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Hyperglycemia during early brain injury (EBI) period after spontaneous subarachnoid hemorrhage (SAH) is associated with poor outcome, but the underlying physiopathology is unknown. This study assessed if hyperglycemia during EBI is associated with markers of neuroaxonal injury and whether these biomarkers partially account for the association between hyperglycemia and poor clinical outcome. Ninety-two SAH patients admitted within 24 h of bleeding onset were prospectively included. Glucose levels were measured at arrival and every 6 h for 72 h. Serum neurofilament light chain (NFL) levels were measured at 72 h. Functional outcome was assessed with the modified Rankin Scale (mRS) at 90 days (poor outcome, mRS > 2). The association between glucose metrics, NFL levels, and clinical outcome was assessed with univariate and multivariate analyses. Mediation analysis was performed to examine the potential chain in which NFL may mediate the relationship between glucose and functional outcome. Higher glucose and NFL levels during EBI were associated with poor clinical outcome in adjusted analysis. NFL levels were associated with older age, higher initial severity, and higher glucose levels during EBI period. In adjusted mediation analyses, the association between glucose and clinical outcome was significantly mediated by NFL levels. The mediator NFL explained 25% of the association between glucose during EBI period and poor functional outcome at 90 days. In SAH, the association between glucose levels during EBI and poor clinical outcome might be significantly mediated by NFL levels. The link between hyperglycemia and poor clinical outcome might be explained in part through secondary neuroaxonal injury.
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INTRODUCTION: Malignant middle cerebral artery infarction (MCI) needs rapid intervention. This study aimed to enhance the prediction of MCI using computed tomography perfusion (CTP) with varied quantitative benchmarks. MATERIALS AND METHODS: We retrospectively analyzed 253 patients from a single-center registry presenting with acute, severe, proximal large vessel occlusion studied with whole-brain CTP imaging at hospital arrival within the first 24 h of symptoms-onset. MCI was defined by clinical and imaging criteria, including decreased level of consciousness, anisocoria, death due to cerebral edema, or need for decompressive craniectomy, together with midline shift ⩾6 mm, or infarction of more than 50% of the MCA territory. The predictive accuracy of baseline ASPECTS and CTP quantifications for MCI was assessed by receiver operating characteristic (ROC) area under the curve (AUC) while F-score was calculated as an indicator of precision and sensitivity. RESULTS: Sixty-three out of 253 patients (25%) fulfilled MCI criteria and had worse clinical and imaging results than the non-MCI group. The capacity to predict MCI was lower for baseline ASPECTS (AUC 0.83, F-score 0.52, Youden's index 6), than with perfusion-based measures: relative cerebral blood volume threshold <40% (AUC 0.87, F-score 0.71, Youden's index 34 mL) or relative cerebral blood flow threshold <35% (AUC 0.87, F-score 0.62, Youden's index 67 mL). CTP based on rCBV measurements identified twice as many MCI as baseline CT ASPECTS. DISCUSSION AND CONCLUSION: CTP-based quantifications may offer enhanced predictive capabilities for MCI compared to non-contrast baseline CT ASPECTS, potentially improving the monitoring of severe ischemic stroke patients at risk of life-threatening edema and its treatment.
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BACKGROUND AND OBJECTIVES: The time taken to achieve blood pressure (BP) control could be pivotal in the benefits of reducing BP in acute intracerebral hemorrhage (ICH). We aimed to assess the relationship between the rapid achievement and sustained maintenance of an intensive systolic BP (SBP) target with radiologic, clinical, and functional outcomes. METHODS: Rapid, Intensive, and Sustained BP lowering in Acute ICH (RAINS) was a multicenter, prospective, observational cohort study of adult patients with ICH <6 hours and SBP ≥150 mm Hg at 4 Comprehensive Stroke Centers during a 4.5-year period. Patients underwent baseline and 24-hour CT scans and 24-hour noninvasive BP monitoring. BP was managed under a rapid (target achievement ≤60 minutes), intensive (target SBP <140 mm Hg), and sustained (target stability for 24 hours) BP protocol. SBP target achievement ≤60 minutes and 24-hour SBP variability were recorded. Outcomes included hematoma expansion (>6 mL or >33%) at 24 hours (primary outcome), early neurologic deterioration (END, 24-hour increase in NIH Stroke Scale score ≥4), and 90-day ordinal modified Rankin scale (mRS) score. Analyses were adjusted by age, sex, anticoagulation, onset-to-imaging time, ICH volume, and intraventricular extension. RESULTS: We included 312 patients (mean age 70.2 ± 13.3 years, 202 [64.7%] male). Hematoma expansion occurred in 70/274 (25.6%) patients, END in 58/291 (19.9%), and the median 90-day mRS score was 4 (interquartile range, 2-5). SBP target achievement ≤60 minutes (178/312 [57.1%]) associated with a lower risk of hematoma expansion (adjusted odds ratio [aOR] 0.43, 95% confidence interval [CI] 0.23-0.77), lower END rate (aOR 0.43, 95% CI 0.23-0.80), and lower 90-day mRS scores (aOR 0.48, 95% CI 0.32-0.74). The mean 24-hour SBP variability was 21.0 ± 7.6 mm Hg. Higher 24-hour SBP variability was not related to expansion (aOR 0.99, 95% CI 0.95-1.04) but associated with higher END rate (aOR 1.15, 95% CI 1.09-1.21) and 90-day mRS scores (aOR 1.06, 95% CI 1.04-1.10). DISCUSSION: Among patients with acute ICH, achieving an intensive SBP target within 60 minutes was associated with lower hematoma expansion risk. Rapid SBP reduction and stable sustention within 24 hours were related to improved clinical and functional outcomes. These findings warrant the design of randomized clinical trials examining the impact of effectively achieving rapid, intensive, and sustained BP control on hematoma expansion. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in adults with spontaneous ICH and initial SBP ≥150 mm Hg, lowering SBP to <140 mm Hg within the first hour and maintaining this for 24 hours is associated with decreased hematoma expansion.
