Background Emerging yet contrasting evidence from animal and human studies associates ischemic preconditioning with improvement of subsequent stroke severity, although long‐term outcome remains ...unclear. The purpose of this study was to analyze how preceding cerebral ischemic events influence subsequent stroke severity and outcome. Methods and Results Data for this retrospective cohort study were extracted from ASTRAL (Acute Stroke Registry and Analysis of Lausanne). This registry includes a sample of all consecutive patients with acute ischemic strokes admitted to the stroke unit and/or intensive care unit of the Lausanne University Hospital, Switzerland. We investigated associations between preceding ischemic events (transient ischemic attacks or ischemic strokes) and the impact on subsequent stroke severity and clinical improvement within 24 hours, measured through National Institute of Health Stroke Scale, as well as 3‐month outcome, determined through a shift in the modified Rankin Scale. Of 3530 consecutive patients with ischemic stroke (43% women, median age 73 years), 1001 (28%) had ≥1 preceding cerebral ischemic events (45% transient ischemic attack, 55% ischemic stroke; 31% multiple events). After adjusting for multiple prehospital, clinical, and laboratory confounders, admission stroke severity was significantly lower in patients preconditioned through a preceding ischemic event, but 24‐hour improvement was not significant and 3‐month outcome was unfavorable. Conclusions Preceding ischemic events were independently associated with a significant reduction in subsequent stroke severity but worsened long‐term clinical outcome. These results, if confirmed by future randomized studies, may help design neuroprotective strategies. The unfavorable effect on stroke outcome is probably a consequence of the cumulative disability burden after multiple ischemic events.
The impact of excess body weight on prognosis after stroke is controversial. Many studies report higher survival rates in obese patients ("obesity paradox"). Recently, obesity has been linked to ...worse outcomes after intravenous (IV) thrombolysis, but the number and sample size of these studies were small. Here, we aimed to assess the relationship between body weight and stroke outcome after IV thrombolysis in a large cohort study.
In a prospective observational multicenter study, we analyzed baseline and outcome data of 896 ischemic stroke patients who underwent IV thrombolysis. Patients were categorized according to body mass index (BMI) as underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), obese (30-34.9 kg/m2) or severely obese (>35 kg/m2). Using uni- and multivariate modeling, we assessed the relationship of BMI with favorable outcome (defined as modified Rankin Scale 0 or 1) and mortality 3 months after stroke as well as the occurrence of symptomatic intracerebral hemorrhages (sICH). We also measured the incidence of patients that had an early neurological improvement of >40% on the National Institutes of Health Stroke Scale (NIHSS) after 24 hours.
Among 896 patients, 321 were normal weight (35.8%), 22 underweight (2.5%), 378 overweight (42.2%), 123 obese (13.7%) and 52 severely obese (5.8%). Three-month mortality was comparable in obese vs. non-obese patients (8.1% vs. 8.3%) and did not differ significantly among different BMI groups. This was also true for favorable clinical outcome, risk of sICH and early neurological improvement on NIHSS at 24 hours. These results remained unchanged after adjusting for potential confounding factors in the multivariate analyses.
BMI was not related to clinical outcomes in stroke patients treated with IVT. Our data suggest that the current weight-adapted dosage scheme of IV alteplase is appropriate for different body weight groups, and challenge the existence of the obesity paradox after stroke.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and Purpose- Although perfusion abnormality is an increasingly important therapeutic target, the natural history of tissue at risk without reperfusion treatment is understudied. Our ...objective was to determine how time affects penumbral salvage and infarct growth in untreated acute ischemic stroke patients and whether collateral status affects this relationship. Methods- We used a prospectively collected, multicenter acute stroke registry to assess acute stroke patients who were not treated with intravenous thrombolysis or endovascular treatment. We analyzed baseline computed tomography angiogram and computed tomography perfusion within 24 hours of stroke onset along with follow-up imaging and assessed time from stroke onset to baseline imaging, ASPECTS (Alberta Stroke Program Early CT Score), vessel occlusion, collaterals, ischemic core, and penumbra. Penumbral salvage and infarct growth were calculated. Correlations between time and penumbral salvage and infarct growth were evaluated with Spearman correlation. Penumbral salvage and infarct growth were compared between subjects with good versus poor collateral status using the Wilcoxon rank-sum test. Clinical and imaging factors affecting penumbral salvage and infarct growth were evaluated by linear regression. Results- Among 94 untreated stroke patients eligible for this analysis, the mean age was 65 years, median National Institutes of Health Stroke Scale score was 13, and median (range) time from stroke onset to baseline imaging was 2.9 (0.4-23) hours. There was no correlation between time and salvaged penumbra ( r=0.06; P=0.56) or infarct growth ( r=-0.05; P=0.61). Infarct growth was higher among those with poor collaterals versus those with good collaterals (median, 52.3 versus 0.9 cm
; P<0.01). Penumbral salvage was lower among those with poor collaterals compared with those with good collaterals (poor, 0 0-0; good, 5.9 cm
0-29.4; P<0.01). Multivariable linear regression demonstrated that collaterals, but not time, were significantly associated with infarct growth and penumbral salvage. Conclusions- In this natural history study, penumbral salvage and infarct growth were less time dependent and more a measure of collateral flow.
