=1604) and was associated with WMG (β, 0.009 [95% CI, −0.0002 to 0.019] P=0.055; N=1602) on the follow-up MRI.Conclusions—Among older adults, TC variability was not associated with incident CBI or worsening WMG but was associated with the number of prevalent CBI on cranial MRI. More work is needed to validate and to clarify the mechanisms underlying such associations.

    更新日期:2019-12-25
  • Substitutions of Oatmeal and Breakfast Food Alternatives and the Rate of Stroke
    Stroke (IF 6.046) Pub Date : 2019-12-12
    Line Lyskjær; Kim Overvad; Anne Tjønneland; Christina C. Dahm

    Background and Purpose—Studies indicate that consuming breakfast every day, and particularly oatmeal, is associated with lower risk of stroke. However, few studies have considered replacement foods when considering foods usually consumed at breakfast. We, therefore, aimed to model substitutions between the breakfast food products oatmeal, eggs, yogurt, or white bread and subsequent risk of stroke.Methods—Participants from the Danish cohort study (Diet, Cancer and Health; n=55 095) were followed for 13.4 years, during which 2260 subjects experienced a first-ever stroke. Breakfast foods were assessed using a validated 192-item food-frequency questionnaire at baseline. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% CIs for associations between hypothetical substitutions of standard portion sizes of breakfast foods and stroke.Results—Modeling replacement of white bread or eggs with oatmeal was associated with a lower rate of total stroke (hazard ratio [HR]=0.96 [95% CI, 0.95–0.98]; HR=0.96 [95% CI, 0.93–0.98], respectively), total ischemic stroke (HR=0.96 [95% CI, 0.94–0.98]; HR=0.96 [95% CI, 0.94–0.99], respectively), and ischemic stroke due to small-artery occlusion (HR=0.95 [95% CI, 0.93–0.98]; HR=0.95 [95% CI, 0.91–0.99], respectively). Furthermore, modeling replacement of eggs with oatmeal was associated with a lower rate of total hemorrhagic stroke (HR=0.94 [95% CI, 0.89–0.99]). Modeling replacement of yogurt with oatmeal was not associated with stroke.Conclusions—Our findings suggest that a diet containing oatmeal instead of white bread or eggs may be associated with a lower rate of stroke.

    更新日期:2019-12-25
  • Blood Pressure Variability and Cerebral Small Vessel Disease
    Stroke (IF 6.046) Pub Date : 2019-11-27
    Yuan Ma; Alex Song; Anand Viswanathan; Deborah Blacker; Meike W. Vernooij; Albert Hofman; Stefania Papatheodorou

    Background and Purpose—Blood pressure (BP) variability may increase the risk of stroke and dementia. It remains inconclusive whether BP variability is associated with cerebral small vessel disease, a common and potentially devastating subclinical disease that contributes significantly to both stroke and dementia.Methods—A systematic review and meta-analysis of prospective cohort studies that examined the association between BP variability and the presence or progression of established markers of cerebral small vessel disease, including white matter hyperintensities, lacunes, and microbleeds on magnetic resonance imaging. We searched MEDLINE, EMBASE, and Web of Science. Ten studies met the criteria for qualitative synthesis and 7 could be included in the meta-analysis. Data were synthetized using random-effect models.Results—These studies included a total of 2796 individuals aged 74 (mean) ±4 (SD) years, with a median follow-up of 4.0 years. A one SD increase in systolic BP variability was associated with increased odds of the presence or progression of white matter hyperintensities (odds ratio, 1.26 [95% CI, 1.06–1.50]). The association of systolic BP variability with the presence of lacunes (odds ratio, 0.93 [95% CI, 0.74–1.16]) and the presence of microbleeds (odds ratio, 1.13 [95% CI, 0.89–1.44]) were not statistically significant.Conclusions—A larger BP variability may be associated with a higher risk of having a higher burden of white matter hyperintensities. Targeting large BP variability has the potential to prevent cerebral small vessel disease and thereby reducing the risk of stroke and dementia. The potential issue of reverse causation and the heterogeneity in the assessment of cerebral small vessel disease markers should be better addressed in future studies.

    更新日期:2019-12-25
  • Classification of Covert Brain Infarct Subtype and Risk of Death and Vascular Events
    Stroke (IF 6.046) Pub Date : 2019-11-26
    Jose Gutierrez; Andrea Gil-Guevara; Srinath Ramaswamy; Janet DeRosa; Marco R. Di Tullio; Ken Cheung; Tatjana Rundek; Ralph L. Sacco; Clinton B. Wright; Mitchell S.V. Elkind

    Background and Purpose—To test the hypothesis that covert brain infarcts (CBIs) are more likely to be located in noneloquent brain areas compared with clinical strokes and that CBI etiological subtypes carry a differential risk of vascular events compared with people without CBI.Methods—We used brain magnetic resonance imaging from 1290 stroke-free participants in the NOMAS (Northern Manhattan Study) to evaluate for CBI. We classified CBI as cardioembolic (ie, known atrial fibrillation), large artery atherosclerosis (extracranial and intracranial), penetrating artery disease, and cryptogenic (no apparent cause). CBI localized in the nonmotor areas of the right hemisphere were considered noneloquent. We then evaluated risk of events by CBI subtype with adjusted Cox proportional models.Results—At the time of magnetic resonance imaging, 236 participants (18%) had CBI (144 [61%] distal cryptogenic, 29 [12%] distal cardioembolic, 26 [11%] large artery atherosclerosis, and 37 [16%] penetrating artery disease). Smaller (per mm, odds ratio, 0.8 [0.8–0.9]) and nonbrain stem infarcts (odds ratio, 0.2 [0.1–0.6]) were more likely to be covert. During the follow-up period (10.4±3.1 years), 398 (31%) died (162 [13%] of vascular death) and 117 (9%) had a stroke (99 [85%]) were ischemic. Risks of events varied by CBI subtype, with the highest risk of stroke (hazard ratio, 2.2 [1.3–3.7]) and vascular death (hazard ratio, 2.24 [1.29–3.88]) noted in participants with intracranial large artery atherosclerosis-related CBI.Conclusions—CBI can be classified into subtypes that have differential outcomes. Certain CBI subtypes such as those related to intracranial large artery atherosclerosis have a high risk of adverse vascular outcomes and could warrant consideration of treatment trials.