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Hipotensión , Accidente Cerebrovascular , Adulto , Humanos , Masculino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Presión Sanguínea/fisiología , Antihipertensivos/uso terapéutico , Antihipertensivos/farmacología , Estudios Prospectivos , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/tratamiento farmacológico , Accidente Cerebrovascular/tratamiento farmacológico , Hematoma/diagnóstico por imagen , Hematoma/tratamiento farmacológico , Resultado del TratamientoRESUMEN
INTRODUCTION: Stroke Units (SU) have been suggested as an alternative to Intensive Care units (ICU) for initial admission of low-grade non-aneurysmal spontaneous subarachnoid haemorrhage (naSAH). We hypothesised that the incidence of in-hospital complications and long-term clinical outcomes in low-grade naSAH patients would be comparable in both settings, and that a cost-minimisation analysis would favour the use of SU. PATIENTS AND METHODS: Retrospective, single-centre study at a third-level stroke-referral hospital, including low-grade spontaneous naSAH patients with WFNS 1-2. Primary outcomes were death and functional status at 3 months. Secondary outcomes were incidence of in-hospital major neurological and systemic complications. Additionally, a cost-minimisation analysis was conducted to estimate the average cost savings that could be achieved with the most efficient approach. RESULTS: Out of 96 naSAH patients, 30 (31%) were initially admitted to ICU and 66 (69%) to SU. Both groups had similar demographic and radiological features except for a higher proportion of WFNS 2 in ICU subgroup. There were no statistically significant differences between ICU and SU-managed subgroups in death rate (2 (7%) and 1 (2%), respectively), functional outcome at 90 days (28 (93%) and 61 (92%) modified Rankin Scale 0-2) or neurological and systemic in-hospital complications. Cost-minimisation analysis demonstrated significant monetary savings favouring the SU strategy. DISCUSSION AND CONCLUSION: Initial admission to the SU appears to be a safe and cost-effective alternative to the ICU for low-grade naSAH patients, with comparable clinical outcomes and a reduction of hospitalisation-related costs. Prospective multicenter randomised studies are encouraged to further evaluate this approach.
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Accidente Cerebrovascular , Hemorragia Subaracnoidea , Humanos , Hospitalización , Hospitales , Unidades de Cuidados Intensivos , Estudios Retrospectivos , Accidente Cerebrovascular/epidemiología , Hemorragia Subaracnoidea/diagnóstico por imagenRESUMEN
OBJECTIVE: Recent data have suggested that ineffective tissue reperfusion despite successful angiographic reperfusion was partly responsible for unfavorable outcomes after endovascular therapy (EVT) and might be modulated by intravenous thrombolysis (IVT) use before EVT. To specifically decipher the effect played by IVT before EVT, we compared the clinical and safety outcomes of patients who experienced a complete reperfusion at the end of EVT according to IVT use before EVT. METHODS: The Endovascular Treatment in Ischemic Stroke (ETIS) registry is an ongoing, prospective, observational study at 21 centers that perform EVT in France. Patients were included if they had an anterior large vessel occlusion of the intracranial internal carotid artery or middle cerebral artery (M1/M2 segments) and complete reperfusion (expanded Thrombolysis in Cerebral Infarction score = 3) with EVT within 6 hours, between January 2015 and December 2021. The cohort was divided into two groups according to IVT use before EVT, and propensity score matching (PSM) was used to balance the two groups. Primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included favorable outcome (mRS 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 90-day mortality. Outcomes were estimated with multivariate logistic models adjusted for age, National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and time from symptom onset to puncture. RESULTS: Among 5,429 patients included in the ETIS registry, 1,093 were included in the study, including 651 patients with complete recanalization treated with IVT before EVT. After PSM, 488 patients treated with IVT before EVT were compared to 337 patients without IVT. In the matched cohort analysis, the IVT+EVT group had a favorable shift in the overall mRS score distribution (adjusted odds ratio [aOR] = 1.41, 95% confidence interval [CI] = 1.04-1.91, p = 0.023) and higher rates of favorable outcome (61.1% vs 48.7%, aOR = 1.49, 95% CI = 1.02-2.20, p = 0.041) at 90 days compared with the EVT alone group. Rates of symptomatic intracerebral hemorrhage were comparable between both groups (6.0% vs 4.3%, aOR = 1.16, 95% CI = 0.53-2.54, p = 0.709). INTERPRETATION: In clinical practice, even after complete angiographic reperfusion by EVT, prior IVT use improves clinical outcomes of patients without increasing bleeding risk. ANN NEUROL 2024;95:762-773.
