RESUMEN
BACKGROUND: Despite the well-established potent benefit of mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke, access to MT has not been studied globally. We conducted a worldwide survey of countries on 6 continents to define MT access (MTA), the disparities in MTA, and its determinants on a global scale. METHODS: Our survey was conducted in 75 countries through the Mission Thrombectomy 2020+ global network between November 22, 2020, and February 28, 2021. The primary end points were the current annual MTA, MT operator availability, and MT center availability. MTA was defined as the estimated proportion of patients with LVO receiving MT in a given region annually. The availability metrics were defined as ([current MT operators×50/current annual number of estimated thrombectomy-eligible LVOs]×100 = MT operator availability) and ([current MT centers×150/current annual number of estimated thrombectomy-eligible LVOs]×100= MT center availability). The metrics used optimal MT volume per operator as 50 and an optimal MT volume per center as 150. Multivariable-adjusted generalized linear models were used to evaluate factors associated with MTA. RESULTS: We received 887 responses from 67 countries. The median global MTA was 2.79% (interquartile range, 0.70-11.74). MTA was <1.0% for 18 (27%) countries and 0 for 7 (10%) countries. There was a 460-fold disparity between the highest and lowest nonzero MTA regions and low-income countries had 88% lower MTA compared with high-income countries. The global MT operator availability was 16.5% of optimal and the MT center availability was 20.8% of optimal. On multivariable regression, country income level (low or lower-middle versus high: odds ratio, 0.08 [95% CI, 0.04-0.12]), MT operator availability (odds ratio, 3.35 [95% CI, 2.07-5.42]), MT center availability (odds ratio, 2.86 [95% CI, 1.84-4.48]), and presence of prehospital acute stroke bypass protocol (odds ratio, 4.00 [95% CI, 1.70-9.42]) were significantly associated with increased odds of MTA. CONCLUSIONS: Access to MT on a global level is extremely low, with enormous disparities between countries by income level. The significant determinants of MT access are the country's per capita gross national income, prehospital LVO triage policy, and MT operator and center availability.
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Arteriopatías Oclusivas , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Isquemia Encefálica/complicaciones , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/cirugía , Trombectomía , Triaje , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate clinical outcomes of endovascular thrombectomy (EVT) for acute basilar artery occlusion (BAO) using population-level data from the United States. METHODS: Weighted discharge data from the National Inpatient Sample were queried to identify adult patients with acute BAO during the period of 2015 to 2019 treated with EVT or medical management only. Complex samples statistical methods and propensity-score adjustment using inverse probability of treatment weighting (IPTW) were performed to assess clinical endpoints. RESULTS: Among 3,950 BAO patients identified, 1,425 (36.1%) were treated with EVT [mean age 66.7 years, median National Institute of Health Stroke Scale (NIHSS) score 22]. On unadjusted analysis, 155 (10.9%) EVT patients achieved favorable functional outcomes (discharge disposition to home without services), while 515 (36.1%) experienced in-hospital mortality, and 20 (1.4%) developed symptomatic intracranial hemorrhage (sICH). Following propensity-score adjustment by IPTW accounting for age, stroke severity, and comorbidity burden, EVT was independently associated with favorable functional outcome [adjusted odds ratio (aOR) 1.25, 95% confidence interval (CI) 1.07, 1.46; p = 0.004], but not with in-hospital mortality or sICH. In an IPTW-adjusted sub-group analysis of patients with NIHSS scores >20, EVT was associated with both favorable functional outcome (discharge disposition to home or to acute rehabilitation) (aOR 1.55, 95% CI 1.24, 1.94; p < 0.001) and decreased mortality (aOR 0.78, 95% CI 0.69, 0.89; p < 0.001), but not with sICH. INTERPRETATION: This retrospective population-based analysis using a large national registry provides real-world evidence of a potential benefit of EVT in acute BAO patients. ANN NEUROL 2023;94:55-60.
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Procedimientos Endovasculares , Accidente Cerebrovascular , Adulto , Humanos , Anciano , Arteria Basilar , Estudios Retrospectivos , Resultado del Tratamiento , Accidente Cerebrovascular/etiología , Trombectomía/métodos , Hemorragias Intracraneales/etiología , Procedimientos Endovasculares/métodosRESUMEN
The therapeutic focus in acute ischemic stroke over the last 2.5 decades has been to balance the benefits of rapid reperfusion therapy with the risks of treatment-related complications. Both intravenous thrombolytics and endovascular thrombectomy are proven to substantially improve outcomes in a time-dependent manner. Each minute saved in achieving successful reperfusion grants an additional week of healthy life and may salvage up to 27 million neurons. The current approach to patient triage is inherited from the preendovascular thrombectomy era of stroke care. Current workflow concentrates on stabilization, diagnosis, and decision-making in the emergency department, followed by thrombolysis if eligible and subsequent transfer to the angiography suite as needed for further treatment. Multiple efforts have been directed toward minimizing the time from first medical contact to reperfusion therapy including prehospital triage and intrahospital workflow. Novel approaches for stroke patient triage such as the direct to angio approach, (also referred to as One Stop Management) are currently in development. The concept was initially introduced as several single-center experiences. In this narrative review article, we will consider various definitions of direct to angio and its variants, discuss its rationale, review its safety and efficacy, assess its feasibility, and delineate its limitations. Further, we will address methods to overcome these limitations and the potential impact of emerging data and new technologies on the direct-to-angio approach.