    更新日期:2019-12-25
  • Effect of Cognitive Reserve on Risk of Cognitive Impairment and Recovery After Stroke
    Stroke (IF 6.046) Pub Date : 2019-12-11
    Minyoung Shin; Min Kyun Sohn; Jongmin Lee; Deog Young Kim; Sam-Gyu Lee; Yong-Il Shin; Gyung-Jae Oh; Yang-Soo Lee; Min Cheol Joo; Eun Young Han; Junhee Han; Jeonghoon Ahn; Won Hyuk Chang; Min A Shin; Ji Yoo Choi; Sung Hyun Kang; Youngtaek Kim; Yun-Hee Kim

    Background and Purpose—The theory of cognitive reserve (CR) was introduced to account for individual differences in the clinical manifestation of neuropathology. This study investigated whether CR has a modulating effect on cognitive impairment and recovery after stroke.Methods—This study is an interim analysis of the Korean Stroke Cohort for Functioning and Rehabilitation. A total of 7459 patients with first-ever stroke were included for analysis. Education, occupation, and composite CR scores derived from those 2 variables were used as CR proxies. Scores from the Korean version of the Mini-Mental State Examination analyzed for 30 months after stroke onset were analyzed.Results—Lower CR increased the risk of cognitive impairment after stroke. The odds ratio was 1.89 (95% CI, 1.64–2.19) in patients with secondary education and 2.42 (95% CI, 2.03–2.90) in patients with primary education compared with patients with higher education. The odds ratio was 1.48 (95% CI, 1.23–1.98) in patients with a skilled manual occupation and 2.01 (95% CI, 1.42–2.83) in patients with a nonskilled manual occupation compared with patients with a managerial or professional occupation. In the multilevel model analysis, the Korean version of the Mini-Mental State Examination total score increased during the first 3 months (1.93 points per month) and then plateaued (0.02 point per month). The slopes were moderated by the level of education, occupation, and composite CR score: the higher the level of education, occupation, or CR score, the faster the recovery. In the older adult group, the Korean version of the Mini-Mental State Examination scores showed a long-term decline that was moderated by education level.Conclusions—Education and occupation can buffer an individual against cognitive impairment caused by stroke and promote rapid cognitive recovery early after stroke. In addition, higher education minimizes long-term cognitive decline after stroke, especially in older patients.Clinical Trial Registration—URL: https://www.clinicaltrials.gov. Unique identifier: NCT03402451.

    更新日期:2019-12-25
  • Association of Baseline Cardiac Troponin With Acute Myocardial Infarction in Stroke Patients Presenting Within 4.5 Hours
    Stroke (IF 6.046) Pub Date : 2019-12-04
    Yuyao Sun; Małgorzata M. Miller; Shadi Yaghi; Brian Silver; Nils Henninger

    Background and Purpose—American Heart Association guidelines recommend obtaining baseline troponin in all patients with acute ischemic stroke. Yet, there is a paucity of data on the prevalence of baseline troponin elevation and specifically its diagnostic yield for acute myocardial infarction (AMI) in patients presenting within the time window for thrombolysis.Methods—We retrospectively analyzed 1072 consecutive patients admitted for acute ischemic stroke or transient ischemic attack, who presented within 4.5 hours of last known well (LKW). Patients who had baseline cardiac troponin I (bcTnI) obtained within 72 hours from LKW (n=525) were included in the study. Multivariable logistic regression was conducted to determine factors independently related to an elevated bcTnI (>0.04 ng/mL). We calculated the area under receiver operator curves, sensitivity, and specificity, to determine the diagnostic accuracy of (i) the bcTnI for AMI stratified by the time to assessment and (ii) the best time cutoff for obtaining bcTnI.Results—Among included subjects, the median time from LKW to the bcTnI was 3.8 hours and 113 (21.5%) subjects had an elevated bcTnI. Assessment of bcTnI within 4.5 hours from LKW was significantly more often associated with normal values as compared to assessment between 4.5 and 72 hours (61.7% versus 38.3%; P=0.001). Fifteen (2.9%) patients were diagnosed with AMI. After adjustment for pertinent confounders, time to bcTnI assessment was independently associated with AMI (odds ratio, 1.04 [95% CI, 1.02–1.07] P=0.001). When stratified by time, bcTnI assessed within 4.5 hours had a sensitivity of 25% and specificity of 83.7% for AMI, whereas bcTnI assessment between 4.5 and 72 hours was associated with a sensitivity of 90.9% and specificity of 74.8%.Conclusions—Assessment of bcTnI after 4.5 hours from LKW was associated with greater diagnostic accuracy than testing within 4.5 hours. This information may inform routine clinical practice.

    更新日期:2019-12-25
  • Prevalence of Intracranial Aneurysms in Patients With Systemic Vessel Aneurysms
    Stroke (IF 6.046) Pub Date : 2019-11-18
    Jihye Song; Yong Cheol Lim; Inseok Ko; Jong-Yeup Kim; Dong-Kyu Kim

    Background and Purpose—Most aneurysms are a focal manifestation of a systemic condition. Some reports have suggested genetic and environmental factors may play a role in pathogenesis. The aim of the present study was to evaluate the prevalence of intracranial aneurysms (IA) in a large cohort of patients with other systemic vessel aneurysms and dissections (OVAD) and identify potential risk factors for IA in this population.Methods—We defined OVAD as systemic vessel aneurysms, excluding aortic dissections and aneurysms. A cohort of 1.1 million patients was extracted from the population-based cohort from the Korea National Health Insurance Service, which holds almost all medical data including diagnostic codes, procedures, and personal information. Using χ2 or Fisher exact test, the prevalence of the IA concerning OVAD status was analyzed.Results—In OVAD individuals, 25.7% (261/1017) of patients had been concurrently diagnosed with IA. The odds ratios for having concurrent IA in patients with OVAD were 56.31 (95% CI, 48.821–64.949; P=0.000). OVAD patients with dyslipidemia were >7× likely to be affected by IA (adjusted odds ratio, 7.7 [95% CI, 6.59–9.01]; P=0.000). Hypertension, diabetes mellitus, old age (>60 years), and male sex had increased odds for having concurrent IA by 5.89, 3.48, 1.83, and 1.35, respectively. Subgroup analysis with socioeconomic or disability revealed that the prevalence of IA was significantly higher in all groups. Uncertainty regarding the temporal sequence of onset and lack of detail on disease severity and subtype prevented more conclusive results.Conclusions—Patients with OVAD have a higher prevalence of IA than control groups. Therefore, we may approach aneurysms as systemic disease, and further investigations about their pathophysiology must follow.

