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Kataike VM, Desmond PM, Steward C, Campbell BCV, Mitchell PJ, Ng F, Venkatraman V. Oxygen extraction fraction changes in ischemic tissue from 24-72 hours to 12 months after successful reperfusion. J Cereb Blood Flow Metab 2025:271678X251333940. [PMID: 40219845 PMCID: PMC11993554 DOI: 10.1177/0271678x251333940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 03/24/2025] [Accepted: 03/25/2025] [Indexed: 04/14/2025]
Abstract
Oxygen Extraction Fraction (OEF) is a critical measure of a tissue's metabolic state post-ischemic stroke. This study investigated OEF changes in stroke-affected tissue compared to healthy tissue, post-reperfusion. OEF maps generated from gradient echo MRI images of 87 ischemic stroke patients at three time points after successful Endovascular Thrombectomy (EVT) were analysed in a prospective longitudinal multicentre study. Regions of interest (ROIs) delineating the infarct areas and corresponding mirror regions were drawn. The MR-derived OEF index values were obtained from the ROIs and compared using Wilcoxon signed rank tests. The cross-sectional comparison of OEF index values revealed lower values in the infarct areas than the corresponding contralateral areas at all three time points after successful EVT, presented as median (interquartile range) [24-72 hours: 20.84 (17.56-26.82)% vs 27.56 (23.22-31.87)%; 3 months: 27.37 (23.28-30.35)% vs 32.55 (28.00-35.81)%; 12 months: 24.38 (22.35-29.77)% vs 29.39 (25.86-34.04)%, p < 0.001 for all three time points]. Longitudinally, relative OEF index values increased gradually over time [24-72 hours: 0.81 (0.67-0.87); 3 months: 0.86 (0.79-0.95); 12 months: 0.88 (0.75-0.95)]. The findings revealed that following successful EVT, OEF in infarct tissue improves over time, indicating potential tissue recovery.Trial registration name and URL: Post-Reperfusion Pathophysiology in Acute Ischemic Stroke https://trialsearch.who.int/Trial2.aspx?TrialID=ACTRN12624000629538.
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Affiliation(s)
| | - Patricia M Desmond
- Department of Radiology, The University of Melbourne, Parkville, VIC, Australia
- Department of Medical Imaging, The Royal Melbourne Hospital, Parkville, VIC, Australia
| | - Christopher Steward
- Department of Radiology, The University of Melbourne, Parkville, VIC, Australia
- Department of Medical Imaging, The Royal Melbourne Hospital, Parkville, VIC, Australia
| | - Bruce CV Campbell
- Department of Medicine at The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia
- Department of Neurology, The Royal Melbourne Hospital, Parkville, VIC, Australia
| | - Peter J Mitchell
- Department of Radiology, The University of Melbourne, Parkville, VIC, Australia
- Department of Medical Imaging, The Royal Melbourne Hospital, Parkville, VIC, Australia
| | - Felix Ng
- Department of Medicine at The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia
- Department of Neurology, The Royal Melbourne Hospital, Parkville, VIC, Australia
- Department of Neurology, Austin Health, Heidelberg, VIC, Australia
| | - Vijay Venkatraman
- Department of Radiology, The University of Melbourne, Parkville, VIC, Australia
- Department of Medical Imaging, The Royal Melbourne Hospital, Parkville, VIC, Australia
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Yang L, Cai X, Yan Y, Hui P. Developing a predictive value for predicting stroke recovery based on transcranial doppler ultrasound parameters. J Neurosci Methods 2025; 416:110383. [PMID: 39892750 DOI: 10.1016/j.jneumeth.2025.110383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 01/08/2025] [Accepted: 01/29/2025] [Indexed: 02/04/2025]
Abstract
BACKGROUND One of the leading causes of disability and death is acute ischemic stroke (AIS) brought on by middle cerebral artery (MCA) obstruction. For the best patient care, it is essential to accurately anticipate the functional prognosis in the early stages of stroke. The ability of conventional clinical evaluations and imaging methods to deliver precise and timely prognostic information is frequently limited. NEW METHOD In this work, a predictive value for predicting functional outcome in patients with acute ischemic stroke caused by MCA blockage was developed utilizing transcranial Doppler (TCD) ultrasonography characteristics. Within 24 h after intravenous thrombolysis (IVT), TCD measures such as pulsatility index (PI), mean flow velocity (Vm), end-diastolic velocity (EDV), and peak systolic velocity (PSV) were assessed. Independent determinants of functional outcome, as determined by the modified Rankin Scale (mRS), were found using logistic regression analysis. These important factors were used to create a prediction model. COMPARISON WITH EXISTING METHODS Favorable functional outcomes were substantially correlated with a number of TCD characteristics, such as the ratio of pulsatility index to mean flow velocity (rPI) and peak systolic velocity to end-diastolic velocity (rPSV). At three months after a stroke, a logistic regression model that included these measures together with additional clinical indicators showed excellent accuracy in predicting functional prognosis. CONCLUSION In individuals who have experienced an acute ischemic stroke as a result of MCA blockage, TCD ultrasonography parameters-in particular, rPSV and rPI-are useful prognostic indicators for forecasting functional prognosis. Early risk classification and individualized treatment plans can benefit from the creation of a quantitative model based on these criteria. Validating and improving this model in bigger and more varied patient groups should be the goal of future research.
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Affiliation(s)
- Liu Yang
- Department of Stroke Center, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
| | - Xinyi Cai
- Department of Stroke Center, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
| | - Yanhong Yan
- Department of Stroke Center, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
| | - Pinjing Hui
- Department of Stroke Center, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
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Zhang M, Wang X, Chen X, Xu J, Guo W, Ren C, Li S, Zhao W, Wu C, Ji X. Role of Circadian Rhythm Changes on Functional Dependence Despite Successful Repercussion in Patients with Endovascular Treatment. Curr Neurovasc Res 2025; 21:427-433. [PMID: 39279112 DOI: 10.2174/0115672026346635240816095721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Revised: 08/25/2024] [Accepted: 08/27/2024] [Indexed: 09/18/2024]
Abstract
BACKGROUND Increasing evidence of circadian biology may influence the physiopathologic mechanism, progression, and recovery of stroke. However, few data have shown about circadian rhythm on futile recanalization (FR) in patients treated with endovascular treatment (EVT). METHODS From 2017 to 2021, an observational cohort of acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) underwent EVT was conducted. FR was defined as the failure to achieve functional independence in patients at 90 days after EVT, although the occluded vessels reached a recanalization. The effect of circadian rhythm on FR was investigated using the logistic regression model. RESULTS Of 783 patients, there were 149 patients who had stroke onset between 23:00-6:59, 318 patients between 7:00-14:59, and 316 patients between 15:00-22:59. Patients suffered from stroke during 15:00-22:59 had shorter OTP (p =0.001) time, shorter OTR (p<0.001) time, higher rate of intravenous thrombolysis (p =0.001) than groups of other time intervals. The rate of FR post-EVT in patients who had a stroke between 15:00-22:59 was significantly higher than in those with stroke onset between 23:00-6:59 (p =0.017). After adjusting for confounding factors, the time of stroke occurring during 15:00-22:59 (adjusted OR [aOR], 1.652; 95%CI, 1.024-2.666, p =0.04) was an independent predictor of FR. CONCLUSION Circadian rhythm can directly or indirectly affect the occurrence, development, and prognosis of AIS. More studies may be needed in the future to validate the results of our study and to explore the potential mechanisms behind the effects of circadian rhythms on FR.
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Affiliation(s)
- Mengke Zhang
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Xian Wang
- Department of Health Medical Center, Sichuan Provincial People's Hospital, Sichuan, China
| | - Xi Chen
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Jiali Xu
- Department of Rehabilitation Medicine, Beijing ShiJiTan Hospital, Capital Medical University, Beijing, China
| | - Wenting Guo
- Department of Neurology, Zhejiang Provincial People's Hospital, Zhejiang, China
| | - Changhong Ren
- Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Sijie Li
- Emergency Department, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Wenbo Zhao
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Chuanjie Wu
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Xunming Ji
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
- Laboratory of Brain Disorders, Laboratory for Clinical Medicine, Beijing Institute of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-based Precision Medicine, Capital Medical University, Beijing, China
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Nie X, Yang J, Li X, Zhan T, Liu D, Yan H, Wei Y, Liu X, Chen J, Gong G, Wu Z, Yang Z, Wen M, Gu W, Pan Y, Jiang Y, Meng X, Liu T, Cheng J, Li Z, Miao Z, Liu L. Prediction of futile recanalisation after endovascular treatment in acute ischaemic stroke: development and validation of a hybrid machine learning model. Stroke Vasc Neurol 2024; 9:631-639. [PMID: 38336369 PMCID: PMC11791634 DOI: 10.1136/svn-2023-002500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 01/23/2024] [Indexed: 02/12/2024] Open
Abstract
BACKGROUND Identification of futile recanalisation following endovascular therapy (EVT) in patients with acute ischaemic stroke is both crucial and challenging. Here, we present a novel risk stratification system based on hybrid machine learning method for predicting futile recanalisation. METHODS Hybrid machine learning models were developed to address six clinical scenarios within the EVT and perioperative management workflow. These models were trained on a prospective database using hybrid feature selection technique to predict futile recanalisation following EVT. The optimal model was validated and compared with existing models and scoring systems in a multicentre prospective cohort to develop a hybrid machine learning-based risk stratification system for futile recanalisation prediction. RESULTS Using a hybrid feature selection approach, we trained and tested multiple classifiers on two independent patient cohorts (n=1122) to develop a hybrid machine learning-based prediction model. The model demonstrated superior discriminative ability compared with other models and scoring systems (area under the curve=0.80, 95% CI 0.73 to 0.87) and was transformed into a web application (RESCUE-FR Index) that provides a risk stratification system for individual prediction (accessible online at fr-index.biomind.cn/RESCUE-FR/). CONCLUSIONS The proposed hybrid machine learning approach could be used as an individualised risk prediction model to facilitate adherence to clinical practice guidelines and shared decision-making for optimal candidate selection and prognosis assessment in patients undergoing EVT.
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Affiliation(s)
- Ximing Nie
- Department of Neurology, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Beijing, China
| | - Jinxu Yang
- School of Computer and Communication Engineering, University of Science and Technology, Beijing, China
| | - Xinxin Li
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Beijing, China
| | - Tianming Zhan
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Beijing, China
| | - Dongdong Liu
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Beijing, China
| | - Hongyi Yan
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Beijing, China
| | - Yufei Wei
- Department of Neurology, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Beijing, China
| | - Xiran Liu
- Department of Neurology, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Beijing, China
| | - Jiaping Chen
- Department of Neurology, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Beijing, China
| | - Guoyang Gong
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Beijing, China
| | - Zhenzhou Wu
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Beijing, China
| | - Zhonghua Yang
- Department of Neurology, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Beijing, China
| | - Miao Wen
- Department of Neurology, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Beijing, China
| | - Weibin Gu
- Department of Radiology, Beijing Tiantan Hospital, Beijing, China
| | - Yuesong Pan
- Department of Neurology, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Beijing, China
| | - Yong Jiang
- Department of Neurology, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Beijing, China
| | - Xia Meng
- Department of Neurology, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Beijing, China
| | - Tao Liu
- Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, School of Biological Science and Medical Engineering International Research Institute for Multidisciplinary Science, Beihang University, Beijing, China
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Computer Science and Engineering, Beihang University, Beijing, China
| | - Jian Cheng
- Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, School of Biological Science and Medical Engineering International Research Institute for Multidisciplinary Science, Beihang University, Beijing, China
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Computer Science and Engineering, Beihang University, Beijing, China
| | - Zixiao Li
- Department of Neurology, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Beijing, China
| | - Zhongrong Miao
- Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Liping Liu
- Department of Neurology, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Beijing, China
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Zhao ZA, Hu HZ, Li W, Qiu J, Zhao YG, Nguyen TN, Chen HS. Intra-arterial cocktail therapy for patients with anterior circulation large vessel occlusion who achieved endovascular reperfusion. Front Neurol 2024; 15:1450156. [PMID: 39711792 PMCID: PMC11660178 DOI: 10.3389/fneur.2024.1450156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 11/20/2024] [Indexed: 12/24/2024] Open
Abstract
Background Clinically ineffective reperfusion (CIR) refers to the discrepancy between successful reperfusion and a favorable functional outcome in patients with large vessel occlusion (LVO) stroke after endovascular treatment (EVT). The Improving Neuroprotective Strategy for Ischemic Stroke with Sufficient Recanalization after Thrombectomy by Intra-arterial Cocktail Therapy (INSIST-CT) trial aimed to explore the safety, feasibility, and efficacy of intra-arterial cocktail therapy using argatroban, dexamethasone, and edaravone in patients who achieved sufficient reperfusion after EVT. Methods In this prospective, single-arm, pilot study, eligible patients with anterior circulation LVO who achieved sufficient reperfusion after EVT were enrolled in the INSIST-CT trial. Consecutive patients who met the inclusion/exclusion criteria were included in the control group retrospectively. In the INSIST-CT group, argatroban, dexamethasone, and edaravone were continuously administered for 30 min into the culprit artery after sufficient recanalization. The primary endpoint was the proportion of favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage (sICH). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses were performed to account for multiple confounders. Results A total of 30 patients were included in the INSIST-CT group, and 261 patients were included in the control group. The proportion of the patients with the primary endpoint was 60% in the INSIST-CT group and 55.9% in the control group (unadjusted odds ratio [OR] 1.18, 95% CI 0.55-2.61, p = 0.67; adjusted OR 1.42, 95% CI 0.62-3.26, p = 0.41). No significant difference in sICH at 48 h after treatment was observed between the two groups (unadjusted OR 0.96, 95% CI 0.15-3.56, p = 0.96; adjusted OR 0.82 95% CI 0.17-3.97, p = 0.809). Similar results were observed after the PSM and IPTW analyses. Conclusion In anterior circulation, LVO patients who achieved sufficient reperfusion after EVT, bridging intra-arterial cocktail therapy with argatroban, dexamethasone, and edaravone may be safe and feasible. However, it did not improve the 90-day functional outcomes. A numerically higher probability of a favorable outcome in the INSIST-CT group suggests the potential promise of this cocktail therapy in reducing clinically ineffective reperfusion. Clinical trial registration ClinicalTrials.gov, NCT04202549.
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Affiliation(s)
- Zi-Ai Zhao
- Department of Neurology, General Hospital of Northern Theater Command, Shenyang, China
| | - Hai-Zhou Hu
- Department of Neurology, General Hospital of Northern Theater Command, Shenyang, China
| | - Wei Li
- Department of Neurology, General Hospital of Northern Theater Command, Shenyang, China
| | - Jing Qiu
- Department of Neurology, General Hospital of Northern Theater Command, Shenyang, China
| | - Yong-Gang Zhao
- Department of Neurology, General Hospital of Northern Theater Command, Shenyang, China
| | - Thanh N. Nguyen
- Department of Neurology and Radiology, Boston Medical Center, Boston, MA, United States
| | - Hui-Sheng Chen
- Department of Neurology, General Hospital of Northern Theater Command, Shenyang, China
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Zhang W, Xing W, Li J, Li Y, He X, Liu Y, He J, Ling L. Failure of early neurological improvement can predict futile recanalization after successful interventional recanalization of anterior circulation tandem lesions. Clin Neurol Neurosurg 2024; 246:108596. [PMID: 39426217 DOI: 10.1016/j.clineuro.2024.108596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 10/02/2024] [Accepted: 10/15/2024] [Indexed: 10/21/2024]
Abstract
PURPOSE To explore whether the failure of early neurological improvement can predict futile recanalization after successful interventional recanalization of anterior circulation tandem lesions. PATIENTS AND METHODS A retrospective analysis was conducted on the clinical data of patients who received successful interventional recanalization treatment of anterior circulation tandem lesions from January 2019 to November 2023. The failure of early neurological improvement is defined as a decrease of less than 4 points in NIHSS score compared to preoperative score at 24 h after surgery. Statistical analysis was conducted using SPSS 26.0 software, and a forest plot and Receiver Operating Characteristic curve related to futile recanalization were drawn. RESULTS A total of 120 patients received successful interventional recanalization of anterior circulation tandems lesion were included, including 68 cases of futile recanalization (56.67 %) and 52 cases of effective recanalization (43.33 %). The rate of failure of early neurological improvement in the futile recanalization group was higher than that in the effective recanalization group (94.12 % vs 34.62 %, P < 0.001). After adjusting for confounding factors, the rate of failure of early neurological improvement in the futile recanalization group was higher than that in the effective recanalization group (adjusted OR: 39.925; 95 % CI: 4.110-387.864; P = 0.001). The area under the Receiver Operating Characteristic curve using failure of neurological improvement for predicting futile recanalization was 0.800. CONCLUSION Failure of early neurological improvement is an effective indicator for predicting futile recanalization after successful interventional recanalization in anterior circulation tandem lesions.
