Stroke, Ahead of Print. Background and Purpose:Coronavirus disease 2019 (COVID-19) may be associated with increased risk for ischemic stroke. We present prevalence and characteristics of strokes in patients with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection enrolled in the American Heart Association COVID-19 Cardiovascular Disease Registry.Methods:In this quality improvement registry study, we examined demographic, baseline clinical characteristics, and in-hospital outcomes among hospitalized COVID-19 patients. The primary outcomes were ischemic stroke or transient ischemic attack (TIA) and in-hospital death.Results:Among 21 073 patients with COVID-19 admitted at 107 hospitals between January 29, 2020, and November 23, 2020, 160 (0.75%) experienced acute ischemic stroke/TIA (55.3% of all acute strokes) and 129 (0.61%) had other types of stroke. Among nonischemic strokes, there were 44 (15.2%) intracerebral hemorrhages, 33 (11.4%) subarachnoid hemorrhages, 21 (7.3%) epidural/subdural hemorrhages, 2 (0.7%) cerebral venous sinus thromboses, and 24 (8.3%) strokes not otherwise classified. Asians and non-Hispanic Blacks were overrepresented among ischemic stroke/TIA patients compared with their overall representation in the registry, but adjusted odds of stroke did not vary by race. Median time from COVID-19 symptom onset to ischemic stroke was 11.5 days (interquartile range, 17.8); median National Institutes of Health Stroke Scale score was 11 (interquartile range, 17). COVID-19 patients with acute ischemic stroke/TIA had higher prevalence of hypertension, diabetes, and atrial fibrillation compared with those without stroke. Intensive care unit admission and mechanical ventilation were associated with higher odds of acute ischemic stroke/TIA, but older age was not a predictor. In adjusted models, acute ischemic stroke/TIA was not associated with in-hospital mortality.Conclusions:Ischemic stroke risk did not vary by race. In contrast to the association between older age and death from COVID-19, ischemic stroke risk was the highest among middle-aged adults after adjusting for comorbidities and illness severity, suggesting a potential mechanism for ischemic stroke in COVID-19 independent of age-related atherosclerotic pathways.
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Associations of Early Systolic Blood Pressure Control and Outcome After Thrombolysis-Eligible Acute Ischemic Stroke: Results From the ENCHANTED Study
Stroke, Ahead of Print. Background and Purpose:In thrombolysis-eligible patients with acute ischemic stroke, there is uncertainty over the most appropriate systolic blood pressure (SBP) lowering profile that provides an optimal balance of potential benefit (functional recovery) and harm (intracranial hemorrhage). We aimed to determine relationships of SBP parameters and outcomes in thrombolyzed acute ischemic stroke patients.Methods:Post hoc analyzes of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), a partial-factorial trial of thrombolysis-eligible and treated acute ischemic stroke patients with high SBP (150–180 mm Hg) assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) alteplase and intensive (target SBP, 130–140 mm Hg) or guideline-recommended (target SBP
Aspiration Versus Stent Retriever Thrombectomy for Posterior Circulation Stroke
Stroke, Ahead of Print. Background and Purpose:Whereas a clear benefit of endovascular treatment for anterior circulation stroke has been established, randomized trials assessing the posterior circulation have failed to show efficacy. Previous studies in anterior circulation stroke suggest that advanced thrombectomy devices were of great importance in achieving clinical benefit. Little is known about the effect of thrombectomy techniques on outcomes in posterior circulation stroke. In this study, we compare first-line strategy of direct aspiration to stent retriever thrombectomy for posterior circulation stroke.Methods:We analyzed data of patients with a posterior circulation stroke who were included in the Multicentre Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry between March 2014 and December 2018, a prospective, nationwide study, in which data were collected from consecutive patients who underwent endovascular treatment for ischemic stroke in the Netherlands. We compared patients who underwent first-line aspiration versus stent retriever thrombectomy. Primary outcome was functional outcome according to the modified Rankin Scale. Secondary outcomes were reperfusion grade, complication rate, and procedure duration. Associations