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Trombectomía , Fibrinolíticos , Triaje , Resultado del Tratamiento , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/cirugíaRESUMEN
BACKGROUND: Aspiration catheters (ASPs) and stentriever thrombectomy devices have comparable safety and efficacy in anterior circulation ischemic strokes. However, there is lack of high-quality comparative data in acute basilar artery occlusions. Our objective is to compare the outcomes and safety of ASPs and stentriever devices in acute basilar artery occlusions. METHODS: This is an analysis of the retrospectively established PC-SEARCH Thrombectomy (Posterior-Circulation Ischemic Stroke Evaluation: Analyzing Radiographic and Intraprocedural Predictors for Mechanical Thrombectomy) registry. Patients were dichotomized based on their first-line thrombectomy device (ASP and stentriever) and associated with their 90-day functional outcomes, intraprocedural metrics, and safety measures. Propensity analysis based on unequal baseline characteristics was performed. Consecutive patients with acute basilar artery occlusions who received mechanical thrombectomy were included from January 2015 to December 2021. Patients received either first-line contact aspiration or stentriever mechanical thrombectomy. Primary clinical and safety outcomes were 90-day functional independence measured by a modified Rankin Scale score of 0 to 3 and symptomatic intracranial hemorrhage, respectively. Secondary outcomes included puncture-recanalization times, first-pass recanalization rates, crossovers to other thrombectomy device, and neurological/hospital complications. RESULTS: Five hundred eighteen patients were included in the registry, and a total of 383 patients were included (mean [SD] age, 65.5 [15] years; 228 [59%] men) in this analysis. Of these, 219 patients were first-line ASP while 164 patients received first-line stentriever devices. Median premorbid modified Rankin Scale was zero and median presenting National Institutes of Health Stroke Scale was 17 (interquartile range, 8-26). The proportion of favorable functional outcome was similar between the 2 techniques before (47.3% versus 42.5%; odds ratio, 1.22 [95% CI, 0.78-1.89]; P=0.38) and after propensity matching (odds ratio, 1.46 [95% CI, 0.85-2.49]; P=0.17). In our propensity-matched cohorts, puncture-recanalization times (18 versus 52 minutes; P<0.01) favored first-line ASP; however, first-pass recanalization rates (43.5% versus 44.5%; P=0.90) were similar between groups. First-line ASP was associated with higher rates of crossover (22% versus 6%; P<0.01), whereas stentriever was associated with higher rates of symptomatic intracranial hemorrhage (9.8% versus 3.4%; P=0.04). CONCLUSIONS: First-line ASP and stentriever methods demonstrated similar functional outcome and recanalization rates. Stentriever methods were associated with higher rates of symptomatic intracranial hemorrhage, whereas ASPs were associated with higher rates of crossover to alternative technique in patients with acute basilar occlusions.
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Arteria Basilar , Accidente Cerebrovascular Isquémico , Estados Unidos , Masculino , Humanos , Anciano , Femenino , Estudios Retrospectivos , Trombectomía/efectos adversos , Hemorragias Intracraneales/epidemiología , Hemorragias Intracraneales/etiología , Sistema de RegistrosRESUMEN
BACKGROUND: An understanding of global, regional, and national macroeconomic losses caused by stroke is important for allocation of clinical and research resources. The authors investigated the macroeconomic consequences of stroke disease burden in the year 2019 in 173 countries. METHODS: Disability-adjusted life year data for overall stroke and its subtypes (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) were collected from the GBD study (Global Burden of Disease) 2019 database. Gross domestic product (GDP, adjusted for purchasing power parity [PPP]) data were collected from the World Bank; GDP and disability-adjusted life year data were combined to estimate macroeconomic losses using a value of lost welfare (VLW) approach. All results are presented in 2017 international US dollars adjusted for PPP. RESULTS: Globally, in 2019, VLW due to stroke was $2059.67 billion or 1.66% of the global GDP. Global VLW/GDP for stroke subtypes was 0.78% (VLW=$964.51 billion) for ischemic stroke, 0.71% (VLW=$882.81 billion) for intracerebral hemorrhage, and 0.17% (VLW=$212.36 billion) for subarachnoid hemorrhage. The Central European, Eastern European, and Central Asian GBD super-region reported the highest VLW/GDP for stroke overall (3.01%), ischemic stroke (1.86%), and for subarachnoid hemorrhage (0.26%). The Southeast Asian, East Asian, and Oceanian GBD super-region reported the highest VLW/GDP for intracerebral hemorrhage (1.48%). CONCLUSIONS: The global macroeconomic consequences related to stroke are vast even when considering stroke subtypes. The present quantification may be leveraged to help justify increased spending of finite resources on stroke in an effort to improve outcomes for patients with stroke globally.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Hemorragia Subaracnoidea , Humanos , Salud Global , Hemorragia Subaracnoidea/epidemiología , Accidente Cerebrovascular/epidemiología , Hemorragia Cerebral/epidemiologíaRESUMEN