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Affiliation(s)
- Wensheng Zhang
- Department of Neurology, Shenzhen Hospital, Southern Medical University, Shenzhen 510181, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China; Department of Neurology, Heyuan People's Hospital, Guangdong Provincial People's Hospital Heyuan Hospital, Guangdong Province 517000, China; Heyuan Key Laboratory of Molecular Diagnosis & Disease Prevention and Treatment, Doctors Station of Guangdong Province, Heyuan People's Hospital, Heyuan, Guangdong 517000, China
| | - Weifang Xing
- Department of Neurology, Heyuan People's Hospital, Guangdong Provincial People's Hospital Heyuan Hospital, Guangdong Province 517000, China
| | - Jie Li
- Department of Neurology, Shenzhen Hospital, Southern Medical University, Shenzhen 510181, China
| | - Yudi Li
- Department of Neurology, Shenzhen Hospital, Southern Medical University, Shenzhen 510181, China
| | - Xiongjun He
- Department of Neurology, Shenzhen Hospital, Southern Medical University, Shenzhen 510181, China
| | - Yajie Liu
- Department of Neurology, Shenzhen Hospital, Southern Medical University, Shenzhen 510181, China
| | - Jinzhao He
- Department of Neurology, Heyuan People's Hospital, Guangdong Provincial People's Hospital Heyuan Hospital, Guangdong Province 517000, China; Heyuan Key Laboratory of Molecular Diagnosis & Disease Prevention and Treatment, Doctors Station of Guangdong Province, Heyuan People's Hospital, Heyuan, Guangdong 517000, China.
| | - Li Ling
- Department of Neurology, Shenzhen Hospital, Southern Medical University, Shenzhen 510181, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China.
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Xu B, Wu Z, Lin Y, Liu Y, Liu L, Zhang Y. Association of plasma VEGF with futile recanalization and intracranial angiogenesis in ischemic stroke post-endovascular treatment. J Clin Neurosci 2024; 129:110831. [PMID: 39265359 DOI: 10.1016/j.jocn.2024.110831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 08/15/2024] [Accepted: 09/05/2024] [Indexed: 09/14/2024]
Abstract
OBJECTIVE This study aimed to compare baseline and subsequent vascular endothelial growth factor (VEGF) levels in predicting futile recanalization (FR) in acute ischemic stroke (AIS) patients undergoing endovascular treatment (EVT), and to explore the association between angiogenesis and VEGF. METHODS 84 participants were recruited, including 46 AIS in the EVT group, 20 AIS in the conventional treatment group, and 18 healthy controls. Plasma VEGF levels were measured at different time points. FR was defined as a modified Rankin scale score of 3-6 at 3 months. Multivariable analysis evaluated whether VEGF levels at different time points independently predicted FR, and receiver operating characteristic (ROC) curves assessed their predictive value. Using intracranial lesion side vascular imaging, the Maas scoring system assessed angiogenesis post-onset, with scores of 4 to 5 indicating angiogenesis. RESULTS In the conventional treatment group, VEGF levels significantly decreased by day 7, while in the EVT group, reduction was observed as early as day 3. After adjusting for potential confounders, only VEGF levels on day 3 emerged as an independent predictor of FR. The combined model incorporating VEGF levels on day 3 with other factors effectively predicted FR (area under the curve = 0.916; sensitivity = 84.21 %; specificity = 100 %, P<0.0001). Plasma VEGF levels were notably higher in patients with angiogenesis in specific brain regions compared to those without angiogenesis at days 1, 3, 7, and 14 (P<0.05). CONCLUSION VEGF levels on the 3rd day post-EVT demonstrate superior predictive value for FR. Elevated VEGF levels correlate with angiogenesis, suggesting its potential as a therapeutic target.
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Affiliation(s)
- Bingdong Xu
- Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Zhengdong Wu
- Department of Neurology, The Fifth Affiliated Hospital of Jinan University, Heyuan, China
| | - Yingze Lin
- Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Yujun Liu
- Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Leiyuan Liu
- Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Yusheng Zhang
- Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
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Lu ZJ, Lai JX, Huang JR, Xie SH, Lai ZH. Predictive value of intracranial high-density areas in neurological function. World J Psychiatry 2024; 14:1080-1086. [PMID: 39050205 PMCID: PMC11262925 DOI: 10.5498/wjp.v14.i7.1080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 05/21/2024] [Accepted: 06/05/2024] [Indexed: 07/12/2024] Open
Abstract
BACKGROUND Intracranial high-density areas (HDAs) have attracted considerable attention for predicting clinical outcomes; however, whether HDAs predict worse neurological function and mental health remains controversial and unclear, which requires further investigation. AIM To investigate the predictive value of intracranial HDAs for neurological function and mental health after endovascular treatment. METHODS In this prospective study, 96 patients with acute ischemic stroke (AIS) who accepted endovascular mechanical thrombectomy (EMT) were included. The enrolled patients underwent cranial computed tomography (CT) examination within 24 hours after EMT. Clinical data in terms of National Institutes of Health Stroke Scale (NIHSS), the 3-month modified Rankin Scale (mRS), self-rating depression scale (SDS), and self-rating anxiety scale (SAS) scores were collected and compared between patients with HDAs and non-HDAs and between patients with good and poor clinical prognosis. RESULTS Compared to patients without HDAs, patients with HDAs presented severe neurological deficits (admission NIHSS score: 18 ± 3 vs 19 ± 4), were more likely to have post-stroke disabilities (mRS < 3: 35% vs 62%), and suffered more severe depression (SDS score: 58 ± 16 vs 64 ± 13) and anxiety disorder (SAS score: 52 ± 8 vs 59 ± 10). Compared to patients with a good prognosis, patients with a poor prognosis presented severe neurological deficits (admission NIHSS score: 17 ± 4 vs 20 ± 3), were more likely to have HDAs on CT images (64% vs 33%), and suffered more severe depression (SDS score: 55 ± 19 vs 65 ± 11) and anxiety (SAS score: 50 ± 8 vs 58 ± 12). Multivariate analysis revealed that HDAs were independent negative prognostic factors. CONCLUSION In conclusion, HDAs on CT images predicted poor prognosis and severe depressive and anxiety symptoms in patients with AIS who underwent EMT.
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Affiliation(s)
- Zhi-Juan Lu
- Department of Neurology, Ganzhou People’s Hospital, Ganzhou 341000, Jiangxi Province, China
| | - Jin-Xing Lai
- Department of Neurology, Ganzhou People’s Hospital, Ganzhou 341000, Jiangxi Province, China
| | - Jing-Ru Huang
- Department of Neurology, Ganzhou People’s Hospital, Ganzhou 341000, Jiangxi Province, China
| | - Shu-Hua Xie
- Department of Neurology, Ganzhou People’s Hospital, Ganzhou 341000, Jiangxi Province, China
| | - Zhao-Hui Lai
- Department of Neurology, Ganzhou People’s Hospital, Ganzhou 341000, Jiangxi Province, China
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Lattanzi S, Cuccurullo C, Orlandi N, Borzì G, Bigliardi G, Maffei S, Giovannini G, Meletti S. Futile recanalization is associated with increased risk of post-stroke epilepsy. J Neurol Sci 2024; 462:123067. [PMID: 38823064 DOI: 10.1016/j.jns.2024.123067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 05/13/2024] [Accepted: 05/27/2024] [Indexed: 06/03/2024]
Abstract
BACKGROUND Endovascular treatment (EVT) is the standard of care of ischaemic stroke due to occlusion of large vessels. Although EVT can significantly improve short- and long-term outcomes, functional dependence can persist despite the achievement of a successful recanalization. The evidence about the predictors of post-stroke epilepsy (PSE) in patients with stroke treated by EVT is limited. We aimed to evaluate the relationship between futile recanalization and the risk of PSE. METHODS We retrospectively identified consecutive adults with first-ever ischaemic stroke of anterior circulation who were treated with EVT. Futile recanalization was defined as poor 3-month functional status (modified Rankin scale score ≥ 3) despite complete or near-complete recanalization. Study outcome was the occurrence of PSE during the follow-up. RESULTS The study included 327 patients with anterior circulation ischaemic stroke treated with EVT. Futile recanalization occurred in 116 (35.5%) patients and 26 (8.0%) developed PSE during a median follow-up of 35 [interquartile range, 22.7-55.2] months. Futile recanalization was more common among patients who developed PSE compared to those who did not (76.9% versus 31.9%; p < 0.001). Futile recanalization [hazard ratio (HR) = 5.63, 95% confidence interval (CI): 1.88-16.84; p = 0.002], large artery atherosclerosis (HR = 3.48, 95% CI: 1.44-8.40; p = 0.006), cortical involvement (HR = 15.51, 95% CI: 2.06-116.98; p = 0.008), and acute symptomatic status epilepticus (HR = 14.40, 95% CI: 2.80-73.98; p = 0.001) increased the risk of PSE. CONCLUSIONS Futile recanalization after EVT is associated with increased risk of PSE in patients with ischaemic stroke due to occlusion of large vessel of the anterior circulation.
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Affiliation(s)
- Simona Lattanzi
- Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy; IRCCS INRCA, Ancona, Italy.
| | - Claudia Cuccurullo
- Neurology and Stroke Unit, Ospedale del Mare Hospital, ASL Napoli 1, Naples, Italy
| | - Niccolò Orlandi
- Neurology Unit, OCB Hospital, AOU Modena, Modena, Italy; Department of Biomedical, Metabolic and Neural Science, Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Modena, Italy
| | - Giuseppe Borzì
- Neurology Unit, OCB Hospital, AOU Modena, Modena, Italy; Stroke Unit, OCB Hospital, AOU, Modena, Italy
| | - Guido Bigliardi
- Neurology Unit, OCB Hospital, AOU Modena, Modena, Italy; Stroke Unit, OCB Hospital, AOU, Modena, Italy
| | - Stefania Maffei
- Neurology Unit, OCB Hospital, AOU Modena, Modena, Italy; Stroke Unit, OCB Hospital, AOU, Modena, Italy
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Sun F, Zhou J, Chen X, Yang T, Wang G, Ge J, Zhang Z, Mei Z. No-reflow after recanalization in ischemic stroke: From pathomechanisms to therapeutic strategies. J Cereb Blood Flow Metab 2024; 44:857-880. [PMID: 38420850 PMCID: PMC11318407 DOI: 10.1177/0271678x241237159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 01/07/2024] [Accepted: 02/18/2024] [Indexed: 03/02/2024]
Abstract
Endovascular reperfusion therapy is the primary strategy for acute ischemic stroke. No-reflow is a common phenomenon, which is defined as the failure of microcirculatory reperfusion despite clot removal by thrombolysis or mechanical embolization. It has been reported that up to 25% of ischemic strokes suffer from no-reflow, which strongly contributes to an increased risk of poor clinical outcomes. No-reflow is associated with functional and structural alterations of cerebrovascular microcirculation, and the injury to the microcirculation seriously hinders the neural functional recovery following macrovascular reperfusion. Accumulated evidence indicates that pathology of no-reflow is linked to adhesion, aggregation, and rolling of blood components along the endothelium, capillary stagnation with neutrophils, astrocytes end-feet, and endothelial cell edema, pericyte contraction, and vasoconstriction. Prevention or treatment strategies aim to alleviate or reverse these pathological changes, including targeted therapies such as cilostazol, adhesion molecule blocking antibodies, peroxisome proliferator-activated receptors (PPARs) activator, adenosine, pericyte regulators, as well as adjunctive therapies, such as extracorporeal counterpulsation, ischemic preconditioning, and alternative or complementary therapies. Herein, we provide an overview of pathomechanisms, predictive factors, diagnosis, and intervention strategies for no-reflow, and attempt to convey a new perspective on the clinical management of no-reflow post-ischemic stroke.
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Affiliation(s)
- Feiyue Sun
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese Medicine and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Jing Zhou
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese Medicine and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Xiangyu Chen
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese Medicine and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Tong Yang
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese Medicine and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Guozuo Wang
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese Medicine and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Jinwen Ge
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese Medicine and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
- Hunan Academy of Chinese Medicine, Changsha, Hunan, China
| | - Zhanwei Zhang
- The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Zhigang Mei
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese Medicine and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
- Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, College of Medicine and Health Sciences, China Three Gorges University, Yichang, Hubei, China
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11
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Lan XY, Li D, Cui Y, Nguyen TN, Li S, Chen HS. Proteomic analysis of jugular venous blood in acute large vessel occlusion stroke with futile recanalization. J Cereb Blood Flow Metab 2024; 44:702-711. [PMID: 38000017 PMCID: PMC11197136 DOI: 10.1177/0271678x231216767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Revised: 09/13/2023] [Accepted: 10/17/2023] [Indexed: 11/26/2023]
Abstract
Futile recanalization (FR) after endovascular treatment (EVT) remains a significant challenge for acute ischemic stroke (AIS) with large vessel occlusion (LVO). The pathogenesis of FR has not been well elucidated. We prospectively enrolled anterior circulation LVO-AIS patients who achieved successful recanalization after EVT. The jugular venous blood ipsilateral to stroke was collected before and immediately after recanalization. Plasma proteomic analysis based on liquid chromatography-mass spectrometry was performed using data-independent acquisition method. Differentially expressed proteins (DEPs) among patients with or without FR in the whole or propensity score matching (PSM) cohorts were screened according to the absolute value of fold change ≥1.5 and P value <0.05. We identified 104 and 34 DEPs between patients with or without FR in the whole cohort and PSM cohort, respectively. Bioinformatic analysis indicated that the identified proteins were primarily related to specific biological processes including immune response, complement activation, oxidative stress, lipid metabolism, protein ubiquitylation as well as autophagy, suggesting that these may be mechanisms in FR pathogenesis. Collectively, we discovered proteins that may be potential research targets for FR. The combination of proteomic and bioinformatic analysis could provide a better understanding of the pathogenesis of FR in a comprehensive manner.
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Affiliation(s)
- Xiao-Yan Lan
- Graduate School, Dalian Medical University, Dalian, China
- Department of Neurology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Neurointervention, Dalian Municipal Central Hospital, Dalian, China
| | - Di Li
- Department of Neurointervention, Dalian Municipal Central Hospital, Dalian, China
| | - Yu Cui
- Department of Neurology, General Hospital of Northern Theater Command, Shenyang, China
| | - Thanh N Nguyen
- Department of Neurology, Radiology, Boston Medical Center, Boston, Massachusetts, USA
| | - Shen Li
- Department of Neurology and Psychiatry, Beijing Shijitan Hospital, Beijing, China
- Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China
| | - Hui-Sheng Chen
- Graduate School, Dalian Medical University, Dalian, China
- Department of Neurology, General Hospital of Northern Theater Command, Shenyang, China
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12
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Yan Y, Zhang K, Zhong W, Yan S, Zhang B, Cheng J, Lou M. Influencing factors of futile recanalization after endovascular intervention in patients with acute basilar artery occlusion. Zhejiang Da Xue Xue Bao Yi Xue Ban 2024; 53:141-150. [PMID: 38501295 PMCID: PMC11057989 DOI: 10.3724/zdxbyxb-2023-0425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Accepted: 12/21/2023] [Indexed: 03/20/2024]
Abstract
OBJECTIVES To explore the influence factors for futile recanalization following endovascular treatment (EVT) in patients with acute basilar artery occlusion (BAO). METHODS Clinical data of patients with acute BAO, who underwent endovascular treatment within 24 h of onset from January 2017 to November 2022, were retrospectively analyzed. The futile recanalization was defined as modified thrombolysis in cerebral infarction (mTICI) grade ≥2b or 3 after successful reperfusion, but the modified Rankin Scale score >2 at 3 months after EVT. Binary logistic regression model was used to analyze the influencing factors of futile recanalization. RESULTS A total of 471 patients with a median age of 68 (57, 74) years were included and 68.9% were males, among whom 298 (63.27%) experienced futile recanalization. Multivariate analysis revealed that concomitant atrial fibrillation (OR=0.456, 95%CI: 0.282-0.737, P<0.01), bridging thrombolysis (OR=0.640, 95%CI: 0.416-0.985, P<0.05), achieving mTICI grade 3 (OR=0.554, 95%CI: 0.334-0.918, P<0.05), arterial occlusive lesion (AOL) grade 3 (OR=0.521, 95%CI: 0.326-0.834, P<0.01), and early postoperative statin therapy (OR=0.509, 95%CI: 0.273-0.948, P<0.05) were protective factors for futile recanalization after EVT in acute BAO patients. High baseline National Institutes of Health Stroke Scale (NIHSS) score (OR=1.068, 95%CI: 1.049-1.087, P<0.01), coexisting hypertension (OR=1.571, 95%CI: 1.017-2.427, P<0.05), multiple retrieval attempts (OR=1.237, 95%CI: 1.029-1.488, P<0.05) and postoperative hemorrhagic transformation (OR=8.497, 95%CI: 2.879-25.076, P<0.01) were risk factors. For trial of ORG 10172 in acute stroke treatment (TOAST) classification, cardiogenic embolism (OR=0.321, 95%CI: 0.193-0.534, P<0.01) and other types (OR=0.499, 95%CI: 0.260-0.961, P<0.05) were related to lower incidence of futile recanalization. CONCLUSIONS The incidence of futile recanalization after EVT in patients with acute BAO is high. Bridging venous thrombolysis before operation and an early postoperative statin therapy may reduce the incidence of futile recanalization.