    更新日期:2019-12-25
  • Noncontrast Computed Tomography Signs as Predictors of Hematoma Expansion, Clinical Outcome, and Response to Tranexamic Acid in Acute Intracerebral Hemorrhage
    Stroke (IF 6.046) Pub Date : 2019-11-18
    Zhe Kang Law; Azlinawati Ali; Kailash Krishnan; Adam Bischoff; Jason P. Appleton; Polly Scutt; Lisa Woodhouse; Stefan Pszczolkowski; Lesley A. Cala; Robert A. Dineen; Timothy J. England; Serefnur Ozturk; Christine Roffe; Daniel Bereczki; Alfonso Ciccone; Hanne Christensen; Christian Ovesen; Philip M. Bath; Nikola Sprigg; on behalf of TICH-2 Investigators

    Background and Purpose—Blend, black hole, island signs, and hypodensities are reported to predict hematoma expansion in acute intracerebral hemorrhage. We explored the value of these noncontrast computed tomography signs in predicting hematoma expansion and functional outcome in our cohort of intracerebral hemorrhage.Methods—The TICH-2 (Tranexamic acid for IntraCerebral Hemorrhage-2) was a prospective randomized controlled trial exploring the efficacy and safety of tranexamic acid in acute intracerebral hemorrhage. Baseline and 24-hour computed tomography scans of trial participants were analyzed. Hematoma expansion was defined as an increase in hematoma volume of >33% or >6 mL on 24-hour computed tomography. Poor functional outcome was defined as modified Rankin Scale of 4 to 6 at day 90. Multivariable logistic regression was performed to identify predictors of hematoma expansion and poor functional outcome.Results—Of 2325 patients recruited, 2077 (89.3%) had valid baseline and 24-hour scans. Five hundred seventy patients (27.4%) had hematoma expansion while 1259 patients (54.6%) had poor functional outcome. The prevalence of noncontrast computed tomography signs was blend sign, 366 (16.1%); black hole sign, 414 (18.2%); island sign, 200 (8.8%); and hypodensities, 701 (30.2%). Blend sign (adjusted odds ratio [aOR] 1.53 [95% CI, 1.16–2.03]; P=0.003), black hole (aOR, 2.03 [1.34–3.08]; P=0.001), and hypodensities (aOR, 2.06 [1.48–2.89]; P<0.001) were independent predictors of hematoma expansion on multivariable analysis with adjustment for covariates. Black hole sign (aOR, 1.52 [1.10–2.11]; P=0.012), hypodensities (aOR, 1.37 [1.05–1.78]; P=0.019), and island sign (aOR, 2.59 [1.21–5.55]; P=0.014) were significant predictors of poor functional outcome. Tranexamic acid reduced the risk of hematoma expansion (aOR, 0.77 [0.63–0.94]; P=0.010), but there was no significant interaction between the presence of noncontrast computed tomography signs and benefit of tranexamic acid on hematoma expansion and functional outcome (P interaction all >0.05).Conclusions—Blend sign, black hole sign, and hypodensities predict hematoma expansion while black hole sign, hypodensities, and island signs predict poor functional outcome. Noncontrast computed tomography signs did not predict a better response to tranexamic acid.Clinical Trial Registration—URL: https://www.isrctn.com. Unique identifier: ISRCTN93732214.

    更新日期:2019-12-25
  • Perihematomal Edema After Intracerebral Hemorrhage in Patients With Active Malignancy
    Stroke (IF 6.046) Pub Date : 2019-11-20
    Aaron M. Gusdon; Paul A. Nyquist; Victor M. Torres-Lopez; Audrey C. Leasure; Guido J. Falcone; Kevin N. Sheth; Lauren H. Sansing; Daniel F. Hanley; Rachna Malani

    Background and Purpose—Patients with active malignancy are at risk for intracerebral hemorrhage (ICH). We aimed to characterize perihematomal edema (PHE) and hematoma volumes after spontaneous nontraumatic ICH in patients with cancer without central nervous system involvement.Methods—Patients with active malignancy who developed ICH were retrospectively identified through automated searches of institutional databases. Control patients were identified with ICH and without active cancer. Demographic and cancer-specific data were obtained by chart review. Hematoma and PHE volumes were determined using semiautomated methodology. Univariate and multivariate linear regression models were created to assess which variables were associated with hematoma and PHE expansion.Results—Patients with cancer (N=80) and controls (N=136) had similar demographics (all P>0.20), although hypertension was more prevalent among controls (P=0.004). Most patients with cancer had received recent chemotherapy (n=45, 56%) and had recurrence of malignancy (n=43, 54%). Patients with cancer were thrombocytopenic (median platelet count 90 000 [interquartile range, 17 500–211 500]), and most had undergone blood product transfusion (n=41, 51%), predominantly platelets (n=38, 48%). Thirty-day mortality was 36% (n=29). Patients with cancer had significantly increased PHE volumes (23.67 versus 8.61 mL; P=1.88×10-9) and PHE-to-ICH volume ratios (2.26 versus 0.99; P=2.20×10-16). In multivariate analyses, variables associated with PHE growth among patients with cancer were ICH volume (β=1.29 [95% CI, 1.58–1.30] P=1.30×10-5) and platelet transfusion (β=15.67 [95% CI, 3.61–27.74] P=0.014). Variables associated with 30-day mortality were ICH volume (odds ratio, 1.06 [95% CI, 1.03–1.10] P=6.76×10-5), PHE volume (odds ratio, 1.07 [95% CI, 1.04–1.09] P=7.40×10-6), PHE growth (odds ratio, 1.05 [95% CI, 1.01–1.10] P=0.01), and platelet transfusion (odds ratio, 1.48 [95% CI, 1.22–1.79] P=0.0001).Conclusions—Patients with active cancer who develop ICH have increased PHE volumes. PHE growth was independent of thrombocytopenia but associated with blood product transfusion. Thirty-day mortality was associated with PHE and ICH volumes and blood product transfusion.