Coronavirus disease 2019 (COVID-19) is associated with an increased risk of thrombotic events. Ischemic stroke in COVID-19 patients entails high severity and mortality rates. Here we aimed to analyze ...cerebral thrombi of COVID-19 patients with large vessel occlusion (LVO) acute ischemic stroke to expose molecular evidence for SARS-CoV-2 in the thrombus and to unravel any peculiar immune-thrombotic features. We conducted a systematic pathological analysis of cerebral thrombi retrieved by endovascular thrombectomy in patients with LVO stroke infected with COVID-19 (n = 7 patients) and non-covid LVO controls (n = 23). In thrombi of COVID-19 patients, the SARS-CoV-2 docking receptor ACE2 was mainly expressed in monocytes/macrophages and showed higher expression levels compared to controls. Using polymerase chain reaction and sequencing, we detected SARS-CoV-2 Clade20A, in the thrombus of one COVID-19 patient. Comparing thrombus composition of COVID-19 and control patients, we noted no overt differences in terms of red blood cells, fibrin, neutrophil extracellular traps (NETs), von Willebrand Factor (vWF), platelets and complement complex C5b-9. However, thrombi of COVID-19 patients showed increased neutrophil density (MPO
cells) and a three-fold higher Neutrophil-to-Lymphocyte Ratio (tNLR). In the ROC analysis both neutrophils and tNLR had a good discriminative ability to differentiate thrombi of COVID-19 patients from controls. In summary, cerebral thrombi of COVID-19 patients can harbor SARS-CoV2 and are characterized by an increased neutrophil number and tNLR and higher ACE2 expression. These findings suggest neutrophils as the possible culprit in COVID-19-related thrombosis.
This study aimed to assess if there are sex differences in the functional outcome of intravenous thrombolysis (IVT) among patients with lacunar stroke (LS).
Consecutive patients admitted from 1 ...January 2014 to 31 January 2020 to hospitals participating in the Swiss Stroke Registry presenting with LS and treated with IVT were included. The study population was then divided into two groups based on patient sex, and a multivariable ordinal logistic regression analysis was performed to uncover sex differences in the modified Rankin Scale (mRS) score at 90 days after stroke.
A total of 413 patients with LS were treated with IVT: 177 (42.9%) women and 236 (57.1%) men. Women were older than men (median age 74 years, 25th-75th percentiles 67-84 years versus 70 years, 25th-75th percentiles 60-80 years, value of p 0.001) and, after adjustment for meaningful variables, showed more frequently increased odds of a higher mRS score at 90 days after stroke (adjusted odds ratio 1.49, 95% confidence interval 1.01-2.19, value of p 0.044).
This study showed that female sex increased the odds of a worse functional response to IVT in patients with LS. Future studies should further elucidate the mechanisms underlying such sex differences.
Ischemic stroke affects language production and/or comprehension and leads to devastating long-term consequences for patients and their families. Previous studies have shown that neuroimaging can ...increase our knowledge of the basic mechanisms of language recovery. Currently, models for predicting patients' outcomes have limited use in the clinic for the evaluation and optimization of rehabilitative strategies mostly because that are often based on high-resolution magnetic resonance imaging (MRI) data, which are not always possible to carry out in the clinical routine. Here, we investigate the use of Voxel-Based Morphometry (VBM), multivariate modelling and native Computed Tomography (nCT) scans routinely acquired in the acute stage of stroke for identifying biological signatures that explicate the relationships between brain anatomy and types of impairments.