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Affiliation(s)
- Yi Yan
- Department of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
- Department of Neurology, Zhenhai People's Hospital, Ningbo 315202, Zhejiang Province, China.
| | - Kemeng Zhang
- Department of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Wansi Zhong
- Department of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Shenqiang Yan
- Department of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Bing Zhang
- Department of Neurology, Huzhou Central Hospital, Huzhou 313099, Zhejiang Province, China
| | - Jianhua Cheng
- Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, Zhejiang Province, China
| | - Min Lou
- Department of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
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13
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Dai X, Yan C, Yu F, Li Q, Lu Y, Shan Y, Zhang M, Guo D, Bai X, Jiao L, Ma Q, Lu J. Evolution pattern estimated by computed tomography perfusion post-thrombectomy predicts outcome in acute ischemic stroke. J Stroke Cerebrovasc Dis 2024; 33:107555. [PMID: 38281386 DOI: 10.1016/j.jstrokecerebrovasdis.2024.107555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 12/23/2023] [Accepted: 01/02/2024] [Indexed: 01/30/2024] Open
Abstract
OBJECTIVES Computed tomography perfusion (CTP) and computed tomography angiography (CTA) have been recommended to select acute ischemic stroke (AIS) patients for endovascular thrombectomy (EVT) but are not widely used for post-treatment evaluation. We aimed to observe abnormalities in CTP and CTA before and after EVT and evaluate post-EVT CTP and CTA as potential tools for improving clinical outcome prediction. METHODS Patients with AIS who underwent EVT and received CTP and CTA before and after EVT were retrospectively evaluated. The ischemic core was defined as the volume of relative cerebral blood flow <30% and hypoperfusion as the volume of Tmax >6 s. A reduction in hypoperfusion volume >90% between baseline and post-EVT CTP was defined as tissue optimal reperfusion (TOR). The 90-day modified Rankin scale was used to evaluate the clinical outcome. RESULTS Eighty-three patients were included. Patients with an absent ischemic core or with TOR after EVT had a higher rate of modified Thrombolysis in Cerebral Ischemia score 2c-3 and recanalization of post-treatment vessel condition based on follow-up CTA. Multivariable logistic regression revealed that the baseline ischemic core volume (OR:0.934, p=0.009), TOR (OR:8.322, p=0.029) and immediate NIHSS score after EVT (OR:0.761, p=0.012) were factors significantly associated with good clinical outcome. Combining baseline ischemic core volume and TOR with immediate NIHSS score after EVT showed greatest performance for good outcome prediction after EVT(AUC=0.921). CONCLUSIONS The addition of pretreatment and post-treatment CTP information to purely clinical NIHSS scores might help to improve the efficacy for good outcome prediction after EVT.
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Affiliation(s)
- Xinyu Dai
- Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing, China
| | - Chuming Yan
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Fan Yu
- Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing, China
| | - Qiuxuan Li
- Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing, China
| | - Yao Lu
- Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing, China
| | - Yi Shan
- Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing, China
| | - Miao Zhang
- Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing, China
| | - Daode Guo
- Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing, China
| | - Xuesong Bai
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Liqun Jiao
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Qingfeng Ma
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
| | - Jie Lu
- Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing, China.
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14
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Zhang M, Che R, Xu J, Guo W, Chen X, Zhao W, Ren C, Jia M, Ji X. Long term for patients with futile endovascular reperfusion after stroke. CNS Neurosci Ther 2024; 30:e14588. [PMID: 38475869 PMCID: PMC10933383 DOI: 10.1111/cns.14588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 12/06/2023] [Accepted: 12/20/2023] [Indexed: 03/14/2024] Open
Abstract
AIMS With the progress of thrombectomy technology, the vascular recanalization rate of patients with stroke has been continuously improved, but the proportion of futile recanalization (FR) is still quite a few. The long-term prognosis and survival of patients with FR and its influencing factors remain unclear. METHODS Consecutive patients who received endovascular treatment (EVT) for ischemic stroke were enrolled between 2013 and 2021 from a single-center prospectively registry study. We evaluated the long-term outcome of these patients by Kaplan-Meier survival analysis, and the multivariable logistic regression curve was performed to analyze influencing factors. RESULTS Among 458 patients with FR, 56.4% of patients survived at 1 year, and 50.4% at 2 years. In the multivariate regression analysis, age, premorbid modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), posterior circulation infarct, general anesthesia, symptomatic intracerebral hemorrhage (sICH), and decompressive craniectomy were found to be related to unfavorable outcomes in long-term. Age, premorbid mRS, NIHSS, general anesthesia, and sICH were predictors of long-term mortality. CONCLUSIONS Futile recanalization accounts for a large proportion of stroke patients after thrombectomy. This study on the long-term prognosis of such patients is beneficial to the formulation of treatment plans and the prediction of therapeutic effects.
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Affiliation(s)
- Mengke Zhang
- Department of Neurology, Xuanwu HospitalCapital Medical UniversityBeijingChina
| | - Ruiwen Che
- Department of Neurology, Beijing ShiJiTan HospitalCapital Medical UniversityBeijingChina
| | - Jiali Xu
- Department of Rehabilitation Medicine, Beijing ShiJiTan HospitalCapital Medical UniversityBeijingChina
| | - Wenting Guo
- Department of NeurologyZhejiang Provincial People's HospitalZhejiangChina
| | - Xi Chen
- Department of Neurology, Xuanwu HospitalCapital Medical UniversityBeijingChina
| | - Wenbo Zhao
- Department of Neurology, Xuanwu HospitalCapital Medical UniversityBeijingChina
| | - Changhong Ren
- Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Xuanwu HospitalCapital Medical UniversityBeijingChina
| | - Milan Jia
- Department of Neurology, Xuanwu HospitalCapital Medical UniversityBeijingChina
| | - Xunming Ji
- Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Xuanwu HospitalCapital Medical UniversityBeijingChina
- Department of Neurosurgery, Xuanwu HospitalCapital Medical UniversityBeijingChina
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15
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Deng G, Chu YH, Xiao J, Shang K, Zhou LQ, Qin C, Tian DS. Risk Factors, Pathophysiologic Mechanisms, and Potential Treatment Strategies of Futile Recanalization after Endovascular Therapy in Acute Ischemic Stroke. Aging Dis 2023; 14:2096-2112. [PMID: 37199580 PMCID: PMC10676786 DOI: 10.14336/ad.2023.0321-1] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 03/22/2023] [Indexed: 05/19/2023] Open
Abstract
Endovascular therapy is the first-line treatment for acute ischemic stroke. However, studies have shown that, even with the timely opening of occluded blood vessels, nearly half of all patients treated with endovascular therapy for acute ischemic stroke still have poor functional recovery, a phenomenon called "futile recanalization.". The pathophysiology of futile recanalization is complex and may include tissue no-reflow (microcirculation reperfusion failure despite recanalization of the occluded large artery), early arterial reocclusion (reocclusion of the recanalized artery 24-48 hours post endovascular therapy), poor collateral circulation, hemorrhagic transformation (cerebral bleeding following primary ischemic stroke), impaired cerebrovascular autoregulation, and large hypoperfusion volume. Therapeutic strategies targeting these mechanisms have been attempted in preclinical research; however, translation to the bedside remains to be explored. This review summarizes the risk factors, pathophysiological mechanisms, and targeted therapy strategies of futile recanalization, focusing on the mechanisms and targeted therapy strategies of no-reflow to deepen the understanding of this phenomenon and provide new translational research ideas and potential intervention targets for improving the efficacy of endovascular therapy for acute ischemic stroke.
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Affiliation(s)
- Gang Deng
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Yun-hui Chu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Jun Xiao
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Ke Shang
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Luo-Qi Zhou
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Chuan Qin
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Dai-Shi Tian
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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Baig AA, Bouslama M, Turner RC, Aguirre AO, Kuo CC, Lim J, Malueg MD, Donnelly BM, Lai PMR, Raygor KP, Levy EI, Siddiqui AH. Mechanical thrombectomy in low Alberta stroke program early CT score (ASPECTS) in hyperacute stroke-a systematic review and meta-analysis. Br J Radiol 2023; 96:20230084. [PMID: 37873928 PMCID: PMC10646658 DOI: 10.1259/bjr.20230084] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 08/15/2023] [Accepted: 09/28/2023] [Indexed: 10/25/2023] Open
Abstract
OBJECTIVE Major randomized controlled trials of mechanical thrombectomy (MT) for acute ischemic stroke (AIS) failed to include a substantial number of patients presenting with low baseline Alberta Stroke Program Early CT Score (ASPECTS:0-5). Patients experiencing hyperacute strokes (last known well ≤ 6 h) can potentially benefit most from MT. We conducted a systematic review and meta-analysis to report presentation severity and radiographic and clinical outcomes for hyperacute stroke patients presenting with low-ASPECTS. METHODS Our comprehensive literature search of PubMed, Embase, and Cochrane databases up to August 31, 2022 included articles reporting patients presenting hyperacutely who underwent MT for anterior circulation large vessel occlusion AIS with an ASPECTS ≤ 5 on baseline imaging. Pooled averages were calculated for age and presenting National Institutes of Health Stroke Scale (NIHSS). Fixed- and random-effects meta-analyses for weighted estimation of overall rates were performed. Forest plots were generated for proportions and estimated overall outcome rates. RESULTS 18 studies (1958 patients) were included (mean age = 64.1 years; presenting NIHSS = 18.4). Final modified thrombolysis in cerebral infarction 2b-3 grade was achieved in 76.4%, with symptomatic intracranial hemorrhage in 12.1%. Good (modified Rankin Scale [mRS] 0-2) and ambulatory (mRS 0-3) 3-month outcomes were achieved by 27.4 and 46.7%, respectively; 90-day mortality was 26.4%. CONCLUSION MT in low-ASPECTS hyperacute stroke patients may result in ambulatory clinical outcomes with acceptable hemorrhage risk. Recanalization rates achieved were similar to those in patients presenting with ASPECTS ≥ 6; this did not fully translate to better clinical outcomes. ADVANCES IN KNOWLEDGE MT should be considered for hyperacute strokes with low presenting ASPECTS.
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Affiliation(s)
| | | | | | - Alexander O. Aguirre
- Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
| | - Cathleen C. Kuo
- Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
| | | | - Megan D. Malueg
- Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
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Li L, Jiang W, Yu B, Liang H, Mao S, Hu X, Feng Y, Xu J, Chu L. Quercetin improves cerebral ischemia/reperfusion injury by promoting microglia/macrophages M2 polarization via regulating PI3K/Akt/NF-κB signaling pathway. Biomed Pharmacother 2023; 168:115653. [PMID: 37812891 DOI: 10.1016/j.biopha.2023.115653] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 10/03/2023] [Accepted: 10/03/2023] [Indexed: 10/11/2023] Open
Abstract
The modulation of microglial polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype shows promise as a therapeutic strategy for ischemic stroke. Quercetin, a natural flavonoid abundant in various plants, possesses anti-inflammatory, anti-apoptotic, and antioxidant properties. Nevertheless, its effect and underlying mechanism on microglia/macrophages M1/M2 polarization in the treatment of cerebral ischemia/reperfusion injury (CI/RI) remain poorly explored. In the current study, we observed that quercetin ameliorated neurological deficits, reduced infarct volume, decreased the number of M1 microglia/macrophages (CD16/32+/Iba1+), and enhanced the number of M2 microglia/macrophages (CD206+/Iba1+) after establishing the CI/RI model in rats. Subsequent in vivo and in vitro experiments indicated that quercetin downregulated M1 markers (CD86, iNOS, TNF-α, IL-1β, and IL-6) and upregulated M2 markers (CD206, Arg-1, IL-10, and TGF-β). Network pharmacology analysis and molecular docking revealed that the PI3K/Akt/NF-κB signaling pathway emerged as the core pathway. Western blot confirmed that quercetin upregulated the phosphorylation of PI3K and Akt, while alleviating the phosphorylation of IκBα and NF-κB both in vivo and in vitro. However, the PI3K inhibitor LY294002 reversed the effects of quercetin on M2 polarization and the expression of key proteins in the PI3K/Akt/NF-κB pathway in primary microglia after oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro. Collectively, our findings demonstrate that quercetin facilitates microglia/macrophages M2 polarization by modulating the PI3K/Akt/NF-κB signaling pathway in the treatment of CI/RI. These findings provide novel insights into the therapeutic mechanisms of quercetin in ischemic stroke.
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Affiliation(s)
- Lin Li
- Department of Physiology, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Weifeng Jiang
- Department of Physiology, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Baojian Yu
- Department of Physiology, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Huiqi Liang
- Department of Physiology, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Shihui Mao
- Department of Physiology, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Xiaowei Hu
- Department of Physiology, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Yan Feng
- Department of Physiology, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Jiadong Xu
- Department of Physiology, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Lisheng Chu
- Department of Physiology, Zhejiang Chinese Medical University, Hangzhou 310053, China.
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18
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Nicolini E, Saia V, Lorenzano S, Pracucci G, Iacobucci M, De Michele M, Vallone S, Bergui M, Diomedi M, Nencini P, Tassi R, Saletti A, Puglielli E, Naldi A, Vinci SL, Giannini N, Malfatto L, Roberto M, Romano DG, Cappellari M, Zini A, Sallustio F, Casetta I, Fainardi E, Mangiafico S, Toni D. Mechanical thrombectomy in young patients with large vessel occlusion-related ischemic stroke: Data from the Italian Registry of Endovascular Treatment in Acute Stroke. Eur J Neurol 2023; 30:3751-3760. [PMID: 37565375 DOI: 10.1111/ene.16035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 07/28/2023] [Accepted: 08/08/2023] [Indexed: 08/12/2023]
Abstract
BACKGROUND AND PURPOSE The weight of outcome predictors in acute ischemic stroke (AIS) patients older than 60 years is not necessarily mirrored in the younger population, posing the question of whether outcome determinants specific for the latter might vary. Very few data are available on predictors of outcome in young AIS patients receiving endovascular treatment (EVT). METHODS We analyzed data for patients aged between 16 and 55 years from the Italian Registry of Endovascular Treatment in Acute Stroke. We divided our population into patients <45 years old and patients aged between 45 and 55 years. After testing the differences between groups in terms of 90-day modified Rankin Scale (mRS) 0-2, mortality, and symptomatic intracranial hemorrhage, we looked for predictors of poor outcome (mRS 3-6), death, and symptomatic intracerebral hemorrhage in the two groups. RESULTS A total of 438 patients younger than 45 years and 817 aged 45-55 years were included; 284 (34.8%) patients aged 45-55 years and 112 (25.6%) patients younger than 45 years old showed poor 90-day functional outcome (p = 0.001). Predictors of poor outcome in the older group were baseline National Institutes of Health Stroke Scale (NIHSS; p < 0.001), diabetes (p = 0.027), poor collateral status (p = 0.036), and groin puncture-to-recanalization time (p = 0.010), whereas Thrombolysis in Cerebral Infarction (TICI) 2b-3 had an inverse association (p < 0.001). Predictors of poor outcome in patients younger than 45 years were baseline NIHSS (p < 0.001) and groin puncture-to-recanalization time (p = 0.015), whereas an inverse association was found for baseline Alberta Stroke Program Early CT Score (p = 0.010) and TICI 2b-3 (p < 0.001). CONCLUSIONS Approximately one third of young adults treated with EVT do not reach a good functional outcome. Fast and successful recanalization, rather than common risk factors, has a major role in determining clinical outcome.
