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Background: Whether minor ischemic stroke (MIS) patients can benefit from intravenous thrombolysis (IVT) remains controversial. The association between the efficacy of IVT and baseline National Institute of Health Stroke Scale (NIHSS) score is unclear in MIS, while the association in moderate and severe stroke is known. This study aimed to explore the effect of IVT in patients with MIS and analyze its efficacy in patients with different baseline NIHSS scores., Methods: Patients with a NIHSS score ≤5 within 4.5 h of stroke onset were screened in 32 centers. Patients with and without IVT were matched to a ratio of 1:1 with propensity scores. An excellent outcome was defined as a modified Rankin Scale (mRS) score ≤1 at three months after stroke onset. Safety outcomes included mortality and symptomatic intracranial hemorrhage (sICH). Multivariate analysis was used to compute the adjusted odds ratio (OR) for excellent outcomes. The effect of IVT was further analyzed in subgroups according to the baseline NIHSS score., Results: Of the 23,853 screened, 3336 patients with MIS who arrived at the hospital within 4.5 h of onset were included. The 1163 patients treated with IVT were matched with 1163 patients without IVT. IVT in minor strokes generated an adjusted OR of 1.38 (95% CI: 1.09-1.75, p  = 0.009) for excellent outcomes. There were no significant differences in mortality (0.17% vs. 0.09%, p =  1.000) and sICH (0.69% vs. 0.86%, p =  0.813) between patients with and without IVT. Subgroup analysis showed that there was no significant effect of IVT in the baseline NIHSS 0-1 or 2-3 subgroups, with adjusted OR of 0.816 (95% CI 0.437-1.53, p  = 0.525) and1.22 (95% CI 0.845-1.77, p  = 0.287), respectively. In patients with NIHSS score of 4-5, IVT was significantly effective, with an adjusted OR of 1.53 (95% CI 1.02-2.30, p  = 0.038)., Conclusion: IVT can improve MIS outcomes. The risks of sICH and mortality did not increase, especially in patients with NIHSS scores 4 to 5, who could benefit from IVT significantly.

Background: The ubiquitin-proteasome system (UPS) and autophagy are 2 major protein degradation pathways in eukaryotic cells. We previously identified a switch from UPS to autophagy with changes in BAG3 (B-cell lymphoma 2-associated-athanogene 3) expression after cerebral ischemia in mice. BAG3 is an antiapoptotic-cochaperone that is directly involved in cellular protein quality control as a mediator for selective macroautophagy. Here, we aimed to investigate the role of BAG3 in ischemic stroke., Methods: Middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation were used to mimic cerebral ischemia in vivo and in vitro. The UPS inhibitor MG132 and autophagy inhibitor 3-MA (3-methyladenine) were administered to mice to identify how BAG3 was involved after MCAO/R. Adeno-associated virus and lentiviral vector were used to regulate BAG3 expression in vivo and in vitro, respectively. Behavioral tests, 2,3,5-triphenyltetrazolium chloride staining, and Hematoxylin & Eosin staining were performed to evaluate cerebral injury following MCAO/R, and a Cell Counting kit-8 assay was conducted to assess oxygen-glucose deprivation/reoxygenation-induced injury in cells. Brain tissues and cell lysates were collected and analyzed for UPS activation, autophagy, and apoptosis., Results: The UPS inhibitor alleviated MCAO injury in mice and increased autophagy and BAG3 expression, whereas the autophagy inhibitor exacerbated MCAO/R-induced injury. In addition, BAG3 overexpression significantly improved neurological outcomes, reduced infarct volume in vivo, and enhanced cell survival by activating autophagy and suppressing apoptosis in vitro., Conclusions: Our findings indicate that BAG3 overexpression activates autophagy and inhibits apoptosis to prevent cerebral ischemia/reperfusion and hypoxia/reoxygenation injury, suggesting a potential therapeutic benefit of BAG3 expression in cerebral ischemia., Competing Interests: Disclosures None.