between thrombectomy technique and outcome measures were estimated with multivariable ordinal logistic regression analyses.Results:Overall, 71 of 205 patients (35%) were treated with aspiration, and 134 (65%) with stent retriever thrombectomy. Patients in the aspiration group had a lower pc-ASPECTS on baseline computed tomography, and general anesthesia was more often applied in this group. First-line aspiration was associated with better functional outcome compared with stent retriever thrombectomy (adjusted common odds ratio for a 1-point improvement on the modified Rankin Scale 1.94 [95% CI, 1.03–3.65]). Successful reperfusion (extended Thrombolysis in Cerebral Infarction ≥2B) was achieved more often with aspiration (87% versus 73%,P=0.03). Symptomatic hemorrhage rates were comparable (3% versus 4%). Procedure times were shorter in the aspiration group (49 versus 69 minutesP
Frequency and Prognostic Significance of Clinical Fluctuations Before Hospital Arrival in Stroke
Stroke, Volume 53, Issue 2, Page 482-487, February 1, 2022. Background and Purpose:Clinical fluctuations in ischemic stroke symptoms are common, but fluctuations before hospital arrival have not been previously characterized.Methods:A standardized qualitative assessment of fluctuations before hospital arrival was obtained in an observational study that enrolled patients with mild ischemic stroke symptoms (National Institutes of Health Stroke Scale [NIHSS] score of 0–5) present on arrival to hospital within 4.5 hours of onset, in a subset of 100 hospitals participating in the Get With The Guidelines–Stroke quality improvement program. The number of fluctuations, direction, and the overall improvement or worsening was recorded based on reports from the patient, family, or paramedics. Baseline NIHSS on arrival and at 72 hours (or discharge if before) and final diagnosis and stroke subtype were collected. Outcomes at 90 days included the modified Rankin Scale, Barthel Index, Stroke Impact Scale 16, and European Quality of Life. Prehospital fluctuations were examined in relation to hospital NIHSS change (admission to 72 hours or discharge) and 90-day outcomes.Results:Among 1588 participants, prehospital fluctuations, consisting of improvement, worsening, or both were observed in 35.5%: 25.1% improved once, 5.3% worsened once, and 5.1% had more than 1 fluctuation. Those who improved were less likely and those who worsened were more likely to receive alteplase. Those who improved before hospital arrival had lower change in the hospital NIHSS than those who did not fluctuate. Better adjusted 90-day outcomes were noted in those with prehospital improvement compared to those without any fluctuations.Conclusions:Fluctuations in neurological symptoms and signs are common in the prehospital setting. Prehospital improvement was associated with better 90-day outcomes, controlling for admission NIHSS and alteplase treatment.Registration:URL:https://www.clinicaltrials.gov; Unique identifier: NCT 02072681.
HDL (High-Density Lipoprotein) Subspecies, Prevalent Covert Brain Infarcts, and Incident Overt Ischemic Stroke: Cardiovascular Health Study
Stroke, Ahead of Print. Background and Purpose:Whether HDL (high-density lipoprotein) is associated with risk of vascular brain injury is unclear. HDL is comprised of many apo (apolipoprotein) species, creating distinct subtypes of HDL.Methods:We utilized sandwich ELISA to determine HDL subspecies from plasma collected in 1998/1999 from 2001 CHS (Cardiovascular Health Study) participants (mean age, 80 years).Results:In cross-sectional analyses, participants with higher apoA1 in plasma and lower apoE in HDL were less likely to have prevalent covert magnetic resonance imaging–defined infarcts: odds ratio for apoA1 Q4 versus Q1, 0.68 (95% CI, 0.50–0.93), and odds ratio for apoE Q4 versus Q1, 1.36 (95% CI, 1.01–1.84). Similarly, apoA1 in the subspecies of HDL that lacked apoC3, apoJ, or apoE was inversely related to covert infarcts, and apoE in the subspecies of HDL that lacked apoC3 or apoJ was directly related to covert infarcts in prospective analyses. In contrast, the concentrations of apoA1 and apoE in the complementary subspecies of HDL that contained these apos were unrelated to covert infarcts. Patterns of associations between incident overt ischemic stroke and apoA1, apoE, and apoA1 and apoE in subspecies of HDL were similar to those observed for covert infarcts but less pronounced.Conclusions:This study highlights HDL subspecies defined by apo content as relevant biomarkers of covert and overt vascular brain injury.