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Affiliation(s)
- Ettore Nicolini
- Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy
| | | | - Svetlana Lorenzano
- Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy
| | | | - Marta Iacobucci
- Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy
| | - Manuela De Michele
- Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy
| | | | | | | | | | - Rossana Tassi
- Azienda Ospedaliero Universitaria Senese, Siena, Italy
| | - Andrea Saletti
- Azienda Ospedaliero Universitaria di Ferrara, Ferrara, Italy
| | | | | | | | | | - Laura Malfatto
- Istituti di Ricovero e Cura a Carattere Scientifico - IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | | | - Daniele G Romano
- Azienda Ospedaliera Universitaria S. Giovanni di Dio Ruggi D'Aragona, Salerno, Italy
| | | | - Andrea Zini
- Istituto di Ricovero e Cura a Carattere Scientifico - IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy
| | | | - Ilaria Casetta
- Clinical Neurology, University of Ferrara, Ferrara, Italy
| | | | - Salvatore Mangiafico
- Istituti di Ricovero e Cura a Carattere Scientifico - IRCCS Neuromed, Pozzilli, Italy
| | - Danilo Toni
- Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy
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19
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Sun Y, Jou E, Nguyen TN, Mofatteh M, Liang Q, Abdalkader M, Yan Z, Feng M, Li X, Li G, Luo L, Lai Y, Yang S, Zhou S, Xu Z, Cai X, Chen Y. Predictors of futile recanalization after endovascular treatment in acute ischemic stroke: a multi-center study. Front Neurosci 2023; 17:1279366. [PMID: 38089974 PMCID: PMC10713826 DOI: 10.3389/fnins.2023.1279366] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Accepted: 11/13/2023] [Indexed: 12/06/2024] Open
Abstract
BACKGROUND AND OBJECTIVES Endovascular thrombectomy (EVT) improves long-term outcomes and decreases mortality in ischemic stroke patients. However, a significant proportion of patients do not benefit from EVT recanalization, a phenomenon known as futile recanalization or reperfusion without functional independence (RFI). In this study, we aim to identify the major stroke risk factors and patient characteristics associated with RFI. METHODS This is a retrospective cohort study of 297 consecutive patients with ischemic stroke who received EVT at three academic stroke centers in China from March 2019 to March 2022. Patient age, sex, modified Rankin Scale (mRS), National Institute of Health Stroke Scale (NIHSS), Alberta stroke program early CT score (ASPECTS), time to treatment, risk factors and comorbidities associated with cerebrovascular diseases were collected, and potential associations with futile recanalization were assessed. RFI was successful reperfusion defined as modified thrombolysis in cerebral infarction (mTICI) ≥ 2b without functional independence at 90 days (mRS ≥ 3). RESULTS Of the 297 initial patients assessed, 231 were included in the final analyses after the application of the inclusion and exclusion criteria. Patients were divided by those who had RFI (n = 124) versus no RFI (n = 107). Older age (OR 1.041, 95% CI 1.004 to 1.073; p = 0.010), chronic kidney disease (OR 4.399, 0.904-21.412; p = 0.067), and higher 24-h NIHSS (OR 1.284, 1.201-1.373; p < 0.001) were independent predictors of RFI. Conversely, an mTICI score of 3 was associated with a reduced likelihood of RFI (OR 0.402, 0.178-0.909; p = 0.029). CONCLUSION In conclusion, increased age, higher 24-h NIHSS and lack of an mTICI score of 3 were independently associated with RFI and have potential prognostic values in predicting patients that are less likely to respond to EVT recanalization therapy.
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Affiliation(s)
- Yu Sun
- Department of Neurology and Advanced National Stroke Center, Foshan Sanshui District People's Hospital, Foshan, China
| | - Eric Jou
- Kellogg College, University of Oxford, Oxford, United Kingdom
| | - Thanh N. Nguyen
- Department of Neurology, Radiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, United States
| | - Mohammad Mofatteh
- School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, United Kingdom
| | - Qingjia Liang
- Department of Neurology and Advanced National Stroke Center, Foshan Sanshui District People's Hospital, Foshan, China
- Department of Internal Medicine, Foshan Sanshui District People's Hospital, Foshan, China
| | - Mohamad Abdalkader
- Department of Radiology, Boston University Chobanian & Avedsian School of Medicine, Boston, MA, United States
| | - Zile Yan
- Department of Neurology and Advanced National Stroke Center, Foshan Sanshui District People's Hospital, Foshan, China
| | - Mingzhu Feng
- Department of Neurology and Advanced National Stroke Center, Foshan Sanshui District People's Hospital, Foshan, China
| | - Xinyuan Li
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Medical Intern, Foshan Sanshui District People's Hospital, Foshan, China
| | - Guilan Li
- Department of Neurology and Advanced National Stroke Center, Foshan Sanshui District People's Hospital, Foshan, China
| | - Lanzhu Luo
- Department of Neurology and Advanced National Stroke Center, Foshan Sanshui District People's Hospital, Foshan, China
| | - Yuzheng Lai
- Department of Neurology, Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine (Nanhai District Hospital of Traditional Chinese Medicine of Foshan City), Foshan, China
| | - Shuiquan Yang
- Department of Neurology and Advanced National Stroke Center, Foshan Sanshui District People's Hospital, Foshan, China
| | - Sijie Zhou
- Department of Surgery of Cerebrovascular Diseases, First People's Hospital of Foshan, Foshan, China
| | - Zhiming Xu
- Advanced Stroke Center Management Committee, Foshan Sanshui District People's Hospital, Foshan, China
- Dean Office, Foshan Sanshui District People's Hospital, Foshan, China
| | - Xiaodong Cai
- Department of NeurologyThe Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yimin Chen
- Department of Neurology and Advanced National Stroke Center, Foshan Sanshui District People's Hospital, Foshan, China
- Neuro International Collaboration (NIC), Foshan, China
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20
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Nicolini E, Iacobucci M, De Michele M, Ciacciarelli A, Berto I, Petraglia L, Falcou A, Cirelli C, Biraschi F, Lorenzano S, Linfante I, Toni D. No-reflow phenomenon in acute ischemic stroke: an angiographic evaluation. Neurol Sci 2023; 44:3939-3948. [PMID: 37353724 DOI: 10.1007/s10072-023-06879-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 05/28/2023] [Indexed: 06/25/2023]
Abstract
BACKGROUND Futile recanalization (FR) is de fined as a poor 90-day outcome or lack of neurological improvement at 24 h despite successful recanalization in acute ischemic stroke (AIS) with large vessel occlusion (LVO) treated by mechanical throbectomy (MT). The No-reflow phenomenon (NRP) could be a possible cause of FR, but its evidence in AIS patients is scarce. METHODS We retrospectively analyzed 185 digital subtraction angiographies (DSA) of AIS patients with anterior circulation LVO after endovascular treatment. To better define NRP, we designed a score called the modified capillary index score (mCIS). The score is obtained by dividing the middle cerebral artery territory in three segments. For each segment, we gave 2 points if the capillary blush was present without any delay, 1 if delayed, and 0 if absent. The primary endpoint was to use mCIS to identify NRP on post-interventional DSA and to test whether this marker may predict FR and failure of early neurological improvement (fENI). The secondary endpoint was to search for a correlation between NRP, lesion volume, and hemorrhagic transformation. We used the ROC curve to define mCIS ≤ 3 as the cut-off and marker of NRP. RESULTS NRP was present in 35.1% of patients. NRP predicted fENI at 24 h (aOR 2.825, 95% CI 1.265-6.308, P = 0.011) and at 7 days (aOR 2.191, 95% CI 1.008-4.762, P = 0.048), but not 90-day FR. Moreover, NRP predicted hemorrhagic transformation (aOR 2.444, 95% CI 1.266-4.717, P = 0.008). CONCLUSIONS The modified capillary index score (mCIS) seems useful in identifying NRP in AIS. In addition, mCIS was able to predict NRP that correlated with early clinical outcome and hemorrhagic transformation of the ischemic lesion. An external validation of the score is warranted.
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Affiliation(s)
- Ettore Nicolini
- Department of Human Neurosciences, Sapienza University of Rome, Viale Dell'Università 30, 00185, Rome, Italy.
| | - Marta Iacobucci
- Interventional Neuroradiology Unit, Department of Diagnostic Medicine and Radiology, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
| | - Manuela De Michele
- Emergency Department, Stroke Unit, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
| | - Antonio Ciacciarelli
- Emergency Department, Stroke Unit, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
| | - Irene Berto
- Emergency Department, Stroke Unit, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
| | - Luca Petraglia
- Emergency Department, Stroke Unit, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
| | - Anne Falcou
- Emergency Department, Stroke Unit, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
| | - Carlo Cirelli
- Interventional Neuroradiology Unit, Department of Diagnostic Medicine and Radiology, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
| | - Francesco Biraschi
- Interventional Neuroradiology Unit, Department of Diagnostic Medicine and Radiology, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
| | - Svetlana Lorenzano
- Department of Human Neurosciences, Sapienza University of Rome, Viale Dell'Università 30, 00185, Rome, Italy
| | - Italo Linfante
- Department of Interventional Neuroradiology & Neuroendovascular Surgery, Miami Cardiac and Vascular Institute, Baptist Hospital of Miami, Miami, FL, USA
| | - Danilo Toni
- Department of Human Neurosciences, Sapienza University of Rome, Viale Dell'Università 30, 00185, Rome, Italy
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21
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Yuan X, Ye W, Chen L, Luo D, Zhou L, Qiu Y, Zhuo R, Zhao Y, Peng L, Yang L, Jin X, Zhou Y. URB597 exerts neuroprotective effects against transient brain ischemia injury in mice by regulating autophagic flux and necroptosis. Eur J Pharmacol 2023; 957:175982. [PMID: 37572942 DOI: 10.1016/j.ejphar.2023.175982] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Revised: 07/14/2023] [Accepted: 08/09/2023] [Indexed: 08/14/2023]
Abstract
Ischemic stroke is a leading cause of death and disability, and medical treatments for ischemic stroke are very limited. URB597 is a potent and selective inhibitor of fatty acid amide hydrolase (FAAH). However, the effect of URB597 on ischemic stroke and the underlying molecular mechanisms remain little known. In this study, focal cerebral ischemia was induced by transient middle cerebral artery occlusion in mice. Our results showed that URB597 dose-dependently improved neurological function and reduced brain infarct volume and brain edema 24 h after brain ischemia. The most effective dose was 1 mg/kg and the therapeutic time window was within 3 h after ischemic stroke. To further investigate the underlying mechanism, necroptosis and autophagy flux were detected by Western blot and/or immunofluorescence staining with or without chloroquine, an autophagic flux inhibitor. Our results showed that URB597 promoted autophagic flux and reduced neuronal necroptosis after brain ischemia and these effects could be abolished by chloroquine. In addition, we found that peroxisome proliferator-activated receptor α (PPARα) antagonist GW6471 partly abolished the effect of URB597 against brain ischemia and URB597 upregulated the expressions of PPARα. In conclusion, URB597 exerts a neuroprotective effect in a dose- and time-dependent manner, and this effect may be related to its restoration of autophagic flux and inhibition of neuronal necroptosis. PPARα is involved in the neuroprotective effect of URB597. This study provides novel evidence that URB597 may be a promising agent for the clinical treatment of ischemic stroke.
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Affiliation(s)
- Xiaoqian Yuan
- Department of Basic Medical Science, School of Medicine, Xiamen University, Xiamen, 361102, China; Key Laboratory of Chiral Drugs, Xiamen, 361102, China.
| | - Wenxuan Ye
- Department of Basic Medical Science, School of Medicine, Xiamen University, Xiamen, 361102, China; Key Laboratory of Chiral Drugs, Xiamen, 361102, China
| | - Ling Chen
- Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361102, China; Department of Basic Medical Science, School of Medicine, Xiamen University, Xiamen, 361102, China; Key Laboratory of Chiral Drugs, Xiamen, 361102, China
| | - Doudou Luo
- Department of Basic Medical Science, School of Medicine, Xiamen University, Xiamen, 361102, China; Key Laboratory of Chiral Drugs, Xiamen, 361102, China; State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, 361102, China
| | - Li Zhou
- Department of Basic Medical Science, School of Medicine, Xiamen University, Xiamen, 361102, China
| | - Yan Qiu
- Key Laboratory of Chiral Drugs, Xiamen, 361102, China
| | - Rengong Zhuo
- Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361102, China; Department of Basic Medical Science, School of Medicine, Xiamen University, Xiamen, 361102, China; Key Laboratory of Chiral Drugs, Xiamen, 361102, China
| | - Yun Zhao
- Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361102, China; Department of Basic Medical Science, School of Medicine, Xiamen University, Xiamen, 361102, China; Key Laboratory of Chiral Drugs, Xiamen, 361102, China
| | - Lu Peng
- Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361102, China; Department of Basic Medical Science, School of Medicine, Xiamen University, Xiamen, 361102, China; Key Laboratory of Chiral Drugs, Xiamen, 361102, China
| | - Lichao Yang
- Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361102, China; Department of Basic Medical Science, School of Medicine, Xiamen University, Xiamen, 361102, China; Key Laboratory of Chiral Drugs, Xiamen, 361102, China
| | - Xin Jin
- Department of Basic Medical Science, School of Medicine, Xiamen University, Xiamen, 361102, China; Key Laboratory of Chiral Drugs, Xiamen, 361102, China
| | - Yu Zhou
- Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361102, China; Department of Basic Medical Science, School of Medicine, Xiamen University, Xiamen, 361102, China; Key Laboratory of Chiral Drugs, Xiamen, 361102, China; State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, 361102, China.
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22
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Hou D, Pei C, Yu D, Yang G. miR-188-5p silencing improves cerebral ischemia/reperfusion injury by targeting Lin28a. Metab Brain Dis 2023; 38:2327-2338. [PMID: 37572229 DOI: 10.1007/s11011-023-01273-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 07/16/2023] [Indexed: 08/14/2023]
Abstract
This report aimed to explore whether miR-188-5p regulated the pathological regulatory network of cerebral ischemia/reperfusion (I/R) injury. We simulated the cerebral I/R injury model with MACO/R and OGD/R treatments. Neuronal viability and apoptosis were assessed. The contents of miR-188-5p and Lin 28a were evaluated. The abundances of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were measured. The interaction of miR-188-5p and Lin28a was confirmed. Lin28a silencing was supplemented to determine the delicate regulation of miR-188-5p. We revealed that miR-188-5p was upregulated and Lin28a was downregulated in I/R rats and OGD/R-induced cells. miR-188-5p silencing remarkably reduced the cerebral infarction volume, neurobehavioral score, brain edema, and Evans blue leakage. miR-188-5p silencing enhanced neuronal viability and alleviated apoptosis. The abundance of Bax and cleaved caspase-3 was reduced by miR-188-5p silencing, while Bcl-2 was augmented. miR-188-5p silencing impeded the contents of TNF-α, IL-1β, and IL-6. miR-188-5p interacted with Lin28a and negatively regulated its expression. Interestingly, extra Lin28a silencing reversed apoptosis and the content of inflammatory cytokines. Our studies confirmed that miR-188-5p silencing alleviated neuronal apoptosis and inflammation by mediating the expression of Lin28a. The crosstalk of miR-188-5p and Lin28a offered a different direction for ischemic stroke therapy.
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Affiliation(s)
- Dan Hou
- Department of Neurology, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, Hainan, 570208, China
| | - Chaoying Pei
- Department of Neurology, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, Hainan, 570208, China
| | - Dan Yu
- Department of Neurology, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, Hainan, 570208, China.
| | - Guoshuai Yang
- Department of Neurology, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, Hainan, 570208, China.