    更新日期:2019-12-25
  • Risk of Arterial Ischemic Events After Intracerebral Hemorrhage
    Stroke (IF 6.046) Pub Date : 2019-11-27
    Santosh B. Murthy; Ivan Diaz; Xian Wu; Alexander E. Merkler; Costantino Iadecola; Monika M. Safford; Kevin N. Sheth; Babak B. Navi; Hooman Kamel

    Background and Purpose—The risk of arterial ischemic events after intracerebral hemorrhage (ICH) is poorly understood given the lack of a control group in prior studies. This study aimed to evaluate the risk of acute ischemic stroke and myocardial infarction (MI) among patients with and without ICH.Methods—We performed a retrospective cohort study using claims data from Medicare beneficiaries from 2008 to 2014. Our exposure was acute ICH, identified using validated International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. Our primary outcome was a composite of acute ischemic stroke and MI, whereas secondary outcomes were ischemic stroke alone and MI alone. We used Cox regression analysis to compute hazard ratios during 1-month intervals after ICH. Sensitivity analyses entailed exclusion of patients with atrial fibrillation and valvular heart disease.Results—Among 1 760 439 Medicare beneficiaries, 5924 had ICH. The 1-year cumulative incidence of an arterial ischemic event was 5.7% (95% CI, 4.8–6.8) in patients with ICH and 1.8% (95% CI, 1.7–1.9) in patients without ICH. After adjusting for potential confounders, the risk of an arterial ischemic event remained significantly increased for the first 6 months after ICH and was especially high in the first month (hazard ratio, 6.7 [95% CI, 5.0–8.6]). In secondary analysis, the risk of ischemic stroke was increased in the first 6 months after ICH (hazard ratio, 6.1 [95% CI, 3.5–9.3]) but the risk of MI was not (hazard ratio, 1.6 [95% CI, 0.3–2.9]). In sensitivity analyses excluding patients with atrial fibrillation and valvular heart disease, the association between ICH and arterial ischemic events was similar to that of the primary analysis.Conclusions—In a large population-based cohort, we found that elderly patients with ICH had a substantially increased risk of ischemic stroke in the first 6 months after diagnosis. Further exploration of this risk is needed to determine optimal secondary prevention strategies for these patients.

    更新日期:2019-12-25
  • Hounsfield Unit Value of Interpeduncular Cistern Hematomas Can Predict Symptomatic Vasospasm
    Stroke (IF 6.046) Pub Date : 2019-11-07
    Hideyuki Ishihara; Fumiaki Oka; Reo Kawano; Mizuya Shinoyama; Takuma Nishimoto; Shohei Kudomi; Michiyasu Suzuki

    Background and Purpose—Symptomatic vasospasm is an important factor that affects the outcomes of aneurysmal subarachnoid hemorrhage. Subarachnoid blood volume can predict symptomatic vasospasm, and we postulated that the blood clot density would also be an important factor involved in such events. The present study aimed to determine the relationship between the incidence of symptomatic vasospasm and the Hounsfield unit (HU) value of the interpeduncular cistern that reflects the density of hematomas.Methods—Data from 323 patients admitted and treated at a single center between 2008 and 2017 within 24 hours of subarachnoid hemorrhage onset were retrospectively analyzed. Initial HU values of the interpeduncular cistern were measured using CT, then correlations with the incidence of symptomatic vasospasm and HU values as well as other variables were assessed.Results—Symptomatic vasospasm developed in 54 (16.7%) of the 323 patients. The incidence of symptomatic vasospasm was low (1.8%, 2/166) for HU <50, but this incidence increased greatly when the HU value exceeded 50 (23.7%, 22/93 for HU >50 to ≤60, and 45.3%, 29/64 for HU >60). The odds ratio for symptomatic vasospasm was 2.0 (95% CI, 1.6–2.4) per 5 HU increase. Symptomatic vasospasm correlated significantly with intraventricular hemorrhage (P=0.05) and with intracerebral hematoma (P=0.046) but even more significantly with the HU value of the interpeduncular cistern (P<0.0001).Conclusions—The HU value of the interpeduncular cistern on initial CT is an accurate and reliable predictor of symptomatic vasospasm.

    更新日期:2019-12-25
  • Prevalence and Risk Factors of White Matter Lesions in Tibetan Patients Without Acute Stroke
    Stroke (IF 6.046) Pub Date : 2019-11-04
    Haiqiang Jin; Zhijie Ding; Siqing Lian; Yuhua Zhao; Shihua He; Lewei Zhou; Cidan Zhuoga; Huali Wang; Jun Xu; Ailian Du; Guiying Yan; Yongan Sun

    Background and Purpose—Studies on the prevalence and risk factors of white matter lesions (WMLs) in Tibetans living at high altitudes are scarce. We conducted this study to determine the prevalence and risks of WMLs in Tibetan patients without or with nonacute stroke.Methods—We undertook a retrospective analysis of medical records of patients treated at the People’s Hospital of Tibetan Autonomous Region and identified a total of 301 Tibetan patients without acute stroke. WML severity was graded by the Fazekas Scale. We assessed the overall and age-specific prevalence of WMLs and analyzed associations between WMLs and related factors with univariate and multivariate methods.Results—Of the 301 patients, 87 (28.9%) had peripheral vertigo, 83 (27.3%) had primary headache, 52 (17.3%) had a history of stroke, 36 (12.0%) had an anxiety disorder, 29 (9.6%) had epilepsy, 12 (4.0%) had infections of the central nervous system, and 3 (1.0%) had undetermined diseases. WMLs were present in 245 (81.4%) patients, and 54 (17.9%) were younger than 40 years. Univariate analysis showed that age, history of cerebral infarction, hypertension, the thickness of the common carotid artery intima, and plaque within the intracarotid artery were related risks for WMLs. Ordered logistic analysis showed that age, history of cerebral ischemic stroke, hypertension, male sex, and atrial fibrillation were associated with WML severity.Conclusions—Risk factors for WMLs appear similar for Tibetans residing at high altitudes and individuals living in the plains. Further investigations are needed to determine whether Tibetans residing at high altitudes have a higher burden of WMLs than inhabitants of the plains.