BACKGROUND: The optimal management of patients with isolated posterior cerebral artery occlusion is uncertain. We compared clinical outcomes for endovascular therapy (EVT) versus medical management (MM) in patients with isolated posterior cerebral artery occlusion. METHODS: This multinational case-control study conducted at 27 sites in Europe and North America included consecutive patients with isolated posterior cerebral artery occlusion presenting within 24 hours of time last well from January 2015 to August 2022. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The coprimary outcomes were the 90-day modified Rankin Scale ordinal shift and ≥2-point decrease in the National Institutes of Health Stroke Scale. RESULTS: Of 1023 patients, 589 (57.6%) were male with median (interquartile range) age of 74 (64-82) years. The median (interquartile range) National Institutes of Health Stroke Scale was 6 (3-10). The occlusion segments were P1 (41.2%), P2 (49.2%), and P3 (7.1%). Overall, intravenous thrombolysis was administered in 43% and EVT in 37%. There was no difference between the EVT and MM groups in the 90-day modified Rankin Scale shift (aOR, 1.13 [95% CI, 0.85-1.50]; P=0.41). There were higher odds of a decrease in the National Institutes of Health Stroke Scale by ≥2 points with EVT (aOR, 1.84 [95% CI, 1.35-2.52]; P=0.0001). Compared with MM, EVT was associated with a higher likelihood of excellent outcome (aOR, 1.50 [95% CI, 1.07-2.09]; P=0.018), complete vision recovery, and similar rates of functional independence (modified Rankin Scale score, 0-2), despite a higher rate of SICH and mortality (symptomatic intracranial hemorrhage, 6.2% versus 1.7%; P=0.0001; mortality, 10.1% versus 5.0%; P=0.002). CONCLUSIONS: In patients with isolated posterior cerebral artery occlusion, EVT was associated with similar odds of disability by ordinal modified Rankin Scale, higher odds of early National Institutes of Health stroke scale improvement, and complete vision recovery compared with MM. There was a higher likelihood of excellent outcome in the EVT group despite a higher rate of symptomatic intracranial hemorrhage and mortality. Continued enrollment into ongoing distal vessel occlusion randomized trials is warranted.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular , Humanos , Masculino , Anciano , Anciano de 80 o más Años , Femenino , Isquemia Encefálica/terapia , Trombectomía , Estudios de Casos y Controles , Arteria Cerebral Posterior/diagnóstico por imagen , Procedimientos Endovasculares/efectos adversos , Hemorragias Intracraneales/etiología , Resultado del TratamientoRESUMEN
OBJECTIVES: Addressing traumatic brain injury (TBI) heterogeneity is increasingly recognized as essential for therapy translation given the long history of failed clinical trials. We evaluated differential effects of a promising treatment (glibenclamide) based on dose, TBI type (patient selection), and imaging endophenotype (outcome selection). Our goal to inform TBI precision medicine is contextually timely given ongoing phase 2/planned phase 3 trials of glibenclamide in brain contusion. DESIGN: Blinded randomized controlled preclinical trial of glibenclamide on MRI endophenotypes in two established severe TBI models: controlled cortical impact (CCI, isolated brain contusion) and CCI+hemorrhagic shock (HS, clinically common second insult). SETTING: Preclinical laboratory. SUBJECTS: Adult male C57BL/6J mice (n = 54). INTERVENTIONS: Mice were randomized to naïve, CCI±HS with vehicle/low-dose (20 µg/kg)/high-dose glibenclamide (10 µg/mouse). Seven-day subcutaneous infusions (0.4 µg/hr) were continued. MEASUREMENTS AND MAIN RESULTS: Serial MRI (3 hr, 6 hr, 24 hr, and 7 d) measured hematoma and edema volumes, T2 relaxation (vasogenic edema), apparent diffusion coefficient (ADC, cellular/cytotoxic edema), and 7-day T1-post gadolinium values (blood-brain-barrier [BBB] integrity). Linear mixed models assessed temporal changes. Marked heterogeneity was observed between CCI versus CCI+HS in terms of different MRI edema endophenotypes generated (all p < 0.05). Glibenclamide had variable impact. High-dose glibenclamide reduced hematoma volume ~60% after CCI (p = 0.0001) and ~48% after CCI+HS (p = 4.1 × 10-6) versus vehicle. Antiedema benefits were primarily in CCI: high-dose glibenclamide normalized several MRI endophenotypes in ipsilateral cortex (all p < 0.05, hematoma volume, T2, ADC, and T1-post contrast). Acute effects (3 hr) were specific to hematoma (p = 0.001) and cytotoxic edema reduction (p = 0.0045). High-dose glibenclamide reduced hematoma volume after TBI with concomitant HS, but antiedema effects were not robust. Low-dose glibenclamide was not beneficial. CONCLUSIONS: High-dose glibenclamide benefitted hematoma volume, vasogenic edema, cytotoxic edema, and BBB integrity after isolated brain contusion. Hematoma and cytotoxic edema effects were acute; longer treatment windows may be possible for vasogenic edema. Our findings provide new insights to inform interpretation of ongoing trials as well as precision design (dose, sample size estimation, patient selection, outcome selection, and Bayesian analysis) of future TBI trials of glibenclamide.