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23
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Rosso C, Belkacem S, Amor-Sahli M, Clarençon F, Leger A, Baronnet F, Dormont D, Alamowitch S, Lehericy S, Samson Y. Persistent perfusion abnormalities at day 1 correspond to different clinical trajectories after stroke. J Neurointerv Surg 2023; 15:e26-e32. [PMID: 35701108 DOI: 10.1136/neurintsurg-2022-018953] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 06/01/2022] [Indexed: 11/03/2022]
Abstract
BACKGROUND Perfusion abnormalities after thrombolysis are frequent within and surrounding ischemic lesions, but their relative frequency is not well known. OBJECTIVE To describe the different patterns of perfusion abnormalities observed at 24 hours and compare the characteristics of the patients according to their perfusion pattern. METHODS From our thrombolysis registry, we included 226 consecutive patients with an available arterial spin labeling (ASL) perfusion sequence at day 1. We performed a blinded assessment of the perfusion status (hypoperfusion-h, hyperperfusion-H, or normal-N) in the ischemic lesion and in the surrounding tissue. We compared the time course of clinical recovery, the rate of arterial recanalization, and hemorrhagic transformations in the different perfusion profiles. RESULTS We identified seven different perfusion profiles at day 1. Four of these (h/h, h/H, H/H, and H/N) represented the majority of the population (84.1%). The H/H profile was the most frequent (34.5%) and associated with 3-month good outcome (modified Rankin Scale (mRS): 63.5%). Patients with persistent hypoperfusion within and outside the lesion (h/h, 12.4%) exhibited worse outcomes after treatment (mRS score 0-2: 23.8%) than other patients, were less frequently recanalized (40.7%), and had more parenchymal hematoma (17.8%). The h/H profile had an intermediate clinical trajectory between the h/h profile and the hyperperfused profiles. CONCLUSION ASL hypoperfusion within the infarct and the surrounding tissue was associated with poor outcome. A more comprehensive view of the mechanisms in the hypoperfused surrounding tissue could help to design new therapeutic approaches during and after reperfusion therapies.
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Affiliation(s)
- Charlotte Rosso
- APHP-Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Paris, France
- STARE team, iCRIN, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France
- Inserm U 1127, CNRS UMR 7225, Sorbonne Université, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France
| | - Samia Belkacem
- APHP-Neuroradiology Department, Hôpital Pitié-Salpêtrière, Paris, France
| | - Mélika Amor-Sahli
- APHP-Neuroradiology Department, Hôpital Pitié-Salpêtrière, Paris, France
| | - Frédéric Clarençon
- STARE team, iCRIN, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France
- APHP-Interventional Neuroradiology Department, Hôpital Pitié-Salpêtrière, Paris, France
| | - Anne Leger
- APHP-Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Paris, France
- STARE team, iCRIN, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France
| | - Flore Baronnet
- APHP-Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Paris, France
- STARE team, iCRIN, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France
| | - Didier Dormont
- Inserm U 1127, CNRS UMR 7225, Sorbonne Université, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France
- APHP-Neuroradiology Department, Hôpital Pitié-Salpêtrière, Paris, France
| | - Sonia Alamowitch
- APHP-Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Paris, France
- STARE team, iCRIN, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France
| | - Stéphane Lehericy
- Inserm U 1127, CNRS UMR 7225, Sorbonne Université, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France
- APHP-Neuroradiology Department, Hôpital Pitié-Salpêtrière, Paris, France
| | - Yves Samson
- APHP-Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Paris, France
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24
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Luo Y, Sun X, Kong X, Tong X, Xi F, Mao Y, Miao Z, Ma J. A DWI-based radiomics-clinical machine learning model to preoperatively predict the futile recanalization after endovascular treatment of acute basilar artery occlusion patients. Eur J Radiol 2023; 161:110731. [PMID: 36804312 DOI: 10.1016/j.ejrad.2023.110731] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Accepted: 02/03/2023] [Indexed: 02/10/2023]
Abstract
OBJECTIVE To develop an effective machine learning model to preoperatively predict the occurrence of futile recanalization (FR) of acute basilar artery occlusion (ABAO) patients with endovascular treatment (EVT). MATERIALS AND METHODS Data from 132 ABAO patients (109 male [82.6 %]; mean age ± standard deviation, 59.1 ± 12.5 years) were randomly divided into the training (n = 106) and test cohort (n = 26) with a ratio of 8:2. FR is defined as a poor outcome [modified Rankin Scale (mRS) 4-6] despite a successful recanalization [modified Thrombolysis in Cerebral Infarction (mTICI) ≥ 2b]. A total of 1130 radiomics features were extracted from diffusion-weighted imaging (DWI) images. The least absolute shrinkage and selection operator (LASSO) regression method was applicated to select features. Support vector machine (SVM) was applicated to construct radiomics and clinical models. Finally, a radiomics-clinical model that combined clinical with radiomics features was developed. The models were evaluated by receiver operating characteristic (ROC) curve and decision curve. RESULTS The area under the receiver operating characteristic (ROC) curve (AUC) of the radiomics-clinical model was 0.897 (95 % confidence interval, 0.837-0.958) in the training cohort and 0.935 (0.833-1.000) in the test cohort. The AUC of the radiomics model was 0.887 (0.824-0.951) in the training cohort and 0.840 (0.680-1.000) in the test cohort. The AUC of the clinical model was 0.746 (0.652-0.840) in the training cohort and 0.766 (0.569-0.964) in the test cohort. The AUC of the radiomics-clinical model was significantly larger than the clinical model (p = 0.016). A radiomics-clinical nomogram was developed. The decision curve analysis indicated its clinical usefulness. CONCLUSION The DWI-based radiomics-clinical machine learning model achieved satisfactory performance in predicting the FR of ABAO patients preoperatively.
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Affiliation(s)
- Yuqi Luo
- Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China
| | - Xuan Sun
- Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China.
| | - Xin Kong
- Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China
| | - Xu Tong
- Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China
| | - Fengjun Xi
- Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China
| | - Yu Mao
- Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China
| | - Zhongrong Miao
- Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China.
| | - Jun Ma
- Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China.
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Zhang T, Deng D, Huang S, Fu D, Wang T, Xu F, Ma L, Ding Y, Wang K, Wang Y, Zhao W, Chen X. A retrospect and outlook on the neuroprotective effects of anesthetics in the era of endovascular therapy. Front Neurosci 2023; 17:1140275. [PMID: 37056305 PMCID: PMC10086253 DOI: 10.3389/fnins.2023.1140275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Accepted: 03/13/2023] [Indexed: 03/30/2023] Open
Abstract
Studies on the neuroprotective effects of anesthetics were carried out more than half a century ago. Subsequently, many cell and animal experiments attempted to verify the findings. However, in clinical trials, the neuroprotective effects of anesthetics were not observed. These contradictory results suggest a mismatch between basic research and clinical trials. The Stroke Therapy Academic Industry Roundtable X (STAIR) proposed that the emergence of endovascular thrombectomy (EVT) would provide a proper platform to verify the neuroprotective effects of anesthetics because the haemodynamics of patients undergoing EVT is very close to the ischaemia–reperfusion model in basic research. With the widespread use of EVT, it is necessary for us to re-examine the neuroprotective effects of anesthetics to guide the use of anesthetics during EVT because the choice of anesthesia is still based on team experience without definite guidelines. In this paper, we describe the research status of anesthesia in EVT and summarize the neuroprotective mechanisms of some anesthetics. Then, we focus on the contradictory results between clinical trials and basic research and discuss the causes. Finally, we provide an outlook on the neuroprotective effects of anesthetics in the era of endovascular therapy.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Xiangdong Chen
- *Correspondence: Xiangdong Chen, ; orcid.org/0000-0003-3347-2947
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Nie X, Leng X, Miao Z, Fisher M, Liu L. Clinically Ineffective Reperfusion After Endovascular Therapy in Acute Ischemic Stroke. Stroke 2023; 54:873-881. [PMID: 36475464 DOI: 10.1161/strokeaha.122.038466] [Citation(s) in RCA: 65] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Endovascular treatment is a highly effective therapy for acute ischemic stroke due to large vessel occlusion. However, in clinical practice, nearly half of the patients do not have favorable outcomes despite successful recanalization of the occluded artery. This unfavorable outcome can be defined as having clinically ineffective reperfusion. The objective of the review is to describe clinically ineffective reperfusion after endovascular therapy and its underlying risk factors and mechanisms, including initial tissue damage, cerebral edema, the no-reflow phenomenon, reperfusion injury, procedural features, and variations in postprocedural management. Further research is needed to more accurately identify patients at a high risk of clinically ineffective reperfusion after endovascular therapy and to improve individualized periprocedural management strategies, to increase the chance of achieving favorable clinical outcomes.
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Affiliation(s)
- Ximing Nie
- Department of Neurology (X.N., L.L.), Beijing Tiantan Hospital, Capital Medical University, China.,China National Clinical Research Center for Neurological Diseases, Beijing (X.N., L.L.)
| | - Xinyi Leng
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, SAR (X.L.)
| | - Zhongrong Miao
- Department of Interventional Neuroradiology (Z.M.), Beijing Tiantan Hospital, Capital Medical University, China
| | - Marc Fisher
- Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (M.F.)
| | - Liping Liu
- Department of Neurology (X.N., L.L.), Beijing Tiantan Hospital, Capital Medical University, China.,China National Clinical Research Center for Neurological Diseases, Beijing (X.N., L.L.)
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Sohn JH, Kim C, Lee M, Kim Y, Jung Mo H, Yu KH, Lee SH. Effects of prior antiplatelet use on futile reperfusion in patients with acute ischemic stroke receiving endovascular treatment. Eur Stroke J 2022; 8:208-214. [PMID: 37021175 PMCID: PMC10069215 DOI: 10.1177/23969873221144814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Introduction: We evaluated the effects of prior antiplatelet use (APU) on futile reperfusion (FR) after endovascular treatment (EVT) in acute ischemic stroke. Material and methods: We consecutively collected data of 9369 patients with acute ischemic stroke from four university-affiliated multicenter registry databases over 92 months. We enrolled 528 patients with acute stroke receiving EVT. Among them, we defined FR in subjects as a 3-month modified Rankin Scale score of >2 despite successful reperfusion after EVT. We classified patients into two groups: prior APU and no prior APU. We used propensity score matching (PSM) to overcome the imbalance in multiple covariates between the two groups. After PSM, we compared the baseline characteristics between the two groups and performed multivariate analysis to determine whether prior APU affected FR and other stroke outcomes. Results: The overall FR rate in the present study was 54.2%. In the PSM cohort, the FR was lower in the prior APU group than that in the no prior APU group (66.2% vs 41.5%, p < 0.001). In the multivariate analysis using the PSM cohort, prior APU significantly reduced the risk of FR (odds ratio (OR), 0.32; 95% confidence interval (CI), 0.18–0.55; p = 0.001) and stroke progression (OR, 0.38; 95% CI, 0.15–0.93; p = 0.03). Prior APU was not associated with symptomatic hemorrhagic transformation in this study. Conclusion: Prior APU potentially reduced FR and stroke progression. Further, prior APU was not associated with symptomatic hemorrhagic transformation in patients receiving EVT. APU pretreatment can be a modifiable predictor of FR in clinical practice.
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Affiliation(s)
- Jong-Hee Sohn
- Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, South Korea
- Institute of New Frontier research Team, Hallym University, Chuncheon, South Korea
| | - Chulho Kim
- Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, South Korea
- Institute of New Frontier research Team, Hallym University, Chuncheon, South Korea
| | - Minwoo Lee
- Department of Neurology, Hallym Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea
| | - Yerim Kim
- Department of Neurology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea
| | - Hee Jung Mo
- Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, South Korea
| | - Kyung-Ho Yu
- Department of Neurology, Hallym Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea
| | - Sang-Hwa Lee
- Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, South Korea
- Institute of New Frontier research Team, Hallym University, Chuncheon, South Korea
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28
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Elucidating the Role of Baseline Leukoaraiosis on Forecasting Clinical Outcome of Acute Ischemic Stroke Patients Undergoing Reperfusion Therapy. Neurol Int 2022; 14:923-942. [PMID: 36412696 PMCID: PMC9680372 DOI: 10.3390/neurolint14040074] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/06/2022] [Accepted: 11/08/2022] [Indexed: 11/12/2022] Open
Abstract
Stroke stands as a major cause of death and disability with increasing prevalence. The absence of clinical improvement after either intravenous thrombolysis (IVT) or mechanical thrombectomy (MT) represents a frequent concern in the setting of acute ischemic stroke (AIS). In an attempt to optimize overall stroke management, it is clinically valuable to provide important insight into functional outcomes after reperfusion therapy among patients presenting with AIS. The aim of the present review is to explore the predictive value of leukoaraiosis (LA) in terms of clinical response to revascularization poststroke. A literature research of two databases (MEDLINE and Scopus) was conducted in order to trace all relevant studies published between 1 January 2012 and 1 November 2022 that focused on the potential utility of LA severity regarding reperfusion status and clinical outcome after revascularization. A total of 37 articles have been traced and included in this review. LA burden assessment is indicative of functional outcome post-intervention and may be associated with hemorrhagic events' incidence among stroke individuals. Nevertheless, LA may not solely guide decision-making about treatment strategy poststroke. Overall, the evaluation of LA upon admission seems to have interesting prognostic potential and may substantially enhance individualized stroke care.
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Lee M, Kim Y, Oh MS, Yu KH, Lee BC, Kim CH, Mo HJ. Cerebral Small Vessel Disease Burden and Futile Reperfusion after Endovascular Treatment for Patients with Acute Ischemic Stroke. Cerebrovasc Dis 2022; 52:427-434. [PMID: 36273453 DOI: 10.1159/000527020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 09/05/2022] [Indexed: 09/05/2023] Open
Abstract
INTRODUCTION Cerebral small vessel disease (SVD) burden includes increased risk of poor functional outcomes after acute ischemic stroke (AIS). We aimed to investigate the impact of cerebral SVD on 3-month functional outcomes in patients with AIS who received endovascular treatment (EVT) and to determine whether SVD is associated with futile reperfusion (FR). METHODS Using a multicenter stroke registry, we analyzed consecutive patients with AIS with either intracranial and/or extracranial anterior circulation large artery occlusion, who were treated with EVT and achieved successful reperfusion (thrombolysis in cerebral infarction grade 2b-3). The cerebral SVD burden was evaluated using baseline brain magnetic resonance imaging using a modified Fazekas score (mFS). The main outcome variable was FR, defined as poor functional outcomes (modified Rankin scale 3-6) at 3 months after stroke, despite successful recanalization. Secondary outcomes included stroke progression/recurrence and any hemorrhagic transformation. RESULTS Among 10,890 patients with AIS, 577 (5.3%) received EVT within 12 h of onset, including 354 who met study eligibility criteria. FR was observed in 191 patients (53.5%) and was positively associated with SVD burden. After adjustment for covariates including age, sex, stroke etiology, initial stroke severity, collateral status, Alberta stroke program early CT score, initial serum glucose, systemic blood pressure, and vascular risk factors, mFS grade 3 was significantly associated with FR (odds ratio: 3.93, 95% confidence interval: 1.602-9.619; p = 0.003). CONCLUSIONS We demonstrated that cerebral SVD assessed with baseline brain MRI is associated with the futility of successful recanalization after EVT and any hemorrhagic transformation but not with early stroke progression or recurrence. Nevertheless, our findings do not justify withholding EVT in otherwise eligible patients with AIS based on the presence of severe SVD.
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Affiliation(s)
- Minwoo Lee
- Department of Neurology, Hallym University Sacred Heart Hospital, Hallym Neurological Institute, Hallym University College of Medicine, Anyang, Republic of Korea,
- Institute of New Frontier Research Team, Hallym University, Chuncheon, Republic of Korea,
| | - Yerim Kim
- Department of Neurology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Mi Sun Oh
- Department of Neurology, Hallym University Sacred Heart Hospital, Hallym Neurological Institute, Hallym University College of Medicine, Anyang, Republic of Korea
| | - Kyung-Ho Yu
- Department of Neurology, Hallym University Sacred Heart Hospital, Hallym Neurological Institute, Hallym University College of Medicine, Anyang, Republic of Korea
| | - Byung-Chul Lee
- Department of Neurology, Hallym University Sacred Heart Hospital, Hallym Neurological Institute, Hallym University College of Medicine, Anyang, Republic of Korea
| | - Chul-Ho Kim
- Institute of New Frontier Research Team, Hallym University, Chuncheon, Republic of Korea
- Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Republic of Korea
| | - Hee Jung Mo
- Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
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30
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Feng Y, Bai X, Li W, Cao W, Xu X, Yu F, Fu Z, Tian Q, Guo X, Wang T, Sha A, Chen Y, Gao P, Wang Y, Chen J, Ma Y, Chen F, Dmytriw AA, Regenhardt RW, Lu J, Ma Q, Yang B, Jiao L. Postoperative neutrophil-lymphocyte ratio predicts unfavorable outcome of acute ischemic stroke patients who achieve complete reperfusion after thrombectomy. Front Immunol 2022; 13:963111. [PMID: 36275640 PMCID: PMC9585914 DOI: 10.3389/fimmu.2022.963111] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 09/27/2022] [Indexed: 11/13/2022] Open
Abstract
Purpose Only approximately half of anterior circulation large vessel occlusion (LVO) patients receiving endovascular treatment (EVT) have a favorable outcome. The aim of this study was to explore the association of dynamic inflammatory markers (i.e., neutrophil to lymphocyte ratios, NLR, measured at different times after EVT) as well as other potential influencing factors with unfavorable outcome among acute ischemic stroke (AIS) patients who achieved complete reperfusion after EVT. Methods Patients treated with EVT for LVO between January 2019 to December 2021 were prospectively enrolled. Complete reperfusion was defined as modified thrombolysis in cerebral infarction (mTICI) grade 3. A modified Rankin scale at 90 days (mRS90) of 3-6 was defined as unfavorable outcome (i.e., futile reperfusion). A logistic regression analysis was performed with unfavorable outcome as a dependent variable. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were then used to determine the diagnostic values of NLR and other relevant factors. Results 170 patients with complete reperfusion (mTICI 3) were included in this study. Unfavorable outcome was observed in 70 (41.2%). Higher NLR within 24h (p=0.017) and at 3-7d (p=0.008) after EVT were an independent risk factors for unfavorable outcome at 3 months. In addition, older age, higher NIHSS scores, poor collaterals, and general anesthesia were independent predictors of unfavorable outcomes. When accounting for NLR, the diagnostic efficiency improved compared to conventional characteristics. Conclusion Our findings suggest that advanced age, increased stroke severity, poor collaterals, general anesthesia, and NLR are independent predictors for an unfavorable clinical outcome following complete reperfusion after EVT. Neuroinflammation may merit particular attention in future studies.