    更新日期:2019-12-25
  • Microemboli After Successful Thrombectomy Do Not Affect Outcome but Predict New Embolic Events
    Stroke (IF 6.046) Pub Date : 2019-12-04
    Faheem Sheriff; Mariana Diz-Lopes; Ayaz Khawaja; Farzaneh Sorond; Can Ozan Tan; Elsa Azevedo; Maria Angela Franceschini; Henri Vaitkevicius; Karen Li; Andrew Donald Monk; Sarah LaRose Michaud; Steven K. Feske; Pedro Castro

    Background and Purpose—We aimed to determine if microemboli after endovascular thrombectomy correlate with unfavorable outcomes despite successful recanalization.Methods—This is a prospective multicenter study of consecutive patients with ischemic stroke and occlusion of anterior circulation vessels (terminal internal carotid or main trunk of the middle cerebral artery/first-order branch of the main trunk of the middle cerebral artery segments of middle cerebral artery) after successful thrombectomy (modified Treatment In Cerebral Ischemia grades 2b-3). Microembolic signals (MES) were assessed by 30 minutes of transcranial Doppler monitoring within 72 hours of the last-seen-well time. Major outcomes included modified Rankin Scale at 90 days and infarct volume on head computed tomography at 24 hours. We also assessed early outcomes based on National Institutes of Health Stroke Scale variation and recurrence of stroke, transient ischemic attack, or systemic embolism within 90 days.Results—Among 111 patients, MES were detected in 43 (39%), with a median rate of 4 counts/h (interquartile range 2–12). The occurrence of MES was not associated with a significant difference in modified Rankin Scale (ordinal shift analysis, adjusted odds ratio, 1.06 [95% CI, 0.48–2.34] P=0.85) nor in functional independence (modified Rankin Scale, 0–2: adjusted odds ratio, 0.52 [95% CI, 0.19–1.39] P=0.19). Patients with and without MES had similar infarct volumes (adjusted beta, 11.2 [95% CI, −46.6 to +22.9] P=0.51) on 24-hour computed tomography. MES did predict new embolic events (adjusted Cox hazard ratio, 6.78 [95% CI, 1.63–27.8] P=0.01).Conclusions—MES detected by transcranial Doppler following endovascular treatment of anterior circulation occlusions do not predict clinical or radiological outcome. However, such emboli are an independent marker of recurrent embolic events within 90 days.

    更新日期:2019-12-25
  • Effect of Heart Rate on Stroke Recurrence and Mortality in Acute Ischemic Stroke With Atrial Fibrillation
    Stroke (IF 6.046) Pub Date : 2019-12-04
    Keon-Joo Lee; Beom Joon Kim; Moon-Ku Han; Joon-Tae Kim; Kang-Ho Choi; Dong-Ick Shin; Min-Ju Yeo; Jae-Kwan Cha; Dae-Hyun Kim; Hyun-Wook Nah; Dong-Eog Kim; Wi-Sun Ryu; Jong-Moo Park; Kyusik Kang; Soo Joo Lee; Jae Guk Kim; Mi-Sun Oh; Kyung-Ho Yu; Byung-Chul Lee; Keun-Sik Hong; Yong-Jin Cho; Jay Chol Choi; Tai Hwan Park; Sang-Soon Park; Jee-Hyun Kwon; Wook-Joo Kim; Jun Lee; Ji Sung Lee; Juneyoung Lee; Philip B. Gorelick; Hee-Joon Bae; on the behalf of the CRCS-K (Clinical Research Collaboration for Stroke in Korea) Investigators

    Background and Purpose—There is a paucity of information about the role of resting heart rate in the prediction of outcome events in patients with ischemic stroke with atrial fibrillation. We aimed to investigate the relationships between the level and variability of heart rate in the acute stroke period and stroke recurrence and mortality after acute ischemic stroke in patients with atrial fibrillation.Methods—Acute patients with ischemic stroke who had atrial fibrillation and were hospitalized within 48 hours of stroke onset were identified from a multicenter prospective stroke registry database. The acute stroke period was divided into early (within 24 hours of hospitalization) and late (72 hours to 7 days from onset) stages, and data on heart rate in both stages were collected. Moreover, the level and variability of heart rate were assessed using mean values and coefficients of variation. Outcome events were prospectively monitored up to 1 year after the index stroke.Results—Among 2046 patients eligible for the early acute stage analysis, 102 (5.0%) had a stroke recurrence, and 440 (21.5%) died during the first year after stroke. A statistically significant nonlinear J-shaped association was observed between mean heart rate and mortality (P<0.04 for quadratic and overall effect) but not between mean heart rate and stroke recurrence (P>0.1 for quadratic and overall effect). The nonlinear and overall effects of the coefficients of variation of heart rate were not significant for all outcome variables. The same results were observed in the late acute stage analysis (n=1576).Conclusions—In patients with atrial fibrillation hospitalized for acute ischemic stroke, the mean heart rate during the acute stroke period was not associated with stroke recurrence but was associated with mortality (nonlinear, J-shaped association). The relationships between heart rate and outcomes were not observed with respect to heart rate variability.