Background: The serum orexin A level was significantly lower among patients with acute ischemic stroke (AIS) and negatively related to the volume of the infarction, but the relationship between serum orexin A and prognosis of AIS was still unclear. We aimed to clarify the association between serum orexin A and the short-term neurological improvement in patients with mild to moderate AIS., Methods: We consecutively enrolled patients with first ever mild to moderate AIS admitted to hospital within 48 h from symptom onset in this prospective observational study. The serum orexin A concentrations were determined on the second morning since the admission. The short-term neurological improvement was defined as more than 1 point decrease in the National Institute of Health Stroke Scale score within 7 days after admission., Results: We detected increased serum orexin A level in mild to moderate AIS patients with early onset of stroke-related insomnia (33.44 vs 18.66 pg/ml, p = .004) as well as in patients with short-term neurological improvement compared to those without improvement (31.78 vs 16.24 pg/ml, p = .038). The serum orexin A level was positively associated with the short-term neurological improvement after adjusting for sleep condition and other related variables., Conclusion: Serum orexin A might be a useful biomarker for the assessment of early prognosis in patients with mild to moderate AIS., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Dynamic cerebral autoregulation (CA) is known to be impaired in patients with acute ischemic stroke (AIS), but whether or not dynamic CA can predict long-term outcomes is unclear., Materials and Methods: This prospective study included 103 patients with AIS between September 2017 and April 2019. We measured the middle cerebral artery blood flow velocity and blood pressure within 7 days of AIS onset using a transcranial Doppler and Finometer, respectively. We conducted transfer function analysis to calculate dynamic CA indices (phase and gain), with lower phase and higher gain parameters reflecting less efficient CA. We followed up all patients after 3 and 12 months. Patients with 12-month modified Rankin Scale scores of <2 and ≥2 were defined as having favorable and unfavorable outcomes, respectively. We then analyzed the predictors of unfavorable outcomes after 3 and 12 months using logistic regression., Results: The ipsilesional phase parameter was significantly lower in patients with unfavorable outcomes than in those with favorable outcomes. Multiple logistic regression analysis revealed that the ipsilesional phase parameter and the National Institutes of Health Stroke Scale score were nonmodifiable predictors of short-term and long-term outcomes. Moreover, in receiver operating characteristic analysis, the area under the curve of the ipsilesional phase parameter was 0.646 (95% confidence interval: 0.513-0.779, P =0.044). Notably, the optimal cut-off value was 20.33 degrees (sensitivity: 63%, specificity: 70%)., Conclusion: Dynamic CA is an independent predictor of outcomes at 3 and 12 months in patients with AIS., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Existing data suggest that cerebral autoregulation (CA) varies among different subtypes of ischaemic stroke. CA is globally impaired in patients with small artery occlusion (SAO). However, the factors influencing CA impairment in patients remains to be elucidated., Methods: Stroke patients with SAO who underwent brain magnetic resonance imaging (MRI) were prospectively studied. Within 7 days after stroke onset, CA was recorded from the middle cerebral artery blood flow velocity and arterial blood pressure was simultaneously measured. Transfer function analysis was used to derive CA parameters, including gain and phase. Clinical characteristics, mean arterial pressure (MAP), biochemical findings, and cerebral small vessel disease (CSVD) markers on MRI were assessed in each patient. Factors associated with CA parameters were investigated. Univariate and multivariate linear regression analyses were conducted to determine the relationship between clinical factors and CA parameters., Results: Sixty-three SAO patients (age, 56.3 ± 9.9 years; 55 men) were enrolled in the study. In the multiple linear regression analysis, after controlling for relevant clinical factors, MAP on admission (ipsilateral OR = 0.99 and contralateral OR = 0.99, both P < 0.005) was a significant independent predictor of bilateral gain. MAP > 105 mmHg on admission (OR = 0.77, P = 0.019) was significantly associated with ipsilateral gain. Diabetes mellitus was a significant predictive factor for bilateral gain (ipsilateral OR = 1.32 and contralateral OR = 1.22, both P < 0.005). No correlations were found between CA parameters and CSVD characteristics., Conclusion: In SAO-related ischaemic stroke, patients with MAP > 105 mmHg on admission tended to have better ipsilateral CA. Diabetes mellitus appears to be an independent risk factor for CA impairment in patients with SAO-related stroke. CSVD may not be the main factor affecting bilateral CA in patients with SAO., (© 2022. The Author(s).)