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Affiliation(s)
- Yao Feng
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
- China International Neuroscience Institute (China-INI), Beijing, China
| | - Xuesong Bai
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
- China International Neuroscience Institute (China-INI), Beijing, China
| | - Wei Li
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
- Department of Neurosurgery, Liaocheng Brain Hospital, Liaocheng, China
| | - Wenbo Cao
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
- China International Neuroscience Institute (China-INI), Beijing, China
| | - Xin Xu
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
- China International Neuroscience Institute (China-INI), Beijing, China
| | - Fan Yu
- Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing, China
| | - Zhaolin Fu
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
- China International Neuroscience Institute (China-INI), Beijing, China
| | - Qiuyue Tian
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
| | - Xiaofan Guo
- Department of Neurology, Loma Linda University Health, Loma Linda, CA, United States
| | - Tao Wang
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
- China International Neuroscience Institute (China-INI), Beijing, China
| | - Arman Sha
- Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing, China
| | - Yanfei Chen
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
- China International Neuroscience Institute (China-INI), Beijing, China
| | - Peng Gao
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
- China International Neuroscience Institute (China-INI), Beijing, China
- Department of Interventional Neuroradiology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yabing Wang
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
- China International Neuroscience Institute (China-INI), Beijing, China
| | - Jian Chen
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yan Ma
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
- China International Neuroscience Institute (China-INI), Beijing, China
| | - Fei Chen
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Adam A Dmytriw
- Neuroendovascular Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Robert W Regenhardt
- Neuroendovascular Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Jie Lu
- Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing, China
| | - Qingfeng Ma
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Bin Yang
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
- China International Neuroscience Institute (China-INI), Beijing, China
| | - Liqun Jiao
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
- China International Neuroscience Institute (China-INI), Beijing, China
- Department of Interventional Neuroradiology, Xuanwu Hospital, Capital Medical University, Beijing, China
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Liu S, Li F, Yang J, Xie D, Yue C, Luo W, Hu J, Song J, Li L, Huang J, Zhao C, Gong Z, Yang Q, Zi W. Efficacy and safety of 3-n-butylphthalide combined with endovascular treatment in acute ischemic stroke due to large vessel occlusion. CNS Neurosci Ther 2022; 28:2298-2307. [PMID: 36184804 PMCID: PMC9627349 DOI: 10.1111/cns.13978] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 08/19/2022] [Accepted: 09/03/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The drug 3-n-butylphthalide (NBP) was developed and approved in China, where it has been used to treat ischemic cerebrovascular diseases. It is also considered to have a neuroprotective effect. This study aimed to evaluate whether NBP combined with endovascular treatment (EVT) can improve the clinical outcome and safety in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). METHODS Data from three studies of patients treated with EVT for AIS due to LVO were combined in this study. Patients of LVO undergoing EVT were dichotomized into NBP and non-NBP subgroups. The primary efficacy outcome was the shift of the modified Rankin Scale (mRS) score at 90 days. The secondary efficacy outcome included favorable functional outcomes, functional independence, and excellent outcome (defined as an mRS score of 3 or less) at 90 days. Safety outcomes included mortality within 90 days and symptomatic intracranial hemorrhage (sICH) within 48 h. RESULTS A total of 1820 patients undergoing EVT were included in this study; 628 (37.5%) patients received NBP treatment, whereas 1138 (62.5%) did not. After adjusting for multiple factors, NBP was associated with the improvement of functional outcomes at 90 days (adjusted common odds ratio [OR]: 1.503; 95% confidence interval (CI): 1.254-1.801; p < 0.001). NBP was associated with a higher rate of 90-day favorable outcomes (adjusted OR: 1.589; 95% CI: 1.251-2.020; p < 0.001) and a lower rate of 90-day mortality (adjusted OR: 0.486 [95% CI: 0.372-0.635]; p < 0.001). sICH occurred in 74 of 682 (10.9%) patients in the NBP group and 155 of 1126 (13.8%) patients in the non-NBP group; no statistical difference was detected (adjusted OR: 0.787 [95% CI: 0.567-1.092]; p = 0.152). CONCLUSION Among patients with AIS due to LVO, NBP combined with EVT is associated with better functional outcomes and reduced mortality risk without increasing the risk of sICH.
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Affiliation(s)
- Shuai Liu
- Department of Neurology, Xinqiao Hospital and The Second Affiliated HospitalArmy Medical University (Third Military Medical University)ChongqingChina,Department of Neurology, Chongqing Institute for Brain and IntelligenceGuangyang Bay LaboratoryChongqingChina
| | - Fengli Li
- Department of Neurology, Xinqiao Hospital and The Second Affiliated HospitalArmy Medical University (Third Military Medical University)ChongqingChina,Department of Neurology, Chongqing Institute for Brain and IntelligenceGuangyang Bay LaboratoryChongqingChina
| | - Jie Yang
- Department of Neurology, Xinqiao Hospital and The Second Affiliated HospitalArmy Medical University (Third Military Medical University)ChongqingChina,Department of Neurology, Chongqing Institute for Brain and IntelligenceGuangyang Bay LaboratoryChongqingChina
| | - Dongjie Xie
- Department of Neurology, Xinqiao Hospital and The Second Affiliated HospitalArmy Medical University (Third Military Medical University)ChongqingChina,Department of Neurology, Chongqing Institute for Brain and IntelligenceGuangyang Bay LaboratoryChongqingChina
| | - Chengsong Yue
- Department of Neurology, Xinqiao Hospital and The Second Affiliated HospitalArmy Medical University (Third Military Medical University)ChongqingChina,Department of Neurology, Chongqing Institute for Brain and IntelligenceGuangyang Bay LaboratoryChongqingChina
| | - Weidong Luo
- Department of Neurology, Xinqiao Hospital and The Second Affiliated HospitalArmy Medical University (Third Military Medical University)ChongqingChina,Department of Neurology, Chongqing Institute for Brain and IntelligenceGuangyang Bay LaboratoryChongqingChina
| | - Jinrong Hu
- Department of Neurology, Xinqiao Hospital and The Second Affiliated HospitalArmy Medical University (Third Military Medical University)ChongqingChina,Department of Neurology, Chongqing Institute for Brain and IntelligenceGuangyang Bay LaboratoryChongqingChina
| | - Jiaxing Song
- Department of Neurology, Xinqiao Hospital and The Second Affiliated HospitalArmy Medical University (Third Military Medical University)ChongqingChina,Department of Neurology, Chongqing Institute for Brain and IntelligenceGuangyang Bay LaboratoryChongqingChina
| | - Linyu Li
- Department of Neurology, Xinqiao Hospital and The Second Affiliated HospitalArmy Medical University (Third Military Medical University)ChongqingChina,Department of Neurology, Chongqing Institute for Brain and IntelligenceGuangyang Bay LaboratoryChongqingChina
| | - Jiacheng Huang
- Department of Neurology, Xinqiao Hospital and The Second Affiliated HospitalArmy Medical University (Third Military Medical University)ChongqingChina,Department of Neurology, Chongqing Institute for Brain and IntelligenceGuangyang Bay LaboratoryChongqingChina
| | - Chenhao Zhao
- Department of Neurology, Xinqiao Hospital and The Second Affiliated HospitalArmy Medical University (Third Military Medical University)ChongqingChina,Department of Neurology, Chongqing Institute for Brain and IntelligenceGuangyang Bay LaboratoryChongqingChina
| | - Zili Gong
- Department of Neurology, Xinqiao Hospital and The Second Affiliated HospitalArmy Medical University (Third Military Medical University)ChongqingChina,Department of Neurology, Chongqing Institute for Brain and IntelligenceGuangyang Bay LaboratoryChongqingChina
| | - Qingwu Yang
- Department of Neurology, Xinqiao Hospital and The Second Affiliated HospitalArmy Medical University (Third Military Medical University)ChongqingChina,Department of Neurology, Chongqing Institute for Brain and IntelligenceGuangyang Bay LaboratoryChongqingChina
| | - Wenjie Zi
- Department of Neurology, Xinqiao Hospital and The Second Affiliated HospitalArmy Medical University (Third Military Medical University)ChongqingChina,Department of Neurology, Chongqing Institute for Brain and IntelligenceGuangyang Bay LaboratoryChongqingChina
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Association between CHADS 2, CHA 2DS 2-VASc, ATRIA, and Essen Stroke Risk Scores and Functional Outcomes in Acute Ischemic Stroke Patients Who Received Endovascular Thrombectomy. J Clin Med 2022; 11:jcm11195599. [PMID: 36233464 PMCID: PMC9570925 DOI: 10.3390/jcm11195599] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 09/19/2022] [Accepted: 09/21/2022] [Indexed: 11/25/2022] Open
Abstract
Background: CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke risk scores are used to estimate thromboembolism risk. We aimed to investigate the association between unfavorable outcomes and stroke risk scores in patients who received endovascular thrombectomy (EVT). Methods: This study was performed using data from a nationwide, multicenter registry to explore the selection criteria for patients who would benefit from reperfusion therapies. We calculated pre-admission CHADS2, CHA2DS2-VASc, ATRIA, and Essen scores for each patient who received EVT and compared the relationship between these scores and 3-month modified Rankin Scale (mRS) records. Results: Among the 404 patients who received EVT, 213 (52.7%) patients had unfavorable outcomes (mRS 3−6). All scores were significantly higher in patients with unfavorable outcomes than in those with favorable outcomes. Multivariable logistic regression analysis indicated that CHADS2 and the ATRIA score were positively correlated with unfavorable outcomes after adjusting for body mass index and variables with p < 0.1 in the univariable analysis (CHADS2 score: odds ratio [OR], 1.484; 95% confidence interval [CI], 1.290−1.950; p = 0.005, ATRIA score, OR, 1.128; 95% CI, 1.041−1.223; p = 0.004). Conclusions: The CHADS2 and ATRIA scores were positively correlated with unfavorable outcomes and could be used to predict unfavorable outcomes in patients who receive EVT.
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33
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Lattanzi S, Norata D, Broggi S, Meletti S, Świtońska M, Słomka A, Silvestrini M. Neutrophil-to-Lymphocyte Ratio Predicts Early Neurological Deterioration after Endovascular Treatment in Patients with Ischemic Stroke. Life (Basel) 2022; 12:life12091415. [PMID: 36143451 PMCID: PMC9503346 DOI: 10.3390/life12091415] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 08/27/2022] [Accepted: 09/08/2022] [Indexed: 11/16/2022] Open
Abstract
The worsening of neurological status that occurs early after acute ischemic stroke (AIS) remains a serious issue, and the inflammatory response plays a key role in stroke pathobiology. Recently, endovascular treatment (EVT) has revolutionized the management and outcome of patients with AIS due to either extracranial carotid disease or intracranial disease. The neutrophil-to-lymphocyte ratio (NLR) represents an easily available inflammatory biomarker. The aim of the study was to assess the relationship between the NLR at admission and the occurrence of early neurological deterioration (END) in patients with AIS who underwent EVT. Patients with AIS and proximal arterial occlusion in the anterior circulation undergoing EVT were retrospectively identified. Absolute neutrophil count (ANC) and absolute lymphocyte count (ALC) were collected from admission blood work to calculate the NLR. The study outcome was END defined as an increase in at least 4 points in NIHSS score or death between baseline and 24 h after the ischemic event. Patients included were 211, and END occurred in 30 (14.2%). Patients with older age (OR = 1.07, 95% CI: 1.02−1.13), higher serum glucose (OR = 1.01, 95% CI: 1.01−1.02), and higher NLR (OR = 1.011, 95% CI: 1.04−1.18) had an increased risk of END. The best predictive cut-off value of NLR was 6.4, and END occurred in 24.1% and 3.9% of the patients with NLR ≥ 6.4 and <6.4, respectively (p < 0.001). In patients with AIS undergoing EVT, higher NLR values predicted a higher risk of END. Biomarkers able to identify inflammatory mechanisms might identify novel treatment targets and enhance proof-of-concept trials of immunomodulation in stroke.
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Affiliation(s)
- Simona Lattanzi
- Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, 60121 Ancona, Italy
- Correspondence:
| | - Davide Norata
- Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, 60121 Ancona, Italy
| | - Serena Broggi
- Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, 60121 Ancona, Italy
| | - Stefano Meletti
- Neurology Unit, OCB Hospital, AOU Modena, 41125 Modena, Italy
- Department of Biomedical, Metabolic and Neural Science, Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, 41121 Modena, Italy
| | - Milena Świtońska
- Department of Neurosurgery and Neurology, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum, Faculty of Health Sciences, 85-067 Bydgoszcz, Poland
| | - Artur Słomka
- Department of Pathophysiology, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, 85-067 Bydgoszcz, Poland
| | - Mauro Silvestrini
- Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, 60121 Ancona, Italy
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Zeng M, Oakden-Rayner L, Bird A, Smith L, Wu Z, Scroop R, Kleinig T, Jannes J, Jenkinson M, Palmer LJ. Pre-thrombectomy prognostic prediction of large-vessel ischemic stroke using machine learning: A systematic review and meta-analysis. Front Neurol 2022; 13:945813. [PMID: 36158960 PMCID: PMC9495610 DOI: 10.3389/fneur.2022.945813] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 08/18/2022] [Indexed: 11/20/2022] Open
Abstract
Introduction Machine learning (ML) methods are being increasingly applied to prognostic prediction for stroke patients with large vessel occlusion (LVO) treated with endovascular thrombectomy. This systematic review aims to summarize ML-based pre-thrombectomy prognostic models for LVO stroke and identify key research gaps. Methods Literature searches were performed in Embase, PubMed, Web of Science, and Scopus. Meta-analyses of the area under the receiver operating characteristic curves (AUCs) of ML models were conducted to synthesize model performance. Results Sixteen studies describing 19 models were eligible. The predicted outcomes include functional outcome at 90 days, successful reperfusion, and hemorrhagic transformation. Functional outcome was analyzed by 10 conventional ML models (pooled AUC=0.81, 95% confidence interval [CI]: 0.77-0.85, AUC range: 0.68-0.93) and four deep learning (DL) models (pooled AUC=0.75, 95% CI: 0.70-0.81, AUC range: 0.71-0.81). Successful reperfusion was analyzed by three conventional ML models (pooled AUC=0.72, 95% CI: 0.56-0.88, AUC range: 0.55-0.88) and one DL model (AUC=0.65, 95% CI: 0.62-0.68). Conclusions Conventional ML and DL models have shown variable performance in predicting post-treatment outcomes of LVO without generally demonstrating superiority compared to existing prognostic scores. Most models were developed using small datasets, lacked solid external validation, and at high risk of potential bias. There is considerable scope to improve study design and model performance. The application of ML and DL methods to improve the prediction of prognosis in LVO stroke, while promising, remains nascent. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021266524, identifier CRD42021266524.