    更新日期:2019-12-25
  • Global Burden of Small Vessel Disease–Related Brain Changes on MRI Predicts Cognitive and Functional Decline
    Stroke (IF 6.046) Pub Date : 2019-11-08
    Hanna Jokinen; Juha Koikkalainen; Hanna M. Laakso; Susanna Melkas; Tuomas Nieminen; Antti Brander; Antti Korvenoja; Daniel Rueckert; Frederik Barkhof; Philip Scheltens; Reinhold Schmidt; Franz Fazekas; Sofia Madureira; Ana Verdelho; Anders Wallin; Lars-Olof Wahlund; Gunhild Waldemar; Hugues Chabriat; Michael Hennerici; John O’Brien; Domenico Inzitari; Jyrki Lötjönen; Leonardo Pantoni; Timo Erkinjuntti

    Background and Purpose—Cerebral small vessel disease is characterized by a wide range of focal and global brain changes. We used a magnetic resonance imaging segmentation tool to quantify multiple types of small vessel disease–related brain changes and examined their individual and combined predictive value on cognitive and functional abilities.Methods—Magnetic resonance imaging scans of 560 older individuals from LADIS (Leukoaraiosis and Disability Study) were analyzed using automated atlas- and convolutional neural network–based segmentation methods yielding volumetric measures of white matter hyperintensities, lacunes, enlarged perivascular spaces, chronic cortical infarcts, and global and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years.Results—The strongest predictors of cognitive performance and functional outcome over time were the total volumes of white matter hyperintensities, gray matter, and hippocampi (P<0.001 for global cognitive function, processing speed, executive functions, and memory and P<0.001 for poor functional outcome). Volumes of lacunes, enlarged perivascular spaces, and cortical infarcts were significantly associated with part of the outcome measures, but their contribution was weaker. In a multivariable linear mixed model, volumes of white matter hyperintensities, lacunes, gray matter, and hippocampi remained as independent predictors of cognitive impairment. A combined measure of these markers based on Z scores strongly predicted cognitive and functional outcomes (P<0.001) even above the contribution of the individual brain changes.Conclusions—Global burden of small vessel disease–related brain changes as quantified by an image segmentation tool is a powerful predictor of long-term cognitive decline and functional disability. A combined measure of white matter hyperintensities, lacunar, gray matter, and hippocampal volumes could be used as an imaging marker associated with vascular cognitive impairment.

    更新日期:2019-12-25
  • Long-Term Trends in Stroke Survivors Discharged to Care Homes
    Stroke (IF 6.046) Pub Date : 2019-11-06
    Amanda Clery; Ajay Bhalla; Alessandra Bisquera; Lesli E. Skolarus; Iain Marshall; Christopher McKevitt; Anthony Rudd; Catherine Sackley; Finbarr C. Martin; Jill Manthorpe; Charles Wolfe; Yanzhong Wang

    Background and Purpose—Care homes provide care to many stroke survivors, yet little is known about changes in care home use over time. We aim to determine trends in discharge to care homes, to explore the characteristics of stroke survivors over time (1995–2018), and to identify the associations between these characteristics and discharge to care homes poststroke.Methods—Using data from the South London Stroke Register between 1995 and 2018, we estimated the proportions discharged to care homes and their characteristics over time, assessed by tests for trends. Multivariable logistic regression models were built to assess the associations between their characteristics and discharge destination.Results—Of 4172 stroke survivors, 484 (12%) were discharged to care homes. This proportion has decreased from 24% in 1995 to 2000 to 5% in 2013 to 2018. The mean age of those discharged to care homes has increased over time, from 73 to 75 (P<0.001). Among stroke survivors discharged to a care home, the proportion with a prestroke Barthel Index <15 has also increased over time from 7% to 21% (P=0.027), while the proportion with a 7-day poststroke Barthel Index <15 remains largely unchanged over time (93% in 1995–2000, 90% in 2013–2018). The characteristics most strongly associated with discharge to care homes were (odds ratio [95% CI]) age (1.05 [1.04–1.07] per year), stroke subtype (hemorrhagic; 0.64 [0.43–0.95]), stroke severity (Glasgow Coma Scale score, <13; 1.67 [1.19–2.35]), failed swallow test at admission (1.65 [1.20–2.25]), 7-day poststroke Barthel Index <15 (3.58 [2.20–6.03]), and a longer hospital stay (1.02 [1.02–1.03] per day).Conclusions—Over >20 years, there has been an 80% reduction in the proportion of stroke survivors discharged to care homes, influenced by changes in the demographics, disability, and stroke care in the underlying stroke population. In those moving to care homes, the level of poststroke disability remains high, requiring continued attention and investment.

    更新日期:2019-12-25
  • Regional Arterial Spin Labeling Perfusion Defect Is Associated With Early Ischemic Recurrence in Patients With a Transient Ischemic Attack
    Stroke (IF 6.046) Pub Date : 2019-11-13
    Ki-Woong Nam; Chi Kyung Kim; Sang-Bae Ko; Byung-Woo Yoon; Roh-Eul Yoo; Chul-Ho Sohn

    Background and Purpose—With the lack of confirmatory examinations, the distinction of a transient ischemic attack (TIA) from various TIA-mimicking diseases is difficult, particularly in diffusion-weighted imaging (DWI)-negative TIAs. In this study, we aimed to evaluate the relationship between arterial spin labeling (ASL) perfusion defects and early ischemic recurrence (FU-DWI [+]) in patients with DWI-negative TIAs.Methods—We assessed consecutive patients with a DWI-negative TIA within 24 hours of symptom onset, who underwent both ASL images and follow-up magnetic resonance imaging during the acute period. As markers of the ASL images, we evaluated the ASL perfusion defects in each hemisphere. Arterial transit artifact (ATA) and intraarterial high-intensity signal (IAS) were also rated as markers of collateral status and blood stagnation due to large vessel occlusion, respectively.Results—Among the 136 patients with a DWI-negative TIA, 33 patients had FU-DWI (+) lesions in 36 hemispheres. In the multivariable analysis, ASL defects remained an independent predictor of FU-DWI (+) (adjusted odds ratio, 13.94 [95% CI, 5.77–33.70], P<0.001). In the evaluation of the interactive relationship between ASL defects and ATA/IAS, the (ASL [+] ATA [−]) group showed the highest frequencies of FU-DWI (+) events (55.6%) with the highest adjusted odds ratio values (adjusted odds ratio, 14.86 [95% CI, 5.63–39.24], P<0.001), indicating a negative synergistic effect between the ASL defects and ATA. Meanwhile, the (ASL [+] IAS [+]) group showed higher frequencies of FU-DWI (+) and higher adjusted odds ratio values than those of the (ASL [+] IAS [−]) and (ASL [−] IAS [−]) groups, indicating a positive synergistic effect.Conclusions—We demonstrated that ASL perfusion defects were associated with ipsilateral FU-DWI (+) in patients with a DWI-negative TIA. Furthermore, this association was enhanced with IASs and attenuated with ATAs.