Background: Ischaemic stroke and transient ischaemic attack (TIA) share a common cause. We aim to develop and validate a concise prognostic nomogram for patients with minor stroke and TIA., Methods: A total of 994 patients with minor stroke and TIA were included. They were split into a derivation (n=746) and validation (n=248) cohort. The modified Rankin Scale (mRS) scores 3 months after onset were used to assess the prognosis as unfavourable outcome (mRS≥2) or favourable outcome (mRS<2)., Result: The final model included seven independent predictors: gender, age, baseline National Institute of Health Stroke Scale (NIHSS), hypertension, diabetes mellitus, white blood cell and serum uric acid. The Harrell's concordance index (C-index) of the nomogram for predicting the outcome was 0.775 (95% CI 0.735 to 0.814), which was confirmed by the validation cohort (C-index=0.787 (95% CI 0.722 to 0.853)). The calibration curve showed that the nomogram-based predictions were consistent with actual observation in both derivation cohort and validation cohort., Conclusion: The proposed nomogram showed favourable predictive accuracy for minor stroke and TIA. This has the potential to contribute to clinical decision-making., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Symptomatic intracranial hemorrhage (sICH) is a serious hemorrhagic complication after intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients. Most existing predictive scoring systems were derived from Western countries., Objective: The objective of this study is to develop a nomogram to predict the possibility of sICH after IVT in Asian population., Methods: This retrospective cohort study included AIS patients treated with recombinant tissue plasminogen activator (rt-PA) in a tertiary hospital in Shenzhen, China, from January 2014 to December 2020. The endpoint was sICH within 36 hours of IVT treatment. Multivariable logistic regression was used to identify risk factors of sICH, and a predictive nomogram was developed. Area under the curve of receiver operating characteristic curves (AUC), calibration curve, and decision curve analyses were performed. The nomogram was validated by bootstrap resampling., Results: Data on a total of 462 patients were collected, of whom 20 patients (4.3 %) developed sICH. In the multivariate logistic regression model, the National Institute of Health stroke scale scores (NIHSS) (odds ratio (OR), 1.14; 95 % confidence interval (CI), 1.06-1.23, P < 0.001), onset to treatment time (OTT) (OR, 1.02; 95 % CI, 1.01-1.03, P < 0.001), neutrophil to lymphocyte ratio (NLR) (OR, 1.22; 95 % CI, 1.09-1.35, P < 0.001), and cardioembolism (OR, 3.74; 95 % CI, 1.23-11.39, P = 0.020) were independent predictors for sICH and were used to construct a nomogram. Our nomogram exhibited favorable discrimination ability (AUC, 0.878; specificity, 87.35 %; and sensitivity, 73.81 %). Bootstrapping for 500 repetitions was performed to further validate the nomogram. The AUC of the bootstrap model was 0.877 (95 % CI: 0.823-0.922). The calibration curve exhibited good fit and calibration. The decision curve revealed good positive net benefits and clinical effects., Conclusion: The nomogram consisting of the predictors NIHSS, OTT, NLR, and cardioembolism could be used as an auxiliary tool to predict the individual risk of sICH in Chinese AIS patients after IVT. Further external verification among more diverse patient populations is needed to demonstrate the accuracy of the model's predictions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Baseline systolic blood pressure (SBP) is an important parameter that can significantly influence the outcome in ischemic stroke patients who received intravenous thrombolysis, but the target baseline SBP for optimal outcome is uncertain. This study aimed to assess the relationship between baseline SBP and outcome., Materials and Methods: Studies that evaluated the association between the baseline SBP and the outcome of patients undergoing thrombolytic therapy were sought. Data were extracted according to a predefined data extraction form and then analyzed by STATA 12.0 software. The primary endpoint was the occurrence of good outcomes measured by a modified Rankin Scale score at 3 months, while the secondary endpoint was the occurrence of intracranial hemorrhage and death., Results: Eleven studies involving a total of 33,263 patients were included. Pooled data suggested that the odds of good outcome was decreased by 7% per 10 mm Hg increase in baseline SBP (odds ratio=0.93; 95% confidence interval: 0.91-0.94; P<0.001). Patients with higher baseline SBP were more likely to have intracranial hemorrhage (odds ratio=1.12 per 10 mm Hg increase; 95% confidence interval: 1.08-1.16, P<0.001)., Conclusions: This study suggested that lower baseline SBP may be positively associated with a greater chance of good outcome and less chance of intracranial hemorrhage. However, this effect was reliable only when the baseline SBP was within a certain range, which has not been explicitly stated. Therefore, more well-designed studies are needed to define the optimal baseline SBP.