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Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Terapia Trombolítica , Humanos , Procedimientos Endovasculares/efectos adversos , Fibrinolíticos/efectos adversos , Accidente Cerebrovascular Isquémico/terapia , Estudios Prospectivos , Terapia Trombolítica/efectos adversos , Resultado del Tratamiento , Hemorragia Cerebral/epidemiologíaRESUMEN
Uric acid (UA) is a strong endogenous antioxidant that neutralizes the toxicity of peroxynitrite and other reactive species on the neurovascular unit generated during and after acute brain ischemia. The realization that a rapid reduction of UA levels during an acute ischemic stroke was associated with a worse stroke outcome paved the way to investigate the value of exogenous UA supplementation to counteract the progression of redox-mediated ischemic brain damage. The long translational journey for UA supplementation recently reached a critical milestone when the results of the multicenter NIH stroke preclinical assessment network (SPAN) were reported. In a novel preclinical paradigm, 6 treatment candidates including UA supplementation were selected and tested in 6 independent laboratories following predefined criteria and strict methodological rigor. UA supplementation was the only intervention in SPAN that exceeded the prespecified efficacy boundary with male and female animals, young mice, young rats, aging mice, obese mice, and spontaneously hypertensive rats. This unprecedented achievement will allow UA to undergo clinical testing in a pivotal clinical trial through a NIH StrokeNet thrombectomy endovascular platform created to assess new treatment strategies in patients treated with mechanical thrombectomy. UA is a particularly appealing adjuvant intervention for mechanical thrombectomy because it targets the microcirculatory hypoperfusion and oxidative stress that limits the efficacy of this therapy. This descriptive review aims to summarize the translational development of UA supplementation, highlighting those aspects that likely contributed to its success. It includes having a well-defined target and mechanism of action, and an approach that simultaneously integrated rigorous preclinical assessment, with epidemiologic and preliminary human intervention studies. Validation of the clinical value of UA supplementation in a pivotal trial would confirm the translational value of the SPAN paradigm in preclinical research.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Ratas , Ratones , Animales , Ácido Úrico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Microcirculación , Accidente Cerebrovascular/complicaciones , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/complicaciones , Estudios Multicéntricos como AsuntoRESUMEN
Patent foramen ovale (PFO) closure, along with medical therapy, has emerged as the therapeutic gold standard in younger (<60-year-old) patients with a PFO-related stroke for preventing recurrent events. However, PFO management guidelines lack definite recommendations for older (>60 years) patients with a PFO-related cerebrovascular event, a complex group of patients who were mostly excluded from PFO closure clinical trials. Nevertheless, several studies have shown a higher prevalence of PFO among older patients with cryptogenic stroke, and its presence has been associated with an increased risk of recurrent events. Furthermore, older patients exhibit a higher prevalence of high-risk PFO anatomical features, present inherent age-related risk factors that might increase the risk of paradoxical embolism through a PFO, and have a higher incidence of ischemic events after a PFO-related event. Additionally, observational studies have shown the safety and preliminary efficacy of PFO closure in older PFO-related stroke patients. Yet, higher rates of recurrent cerebrovascular events and new-onset atrial fibrillation were observed in some studies among older patients compared to their younger counterparts. After careful case-by-case evaluation, including the assessment of hidden potential cardioembolic sources of a cryptogenic stroke other than PFO, transcatheter PFO closure might be a safe and effective therapeutic option for preventing recurrent thromboembolic events in patients >60 years with a high-risk PFO-associated stroke. Ongoing trials will provide important insights into the role of PFO closure in the elderly population.