    更新日期:2019-12-25
  • 1/2SH
    Stroke (IF 6.046) Pub Date : 2019-12-04
    Biao Zhao; Wan-bing Jia; Li-ying Zhang; Ting-zhong Wang

    Background and Purpose—1/2ABC has been used widely for assessing the volume of intracerebral hematoma. However, it is only suitable for calculating regular and small volume hematomas. Therefore, we re-explored the formula of hematoma volume to find a method that can calculate hematoma volumes accurately, reliably, and quickly.Methods—Computed tomography imaging data of 257 patients with intracerebral hemorrhage were collected. Hematoma volumes were estimated using 3-dimensional Slicer and 7 formulas (π/6ABC, 1/2ABC, 1/3ABC, 2/3SH, 1/2SH, π/6SH, and 2.5/6ABC). Taking the hematoma volumes measured by 3-dimensional Slicer as the reference standard, the accuracy and reliability of the 7 formulas were evaluated. Furthermore, the time needed to calculate hematoma volumes by the 1/2SH method was noted for further analysis.Results—(1) The accuracy of the 7 formulas based on the error analysis from the highest to the lowest was: π/6SH, 1/2SH, 2.5/6ABC, 1/3ABC, 1/2ABC, and π/6ABC or 2/3SH. According to concordance analysis and receiver operating characteristic curve analysis, the results from the highest to lowest were as follows: 1/2SH, π/6SH, 2.5/6ABC, 1/3ABC, 1/2ABC, 2/3SH, and π/6ABC. After categorizing cases according to size, shape, and location of hematoma, the results were almost the same as the results for overall accuracy evaluation in any subgroup. (2) Intraclass correlation coefficient (ICC) of 1/2SH in intra and inter-researcher were 0.998 and 0.989, respectively. For the formula π/6SH, intraclass correlation coefficient was the same as that of 1/2ABC. Kappa values of 1/2SH for intra- and inter-observer were 0.992 and 0.913, respectively. For π/6SH, kappa values of within- and between-reader were 0.984 and 0.904, respectively. (3) The average time taken to calculate hematoma volumes by 1/2SH was 74 seconds.Conclusions—The 1/2SH and π/6SH are accurate, reliable, and rapid methods for calculating hematoma volumes. The accuracy and reliability of 1/2SH were slightly higher than those of π/6SH.

    更新日期:2019-12-25
  • Superficial Cerebellar Microbleeds and Cerebral Amyloid Angiopathy
    Stroke (IF 6.046) Pub Date : 2019-11-15
    Hsin-Hsi Tsai; Marco Pasi; Li-Kai Tsai; Ya-Fang Chen; Yu-Wei Chen; Sung-Chun Tang; M. Edip Gurol; Ruoh-Fang Yen; Jiann-Shing Jeng

    Background and Purpose—The differentiation between cerebral amyloid angiopathy (CAA) and hypertensive small vessel disease in primary intracerebral hemorrhage is mainly based on hemorrhagic neuroimaging markers in the supratentorial regions, and the cause for cerebellar microbleeds remains unknown. Our aim was to investigate whether superficial cerebellar microbleeds are more likely to be related to CAA rather than hypertensive small vessel disease.Methods—Two hundred seventy-five consecutive patients with intracerebral hemorrhage were retrospectively reviewed from a prospectively maintained hospital-based stroke registry. Eighty-five (33.1%) patients had cerebellar microbleeds and were categorized into superficial (gray matter, vermis), deep (white matter, deep nucleus, cerebellar peduncle), or mixed type based on the location of cerebellar hemorrhagic lesions. Amyloid imaging was obtained using 11C-Pittsburgh Compound B–positron emission tomography in a subgroup of patients. The associations between cerebellar microbleed locations and the type of small vessel disease (CAA versus hypertensive small vessel disease) based on distribution of supratentorial hemorrhagic lesions as well as other magnetic resonance imaging and positron emission tomography markers were analyzed.Results—The presence of cerebellar microbleed was independently associated with supratentorial microbleed and lacunar infarcts (both P<0.01). Strictly superficial cerebellar microbleeds were significantly related to CAA–intracerebral hemorrhage, cortical superficial siderosis and high-grade enlarged perivascular space in centrum semiovale (all P<0.05); deep or mixed cerebellar microbleeds were related to hypertension and deep microbleed (all P<0.05). In multivariable models, superficial cerebellar microbleeds were independently associated with CAA–intracerebral hemorrhage (P=0.03). Of 33 patients assessed by amyloid positron emission tomography, cerebral and cerebellar amyloid load (standardized uptake value ratio) was higher in patients with superficial cerebellar microbleeds compared with deep/mixed cerebellar microbleeds (cerebrum standardized uptake value ratio [reference: cerebellum] 1.33±0.24 versus 1.05±0.09, P<0.001; cerebellum standardized uptake value ratio [reference: pons] 0.58±0.08 versus 0.51±0.09, P=0.03).Conclusions—Patients with strictly superficial cerebellar microbleeds are associated with a clinicoradiological diagnosis of CAA as well as increased cerebral and cerebellar amyloid deposition on Pittsburgh Compound B–positron emission tomography, suggesting underlying CAA pathology.

    更新日期:2019-12-25
  • Quantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial
    Stroke (IF 6.046) Pub Date : 2019-10-30
    Bastian Cheng; Florent Boutitie; Alina Nickel; Anke Wouters; Tae-Hee Cho; Martin Ebinger; Matthias Endres; Jochen B. Fiebach; Jens Fiehler; Ivana Galinovic; Josep Puig; Vincent Thijs; Robin Lemmens; Keith W. Muir; Norbert Nighoghossian; Salvador Pedraza; Claus Z. Simonsen; Christian Gerloff; Götz Thomalla

    Background and Purpose—Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase.Methods—FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume.Results—FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 (P=0.169) and shift analysis (P=0.086) but reached significance for mRS score of 0 to 2 (P=0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI.Conclusions—In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset.