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Contusión Encefálica , Edema Encefálico , Lesiones Traumáticas del Encéfalo , Lesiones Encefálicas , Animales , Masculino , Ratones , Teorema de Bayes , Contusión Encefálica/complicaciones , Contusión Encefálica/tratamiento farmacológico , Edema Encefálico/diagnóstico por imagen , Edema Encefálico/tratamiento farmacológico , Edema Encefálico/etiología , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/complicaciones , Modelos Animales de Enfermedad , Endofenotipos , Gliburida/farmacología , Gliburida/uso terapéutico , Imagen por Resonancia Magnética , Ratones Endogámicos C57BLRESUMEN
Despite the high incidence and burden of stroke, biological biomarkers are not used routinely in clinical practice to diagnose, determine progression, or prognosticate outcomes of acute ischemic stroke (AIS). Because of its direct interface with neural tissue, cerebrospinal fluid (CSF) is a potentially valuable source for biomarker development. This systematic review was conducted using three databases. All trials investigating clinical and preclinical models for CSF biomarkers for AIS diagnosis, prognostication, and severity grading were included, yielding 22 human trials and five animal studies for analysis. In total, 21 biomarkers and other multiomic proteomic markers were identified. S100B, inflammatory markers (including tumor necrosis factor-alpha and interleukin 6), and free fatty acids were the most frequently studied biomarkers. The review showed that CSF is an effective medium for biomarker acquisition for AIS. Although CSF is not routinely clinically obtained, a potential benefit of CSF studies is identifying valuable biomarkers from the pathophysiologic microenvironment that ultimately inform optimization of targeted low-abundance assays from peripheral biofluid samples (e.g., plasma). Several important catabolic and anabolic markers can serve as effective measures of diagnosis, etiology identification, prognostication, and severity grading. Trials with large cohorts studying the efficacy of biomarkers in altering clinical management are still needed.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/diagnóstico , Proteómica , Accidente Cerebrovascular/diagnóstico , Biomarcadores , Ácidos Grasos no EsterificadosRESUMEN
BACKGROUND AND PURPOSE: Achieving complete revascularization after a single pass of a mechanical thrombectomy device (first pass effect [FPE]) is associated with good clinical outcomes in patients with acute ischemic stroke due to large vessel occlusion. We assessed patient characteristics, outcomes, and predictors of FPE among a large real-world cohort of patients (Systematic Evaluation of Patients Treated with Stroke Devices for Acute Ischemic Stroke registry). METHODS: Demographics, clinical outcomes, and procedural characteristics were analyzed among patients in whom FPE (modified Thrombolysis in Cerebral Infarction 2c/3 after first pass) was achieved versus those requiring multiple passes (MP). Modified FPE and modified MP included patients achieving modified Thrombolysis in Cerebral Infarction 2B-3. Primary outcomes included 90-day modified Rankin Scale (mRS) score and mortality. RESULTS: Among 984 Systematic Evaluation of Patients Treated with Stroke Devices for Acute Ischemic Stroke patients, 930 had complete 90-day follow-up. FPE was achieved in 40.5% (377/930) of patients and MP in 20.0% (186/930). Baseline characteristics were similar across all groups. The FPE group had fewer internal carotid artery occlusions compared with MP (P=0.029). The FPE group had faster puncture to recanalization time (P≤0.001), higher rates of 90-day mRS score of 0 to 1 (52.6% versus 38.6%, P=0.003), mRS score of 0 to 2 (65.4% versus 52.0%, P=0.003), and lower 90-day mortality compared with the MP group (12.0% versus 18.7%, P=0.038). Similarly, compared with modified MP patients, the modified FPE group had fewer internal carotid artery occlusions (P=0.004), faster puncture to recanalization time (P≤0.001), and higher rates of 90-day mRS score of 0 to 1 (P=0.002) and mRS score of 0 to 2 (P=0.003). CONCLUSIONS: Our findings demonstrate that FPE and modified FPE are associated with superior clinical outcomes.
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Accidente Cerebrovascular Isquémico/cirugía , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Estenosis Carotídea/complicaciones , Catéteres , Infarto Cerebral/etiología , Infarto Cerebral/terapia , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Accidente Cerebrovascular Isquémico/mortalidad , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Recuperación de la Función , Sistema de Registros , Factores de Riesgo , Stents , Accidente Cerebrovascular/mortalidad , Resultado del TratamientoRESUMEN
BACKGROUND: The optimal imaging paradigm for endovascular thrombectomy (EVT) patient selection in early time window (0-6 hours) treated acute ischemic stroke patients remains uncertain. We aimed to compare post-EVT outcomes between patients who underwent prerandomization basic (noncontrast computed tomography [CT], CT angiography only) versus additional advanced imaging (computed tomography perfusion [CTP] imaging) and to determine the association of performance of prerandomization CTP imaging with clinical outcomes. METHODS: The HERMES collaboration (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) pooled patient-level data from randomized controlled trials comparing EVT with usual care for acute ischemic stroke due to anterior circulation large vessel occlusion. Good functional outcome, defined as modified Rankin Scale score 0 to 2 at 90 days, was compared between randomized patients with and without CTP baseline imaging. Univariable and multivariable binary logistic regression analysis was performed to determine the association of baseline CTP imaging and good functional outcome. RESULTS: We analyzed 1348 patients 610 (45.3%) of whom underwent CTP prerandomization. The benefit of EVT compared with best medical management was maintained irrespective of the baseline imaging paradigm (90-day modified Rankin Scale score 0-2 in EVT versus control patients: with CTP: 46.0% (137/298) versus 28.9% (88/305), without CTP: 44.1% (162/367) versus 27.3% (100/366). Performance of CTP baseline imaging compared with baseline noncontrast CT and CT angiography only yielded similar rates of good outcome (odds ratio, 1.05 [95% CI, 0.82-1.33], adjusted odds ratio, 1.04, [95% CI, 0.80-1.35]). CONCLUSIONS: Rates of good functional outcome were similar among patients in whom CTP was or was not performed, and EVT treatment effect in the 0- to 6-hour time window was similar in patients with and without baseline CTP imaging.