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Human diseases may be modeled in animals to allow preclinical assessment of putative new clinical interventions. Recent, highly publicized failures of large clinical trials called into question the rigor, design, and value of preclinical assessment. We established the Stroke Preclinical Assessment Network (SPAN) to design and implement a randomized, controlled, blinded, multi-laboratory trial for the rigorous assessment of candidate stroke treatments combined with intravascular thrombectomy. Efficacy and futility boundaries in a multi-arm multi-stage statistical design aimed to exclude from further study highly effective or futile interventions after each of four sequential stages. Six independent research laboratories performed a standard focal cerebral ischemic insult in five animal models that included equal numbers of males and females: young mice, young rats, aging mice, mice with diet-induced obesity, and spontaneously hypertensive rats. The laboratories adhered to a common protocol and efficiently enrolled 2615 animals with full data completion and comprehensive animal tracking. SPAN successfully implemented treatment masking, randomization, prerandomization inclusion and exclusion criteria, and blinded assessment of outcomes. The SPAN design and infrastructure provide an effective approach that could be used in similar preclinical, multi-laboratory studies in other disease areas and should help improve reproducibility in translational science.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Femenino , Humanos , Masculino , Ratas , Animales , Ratones , Roedores , Laboratorios , Reproducibilidad de los Resultados , Accidente Cerebrovascular/terapiaRESUMEN
BACKGROUND: Predicting a challenging clot when performing mechanical thrombectomy in acute stroke can be difficult. One reason for this difficulty is a lack of agreement on how to precisely define these clots. We explored the opinions of stroke thrombectomy and clot research experts regarding challenging clots, defined as difficult to recanalize clots by endovascular approaches, and clot/patient features that may be indicative of such clots. METHODS: A modified DELPHI technique was used before and during the CLOTS 7.0 Summit, which included experts in thrombectomy and clot research from different specialties. The first round included open-ended questions and the second and final rounds each consisted of 30 closed-ended questions, 29 on various clinical and clot features, and 1 on number of passes before switching techniques. Consensus was defined as agreement ≥â¯50%. Features with consensus and rated ≥â¯3 out of 4 on the certainty scale were included in the definition of a challenging clot. RESULTS: Three DELPHI rounds were performed. Panelists achieved consensus on 16/30 questions, of which 8 were rated 3 or 4 on the certainty scale, namely white-colored clots (mean certainty score 3.1), calcified clots under histology (3.7) and imaging (3.7), stiff clots (3.0), sticky/adherent clots (3.1), hard clots (3.1), difficult to pass clots (3.1) and clots that are resistant to pulling (3.0). Most panelists considered switching endovascular treatment (EVT) techniques after 2-3 unsuccessful attempts. CONCLUSION: This DELPHI consensus identified 8 distinct features of a challenging clot. The varying degree of certainty amongst the panelists emphasizes the need for more pragmatic studies to enable accurate a priori identification of such occlusions prior to EVT.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular , Trombosis , Humanos , Técnica Delphi , Trombosis/diagnóstico por imagen , Trombosis/terapia , Trombosis/patología , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Procedimientos Endovasculares/métodos , Isquemia Encefálica/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Respiratory and urinary tract infections are frequent complications in patients with severe stroke. Stroke-associated infection is mainly due to opportunistic commensal bacteria of the microbiota that may translocate from the gut. We investigated the mechanisms underlying gut dysbiosis and poststroke infection. METHODS: Using a model of transient cerebral ischemia in mice, we explored the relationship between immunometabolic dysregulation, gut barrier dysfunction, gut microbial alterations, and bacterial colonization of organs, and we explored the effect of several drug treatments. RESULTS: Stroke-induced lymphocytopenia and widespread colonization of lung and other organs by opportunistic commensal bacteria. This effect correlated with reduced gut epithelial barrier resistance, and a proinflammatory sway in the gut illustrated by complement and nuclear factor-κB activation, reduced number of gut regulatory T cells, and a shift of gut lymphocytes to γδT cells and T helper 1/T helper 17 phenotypes. Stroke increased conjugated bile acids in the liver but decreased bile acids and short-chain fatty acids in the gut. Gut fermenting anaerobic bacteria decreased while opportunistic facultative anaerobes, notably Enterobacteriaceae, suffered an expansion. Anti-inflammatory treatment with a nuclear factor-κB inhibitor fully abrogated the Enterobacteriaceae overgrowth in the gut microbiota induced by stroke, whereas inhibitors of the neural or humoral arms of the stress response were ineffective at the doses used in this study. Conversely, the anti-inflammatory treatment did not prevent poststroke lung colonization by Enterobacteriaceae. CONCLUSIONS: Stroke perturbs homeostatic neuro-immuno-metabolic networks facilitating a bloom of opportunistic commensals in the gut microbiota. However, this bacterial expansion in the gut does not mediate poststroke infection.
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Microbioma Gastrointestinal , Neumonía , Accidente Cerebrovascular , Ratones , Animales , FN-kappa B , Bacterias/genética , Accidente Cerebrovascular/complicaciones , PulmónRESUMEN
The recently published SPACE-2 trial (Stent-Supported Percutaneous Angioplasty of the Carotid Artery Versus Endarterectomy-2) compared 3 treatments to prevent stroke in patients with asymptomatic carotid stenosis ≥70%: (1) carotid endarterectomy plus best medical treatment (BMT), (2) transfemoral carotid artery stenting plus BMT, or (3) BMT alone. Because of low enrollment, the findings of similar safety and efficacy for carotid endarterectomy, carotid artery stenting, or BMT alone were inconclusive. Publication of the CREST (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial)-2 results should provide level A evidence that has been lacking for 2 to 3 decades, to guide treatment of asymptomatic patients with severe carotid stenosis. For symptomatic patients with ≥70% stenosis, no trials are underway to update the degree of benefit reported for carotid endarterectomy by NASCET (North American Carotid Endarterectomy Trial) and ECST (European Carotid Surgery Trial), published in 1991. Subsequently, the use of cigarettes has plummeted, and major improvements in medical treatments and in carotid revascularization have emerged. These advances have coincided with abrupt decline in the clinical end points necessary for treatment comparisons in procedural trials. One of the advances in the invasive management of carotid disease has been transcarotid artery revascularization, already with limited approval by the US Food and Drug Administration. Establishing safety and efficacy of transcarotid artery revascularization compared with carotid endarterectomy, carotid artery stenting, or BMT alone may be challenging because of enrollment, regulatory, and funding barriers to design and complete an adequately powered randomized trial.