    更新日期:2019-12-25
  • Effect of Recanalization on Cerebral Edema in Ischemic Stroke Treated With Thrombolysis and/or Endovascular Therapy
    Stroke (IF 6.046) Pub Date : 2019-12-10
    Magnus Thorén; Anand Dixit; Irene Escudero-Martínez; Zuzana Gdovinová; Lukas Klecka; Viiu-Marika Rand; Danilo Toni; Aleksandras Vilionskis; Nils Wahlgren; Niaz Ahmed

    Background and Purpose—A large infarct and expanding cerebral edema (CED) due to a middle cerebral artery occlusion confers a 70% mortality unless treated surgically. Reperfusion may cause blood-brain barrier disruption and a risk for cerebral edema and secondary parenchymal hemorrhage (PH). We aimed to investigate the effect of recanalization on development of early CED and PH after recanalization therapy.Methods—From the SITS-International Stroke Treatment Registry, we selected patients with signs of artery occlusion at baseline (either Hyperdense Artery Sign or computed tomography/magnetic resonance imaging angiographic occlusion). We defined recanalization as the disappearance of radiological signs of occlusion at 22 to 36 hours. Primary outcome was moderate to severe CED and secondary outcome was PH on 22- to 36-hour imaging scans. We used logistic regression with adjustment for baseline variables and PH.Results—Twenty two thousand one hundred eighty-four patients fulfilled the inclusion criteria (n=18 318 received intravenous thrombolysis, n=3071 received intravenous thrombolysis+thrombectomy, n=795 received thrombectomy). Recanalization occurred in 64.1%. Median age was 71 versus 71 years and National Institutes of Health Stroke Scale score 15 versus 16 in the recanalized versus nonrecanalized patients respectively. Recanalized patients had a lower risk for CED (13.0% versus 23.6%), adjusted odds ratio (aOR), 0.52 (95% CI, 0.46–0.59), and a higher risk for PH (8.9% versus 6.5%), adjusted odds ratio, 1.37 (95% CI, 1.22–1.55), than nonrecanalized patients.Conclusions—In patients with acute ischemic stroke, recanalization was associated with a lower risk for early CED even after adjustment for higher rate for PH in recanalized patients.

    更新日期:2019-12-25
  • Efficacy of Clopidogrel-Aspirin Therapy for Stroke Does Not Exist in CYP2C19 Loss-of-Function Allele Noncarriers With Overweight/Obesity
    Stroke (IF 6.046) Pub Date : 2019-11-15
    Jinglin Mo; Zimo Chen; Jie Xu; Anxin Wang; Liye Dai; Aichun Cheng; Xia Meng; Hao Li; Yongjun Wang

    Background and Purpose—The role of dual-antiplatelet therapy with clopidogrel plus aspirin has been demonstrated to substantially decrease the risk of recurrent stroke among patients with minor stroke and transient ischemic attack. We aimed to determine whether the efficacy of clopidogrel-aspirin therapy among patients with minor stroke / transient ischemic attack was influenced by the stratification of CYP2C19 genotype and body mass index (BMI).Methods—CYP2C19 loss-of-function allele (LoFA) carriers were defined as patients with either LoFA of *2 or *3. Low/normal weight and overweight/obesity was defined as BMI <25 and ≥25 kg/m2, respectively. Primary outcome was defined as stroke recurrence at 3 months.Results—In a total of 2933 patients, there were 1726 (58.8%) LoFA carriers and 1275 (43.5%) patients with overweight/obesity (BMI ≥25 kg/m2). Stratified analyses by LoFA carrying status and BMI, hazard ratios (hazard ratios 95% CIs) of the clopidogrel-aspirin therapy for stroke recurrence were 0.90 (0.60–1.36), 0.87 (0.56–1.35), 0.65 (0.39–1.09), and 0.40 (0.22–0.71) among subgroups of LoFA carriers with overweight/obesity, LoFA carriers with low/normal weight, LoFA noncarriers with overweight/obesity, and LoFA noncarriers with low/normal weight, respectively, with P=0.049 for interaction.Conclusions—Efficacy of clopidogrel-aspirin therapy in reducing the risk of stroke recurrence is not present in CYP2C19 LoFA noncarriers with overweight/obesity. Our study suggests that BMI significantly influences the correlation between CYP2C19 genotype and efficacy of clopidogrel-aspirin therapy.Clinical Trial Registration—URL: https://www.clinicaltrials.gov. Unique identifier: NCT00979589.

    更新日期:2019-12-25
  • Benefit of Intravenous Thrombolysis in Acute Ischemic Stroke Patients With High Cerebral Microbleed Burden
    Stroke (IF 6.046) Pub Date : 2019-11-19
    Ludwig Schlemm; Matthias Endres; David J. Werring; Christian H. Nolte

    Background and Purpose—Cerebral microbleeds (CMBs) are a risk factor for intracranial hemorrhage. Whether intravenous thrombolysis (IVT) improves functional outcome in acute ischemic stroke patients with CMBs is unknown. We aimed to estimate the treatment effect of IVT in patients with acute ischemic stroke and a high burden (>10) of CMBs.Methods—We devised a multistep algorithm to model 90-day modified Rankin Scale scores in patients with ≤10 versus >10 CMBs who do or do not receive IVT. Parameters were extracted from recently published meta-analyses and included pairwise relationships between CMBs, IVT, 3-month functional outcome, and intracranial hemorrhage. Uncertainty was quantified in probabilistic sensitivity analyses.Results—In patients with >10 CMBs as compared with ≤10 CMBs, point estimates of the odds ratios for favorable outcome (modified Rankin Scale ≤2) associated with IVT were 7% to 10% lower but still >1 (range, 1.03–1.51). On the other hand, IVT in patients with >10 CMBs significantly increased the odds of mortality. The point estimates for the net treatment effect of IVT (change in the utility-weighted modified Rankin Scale score) in patients with >10 CMBs were in favor of withholding IVT in older patients with more severe strokes and longer treatment delays. However, because the general pretest probability of >10 CMBs is low (0.6%–2.7%), pretreatment magnetic resonance imaging to quantify CMB burden would be justified only if it delayed IVT by <10 minutes.Conclusions—High CMB burden modifies the treatment effect of IVT. In patients with >10 CMBs, IVT is associated with higher mortality and, in older patients with severe strokes and longer treatment delays, a net utility loss. Patients with higher-than-average pretest probability of >10 CMB might profit from magnetic resonance imaging screening if it does not increase the treatment time.

    更新日期:2019-12-25
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