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Affiliation(s)
- Minyan Zeng
- Australian Institute for Machine Learning, University of Adelaide, Adelaide, SA, Australia
- School of Public Health, University of Adelaide, Adelaide, SA, Australia
| | - Lauren Oakden-Rayner
- Australian Institute for Machine Learning, University of Adelaide, Adelaide, SA, Australia
- School of Public Health, University of Adelaide, Adelaide, SA, Australia
- Department of Radiology, Royal Adelaide Hospital, Adelaide, SA, Australia
| | - Alix Bird
- Australian Institute for Machine Learning, University of Adelaide, Adelaide, SA, Australia
- School of Public Health, University of Adelaide, Adelaide, SA, Australia
| | - Luke Smith
- Australian Institute for Machine Learning, University of Adelaide, Adelaide, SA, Australia
- School of Public Health, University of Adelaide, Adelaide, SA, Australia
| | - Zimu Wu
- School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia
| | - Rebecca Scroop
- Department of Radiology, Royal Adelaide Hospital, Adelaide, SA, Australia
- Faculty Health and Medical Science, School of Medicine, University of Adelaide, Adelaide, SA, Australia
| | - Timothy Kleinig
- Faculty Health and Medical Science, School of Medicine, University of Adelaide, Adelaide, SA, Australia
- Department of Neurology, Royal Adelaide Hospital, Adelaide, SA, Australia
| | - Jim Jannes
- Faculty Health and Medical Science, School of Medicine, University of Adelaide, Adelaide, SA, Australia
- Department of Neurology, Royal Adelaide Hospital, Adelaide, SA, Australia
| | - Mark Jenkinson
- Australian Institute for Machine Learning, University of Adelaide, Adelaide, SA, Australia
- Functional Magnetic Resonance Imaging of the Brain Centre, University of Oxford, Oxford, United Kingdom
| | - Lyle J. Palmer
- Australian Institute for Machine Learning, University of Adelaide, Adelaide, SA, Australia
- School of Public Health, University of Adelaide, Adelaide, SA, Australia
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Lin X, Zheng X, Zhang J, Cui X, Zou D, Zhao Z, Pan X, Jie Q, Wu Y, Qiu R, Zhou J, Chen N, Tang L, Ge C, Zou J. Machine learning to predict futile recanalization of large vessel occlusion before and after endovascular thrombectomy. Front Neurol 2022; 13:909403. [PMID: 36062013 PMCID: PMC9437637 DOI: 10.3389/fneur.2022.909403] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 07/05/2022] [Indexed: 11/30/2022] Open
Abstract
Background and purpose Futile recanalization occurs when the endovascular thrombectomy (EVT) is a technical success but fails to achieve a favorable outcome. This study aimed to use machine learning (ML) algorithms to develop a pre-EVT model and a post-EVT model to predict the risk of futile recanalization and to provide meaningful insights to assess the prognostic factors associated with futile recanalization. Methods Consecutive acute ischemic stroke patients with large vessel occlusion (LVO) undergoing EVT at the National Advanced Stroke Center of Nanjing First Hospital (China) between April 2017 and May 2021 were analyzed. The baseline characteristics and peri-interventional characteristics were assessed using four ML algorithms. The predictive performance was evaluated by the area under curve (AUC) of receiver operating characteristic and calibration curve. In addition, the SHapley Additive exPlanations (SHAP) approach and partial dependence plot were introduced to understand the relative importance and the influence of a single feature. Results A total of 312 patients were included in this study. Of the four ML models that include baseline characteristics, the "Early" XGBoost had a better performance {AUC, 0.790 [95% confidence intervals (CI), 0.677-0.903]; Brier, 0.191}. Subsequent inclusion of peri-interventional characteristics into the "Early" XGBoost showed that the "Late" XGBoost performed better [AUC, 0.910 (95% CI, 0.837-0.984); Brier, 0.123]. NIHSS after 24 h, age, groin to recanalization, and the number of passages were the critical prognostic factors associated with futile recanalization, and the SHAP approach shows that NIHSS after 24 h ranks first in relative importance. Conclusions The "Early" XGBoost and the "Late" XGBoost allowed us to predict futile recanalization before and after EVT accurately. Our study suggests that including peri-interventional characteristics may lead to superior predictive performance compared to a model based on baseline characteristics only. In addition, NIHSS after 24 h was the most important prognostic factor for futile recanalization.
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Affiliation(s)
- Xinping Lin
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Department of Pharmacy Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Xiaohan Zheng
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Department of Pharmacy Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Juan Zhang
- Department of Neurology, Nanjing Yuhua Hospital, Yuhua Branch of Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Xiaoli Cui
- Department of Neurology, Nanjing Yuhua Hospital, Yuhua Branch of Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Daizu Zou
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Department of Pharmacy Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Zheng Zhao
- Department of Pharmacy Nanjing First Hospital, Nanjing Medical University, Nanjing, China
- Department of Pharmacy, Nanjing First Hospital, China Pharmaceutical University, Nanjing, China
| | - Xiding Pan
- Department of Pharmacy Nanjing First Hospital, Nanjing Medical University, Nanjing, China
- Department of Pharmacy, Nanjing First Hospital, China Pharmaceutical University, Nanjing, China
| | - Qiong Jie
- Department of Pharmacy Nanjing First Hospital, Nanjing Medical University, Nanjing, China
- Department of Pharmacy, Nanjing First Hospital, China Pharmaceutical University, Nanjing, China
| | - Yuezhang Wu
- Department of Pharmacy Nanjing First Hospital, Nanjing Medical University, Nanjing, China
- Department of Pharmacy, Nanjing First Hospital, China Pharmaceutical University, Nanjing, China
| | - Runze Qiu
- Department of Pharmacy Nanjing First Hospital, Nanjing Medical University, Nanjing, China
- Department of Pharmacy, Nanjing First Hospital, China Pharmaceutical University, Nanjing, China
| | - Junshan Zhou
- Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Nihong Chen
- Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Li Tang
- Department of Pharmacy, Yixing Cancer Hospital, Yixing, China
| | - Chun Ge
- Department of Pharmacy Nanjing First Hospital, Nanjing Medical University, Nanjing, China
- Department of Pharmacy, Nanjing First Hospital, China Pharmaceutical University, Nanjing, China
| | - Jianjun Zou
- Department of Pharmacy Nanjing First Hospital, Nanjing Medical University, Nanjing, China
- Department of Pharmacy, Nanjing First Hospital, China Pharmaceutical University, Nanjing, China
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Monteiro A, Waqas M, Rai HH, Baig AA, Dossani RH, Cappuzzo JM, Levy EI, Siddiqui AH. The impact of brain atrophy on the outcomes of mechanical thrombectomy. Br J Radiol 2022; 95:20210494. [PMID: 35084207 PMCID: PMC9153700 DOI: 10.1259/bjr.20210494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Objective: Pre-existing brain atrophy may affect the outcomes of patients treated with mechanical thrombectomy (MT) for large-vessel-occlusion because it is an indicator of low brain reserve. We performed a systematic literature review to assess the impact of brain atrophy on MT-related clinical outcomes. Methods: We conducted a systematic search of PubMed, MEDLINE, EMBASE, and Cochrane Library databases from inception to March 2021 using keywords with Boolean operators(“brain atrophy”; “atrophy”; “white matter”; and “thrombectomy”). Articles published in English that evaluated the impact of pre-existing brain atrophy on outcomes of MT-treated acute ischemic stroke were eligible for inclusion. Results: Four articles were included. Brain atrophy index was a predictor of mortality (odds ratio [OR]:1.81–1.87, 95% confidence interval [CI]:1.16–2.93) after adjustments for age and white matter lesions. Global cortical atrophy scale was an independent predictor of futile recanalization (OR 1.15, 95% CI 1.08–1.22) in multivariate-adjusted logistic regression. Automated measurement of CSF identified increasing volumes associated with reduced 3-month functional independence and higher modified Rankin scale scores. STandards for ReportIng Vascular changes on Neuroimaging criteria for brain atrophy were associated with unfavorable outcome in ordinal-shift analysis (OR 2.72, 95% CI 1.25–5.91). Conclusions: The few studies available highlight heterogeneity of neuroimaging methodologies for assessing brain atrophy and difficulty addressing the multiple confounders involved in clinical outcomes. More consistent, accurate investigation is needed before proposing brain atrophy as a possible parameter to improve patient selection for MT. Advances in knowledge: Brain atrophy is associated with many of the clinical confounders frequently present in patients with acute ischemic stroke. Heterogeneity in classification methodologies for brain atrophy and complexity analyzing multiple clinical confounders make it difficult to assess the true impact of this radiological finding on MT-related outcomes.
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Affiliation(s)
- Andre Monteiro
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
- Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, New York, USA
| | - Muhammad Waqas
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
- Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, New York, USA
| | - Hamid H. Rai
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
- Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, New York, USA
| | - Ammad A. Baig
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
- Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, New York, USA
| | - Rimal H. Dossani
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
- Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, New York, USA
| | - Justin M. Cappuzzo
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
- Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, New York, USA
| | - Elad I. Levy
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
- Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, New York, USA
- Canon Stroke and Vascular Research Center, University at Buffalo, Buffalo, New York, USA
- Jacobs Institute, Buffalo, New York, USA
- Department of Radiology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
| | - Adnan H. Siddiqui
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
- Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, New York, USA
- Canon Stroke and Vascular Research Center, University at Buffalo, Buffalo, New York, USA
- Jacobs Institute, Buffalo, New York, USA
- Department of Radiology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
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Ouyang K, Kang Z, Liu Z, Hou B, Fang J, Xie Y, Liu Y. Posterior Circulation ASPECTS on CT Angiography Predicts Futile Recanalization of Endovascular Thrombectomy for Acute Basilar Artery Occlusion. Front Neurol 2022; 13:831386. [PMID: 35370881 PMCID: PMC8966670 DOI: 10.3389/fneur.2022.831386] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 02/11/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Acute basilar artery occlusion (BAO) is the most potentially disastrous outcome and has a high risk of recurrence stroke in posterior circulation infarction (PCI). However, the rate of futile recanalization remains high despite successful recanalization. The objective of this study was to investigate 90 days functional outcomes among patients with BAO who underwent endovascular thrombectomy (EVT) and to identify the risk factors associated with futile recanalization. METHODS We retrospectively analyzed 72 patients with acute BAO who received EVT from January 2018 to June 2021. CT angiography source images posterior circulation Acute Stroke Prognosis Early CT Score (CTA-SI pc-ASPECTS) evaluated the extensive hypoattenuation in patients with BAO. Futile recanalization defined an modified Rankin Scale (mRS) of 3-6 at 90 days despite a successful recanalization. Logistic regression analysis was performed to investigate the predictors of futile recanalization. RESULTS Our sample included a total of 55 eligible patients. Patients with poor outcomes showed that the pc-ASPECTS score was lower in patients with poor outcomes than that in patients with good outcomes (P = 0.017). Longer time from symptoms onset-to-the puncture (P = 0.014) and elevation of leucocytes (P = 0.012) were associated with poor outcomes. The multivariable logistic analysis showed that pc-ASPECTS and onset-to-puncture time (OPT) were independent predictors of futile recanalization. CONCLUSIONS This study suggested that pc-ASPECTS and OPT are independent predictors of futile recanalization after EVT in patients with BAO. The lower pc-ASPECTS score and longer puncture time will have a poor clinical outcome.
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Affiliation(s)
| | | | | | | | | | | | - Yumin Liu
- Department of Neurology, Zhongnan Hospital, Wuhan University, Wuhan, China
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Liu C, Qin T, Liu L. Evaluation of Ischemic Penumbra in Stroke Patients Based on Deep Learning and Multimodal CT. JOURNAL OF HEALTHCARE ENGINEERING 2021; 2021:3215107. [PMID: 39290779 PMCID: PMC11407880 DOI: 10.1155/2021/3215107] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 10/29/2021] [Accepted: 11/09/2021] [Indexed: 09/19/2024]
Abstract
In order to investigate the value of multimodal CT for quantitative assessment of collateral circulation, ischemic semidark zone, core infarct volume in patients with acute ischemic stroke (AIS), and prognosis assessment in intravenous thrombolytic therapy, segmentation model which is based on the self-attention mechanism is prone to generate attention coefficient maps with incorrect regions of interest. Moreover, the stroke lesion is not clearly characterized, and lesion boundary is poorly differentiated from normal brain tissue, thus affecting the segmentation performance. To address this problem, a primary and secondary path attention compensation network structure is proposed, which is based on the improved global attention upsampling U-Net model. The main path network is responsible for performing accurate lesion segmentation and outputting segmentation results. Likewise, the auxiliary path network generates loose auxiliary attention compensation coefficients, which compensate for possible attention coefficient errors in the main path network. Two hybrid loss functions are proposed to realize the respective functions of main and auxiliary path networks. It is experimentally demonstrated that both the improved global attention upsampling U-Net and the proposed primary and secondary path attention compensation networks show significant improvement in segmentation performance. Moreover, patients with good collateral circulation have a small final infarct area volume and a good clinical prognosis after intravenous thrombolysis. Quantitative assessment of collateral circulation and ischemic semidark zone by multimodal CT can better predict the clinical prognosis of intravenous thrombolysis.
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Affiliation(s)
- Changhua Liu
- Department of Radiology, Hanyang Hospital Affiliated of Wuhan University of Science and Technology, Wuhan 430050, China
| | - Tao Qin
- Hubei No. 3 People's Hospital of Jianghan University, Department of Radiology, Wuhan, China
| | - Liangjin Liu
- Hubei No. 3 People's Hospital of Jianghan University, Department of Radiology, Wuhan, China
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Conti E, Piccardi B, Sodero A, Tudisco L, Lombardo I, Fainardi E, Nencini P, Sarti C, Allegra Mascaro AL, Baldereschi M. Translational Stroke Research Review: Using the Mouse to Model Human Futile Recanalization and Reperfusion Injury in Ischemic Brain Tissue. Cells 2021; 10:3308. [PMID: 34943816 PMCID: PMC8699609 DOI: 10.3390/cells10123308] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 11/17/2021] [Accepted: 11/19/2021] [Indexed: 12/20/2022] Open
Abstract
The approach to reperfusion therapies in stroke patients is rapidly evolving, but there is still no explanation why a substantial proportion of patients have a poor clinical prognosis despite successful flow restoration. This issue of futile recanalization is explained here by three clinical cases, which, despite complete recanalization, have very different outcomes. Preclinical research is particularly suited to characterize the highly dynamic changes in acute ischemic stroke and identify potential treatment targets useful for clinical translation. This review surveys the efforts taken so far to achieve mouse models capable of investigating the neurovascular underpinnings of futile recanalization. We highlight the translational potential of targeting tissue reperfusion in fully recanalized mouse models and of investigating the underlying pathophysiological mechanisms from subcellular to tissue scale. We suggest that stroke preclinical research should increasingly drive forward a continuous and circular dialogue with clinical research. When the preclinical and the clinical stroke research are consistent, translational success will follow.
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Affiliation(s)
- Emilia Conti
- Neuroscience Institute, National Research Council, Via G. Moruzzi 1, 56124 Pisa, Italy; (E.C.); (A.L.A.M.)
- European Laboratory for Non-Linear Spectroscopy, Via Nello Carrara 1, 50019 Sesto Fiorentino, Italy
| | - Benedetta Piccardi
- Neurofarba Department, University of Florence, Via G. Pieraccini 6, 50139 Florence, Italy; (A.S.); (L.T.); (C.S.)
| | - Alessandro Sodero
- Neurofarba Department, University of Florence, Via G. Pieraccini 6, 50139 Florence, Italy; (A.S.); (L.T.); (C.S.)
| | - Laura Tudisco
- Neurofarba Department, University of Florence, Via G. Pieraccini 6, 50139 Florence, Italy; (A.S.); (L.T.); (C.S.)
| | - Ivano Lombardo
- Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy; (I.L.); (E.F.)
| | - Enrico Fainardi
- Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy; (I.L.); (E.F.)
| | - Patrizia Nencini
- Stroke Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy;
| | - Cristina Sarti
- Neurofarba Department, University of Florence, Via G. Pieraccini 6, 50139 Florence, Italy; (A.S.); (L.T.); (C.S.)
| | - Anna Letizia Allegra Mascaro
- Neuroscience Institute, National Research Council, Via G. Moruzzi 1, 56124 Pisa, Italy; (E.C.); (A.L.A.M.)