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Estenosis Carotídea , Endarterectomía Carotidea , Accidente Cerebrovascular , Humanos , Estenosis Carotídea/cirugía , Resultado del Tratamiento , Stents/efectos adversos , Endarterectomía Carotidea/métodos , Arterias Carótidas/cirugía , Accidente Cerebrovascular/etiología , Factores de RiesgoRESUMEN
BACKGROUND: The first pass effect (FPE) is an independent predictor of functional independence in patients with large vessel occlusion in anterior circulation ischemic strokes. However, whether it predicts outcome in posterior circulation large vessel occlusion (PC-LVO) is uncertain. We aimed to study the frequency, characteristics, and predictors of FPE and its association with clinical outcomes in PC-LVO. METHOD: We performed an analysis from the prospective CICAT Registry. All patients with PC-LVO who underwent endovascular therapy between January 2016 and January 2020 were included. A centrally assessed clinical follow-up was performed at 3 months by blinded investigators. FPE was defined as the achievement of modified Thrombolysis In Cerebral Infarction 3 in a single pass of the endovascular thrombectomy device, and multi-pass effect (MPE) if it was achieved in more than one pass. A multivariable analysis was performed to identify whether FPE is an independent predictor of functional independence defined as a modified Rankin Score of 0-2. RESULTS: We analyzed data from 265 patients in who FPE was achieved in 105 (39.6%). Patients with FPE were more likely to achieve functional independence compared to the non-FPE group (52.4% vs 25.1%, p < .001) and the MPE group (52.4% vs 26.7%, p < .001). FPE was independently associated with functional independence (adjusted odds ratio (aOR): 2.10, 95% confidence interval (CI) 1.01-4.37) but MPE was not (aOR: 0.92, 95% CI 0.40-2.13). Independent predictors of FPE were the use of direct aspiration, embolic mechanism of stroke, and the absence of general anesthesia (GA) use. CONCLUSIONS: FPE is an independent predictor of functional independence in PC-LVO and was associated with a significantly better outcome than MPE.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/etiología , Estudios Prospectivos , Resultado del Tratamiento , Trombectomía , Sistema de Registros , Estudios Retrospectivos , Isquemia Encefálica/terapia , Isquemia Encefálica/etiología , Procedimientos Endovasculares/efectos adversosRESUMEN
BACKGROUND: Acute ischemic stroke patients not referred directly to a comprehensive stroke center (CSC) have reduced access to endovascular treatment (EVT). The RACECAT trial is a population-based cluster-randomized trial, designed to compare mothership and drip-and-ship strategies in acute ischemic stroke patients outside the catchment area of a CSC. AIMS: To analyze the evolution of performance indicators in the regions that participated in RACECAT. METHODS: This retrospective longitudinal observational study included all stroke alerts evaluated by emergency medical services in Catalonia between February 2016 and February 2020. Cases were classified geographically according to the nearest SC: local SC (Local-SC) and CSC catchment areas. We analyzed the evolution of EVT rates and relevant workflow times in Local-SC versus CSC catchment areas over three study periods: P1 (February 2016 to April 2017: before RACECAT initiation), P2 (May 2017 to September 2018), and P3 (October 2018 to February 2020). RESULTS: We included 20603 stroke alerts, 10,694 (51.9%) of which were activated within Local-SC catchment areas. The proportion of patients receiving EVT within Local-SC catchment areas increased (P1 vs. P3: 7.5% (95% confidence interval (CI), 6.4-8.7) to 22.5% (95% CI, 20.8-24.4) p < 0.001). Inequalities in the odds of receiving EVT were reduced for patients from CSC versus Local-SC catchment areas (P1: odds ratio (OR) 3.9 (95% CI, 3.2-5) vs. P3: OR 1.5 (95% CI, 1.3-1.7) In Local-SC, door-to-image (P1: 24 (interquartile range (IQR) 15-36), P2: 24 (15-35), P3: 21 (13-32) min, p < 0.001) and door-to-needle times (P1: 42 (31-60), P2: 41 (29-58), P3: 35 (25-50) p < 0.001) reduced. Time from Local-SC arrival to groin puncture also decreased over time (P1: 188 [151-229], P2: 190 (157-233), P3: 168 (127-215) min, p < 0.001). CONCLUSION: An increase in EVT rates in Local-SC regions with a significant decrease in workflow times occurred during the period of the RACECAT trial.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/terapia , Isquemia Encefálica/terapia , Terapia Trombolítica/métodos , Indicadores de Calidad de la Atención de Salud , Estudios Retrospectivos , Resultado del Tratamiento , TrombectomíaRESUMEN
OBJECTIVE: This study was undertaken to investigate whether adjunct alteplase improves brain reperfusion following successful thrombectomy. METHODS: This single-center, randomized, double-blind, placebo-controlled study included 36 patients (mean [standard deviation] = 70.8 [13.5] years old, 18 [50%] women) with large vessel occlusion undergoing thrombectomy resulting in near-normal (expanded Thrombolysis in Cerebral Infarction [eTICI] b50/67/2c, n = 23, 64%) or normal angiographic reperfusion (eTICI 3, n = 13, 36%). Seventeen patients were randomized to intra-arterial alteplase (0.225mg/kg), and 19 received placebo. At 48 hours, patients had brain perfusion/diffusion-weighted magnetic resonance imaging (MRI) and MRI-spectroscopy. The primary outcome was the difference in the proportion of patients with areas of hypoperfusion on MRI. Secondary outcomes were the infarct expansion ratio (final to initial infarction volume), and the N-acetylaspartate (NAA) peak relative to total creatine as a marker of neuronal integrity. RESULTS: The prevalence of hypoperfusion was 24% with intra-arterial alteplase, and 58% with placebo (adjusted odds ratio = 0.20, 95% confidence interval [CI] = 0.04-0.91, p = 0.03). Among 14 patients with final eTICI 3 scores, hypoperfusion was found in 1 of 7 (14%) in the alteplase group and 3 of 7 (43%) in the placebo group. Abnormal brain perfusion was associated with worse functional outcome at day 90. Alteplase significantly reduced the infarct expansion ratio compared with placebo (median [interquartile range (IQR)] = 0.7 [0.5-1.2] vs 3.2 [1.8-5.7], p = 0.01) and resulted in higher NAA peaks (median [IQR] = 1.13 [0.91-1.36] vs 1.00 [0.74-1.22], p < 0.0001). INTERPRETATION: There is a high prevalence of areas of hypoperfusion following thrombectomy despite successful reperfusion on angiography. Adjunct alteplase enhances brain reperfusion, which results in reduced expansion of the infarction and improved neuronal integrity. ANN NEUROL 2022;92:860-870.