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/cirugía , Infarto Cerebral , Angiografía por Tomografía Computarizada/métodos , Procedimientos Endovasculares/métodos , Imagen de Perfusión , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Acute ischemic stroke (AIS) is a major contributor toward healthcare-associated costs and services. Symptomatic intracranial hemorrhage (sICH) and early neurologic decline (END), defined as a National Health Institute Stroke Scale score decline of ≥ 4 within 24 h (with or without sICH), remain major concerns when administering intravenous tissue plasminogen activator (IV tPA) despite improved functional neurologic outcomes with its use. Given these risks, current guidelines recommend comprehensive stroke care (most often in an intensive care unit setting) for 24 h posttreatment. However, a number of patients may remain stable after IV tPA and thus not require such intensive resources. We sought to determine causes of END, along with timing and predictors of both sICH and END, to identify patients at lower risk of neurological deterioration and those suitable for earlier transition to a lower level of care. METHODS: This present study analyzed patients with AIS that presented within 4.5 h of being last seen well and received IV tPA. Baseline demographic, clinical, and radiographic findings were collected. Outcomes included END from any cause, parenchymal hemorrhage (PH1 or PH2), sICH, and mortality at 90 days. RESULTS: A total of 1238 patients with AIS without acute treatment of large vessel occlusion received IV tPA. 9.4% (116) had presence of any degree of ICH on noncontrast computed tomography head and 7.4% (91) experienced associated END. 2.7% (33) of patients experienced sICH, while 6.7% (83) experienced asymptomatic ICH. Of the patients with END, 63.7% did not have ICH. Predictive factors at presentation for END included an older age (72.6 ± 16.1 vs. 69.1 ± 14.8, p = 0.03), history of tobacco use (odds ratio [OR] 2.1 [1.1-4.3], p = 0.04), and hyperlipidemia (OR 1.7 [1.1-2.8], p = 0.02), along with the presence of an untreated large vessel occlusion (OR 2.1 [1.4-3.1], p = 0.02). Most END occurred within a mean time of 242 ± 251 min (4 ± 4 h). Because of the small proportion of patients suffering from sICH (33), predictors could not be determined; however, for patients with any ICH, predictive factors included an older age (74.6 ± 12.4 vs. 68.8 ± 15.1, p = 0.001), higher baseline National Health Institute Stroke Scale score (14.6 ± 7.3 vs. 10.8 ± 7.9, p = 0.002), and higher baseline glucose levels (155.1 ± 87.5 vs. 140.4 ± 70.5, p = 0.04). CONCLUSIONS: In this study, only a small proportion suffered from either sICH and/or END, typically within 12 h of tPA administration. These findings may support earlier deescalation of higher acuity monitoring in clinically stable post-IV tPA patients without large vessel occlusion.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Isquemia Encefálica/etiología , Fibrinolíticos , Humanos , Hemorragias Intracraneales/etiología , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/etiología , Terapia Trombolítica/efectos adversos , Activador de Tejido Plasminógeno , Resultado del TratamientoRESUMEN
BACKGROUND: Cerebral edema and intracranial hypertension are major contributors to unfavorable prognosis in traumatic brain injury (TBI). Local epigenetic changes, particularly in DNA methylation, may influence gene expression and thus host response/secondary injury after TBI. It remains unknown whether DNA methylation in the central nervous system is associated with cerebral edema severity or intracranial hypertension post TBI. We sought to identify epigenome-wide DNA methylation patterns associated with these forms of secondary injury after TBI. METHODS: We obtained genome-wide DNA methylation profiles of DNA extracted from ventricular cerebrospinal fluid samples at three different postinjury time points from a prospective cohort of patients with severe TBI (n = 89 patients, 254 samples). Cerebral edema and intracranial pressure (ICP) measures were clustered to generate composite end points of cerebral edema and ICP severity. We performed an unbiased epigenome-wide association study (EWAS) to test associations between DNA methylation at 419,895 cytosine-phosphate-guanine (CpG) sites and cerebral edema/ICP severity categories. Given inflated p values, we conducted permutation tests for top CpG sites to filter out potential false discoveries. RESULTS: Our data-driven hierarchical clustering across six cerebral edema and ICP measures identified two groups differing significantly in ICP based on the EWAS-identified CpG site cg22111818 in RGMA (Repulsive guidance molecule A, permutation p = 4.20 × 10-8). At 3-4 days post TBI, patients with severe intracranial hypertension had significantly lower levels of methylation at cg22111818. CONCLUSIONS: We report a novel potential relationship between intracranial hypertension after TBI and an acute, nonsustained reduction in DNA methylation at cg22111818 in the RGMA gene. To our knowledge, this is the largest EWAS in severe TBI. Our findings are further strengthened by previous findings that RGMA modulates axonal repair in other central nervous system disorders, but a role in intracranial hypertension or TBI has not been previously identified. Additional work is warranted to validate and extend these findings, including assessment of its possible role in risk stratification, identification of novel druggable targets, and ultimately our ability to personalize therapy in TBI.
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Edema Encefálico , Lesiones Traumáticas del Encéfalo , Hipertensión Intracraneal , Edema Encefálico/complicaciones , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/genética , Metilación de ADN , Epigenoma , Humanos , Hipertensión Intracraneal/complicaciones , Hipertensión Intracraneal/genética , Presión Intracraneal , Estudios ProspectivosRESUMEN
OBJECTIVES: Transient ischemic attack (TIA) serves a precursor for an acute ischemic stroke (AIS); however, not all TIA patients harbor the same risk for subsequent AIS. We aimed to investigate expediting outpatient management of low-risk TIA patients (ABCD: Giles and Rothwell, 2007 score ≤ 3) via our "Fast-Track" TIA Protocol (FTTP). MATERIALS AND METHODS: A retrospective analysis was performed on patients who presented to our academic network 04/2020 - 2/2021. Patients who presented with ABCD: Giles and Rothwell, 2007 scores ≤ 3 without large vessel occlusion or flow limiting stenosis were eligible for the FTTP. These patients were discharged on dual antiplatelet therapy and statin and received prescriptions for transthoracic echo, holter monitor, LDL, and A1c along with a scheduled follow-up appointment 30 days from presentation. RESULTS: 182 consecutive patients were evaluated during this period, 21 (11%) were excluded from analysis due to NIHSS > 0 and/or infarct present on MRI. 35 (22%) patients qualified for FTTP and were directly discharged from the ED. Median ABCD2 score was 2 for the discharge group and 4 for the admitted group. There was a significant difference with respect to age and hypertension. Additionally, the FTTP patient population were more likely to be smokers than the admitted patient population. 3 FTTP patients re-presented to the ED, but none of them suffered a symptomatic stroke. CONCLUSIONS: A FTTP demonstrated feasibility and safety with low rates of re-presentation and ischemic stroke. Further research is warranted to determine an optimal patient population that can be safely managed in an outpatient setting.