Economic Evaluation of Endovascular Treatment for Acute Ischemic Stroke
Stroke, Ahead of Print. Background and Purpose:Endovascular treatment for acute ischemic stroke has been proven clinically effective, but evidence of the cost-effectiveness based on real-world data is scarce. The aim of this study was to assess whether endovascular therapy plus usual care is cost-effective in comparison to usual care alone in acute ischemic stroke patients.Methods:An economic evaluation was performed from a societal perspective with a 2-year time horizon. Empirical data on health outcomes and the use of resources following endovascular treatment were gathered parallel to the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and its 2-year follow-up study. Incremental cost-effectiveness ratios were calculated as the extra costs per additional patient with functional independence (modified Rankin Scale score 0–2) and the extra cost per quality-adjusted life year gained.Results:The mean costs per patient in the intervention group were $126 494 versus $143 331 in the control group (mean difference, −$16 839 [95% CI, −$38 113 to $5456]). Compared with patients in the control group, more patients in the intervention group achieved functional independence, 37.2% versus 23.9% (absolute difference, 13.3% [95% CI, 4.0%–22.0%]) and they generated more quality-adjusted life years, 0.99 versus 0.83 (mean difference of 0.16 [95% CI, 0.04–0.29]). Endovascular treatment dominated standard treatment with $18 233 saved per extra patient with a good outcome and $105 869 saved per additional quality-adjusted life year.Conclusions:Endovascular treatment added to usual care is clinically effective, and cost saving in comparison to usual care alone in patients with acute ischemic stroke.REGISTRATION:URL:https://www.trialregister.nl/trial/695; Unique identifier: NL695.https://www.isrctn.com/ISRCTN10888758; Unique identifier: ISRCTN10888758.
SLEAP SMART (Sleep Apnea Screening Using Mobile Ambulatory Recorders After TIA/Stroke): A Randomized Controlled Trial
Stroke, Ahead of Print. Background and Purpose:Poststroke/transient ischemic attack obstructive sleep apnea (OSA) is prevalent, linked with numerous unfavorable health consequences, but remains underdiagnosed. Reasons include patient inconvenience and costs associated with use of in-laboratory polysomnography (iPSG), the current standard tool. Fortunately, home sleep apnea testing (HSAT) can accurately diagnose OSA and is potentially more convenient and cost-effective compared with iPSG. Our objective was to assess whether screening for OSA in patients with stroke/transient ischemic attack using HSAT, compared with standard of care using iPSG, increased diagnosis and treatment of OSA, improved clinical outcomes and patient experiences with sleep testing, and was a cost-effective approach.Methods:We consecutively recruited 250 patients who had sustained a stroke/transient ischemic attack within the past 6 months. Patients were randomized (1:1) to use of (1) HSAT versus (2) iPSG. Patients completed assessments and questionnaires at baseline and 6-month follow-up appointments. Patients diagnosed with OSA were offered continuous positive airway pressure. The primary outcome was compared between study arms via an intention-to-treat analysis.Results:At 6 months, 94 patients completed HSAT and 71 patients completed iPSG. A significantly greater proportion of patients in the HSAT arm were diagnosed with OSA (48.8% versus 35.2%,P=0.04) compared with the iPSG arm. Furthermore, patients assigned to HSAT, compared with iPSG, were more likely to be prescribed continuous positive airway pressure (40.0% versus 27.2%), report significantly reduced sleepiness, and a greater ability to perform daily activities. Moreover, a significantly greater proportion of patients reported a positive experience with sleep testing in the HSAT arm compared with the iPSG arm (89.4% versus 31.1%). Finally, a cost-effectiveness analysis revealed that HSAT was economically attractive for the detection of OSA compared with iPSG.Conclusions:In patients with stroke/transient ischemic attack, use of HSAT compared with iPSG increases the rate of OSA diagnosis and treatment, reduces daytime sleepiness, improves functional outcomes and experiences with sleep testing, and could be an economically attractive approach.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT02454023.