80 stroke patients and 30 controls were included. nCT-scans were acquired in the acute ischemia stage and bedside clinical assessment from board-certified neurologist based on the NIH stroke scale. We use a multivariate Principal Component Analyses (PCA) to identify the brain signatures group the patients according to the presence or absence of impairment and identify the association between local Grey Matter (GM) and White Matter (WM) nCT values with the presence or absence of the impairment.
Individual patient's nCT scans were compared to a group of controls' with no radiological signs of stroke to provide an automated delineation of the lesion. Consistently across the whole group the regions that presented significant difference GM and WM values overlap with known areas that support language processing.
In summary, the method applied to nCT scans performed in the acute stage of stroke provided robust and accurate information about brain lesions' location and size, as well as quantitative values. We found that nCT and VBQ analyses are effective for identifying neural signatures of concomitant language impairments at the individual level, and neuroanatomical maps of aphasia at the population level. The signatures explicate the neurophysiological mechanisms underlying aetiology of the stroke. Ultimately, similar analyses with larger cohorts could lead to a more integrated multimodal model of behaviour and brain anatomy in the early stage of ischemic stroke.
Background and purpose
40% of acute ischemic stroke patients treated by mechanical thrombectomy (MT) have a clinical history of atrial fibrillation (AF). The safety of bridging intravenous ...thrombolysis (IVT) (MT + IVT) is currently being discussed. We aimed to analyze the interaction between oral anticoagulation (OAC) status or AF with bridging IVT, regarding the occurrence of symptomatic intracranial hemorrhage (sICH) and functional outcome.
Materials and Methods
Multicentric observational cohort study (BEYOND-SWIFT registry) of consecutive patients undergoing MT between 2010 and 2018 (
n
= 2,941). Multinomial regression models were adjusted for prespecified baseline and plausible pathophysiological covariates identified on a univariate analysis to assess the association of AF and OAC status with sICH and good outcomes (90-day modified Rankin Scale score 0–2).
Results
In the total cohort (median age 74, 50.6% women), 1,347 (45.8%) patients had AF. Higher admission National Institutes of Health Stroke Scale (NIHSS) score (aOR 1.04 95% 1.02–1.06, per point of increase) and prior medication with Vitamin K antagonists (VKA) (aOR 2.19 95% 1.27–3.66) were associated with sICH. Neither AF itself (aOR 0.71 95% 0.41–1.24) nor bridging IVT (aOR 1.08 0.67–1.75) were significantly associated with increased sICH. Receiving bridging IVT (aOR 1.61 95% 1.24–2.11) was associated with good 90-day outcome, with no interaction between AF and IVT (
p
= 0.92).
Conclusion
Bridging IVT appears to be a reasonable clinical option in selected patients with AF. Given the increased sICH risk in patients with VKA, subgroup analysis of the randomized controlled trials should analyze whether patients with VKA might benefit from withholding bridging IVT.
Registration
clinicaltrials.gov
; Unique identifier: NCT03496064.
Introduction: Ischemic stroke is a leading cause of disability and mortality worldwide. As acute stroke patients often lose decision-making capacity, acute management is fraught with complicated ...decisions regarding life-sustaining treatment (LST). We aimed to explore (1) the perspectives and experiences of clinicians regarding the use of predictive scores for LST decision making in severe acute stroke, and (2) clinicians’ awareness of their own cognitive biases in this context. Methods: Four focus groups (FGs) were conducted with 21 physicians (13 residents and 8 attending physicians); two FGs in a university hospital and two in a regional hospital in French-speaking Switzerland. Discussions were audio-recorded and transcribed verbatim. Transcripts were analyzed thematically. Two of the four transcripts were double coded to establish coding framework consistency. Results: Participants reported that predictive tools were not routinely used after severe stroke, although most knew about such scores. Scores were reported as being useful in quantifying prognosis, advancing scientific evidence, and minimizing potential biases in decisions. Their use is, however, limited by the following barriers: perception of inaccuracy, general disbelief in scoring, fear of self-fulfilling prophecy, and preference for clinical judgement. Emotional and cognitive biases were common. Emotional biases distort clinicians’ knowledge and are notably: bias of personal values, negative experience, and cultural bias. Cognitive biases, such as availability, confirmation, and anchoring biases, that produce systematic deviations from rational thinking, were also identified. Conclusions: The results highlight opportunities to improve decision making in severe stroke through the promotion of predictive tools, strategies for communicating prognostic uncertainty, and minimizing cognitive biases among clinicians, in order to promote goal-concordant care.