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Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Hospitalización , Humanos , Ataque Isquémico Transitorio/diagnóstico por imagen , Ataque Isquémico Transitorio/terapia , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológicoRESUMEN
Background and Purpose: Although National Institutes of Health Stroke Scale scores provide an objective measure of clinical deficits, data regarding the impact of neglect or language impairment on outcomes after mechanical thrombectomy (MT) is lacking. We assessed the frequency of neglect and language impairment, rate of their rescue by MT, and impact of rescue on clinical outcomes. Methods: This is a retrospective analysis of a prospectively collected database from a comprehensive stroke center. We assessed right (RHS) and left hemispheric strokes (LHS) patients with anterior circulation large vessel occlusion undergoing MT to assess the impact of neglect and language impairment on clinical outcomes, respectively. Safety and efficacy outcomes were compared between patients with and without rescue of neglect or language impairment. Results: Among 324 RHS and 210 LHS patients, 71% of patients presented with neglect whereas 93% of patients had language impairment, respectively. Mean age was 71±15, 56% were females, and median National Institutes of Health Stroke Scale score was 16 (1220). At 24 hours, MT resulted in rescue of neglect in 31% of RHS and rescue of language impairment in 23% of LHS patients, respectively. RHS patients with rescue of neglect (56% versus 34%, P<0.001) and LHS patients with rescue of language impairment (64 % versus 25%, P<0.01) were observed to have a higher rate of functional independence compared to patients without rescue. After adjusting for confounders including 24-hour National Institutes of Health Stroke Scale, rescue of neglect among RHS patients was associated with functional independence (P=0.01) and lower mortality (P=0.01). Similarly, rescue of language impairment among LHS patients was associated with functional independence (P=0.02) and lower mortality (P=0.001). Conclusions: Majority of LHS-anterior circulation large vessel occlusion and of RHS-anterior circulation large vessel occlusion patients present with the impairment of language and neglect, respectively. In comparison to 24-hour National Institutes of Health Stroke Scale, rescue of these deficits by MT is an independent and a better predictor of functional independence and lower mortality.
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Trastornos del Lenguaje/cirugía , Trastornos de la Percepción/cirugía , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Arteriopatías Oclusivas/complicaciones , Procedimientos Endovasculares/métodos , Femenino , Lateralidad Funcional , Humanos , Vida Independiente , Trastornos del Lenguaje/etiología , Masculino , Persona de Mediana Edad , Trastornos de la Percepción/etiología , Estudios Retrospectivos , Accidente Cerebrovascular/mortalidad , Rehabilitación de Accidente Cerebrovascular , Trombectomía/efectos adversos , Terapia Trombolítica/efectos adversos , Resultado del TratamientoRESUMEN
Background and Purpose: Patient selection for thrombectomy of acute ischemic stroke caused by large vessel occlusion in the delayed time window (>6 hours) is dependent on delineation of clinical-core mismatch or radiological target mismatch using perfusion imaging. Selection paradigms not involving advanced imaging and software processing may reduce time to treatment and broaden eligibility. We aim to develop a conversion factor to approximately determine the volume of hypoperfused tissue using the National Institutes of Health Stroke Scale (NIHSS) score (clinically approximated hypoperfused tissue [CAT] volume) and explore its ability to identify patients eligible for thrombectomy in the late-time window. Methods: We performed a retrospective analysis of anterior circulation large vessel occlusion strokes at 3 comprehensive stroke centers. Demographic, clinical, and imaging (computed tomography perfusion processed using RAPID, IschemaView) information was analyzed. A conversion factor, which is a multiple of the NIHSS score (for NIHSS score <10 and ≥10), was derived from an initial cohort to calculate CAT volumes. Accuracy of CAT-based thrombectomy eligibility criteria (using CAT volume instead of Tmax >6 seconds volume) was tested using DEFUSE-3 criteria (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) eligibility as a gold standard in an independent cohort. Results: Of the 309 large vessel occlusion strokes (age, 70±14, 46% male, median NIHSS 16 [1220]) included in this study, 38% of patients arrived beyond 6 hours of time from last known well. Conversion factors derived (derivation cohort-center A: 187) based on median values of Tmax>6 second volume for NIHSS score <10 subgroup was 15 and for NIHSS score ≥10 subgroup was 6. Subsequently calculated CAT volumebased eligibility criteria yielded a sensitivity of 100% and specificity of 92% in detecting DEFUSE-3 eligible patients (area under the curve, 0.92 [95% CI, 0.821]) in the validation cohort (center B and C:122). Conclusions: Clinical severity of stroke (NIHSS score) may be used to calculate the volume of hypoperfused tissue during large vessel occlusion stroke. CAT volumes for NIHSS score <10 (using a factor of 15) and ≥10 (using a factor of 6) subgroups can accurately identify DEFUSE-3-eligible patients.