Fast Outcome Categorization of the Upper Limb After Stroke
Stroke, Volume 53, Issue 2, Page 578-585, February 1, 2022. Background and Purpose:The ARAT (Action Research Arm Test) has been used to classify upper limb motor outcome after stroke in 1 of 3, 4, or 5 categories. The COVID-19 pandemic has encouraged the development of assessments that can be performed quickly and remotely. The aim of this study was to derive and internally validate decision trees for categorizing upper limb motor outcomes at the late subacute and chronic stages of stroke using a subset of ARAT tasks.Methods:This study retrospectively analyzed ARAT scores obtained in-person at 3 months poststroke from 333 patients. In-person ARAT scores were used to categorize patients’ 3-month upper limb outcome using classification systems with 3, 4, and 5 outcome categories. Individual task scores from in-person assessments were then used in classification and regression tree analyses to determine subsets of tasks that could accurately categorize upper limb outcome for each of the 3 classification systems. The decision trees developed using 3-month ARAT data were also applied to in-person ARAT data obtained from 157 patients at 6 months poststroke.Results:The classification and regression tree analyses produced decision trees requiring 2 to 4 ARAT tasks. The overall accuracy of the cross-validated decision trees ranged from 87.7% (SE, 1.0%) to 96.7% (SE, 2.0%). Accuracy was highest when classifying patients into one of 3 outcome categories and lowest for 5 categories. The decision trees are referred to as FOCUS (Fast Outcome Categorization of the Upper Limb After Stroke) assessments and they remained accurate for 6-month poststroke ARAT scores (overall accuracy range 83.4%–91.7%).Conclusions:A subset of ARAT tasks can accurately categorize upper limb motor outcomes after stroke. Future studies could investigate the feasibility and accuracy of categorizing outcomes using the FOCUS assessments remotely via video call.
Ischemic Stroke in Patients With Hypertrophic Cardiomyopathy According to Presence or Absence of Atrial Fibrillation
Stroke, Volume 53, Issue 2, Page 497-504, February 1, 2022. Background and Purpose:Patients with hypertrophic cardiomyopathy (HCM) have high risk of ischemic stroke (IS), especially if atrial fibrillation (AF) is present. Improvements in risk stratification are needed to help identify those patients with HCM at higher risk of stroke, whether AF is present or not.Methods:This French longitudinal cohort study from the database covering hospital care from 2010 to 2019 analyzed adults hospitalized with isolated HCM. A logistic regression model was used to construct a French HCM score, which was compared with the HCM Risk-CVA and CHA2DS2-VASc scores using c-indexes and calibration analysis.Results:In 32 206 patients with isolated HCM, 12 498 (38.8%) had AF, and 2489 (7.7%) sustained an IS during follow-up. AF in patients with HCM was independently associated with a higher risk for death (hazard ratio, 1.129 [95% CI, 1.088–1.172]), cardiovascular death (hazard ratio, 1.254 [95% CI, 1.177–1.337]), IS (hazard ratio, 1.210 [95% CI, 1.111–1.317]), and other major cardiovascular events. Independent predictors of IS in HCM were older age, heart failure, AF, prior IS, smoking and poor nutrition (allP
Prediction of Stroke Infarct Growth Rates by Baseline Perfusion Imaging
Stroke, Volume 53, Issue 2, Page 569-577, February 1, 2022. Background and Purpose:Computed tomography perfusion imaging allows estimation of tissue status in patients with acute ischemic stroke. We aimed to improve prediction of the final infarct and individual infarct growth rates using a deep learning approach.Methods:We trained a deep neural network to predict the final infarct volume in patients with acute stroke presenting with large vessel occlusions based on the native computed tomography perfusion images, time to reperfusion and reperfusion status in a derivation cohort (MR CLEAN trial [Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands]). The