Background Patient selection for endovascular revascularization treatment (ERT) in acute ischemic stroke depends on the expected benefit–risk ratio. As rapid revascularization is a major determinant ...of good functional outcome, we aimed to identify its predictors after ERT. Methods Consecutive stroke patients from a single stroke center with distal internal carotid artery-, proximal middle cerebral artery- or T-occlusions treated with ERT were retrospectively selected. We assessed admission noncontrast computed tomography and computed tomography angiography for thrombus location, thrombus load (clot burden score), and collateral status. Clinical data were extracted from medical charts. Univariate and multivariate regression analyses were performed to identify predictors of revascularization (thrombolysis in cerebral infarction ≥2b) after ERT. Results A total of 63 patients were identified (median age, 73 years; interquartile range: 62-77; 40 females). Sixteen patients (25.4%) underwent intravenous thrombolysis (ivT) before ERT. Twenty-two patients (34.9%) had additional intra-arterial application of recombinant tissue plasminogen activator. The overall recanalization rate was 66.7%, and 9.5% had symptomatic intracranial bleeding. In-hospital mortality was 15%, and 30% reached good functional outcome at discharge. In the univariate analysis, preceding ivT and the number of passes for thrombectomy (dichotomized ≤2 versus >2) were associated with recanalization. There was a trend for number of thrombectomy passes (as continuous variable) and multimodal ERT. In the multivariate regression analysis, ivT prior to ERT and passes of thrombectomy were identified as independent predictors for recanalization. Conclusion ivT and lower passes of thrombectomy are associated with recanalization after ERT for ischemic stroke with proximal vessel occlusions.
Background Intravenous thrombolysis (IVT) in wake-up stroke (WUS) or stroke with unknown onset (SUO) has been recently proven to be safe and effective using advanced neuroimaging (magnetic resonance ...imaging or computerized tomography-perfusion) for patient selection. However, in most of the thrombolyzing centers advanced neuroimaging is not instantly available. We hypothesize that pragmatic non-contrast computed tomography-based IVT in WUS/SUO may be feasible and safe. Methods and Results TRUST-CT (Thrombolysis in Stroke With Unknown Onset Based on Non-Contrast Computerized Tomography) is an international multicenter registry-based study. WUS/SUO patients undergoing non-contrast computed tomography-based IVT with National Institute of Health Stroke Scale ≥4 and initial Alberta Stroke Program Early Computerized Tomography score ≥7 were included and compared with propensity score matched non-thrombolyzed WUS/SUO controls. Primary end point was the incidence of symptomatic intracranial hemorrhage; secondary end points included 24-hour National Institute of Health Stroke Scale improvement of ≥4 and modified Rankin Scale at 90 days. One hundred and seventeen WUS/SUO patients treated with non-contrast computed tomography-based IVT were included. As compared with 112 controls, the median admission National Institute of Health Stroke Scale was 10 and the median Alberta Stroke Program Early Computerized Tomography score was 10 in both groups. Four (3.4%) IVT patients and one control patient (0.9%) suffered symptomatic intracranial hemorrhage (adjusted odds ratio 7.9, 95% CI 0.65-96,
=0.1). A decrease of ≥4 National Institute of Health Stroke Scale points was observed in 67 (57.3%) of IVT patients as compared with 25 (22.3%) in controls (adjusted odds ratio 5.8, CI 3.0-11.2,
<0.001). A months, 39 (33.3%) IVT patients reached a modified Rankin Scale score of 0 or 1 versus 23 (20.5%) controls (adjusted odds ratio 1.94, CI 1.0-3.76,
=0.05). Conclusions Non-contrast computed tomography-based thrombolysis in WUS/SUO seems feasible and safe and may be effective. Randomized prospective comparisons are warranted. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT03634748.
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