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Volumen Sanguíneo Cerebral , Accidente Cerebrovascular Isquémico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/fisiopatología , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND AND PURPOSE: The pandemic caused by the novel coronavirus disease 2019 (COVID-19) has led to an unprecedented paradigm shift in medical care. We sought to evaluate whether the COVID-19 pandemic may have contributed to delays in acute stroke management at comprehensive stroke centers. METHODS: Pooled clinical data of consecutive adult stroke patients from 14 US comprehensive stroke centers (January 1, 2019, to July 31, 2020) were queried. The rate of thrombolysis for nontransferred patients within the Target: Stroke goal of 60 minutes was compared between patients admitted from March 1, 2019, and July 31, 2019 (pre-COVID-19), and March 1, 2020, to July 31, 2020 (COVID-19). The time from arrival to imaging and treatment with thrombolysis or thrombectomy, as continuous variables, were also assessed. RESULTS: Of the 2955 patients who met inclusion criteria, 1491 were admitted during the pre-COVID-19 period and 1464 were admitted during COVID-19, 15% of whom underwent intravenous thrombolysis. Patients treated during COVID-19 were at lower odds of receiving thrombolysis within 60 minutes of arrival (odds ratio, 0.61 [95% CI, 0.38-0.98]; P=0.04), with a median delay in door-to-needle time of 4 minutes (P=0.03). The lower odds of achieving treatment in the Target: Stroke goal persisted after adjustment for all variables associated with earlier treatment (adjusted odds ratio, 0.55 [95% CI, 0.35-0.85]; P<0.01). The delay in thrombolysis appeared driven by the longer delay from imaging to bolus (median, 29 [interquartile range, 18-41] versus 22 [interquartile range, 13-37] minutes; P=0.02). There was no significant delay in door-to-groin puncture for patients who underwent thrombectomy (median, 83 [interquartile range, 63-133] versus 90 [interquartile range, 73-129] minutes; P=0.30). Delays in thrombolysis were observed in the months of June and July. CONCLUSIONS: Evaluation for acute ischemic stroke during the COVID-19 period was associated with a small but significant delay in intravenous thrombolysis but no significant delay in thrombectomy time metrics. Taking steps to reduce delays from imaging to bolus time has the potential to attenuate this collateral effect of the pandemic.
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COVID-19 , Accidente Cerebrovascular Isquémico/terapia , Tiempo de Tratamiento/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Trombectomía/estadística & datos numéricos , Terapia Trombolítica/estadística & datos numéricosRESUMEN
OBJECTIVE: Acute basilar artery occlusion (BAO) harbors a more guarded prognosis after thrombectomy compared with anterior circulation large-vessel occlusion. Whether this is a function of a greater proportion of atherosclerotic/intrinsic lesions is not well studied. The authors aimed to elucidate the prevalence and predictors of intracranial intrinsic atherosclerotic disease in patients with acute BAO and to compare angiographic and clinical outcomes between patients with BAO secondary to embolic versus intrinsic disease. METHODS: A prospectively maintained stroke database was reviewed for all patients presenting between January 2013 and December 2019 to a tertiary care academic comprehensive stroke center with acute, nontandem BAO. Patient data were extracted, subdivided by stroke mechanism and treatment modality (embolic [thrombectomy only] and intrinsic [thrombectomy + stenting]), and angiographic and clinical results were compared. RESULTS: Of 107 patients, 83 (78%) had embolic occlusions (thrombectomy only) and 24 (22%) had intrinsic disease (thrombectomy + stenting). There was no significant difference in patient age, presenting National Institutes of Health Stroke Scale score, time to presentation, selected medical comorbidities (hypertension, hyperlipidemia, diabetes, and atrial fibrillation), prior stroke, and posterior circulation Alberta Stroke Program Early CT Score. Patients with intrinsic disease were more likely to be active smokers (50% vs 26%, p = 0.04) and more likely to be male (88% vs 48%, p = 0.001). Successful recanalization, defined as a modified Thrombolysis in Cerebral Infarction (mTICI) grade of 2b or 3, was achieved in 90% of patients and did not differ significantly between the embolic versus intrinsic groups (89% vs 92%, p > 0.99). A 90-day good outcome (modified Rankin Scale [mRS] score 0-2) was found in 37% of patients overall and did not differ significantly between the two groups (36% vs 41%, p = 0.41). Mortality was 40% overall and did not significantly differ between groups (41% vs 36%, p = 0.45). CONCLUSIONS: In the current study, demographic and clinical results for acute BAO showed that compared with intrinsic disease, thromboembolic disease is a more common mechanism of acute BAO, with 78% of patients undergoing thrombectomy alone. However, there was no significant difference in revascularization and outcome results between patients with embolic disease and those with intrinsic disease.