model was internally validated in a 5-fold cross-validation and externally in an independent dataset (CRISP study [CT Perfusion to Predict Response to Recanalization in Ischemic Stroke Project]). We calculated the mean absolute difference between the predictions of the deep learning model and the final infarct volume versus the mean absolute difference between computed tomography perfusion imaging processing by RAPID software (iSchemaView, Menlo Park, CA) and the final infarct volume. Next, we determined infarct growth rates for every patient.Results:We included 127 patients from the MR CLEAN (derivation) and 101 patients of the CRISP study (validation). The deep learning model improved final infarct volume prediction compared with the RAPID software in both the derivation, mean absolute difference 34.5 versus 52.4 mL, and validation cohort, 41.2 versus 52.4 mL (P
Role of Apparent Diffusion Coefficient Gradient Within Diffusion Lesions in Outcomes of Large Stroke After Thrombectomy
Stroke, Ahead of Print. Background and Purpose:The outcome of endovascular treatment in stroke patients with a large ischemic core is not always satisfactory. We evaluated whether the severity of baseline diffusion-weighted imaging abnormalities, as assessed by different apparent diffusion coefficient (ADC) thresholds, correlates with the clinical outcome in these patients after successful endovascular treatment.Methods:In 82 consecutive patients with a large vessel occlusion in the anterior circulation admitted ≤24 hours after onset, a baseline diffusion lesion volume (ADC ≤620×10−6mm2/s [ADC620]) ≥50 mL and successful recanalization by endovascular treatment were retrospectively investigated. Lesion volumes of 3 ADC thresholds (ADC620, ADC ≤520×10−6mm2/s [ADC520], and ADC ≤540×10−6mm2/s [ADC540]) were measured using an automated Olea software program. The performance of the ADC520/ADC620and ADC540/ADC620ratios in predicting the functional outcome was assessed by receiver operating characteristic curve analysis. The ADC ratio with optimal threshold showing better receiver operating characteristic performance was dichotomized at its median value into low versus high subgroup and its association with the outcome subsequently evaluated in a multivariable logistic regression model.Results:The median baseline diffusion lesion volume was 80.8 mL (interquartile range, 64.4–105.4). A good functional outcome (modified Rankin Scale score, ≤2) was achieved in 35 patients (42.7%). The optimal threshold for predicting the functional outcome was identified as ADC540/ADC620(area under the curve, 0.833) and dichotomized at 0.674. After adjusting for age, baseline National Institutes of Health Stroke Scale score, intravenous tissue-type plasminogen activator, baseline diffusion lesion volume, and onset-to-recanalization time, a low ADC540/ADC620was independently associated with a good functional outcome (adjusted odds ratio, 10.72 [95% CI, 3.06–37.50];P
The Stockholm Stroke Triage Project: Outcomes of Endovascular Thrombectomy Before and After Triage Implementation
Stroke, Volume 53, Issue 2, Page 473-481, February 1, 2022. Background and Purpose:The Stockholm Stroke Triage System (SSTS) is a prehospital algorithm for detection of endovascular thrombectomy (EVT)-eligible patients, combining symptom severity assessment and ambulance-to-hospital teleconsultation, leading to a decision on primary stroke center bypass. In the Stockholm Region (6 primary stroke centers, 1 EVT center), SSTS implementation in October 2017 reduced onset-to-EVT time by 69 minutes. We compared clinical outcomes before and after implementation of SSTS in an observational study.Methods:We prospectively recruited patients transported by Code Stroke ambulance within the Stockholm region under the SSTS, treated with EVT during October 2017 to October 2019, and compared to EVT patients from 2 previous years. Outcomes: shift in modified Rankin Scale (mRS) scores, mRS score 0 to 1, mRS score 0 to 2, and death (all 3 months), National Institutes of Health Stroke Scale (NIHSS) score change 24-hour post-EVT, recanalization (Thrombolysis in Cerebral Infarction 2b-3), and symptomatic intracranial hemorrhage. mRS outcomes were adjusted for age and baseline NIHSS.Results:Patients with EVT in the SSTS group (n=244) were older and had higher baseline NIHSS versus historical controls (n=187): median age 74 (interquartile range, 63–81) versus 71 (61–78); NIHSS score 17 (11.5–21) versus 15 (10–20). During SSTS, median onset-to-puncture time was 136 versus 205 minutes (P