Introduction: Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is a well-known risk factor of atherosclerotic vascular diseases. Nevertheless, its role in the acute phase of ischemic stroke is still unclear. The aim of this study is to identify the relationship between Lp-PLA 2 levels and early neurological deterioration (END) in acute ischemic stroke patients with Trial of Org 10 172 in Acute Stroke Treatment (TOAST) subtype of large arterial atherosclerosis (LAA). Methods: We enrolled Chinese patients with first ever acute ischemic stroke admitted to Neurology Department of Shenzhen Second People's Hospital within 48 h from onset of symptoms during January - November 2015. Demographic and laboratory information were collected while END was defined as an increase in the National Institute of Health Stroke Scale score by ≥ 1 point in motor power, or ≥ 2 points in the total score within 10 days after admission. Results: Overall 181 patients were involved; END was diagnosed in 30 patients within 10 days after admission. The odds ratio for END increased with increasing levels of Lp-PLA 2 (intermediate level, OR = 1.96, 95%CI 1.02-4.27, p  = 0.041; high level, OR = 2.99, 95%CI 1.26-5.73, p  = 0.023). Conclution: Intermediate and high level of Lp-PLA 2 was identified as independent predictor of END in multivariate analysis. Lp-PLA 2 could be valued as a risk factor of END in patients with acute ischemic stroke with TOAST subtype of LAA.

The efficacy of thrombolytic therapy for acute ischemic stroke (AIS) decreases when the administration of tissue plasminogen activator (tPA) is delayed. Derived from Toyota Production System, lean production aims to create top-quality products with high-efficiency procedures, a concept that easily applies to emergency medicine. In this study, we aimed to determine whether applying lean principles to flow optimization could hasten the initiation of thrombolysis. A multidisciplinary team (Stroke Team) was organized to implement an ongoing, continuous loop of lean production that contained the following steps: decomposition, recognition, intervention, reengineering and assessment. The door-to-needle time (DNT) and the percentage of patients with DNT ≤ 60 min before and after the adoption of lean principles were used to evaluate the efficiency of our flow optimization. Thirteen patients with AIS in the pre-lean period and 43 patients with AIS in the lean period (23 in lean period I and 20 patients in lean period II) were consecutively enrolled in our study. After flow optimization, we reduced DNT from 90 to 47 min (p < 0.001 ¤ ). In addition, the percentage of patients treated ≤60 min after hospital arrival increased from 38.46 to 75.0 % (p = 0.015 ¤ ). Adjusted analysis of covariance confirmed a significant influence of optimization on delay of tPA administration (p < 0.001). The patients were more likely to have a good prognosis (mRS ≤ 2 at 90 days) after the flow optimization (30.77-75.00 %, p = 0.012 ¤ ). Our study may offer an effective approach for optimizing the thrombolytic flow in the management of AIS.

Objectives: To compare visualization of joint intracranial and carotid vessel walls between 5× compressed sensing accelerated three-dimensional DANTE-SPACE sequence (CS VWI) acquired in 5 min and the same sequence accelerated by 2.7× parallel imaging (PI VWI) which takes 9-10 min currently.Methods: Following institutional review board approval and informed consent, 28 subjects including 20 stroke patients underwent PI and CS VWI examinations with an acquired spatial resolution of isotropic 0.55 mm and joint coverage of intracranial and carotid arteries. Quantitative wall thickness measurements of CS VWI and PI VWI were compared on healthy volunteers and patients with wall thickening respectively. Subjective wall visualizations of the two VWI methods on patients were scored by two radiologists blindly and independently using a 4-point scale followed by inter-rater reproducibility analysis.Results: Linear regression analysis of wall thickness measurements showed excellent agreement between CS VWI and PI VWI in both healthy volunteers (r = 0.99) and stroke patients with wall thickening (r = 0.99). Subjective wall visualization score of CS VWI was slightly lower than PI VWI (3.13 ± 0.41 vs. 3.31 ± 0.79) but still had good diagnostic quality (> 3 based on a 4-point scale). The two radiologists' scores agreed excellently, evidenced by the intraclass correlation coefficient (ICC) values being higher than 0.75 (p < 0.001).Conclusions: Compressed sensing expedients joint intracranial and carotid VWI acquired at an isotropic resolution of 0.55 mm in 5 min without compromising quantitative vessel wall thickness measurement or diagnostic wall visualization.Key Points: • CS VWI facilitates comprehensive visualization of intracranial and carotid vessel walls at an acquired isotropic resolution of 0.55 mm in a single 5-min scan. • CS VWI affords comparable vessel wall visualization and morphology measurement as PI VWI with a shortened acquisition time by 45%. • CS VWI alleviates the intensive trade-off between imaging resolution and scan time, and benefits the scan efficiency, motion robustness, and patient tolerance of high-resolution joint intracranial and carotid VWI. [ABSTRACT FROM AUTHOR]