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Procedimientos Endovasculares , Accidente Cerebrovascular , Arteria Basilar , Femenino , Humanos , Masculino , Estudios Retrospectivos , Stents , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Trombectomía , Resultado del TratamientoRESUMEN
OBJECTIVE: Although intravenous thrombolysis (IVT) is recommended among acute ischemic stroke (AIS) patients secondary to large vessel occlusion (LVO) undergoing mechanical thrombectomy (MT), time delays with bridging therapy (IVT prior to MT) and its potential benefit remains unclear. We compared the time delays and clinical outcomes among AIS SECONDARY TO LVO patients treated with bridging therapy or direct MT (dMT) at a comprehensive stroke center (CSC). METHODS: We performed a retrospective analysis of prospectively collected data of AIS secondary to LVO patients admitted between 2012 and 2017 at a large volume CSC. AIS secondary to LVO patients arriving directly from field to CSC within 4.5 h were included. Demographic characteristics, clinical and radiological data, treatment and procedural information were extracted and analyzed. RESULTS: Among 777 AIS secondary to LVO patients treated with MT, 237 patients (156 dMT, 81 bridging therapy) were included. Mean age was 70.3 year-old, median NIHSS score was 18, and door-to-needle time was 40 min (IQR 31-56 min). The median door-to-puncture (DTP) time was 22 min longer in bridging therapy group in comparison to dMT group, 74 vs 52 min (p<0.001). Additionally, no difference was observed between the groups for successful recanalization or functional independence. CONCLUSION: At a large volume CSC, bridging therapy (vs. dMT) was observed to have a longer DTP time without any difference in successful recanalization or clinical outcomes.
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Procedimientos Endovasculares , Fibrinolíticos/administración & dosificación , Accidente Cerebrovascular Isquémico/terapia , Trombectomía , Terapia Trombolítica , Tiempo de Tratamiento , Activador de Tejido Plasminógeno/administración & dosificación , Administración Intravenosa , Anciano , Anciano de 80 o más Años , Procedimientos Endovasculares/efectos adversos , Femenino , Fibrinolíticos/efectos adversos , Humanos , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/fisiopatología , Masculino , Persona de Mediana Edad , Punciones , Estudios Retrospectivos , Trombectomía/efectos adversos , Terapia Trombolítica/efectos adversos , Factores de Tiempo , Activador de Tejido Plasminógeno/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVES: While telestroke 'hub-and-spoke' systems are a well-established model for improving acute stroke care at spoke facilities, utility beyond the hyperacute phase is unknown. In patients receiving intravenous thrombolysis via telemedicine, care at spoke facilities has been shown to be associated with longer length of stay and worse outcomes. We sought to explore the impact of ongoing stroke care by a vascular neurologist via telemedicine compared to care provided by local neurologists. METHODS: A network spoke facility protocol was revised to pilot telestroke consultation with a hub vascular neurologist for all patients presenting to the emergency department with ischemic stroke or transient ischemic attack regardless of time since onset or severity. Subsequent telestroke rounds were performed for patients who received initial telestroke consultation. Key outcome measures were length of stay, 30-day readmission and mortality and 90-day mRS. Results during the pilot (post-cohort) were compared to the same hospital's previous outcomes (pre-cohort). RESULTS: Of 257 enrolled patients, 67% were in the post-cohort. Forty percent (69) of the post-cohort received an initial telestroke consult. In spoke-retained patients followed by telestroke rounds (55), median length of stay decreased by 0.8 days (P = 0.01). Readmission and mortality rates did not differ significantly between groups (19.5 vs. 9.1%, P = 0.14 and 3.9 vs. 3.6%, P = 1, respectively). The favorable functional outcome rate was similar between groups (47.3% vs 65.9%, P = 0.50). CONCLUSIONS: Longitudinal stroke care via telestroke may be economically viable through length of stay reduction. Randomized prospective studies are needed to confirm our findings and further investigate this model's potential benefits.
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Servicio de Urgencia en Hospital , Pacientes Internos , Ataque Isquémico Transitorio/terapia , Accidente Cerebrovascular Isquémico/terapia , Consulta Remota , Anciano , Anciano de 80 o más Años , Evaluación de la Discapacidad , Femenino , Estado Funcional , Humanos , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/mortalidad , Ataque Isquémico Transitorio/fisiopatología , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/mortalidad , Accidente Cerebrovascular Isquémico/fisiopatología , Tiempo de Internación , Masculino , Persona de Mediana Edad , Admisión del Paciente , Readmisión del Paciente , Transferencia de Pacientes , Proyectos Piloto , Recuperación de la Función , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Benefits of revascularization for moderate and severe (≥50%) carotid stenosis were established based on digital subtraction angiography (DSA). We aimed to assess the discrepancy between invasive and non-invasive angiography in a consecutive, prospective cohort of patients with recent stroke and non-invasive imaging suggesting ≥50% ipsilateral carotid stenosis. MATERIALS AND METHODS: We reviewed prospectively-collected data for consecutive patients admitted with recent stroke/TIA and ≥50% ipsilateral carotid stenosis on non-invasive imaging over 28 months. All patients underwent DSA to confirm the degree of stenosis per NASCET criteria. All patients with <50% stenosis by DSA were treated with medical therapy only and their recurrent event rates were assessed at 6 months. RESULTS: 148 symptomatic patients with ≥50% ipsilateral carotid stenosis on CTA (82%) and MRA (18%) underwent DSA to confirm degree of stenosis. Median age was 73 years and 64% were male. DSA demonstrated <50% stenosis in 28 patients (19%). Median presenting NIHSS was 1 (IQR 0-3). Median carotid stenosis evaluated by non-invasive imaging was 70% (IQR 60-85%) and by DSA was 40% (IQR 30-45%). One of 28 patients (4%) experienced recurrent nondisabling stroke (NIHSS 1) after stopping dual antiplatelet therapy. CONCLUSION: In nearly one-in-five cases with recent stroke due to ipsilateral carotid stenosis deemed to be candidates for revascularization based on CTA or MRA, DSA led to institution of medical therapy only due to insufficiently severe stenosis. In patients treated with medical therapy based on the findings of <50% stenosis on DSA, the rate of recurrent stroke is low.