Endovascular Treatment of Acute Ischemic Stroke With the Penumbra System in Routine Practice: COMPLETE Registry Results
Stroke, Ahead of Print. Background and Purpose:The purpose of the COMPLETE (International Acute Ischemic Stroke Registry With the Penumbra System Aspiration Including the 3D Revascularization Device) registry was to evaluate the generalizability of the safety and efficacy of the Penumbra System (Penumbra, Inc, Alameda) in a real-world setting.Methods:COMPLETE was a global, prospective, postmarket, multicenter registry. Patients with large vessel occlusion–acute ischemic stroke who underwent mechanical thrombectomy using the Penumbra System with or without the 3D Revascularization Device as frontline approach were enrolled at 42 centers (29 United States, 13 Europe) from July 2018 to October 2019. Primary efficacy end points were successful postprocedure angiographic revascularization (modified Thrombolysis in Cerebral Infarction ≥2b) and 90-day functional outcome (modified Rankin Scale score 0–2). The primary safety end point was 90-day all-cause mortality. An imaging core lab determined modified Thrombolysis in Cerebral Infarction scores, Alberta Stroke Program Early CT Scores, clot location, and occurrence of intracranial hemorrhage at 24 hours. Independent medical reviewers adjudicated safety end points.Results:Six hundred fifty patients were enrolled (median age 70 years, 54.0% female, 49.2% given intravenous recombinant tissue plasminogen activator before thrombectomy). Rate of modified Thrombolysis in Cerebral Infarction 2b to 3 postprocedure was 87.8% (95% CI, 85.3%–90.4%). First pass and postprocedure rates of modified Thrombolysis in Cerebral Infarction 2c to 3 were 41.5% and 66.2%, respectively. At 90 days, 55.8% (95% CI, 51.9%–59.7%) had modified Rankin Scale score 0 to 2, and all-cause mortality was 15.5% (95% CI, 12.8%–18.3%).Conclusions:Using Penumbra System for frontline mechanical thrombectomy treatment of patients with large vessel occlusion–acute ischemic stroke in a real-world setting was associated with angiographic, clinical, and safety outcomes that were comparable to prior randomized clinical trials with stringent site and operator selection criteria.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT03464565.
Phenotypes of Chronic Covert Brain Infarction in Patients With First-Ever Ischemic Stroke: A Cohort Study
Stroke, Volume 53, Issue 2, Page 558-568, February 1, 2022. Background and Purpose:The aim of this study was to assess the rate of chronic covert brain infarctions (CBIs) in patients with acute ischemic stroke (AIS) and to describe their phenotypes and diagnostic value.Methods:This is a single-center cohort study including 1546 consecutive patients with first-ever AIS on magnetic resonance imaging imaging from January 2015 to December 2017. The main study outcomes were CBI phenotypes, their relative frequencies, location, and association with vascular risk factors.Results:Any CBI was present in 574/1546 (37% [95% CI, 35%–40%]) of patients with a total of 950 CBI lesions. The most frequent locations of CBI were cerebellar in 295/950 (31%), subcortical supratentorial in 292/950 (31%), and cortical in 213/950 (24%). CBI phenotypes included lacunes (49%), combined gray and white matter lesions (30%), gray matter lesions (13%), and large subcortical infarcts (7%). Vascular risk profile and white matter hyperintensities severity (19% if no white matter hyperintensity, 63% in severe white matter hyperintensity,P