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular , Femenino , Humanos , Masculino , Encéfalo/diagnóstico por imagen , Encéfalo/cirugía , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/cirugía , Infarto Cerebral , Creatina/uso terapéutico , Fibrinolíticos/uso terapéutico , Reperfusión/métodos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno/uso terapéutico , Resultado del Tratamiento , Persona de Mediana Edad , Anciano , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Nelonemdaz is a multitarget neuroprotectant that selectively blocks N-methyl-D-aspartate receptors and scavenges free radicals, as proven in preclinical ischemia-reperfusion studies. We aimed to evaluate the safety and efficacy of nelonemdaz in patients with acute ischemic stroke receiving endovascular reperfusion therapy. METHODS: This phase II randomized trial involved participants with large-artery occlusion in the anterior circulation at baseline who received endovascular reperfusion therapy <8 hours from symptom onset at 7 referral stroke centers in South Korea between October 29, 2016, and June 1, 2020. Two hundred thirteen patients were screened and 209 patients were randomly assigned at a 1:1:1 ratio using a computer-generated randomization system. Patients were divided into 3 groups based on the medication received-placebo, low-dose (2750 mg) nelonemdaz, and high-dose (5250 mg) nelonemdaz. The primary outcome was the proportion of patients with modified Rankin Scale scores of 0-2 at 12 weeks. RESULTS: Two hundred eight patients were assigned to the placebo (n=70), low-dose (n=71), and high-dose (n=67) groups. The groups had similar baseline characteristics. The primary outcome was achieved in 183 patients, and it did not differ among the groups (33/61 [54.1%], 40/65 [61.5%], and 36/57 [63.2%] patients; P=0.5578). The common odds ratio (90% CI) indicating a favorable shift in the modified Rankin Scale scores at 12 weeks was 1.55 (0.92-2.60) between the placebo and low-dose groups and 1.61 (0.94-2.76) between the placebo and high-dose groups. No serious adverse events were reported. CONCLUSIONS: The study arms showed no significant difference in the proportion of patients achieving modified Rankin Scale scores of 0-2 at 12 weeks. Nevertheless, nelonemdaz-treated patients showed a favorable tendency toward achieving these scores at 12 weeks, without serious adverse effects. Thus, a large-scale phase III trial is warranted. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02831088.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Fármacos Neuroprotectores , Accidente Cerebrovascular , Humanos , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/cirugía , Isquemia Encefálica/diagnóstico , Trombectomía/efectos adversos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/cirugía , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/cirugía , Fármacos Neuroprotectores/uso terapéutico , Receptores de N-Metil-D-Aspartato , Procedimientos Endovasculares/efectos adversos , Resultado del Tratamiento , ReperfusiónRESUMEN
BACKGROUND: We analyzed the main factors associated with intravenous thrombolysis (IVT) in patients with minor ischemic stroke. METHODS: Data were obtained from a prospective, government-mandated, population-based registry of stroke code patients in Catalonia (6 Comprehensive Stroke Centers, 8 Primary Stroke Centers, and 14 TeleStroke Centers). We selected patients diagnosed with ischemic stroke and National Institutes of Health Stroke Scale (NIHSS) ≤5 at hospital admission from January 2016 to December 2020. We excluded patients with a baseline modified Rankin Scale score of ≥3, absolute contraindication for IVT, unknown stroke onset, or admitted to hospital beyond 4.5 after stroke onset. The main outcome was treatment with IVT. We performed univariable and binary logistic regression analyses to identify the most important factors associated with IVT. RESULTS: We included 2975 code strokes; 1433 (48.2%) received IVT of which 30 (2.1%) had a symptomatic hemorrhagic transformation. Patients treated with IVT as compared to patients who did not receive IVT were more frequently women, had higher NIHSS, arrived earlier to hospital, were admitted to a Comprehensive Stroke Centers, and had large vessel occlusion. After binary logistic regression, NIHSS score 4 to 5 (odds ratio, 40.62 [95% CI, 31.73-57.22]; P<0.001) and large vessel occlusion (odds ratio, 16.39 [95% CI, 7.25-37.04]; P<0.001) were the strongest predictors of IVT. Younger age, female sex, baseline modified Rankin Scale score of 0, earlier arrival to hospital (<120 minutes after stroke onset), and the type of stroke center were also independently associated with IVT. The weight of large vessel occlusion on IVT was higher in patients with lower NIHSS. CONCLUSIONS: Minor stroke female patients, with higher NIHSS, arriving earlier to the hospital, presenting with large vessel occlusion and admitted to a Comprehensive Stroke Centers were more likely to receive intravenous thrombolysis.
Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Femenino , Humanos , Isquemia Encefálica/terapia , Estudios Prospectivos , Resultado del Tratamiento , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/complicaciones , Terapia Trombolítica , Trombectomía , Fibrinolíticos/uso terapéuticoAsunto(s)
Fibrinolíticos , Accidente Cerebrovascular Isquémico , Activador de Tejido Plasminógeno , Arteriopatías Oclusivas/complicaciones , Arteriopatías Oclusivas/tratamiento farmacológico , Arteriopatías Oclusivas/cirugía , Fibrinolíticos/administración & dosificación , Fibrinolíticos/uso terapéutico , Humanos , Infusiones Intraarteriales , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular Isquémico/cirugía , Trombectomía , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/uso terapéutico , Resultado del TratamientoRESUMEN
Importance: In nonurban areas with limited access to thrombectomy-capable centers, optimal prehospital transport strategies in patients with suspected large-vessel occlusion stroke are unknown. Objective: To determine whether, in nonurban areas, direct transport to a thrombectomy-capable center is beneficial compared with transport to the closest local stroke center. Design, Setting, and Participants: Multicenter, population-based, cluster-randomized trial including 1401 patients with suspected acute large-vessel occlusion stroke attended by emergency medical services in areas where the closest local stroke center was not capable of performing thrombectomy in Catalonia, Spain, between March 2017 and June 2020. The date of final follow-up was September 2020. Interventions: Transportation to a thrombectomy-capable center (n = 688) or the closest local stroke center (n = 713). Main Outcomes and Measures: The primary outcome was disability at 90 days based on the modified Rankin Scale (mRS; scores range from 0 [no symptoms] to 6 [death]) in the target population of patients with ischemic stroke. There were 11 secondary outcomes, including rate of intravenous tissue plasminogen activator administration and thrombectomy in the target population and 90-day mortality in the safety population of all randomized patients. Results: Enrollment was halted for futility following a second interim analysis. The 1401 enrolled patients were included in the safety analysis, of whom 1369 (98%) consented to participate and were included in the as-randomized analysis (56% men; median age, 75 [IQR, 65-83] years; median National Institutes of Health Stroke Scale score, 17 [IQR, 11-21]); 949 (69%) comprised the target ischemic stroke population included in the primary analysis. For the primary outcome in the target population, median mRS score was 3 (IQR, 2-5) vs 3 (IQR, 2-5) (adjusted common odds ratio [OR], 1.03; 95% CI, 0.82-1.29). Of 11 reported secondary outcomes, 8 showed no significant difference. Compared with patients first transported to local stroke centers, patients directly transported to thrombectomy-capable centers had significantly lower odds of receiving intravenous tissue plasminogen activator (in the target population, 229/482 [47.5%] vs 282/467 [60.4%]; OR, 0.59; 95% CI, 0.45-0.76) and significantly higher odds of receiving thrombectomy (in the target population, 235/482 [48.8%] vs 184/467 [39.4%]; OR, 1.46; 95% CI, 1.13-1.89). Mortality at 90 days in the safety population was not significantly different between groups (188/688 [27.3%] vs 194/713 [27.2%]; adjusted hazard ratio, 0.97; 95% CI, 0.79-1.18). Conclusions and Relevance: In nonurban areas in Catalonia, Spain, there was no significant difference in 90-day neurological outcomes between transportation to a local stroke center vs a thrombectomy-capable referral center in patients with suspected large-vessel occlusion stroke. These findings require replication in other settings. Trial Registration: ClinicalTrials.gov Identifier: NCT02795962.
Asunto(s)
Arteriopatías Oclusivas , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Trombectomía , Activador de Tejido Plasminógeno , Anciano , Anciano de 80 o más Años , Arteriopatías Oclusivas/complicaciones , Arteriopatías Oclusivas/tratamiento farmacológico , Arteriopatías Oclusivas/cirugía , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/etiología , Isquemia Encefálica/cirugía , Femenino , Instituciones de Salud , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular Isquémico/cirugía , Masculino , España , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/cirugía , Trombectomía/efectos adversos , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/efectos adversos , Resultado del Tratamiento , Población UrbanaRESUMEN
Importance: It is estimated that only 27% of patients with acute ischemic stroke and large vessel occlusion who undergo successful reperfusion after mechanical thrombectomy are disability free at 90 days. An incomplete microcirculatory reperfusion might contribute to these suboptimal clinical benefits. Objective: To investigate whether treatment with adjunct intra-arterial alteplase after thrombectomy improves outcomes following reperfusion. Design, Setting, and Participants: Phase 2b randomized, double-blind, placebo-controlled trial performed from December 2018 through May 2021 in 7 stroke centers in Catalonia, Spain. The study included 121 patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and with an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3. Interventions: Participants were randomized to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes (n = 61) or placebo (n = 52). Main Outcomes and Measures: The primary outcome was the difference in proportion of patients achieving a score of 0 or 1 on the 90-day modified Rankin Scale (range, 0 [no symptoms] to 6 [death]) in all patients treated as randomized. Safety outcomes included rate of symptomatic intracranial hemorrhage and death. Results: The study was terminated early for inability to maintain placebo availability and enrollment rate because of the COVID-19 pandemic. Of 1825 patients with acute ischemic stroke treated with thrombectomy at the 7 study sites, 748 (41%) patients fulfilled the angiographic criteria, 121 (7%) patients were randomized (mean age, 70.6 [SD, 13.7] years; 57 women [47%]), and 113 (6%) were treated as randomized. The proportion of participants with a modified Rankin Scale score of 0 or 1 at 90 days was 59.0% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% CI, 0.3%-36.4%; P = .047). The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, -3.8%; 95% CI, -13.2% to 2.5%). Ninety-day mortality was 8% with alteplase and 15% with placebo (risk difference, -7.2%; 95% CI, -19.2% to 4.8%). Conclusions and Relevance: Among patients with large vessel occlusion acute ischemic stroke and successful reperfusion following thrombectomy, the use of adjunct intra-arterial alteplase compared with placebo resulted in a greater likelihood of excellent neurological outcome at 90 days. However, because of study limitations, these findings should be interpreted as preliminary and require replication. Trial Registration: ClinicalTrials.gov Identifier: NCT03876119; EudraCT Number: 2018-002195-40.
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Arterias Cerebrales , Fibrinolíticos/administración & dosificación , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/cirugía , Trombectomía , Activador de Tejido Plasminógeno/administración & dosificación , Anciano , Anciano de 80 o más Años , Arteriopatías Oclusivas/complicaciones , Terapia Combinada , Método Doble Ciego , Femenino , Humanos , Accidente Cerebrovascular Isquémico/complicaciones , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVES: After an acute ischemic stroke, patients with a large CT perfusion (CTP) predicted infarct core (pIC) have poor clinical outcome. However, previous research suggests that this relationship may be relevant for subgroups of patients determined by pretreatment and treatment-related variables while negligible for others. We aimed to identify these variables. METHODS: We included a cohort of 828 patients with acute proximal carotid arterial occlusions imaged with a whole-brain CTP within 8 h from stroke onset. pIC was computed on CTP Maps (cerebral blood flow < 30%), and poor clinical outcome was defined as a 90-day modified Rankin Scale score > 2. Potential mediators of the association between pIC and clinical outcome were evaluated through first-order and advanced interaction analyses in the derivation cohort (n = 654) for obtaining a prediction model. The derived model was further validated in an independent cohort (n = 174). RESULTS: The volume of pIC was significantly associated with poor clinical outcome (OR = 2.19, 95% CI = 1.73 - 2.78, p < 0.001). The strength of this association depended on baseline National Institute of Health Stroke Scale, glucose levels, the use of thrombectomy, and the interaction of age with thrombectomy. The model combining these variables showed good discrimination for predicting clinical outcome in both the derivation cohort and validation cohorts (area under the receiver operating characteristic curve 0.780 (95% CI = 0.746-0.815) and 0.782 (95% CI = 0.715-0.850), respectively). CONCLUSIONS: In patients imaged within 8 h from stroke onset, the association between pIC and clinical outcome is significantly modified by baseline and therapeutic variables. These variables deserve consideration when evaluating the prognostic relevance of pIC. KEY POINTS: â¢The volume of CT perfusion (CTP) predicted infarct core (pIC) is associated with poor clinical outcome in acute ischemic stroke imaged within 8 h of onset. â¢The relationship between pIC and clinical outcome may be modified by baseline clinical severity, glucose levels, thrombectomy use, and the interaction of age with thrombectomy. â¢CTP pIC should be evaluated in an individual basis for predicting clinical outcome in patients imaged within 8 h from stroke onset.