- European Laboratory for Non-Linear Spectroscopy, Via Nello Carrara 1, 50019 Sesto Fiorentino, Italy
| | - Marzia Baldereschi
- Neuroscience Institute, National Research Council, Via Madonna del Piano 10, 50019 Sesto Fiorentino, Italy;
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Nomani AZ, Kamtchum Tatuene J, Rempel JL, Jeerakathil T, Winship IR, Khan KA, Buck BH, Shuaib A, Jickling GC. Association of CT-Based Hypoperfusion Index With Ischemic Core Enlargement in Patients With Medium and Large Vessel Stroke. Neurology 2021; 97:e2079-e2087. [PMID: 34607925 PMCID: PMC8610618 DOI: 10.1212/wnl.0000000000012855] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 09/15/2021] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND AND OBJECTIVES The rate of infarct core progression in patients with acute ischemic stroke is variable and affects outcome of reperfusion therapy. We evaluated the hypoperfusion index (HI) to estimate the initial rate of core progression in patients with medium vessel occlusion (MeVO) compared to large vessel occlusion (LVO) stroke and within a larger time frame since stroke onset. METHODS Core progression was assessed in 106 patients with acute stroke and CT perfusion. Using reperfusion trial core time criteria, fast progressors had core >70 mL within 6 hours of stroke onset and slow progressors had core ≤70 mL, mismatch ≥15 mL, and mismatch to core ratio ≥1.8 within 6 to 24 hours. The relationship between HI and infarct core progression (core/time) was examined using receiver operating characteristics to determine optimal HI cutoff. The HI cutoff was then tested in the overall cohort, compared between MeVO and LVO, and evaluated in patients up to 24 hours from stroke onset to differentiate fast from slow rate of core progression. HI threshold was assessed in a second independent cohort of 110 patients with acute ischemic stroke. RESULTS In 106 patients with acute stroke, 6.6% were fast progressors, 27.4% were slow progressors, and 66% were not classified as fast or slow progressor by reperfusion trial core time criteria. HI >0.5 was associated with fast progression and able to distinguish fast from slow progressors (area under the curve [AUC] 0.94; 95% confidence interval [CI] 0.80-0.99). In MeVO (n = 26) HI >0.5 had a core progression of 0.30 mL/min compared to 0.03 mL/min for HI ≤0.5 (p < 0.001). In LVO (n = 80), HI >0.5 had a core progression of 0.26 mL/min compared to 0.02 mL/min for HI ≤0.5 (p < 0.001). In patients not classified as fast or slow progressor by reperfusion trial criteria, those with HI >0.5 had progression rate of 0.21 mL/min compared to 0.03 mL/min for those with HI ≤0.5 (p < 0.001). Validation in a second cohort of patients with acute ischemic stroke (n = 110; MeVO = 42, LVO = 68) yielded similar results for HI >0.5 to distinguish fast and slow core progression with an AUC of 0.84 (95% CI 0.72-0.97). DISCUSSION HI can differentiate fast from slow core progression in MeVO and LVO within the first 24 hours of acute ischemic stroke. Consideration of core progression rate at time of stroke evaluation may have implications in the selection of patients with MeVO and LVO stroke for reperfusion therapy that warrant further study.
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Affiliation(s)
- Ali Z Nomani
- From the Division of Neurology, Department of Medicine (A.Z.N., T.J., I.W., K.A.K., B.H.B., A.S., G.C.J.), Neuroscience and Mental Health Institute, Department of Medicine and Dentistry (J.K.T.), Department of Radiology (J.L.R.), and Department of Psychiatry (I.W.), University of Alberta, Edmonton; and Red Deer Regional Hospital (A.Z.N.), Canada.
| | - Joseph Kamtchum Tatuene
- From the Division of Neurology, Department of Medicine (A.Z.N., T.J., I.W., K.A.K., B.H.B., A.S., G.C.J.), Neuroscience and Mental Health Institute, Department of Medicine and Dentistry (J.K.T.), Department of Radiology (J.L.R.), and Department of Psychiatry (I.W.), University of Alberta, Edmonton; and Red Deer Regional Hospital (A.Z.N.), Canada
| | - Jeremy L Rempel
- From the Division of Neurology, Department of Medicine (A.Z.N., T.J., I.W., K.A.K., B.H.B., A.S., G.C.J.), Neuroscience and Mental Health Institute, Department of Medicine and Dentistry (J.K.T.), Department of Radiology (J.L.R.), and Department of Psychiatry (I.W.), University of Alberta, Edmonton; and Red Deer Regional Hospital (A.Z.N.), Canada
| | - Thomas Jeerakathil
- From the Division of Neurology, Department of Medicine (A.Z.N., T.J., I.W., K.A.K., B.H.B., A.S., G.C.J.), Neuroscience and Mental Health Institute, Department of Medicine and Dentistry (J.K.T.), Department of Radiology (J.L.R.), and Department of Psychiatry (I.W.), University of Alberta, Edmonton; and Red Deer Regional Hospital (A.Z.N.), Canada
| | - Ian R Winship
- From the Division of Neurology, Department of Medicine (A.Z.N., T.J., I.W., K.A.K., B.H.B., A.S., G.C.J.), Neuroscience and Mental Health Institute, Department of Medicine and Dentistry (J.K.T.), Department of Radiology (J.L.R.), and Department of Psychiatry (I.W.), University of Alberta, Edmonton; and Red Deer Regional Hospital (A.Z.N.), Canada
| | - Khurshid A Khan
- From the Division of Neurology, Department of Medicine (A.Z.N., T.J., I.W., K.A.K., B.H.B., A.S., G.C.J.), Neuroscience and Mental Health Institute, Department of Medicine and Dentistry (J.K.T.), Department of Radiology (J.L.R.), and Department of Psychiatry (I.W.), University of Alberta, Edmonton; and Red Deer Regional Hospital (A.Z.N.), Canada
| | - Brian H Buck
- From the Division of Neurology, Department of Medicine (A.Z.N., T.J., I.W., K.A.K., B.H.B., A.S., G.C.J.), Neuroscience and Mental Health Institute, Department of Medicine and Dentistry (J.K.T.), Department of Radiology (J.L.R.), and Department of Psychiatry (I.W.), University of Alberta, Edmonton; and Red Deer Regional Hospital (A.Z.N.), Canada
| | - Ashfaq Shuaib
- From the Division of Neurology, Department of Medicine (A.Z.N., T.J., I.W., K.A.K., B.H.B., A.S., G.C.J.), Neuroscience and Mental Health Institute, Department of Medicine and Dentistry (J.K.T.), Department of Radiology (J.L.R.), and Department of Psychiatry (I.W.), University of Alberta, Edmonton; and Red Deer Regional Hospital (A.Z.N.), Canada
| | - Glen C Jickling
- From the Division of Neurology, Department of Medicine (A.Z.N., T.J., I.W., K.A.K., B.H.B., A.S., G.C.J.), Neuroscience and Mental Health Institute, Department of Medicine and Dentistry (J.K.T.), Department of Radiology (J.L.R.), and Department of Psychiatry (I.W.), University of Alberta, Edmonton; and Red Deer Regional Hospital (A.Z.N.), Canada
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Seo WK, Nam HS, Chung JW, Kim YD, Kim KH, Bang OY, Kim BM, Kim GM, Jeon P, Heo JH. TAB-TICI Score: Successful Recanalization Score After Endovascular Thrombectomy in Acute Stroke. Front Neurol 2021; 12:692490. [PMID: 34721254 PMCID: PMC8551570 DOI: 10.3389/fneur.2021.692490] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 08/06/2021] [Indexed: 11/13/2022] Open
Abstract
Background and Purpose: Successful reperfusion therapy is supposed to be comprehensive and validated beyond the grade of recanalization. This study aimed to develop a novel scoring system for defining the successful recanalization after endovascular thrombectomy. Methods: We analyzed the data of consecutive acute stroke patients who were eligible to undergo reperfusion therapy within 24 h of onset and who underwent mechanical thrombectomy using a nationwide multicenter stroke registry. A new score was produced using the predictors which were directly linked to the procedure to evaluate the performance of the thrombectomy procedure. Results: In total, 446 patients in the training population and 222 patients in the validation population were analyzed. From the potential components of the score, four items were selected: Emergency Room-to-puncture time (T), adjuvant devices used (A), procedural intracranial bleeding (B), and post-thrombectomy reperfusion status [Thrombolysis in Cerebral Infarction (TICI)]. Using these items, the TAB-TICI score was developed, which showed good performance in terms of discriminating early neurological aggravation [AUC 0.73, 95% confidence interval (CI) 0.67–0.78, P < 0.01] and favorable outcomes (AUC 0.69, 95% CI 0.64–0.75, P < 0.01) in the training population. The stability of the TAB-TICI score was confirmed by external validation and sensitivity analyses. The TAB-TICI score and its derived grade of successful recanalization were significantly associated with the volume of thrombectomy cases at each site and in each admission year. Conclusion: The TAB-TICI score is a valid and easy-to-use tool to more comprehensively define successful recanalization after endovascular thrombectomy in acute stroke patients with large vessel occlusion.
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Affiliation(s)
- Woo-Keun Seo
- Department of Neurology and Stroke Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.,Department of Digital Health, Samsung Advanced Institute for Health Science & Technology (SAIHST), Sungkyunkwan University, Seoul, South Korea
| | - Hyo Suk Nam
- Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea
| | - Jong-Won Chung
- Department of Neurology and Stroke Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Young Dae Kim
- Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea
| | - Keon-Ha Kim
- Department of Radiology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea
| | - Oh Young Bang
- Department of Neurology and Stroke Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Byung Moon Kim
- Interventional Neuroradiology, Yonsei University College of Medicine, Seoul, South Korea
| | - Gyeung-Moon Kim
- Department of Neurology and Stroke Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Pyoung Jeon
- Department of Radiology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea
| | - Ji Hoe Heo
- Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea
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Lee SH, Jang MU, Kim Y, Park SY, Kim C, Kim YJ, Sohn JH. Impact of Prior Statin Use on Reperfusion Rate and Stroke Outcomes in Patients Receiving Endovascular Treatment. J Clin Med 2021; 10:jcm10215147. [PMID: 34768673 PMCID: PMC8584468 DOI: 10.3390/jcm10215147] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 10/18/2021] [Accepted: 10/30/2021] [Indexed: 01/01/2023] Open
Abstract
Background: We evaluated the impact of prior statin use on successful reperfusion and stroke outcomes after endovascular treatment (EVT). Method: Using consecutive multicenter databases, we enrolled acute ischemic stroke patients receiving EVT between 2015 and 2021. Patients were classified into prior statin users and no prior statin users after a review of premorbid medications. The primary outcome measure was successful reperfusion defined as modified TICI grade 2b or 3 after EVT. Secondary outcome measures were early neurologic deterioration (END) and a 3-month modified Rankin Scale (mRS) score of 0 to 2. Results: Among 385 patients receiving EVT, 74 (19.2%) were prior statin users, who had a significantly higher successful reperfusion rate compared with no prior statin users (94.6% versus 78.8%, p = 0.002). Successful reperfusion and END occurrence were improved according to statin intensity with a dose–response relationship. In multivariate analysis, prior statin was associated with successful reperfusion after EVT (adjusted odds ratio (95% confidence interval) 5.31 (1.67–16.86)). In addition, prior statin was associated with a lower occurrence of END and good functional status. Conclusion: Our study showed that prior statin use before ischemic stroke might improve successful reperfusion and stroke outcomes after EVT.
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Affiliation(s)
- Sang-Hwa Lee
- Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon 24253, Korea; (S.-H.L.); (C.K.); (Y.J.K.)
- Institute of New Frontier Research, Hallym University, Chuncheon 24252, Korea
| | - Min Uk Jang
- Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong 18450, Korea;
| | - Yerim Kim
- Department of Neurology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul 05355, Korea;
| | - So Young Park
- Department of Endocrinology and Metabolism, Kyung Hee University Hospital, Seoul 02447, Korea;
| | - Chulho Kim
- Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon 24253, Korea; (S.-H.L.); (C.K.); (Y.J.K.)
- Institute of New Frontier Research, Hallym University, Chuncheon 24252, Korea
| | - Yeo Jin Kim
- Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon 24253, Korea; (S.-H.L.); (C.K.); (Y.J.K.)
| | - Jong-Hee Sohn
- Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon 24253, Korea; (S.-H.L.); (C.K.); (Y.J.K.)
- Institute of New Frontier Research, Hallym University, Chuncheon 24252, Korea
- Correspondence: ; Tel.: +82-33-240-5255; Fax: +82-33-255-1338
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Haranhalli N, Javed K, Boyke A, Dardick J, Naidu I, Ryvlin J, Kadaba D, Fluss R, Derby C, Altschul D. A Predictive Model for Functional Outcome in Patients with Acute Ischemic Stroke Undergoing Endovascular Thrombectomy. J Stroke Cerebrovasc Dis 2021; 30:106054. [PMID: 34508988 DOI: 10.1016/j.jstrokecerebrovasdis.2021.106054] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 08/01/2021] [Accepted: 08/05/2021] [Indexed: 12/01/2022] Open
Abstract
INTRODUCTION Endovascular thrombectomy (EVT) is a well-established treatment of acute ischemic stroke. Variability in outcomes among thrombectomy patients results in a need for patient centered approaches to recovery. Identifying key factors that are associated with outcomes can help prognosticate and direct resources for continued improvement post-treatment. Thus, we developed a comprehensive predictive model of short-term outcomes post-thrombectomy. METHODS This is a retrospective chart review of adult patients who underwent EVT at our institution over the last four years. Primary outcome was dichotomized 90-day mRS (mRS 0-2 v mRS 3-6). Bivariate analyses were conducted, followed by logistic regression modelling via a backward-elimination approach to identify the best fit predictive model. RESULTS 326 thrombectomies were performed; 230 cases were included in the model. In the final predictive model, adjusting for age, gender, race, diabetes, and presenting NIHSS, pre-admission mRS = 0-2 (OR 18.1; 95% 3.44-95.48; p < 0.001) was the strongest predictor of a good outcome at 90-days. Other independent predictors of good outcomes included being a non-smoker (OR 5.4; 95% CI 1.53-19.00; p = 0.01) and having a post-thrombectomy NIHSS<10 (OR 9.7; 95% CI 3.90-24.27; p < 0.001). A decompressive hemicraniectomy (DHC) was predictive of a poor outcome at 90-days (OR 0.07; 95% CI 0.01-0.72; p = 0.03). This model had a Sensitivity of 79%, a Specificity of 89% and an AUC=0.89. CONCLUSION Our model identified low pre-admission mRS score, low post-thrombectomy NIHSS, non-smoker status and not requiring a DHC as predictors of good functional outcomes at 90-days. Future works include developing a prognostic scoring system.
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Affiliation(s)
- Neil Haranhalli
- Dept. of Neurosurgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY USA.
| | - Kainaat Javed
- Dept. of Neurosurgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY USA
| | - Andre Boyke
- Dept. of Neurosurgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY USA
| | - Joseph Dardick
- Dept. of Neurosurgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY USA
| | - Ishan Naidu
- Dept. of Neurosurgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY USA
| | - Jessica Ryvlin
- Dept. of Neurosurgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY USA
| | - Devikarani Kadaba
- Dept. of Neurosurgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY USA
| | - Rose Fluss
- Dept. of Neurosurgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY USA
| | - Carol Derby
- Dept. of Neurology, Dept. of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx NY USA
| | - David Altschul
- Dept. of Neurosurgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY USA
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Zhou T, Yi T, Li T, Zhu L, Li Y, Li Z, Wang M, Li Q, He Y, Yang P, Zhang Y, Li Z, Zhang Y, Ye X, Chen W, Wang S, Liu J. Predictors of futile recanalization in patients undergoing endovascular treatment in the DIRECT-MT trial. J Neurointerv Surg 2021; 14:752-755. [PMID: 34475255 DOI: 10.1136/neurintsurg-2021-017765] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 08/23/2021] [Indexed: 01/01/2023]
Abstract
BACKGROUND Futile recanalization-when patients have a successful recanalization but fail to achieve a satisfactory functional outcome- is a common phenomenon of endovascular treatment of acute ischemic stroke (AIS). The present study aimed to identify the predictors of futile recanalization in AIS patients who received endovascular treatment. METHODS This is a post-hoc analysis of the DIRECT-MT trial. Demographics, clinical characteristics, acute stroke workflow interval times, biochemical parameters, and imaging characteristics were compared between futile and meaningful recanalization groups. Multivariate analysis was performed to identify the predictors of futile recanalization. RESULTS Futile recanalization was observed in 277 patients. In multivariable logistic regression analysis, older age (p<0.001), higher baseline systolic blood pressure (SBP) (p=0.032), incomplete reperfusion defined by extended Thrombolysis In Cerebral Infarction (eTICI) grades (p=0.020), and larger final infarct volume (FIV) (p<0.001) were independent predictors of futile recanalization. CONCLUSIONS Old age, high baseline SBP, incomplete reperfusion defined by eTICI, and large FIV were independent predictors of futile recanalization after endovascular therapy for AIS.
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Affiliation(s)
- Tengfei Zhou
- Department of Cerebrovascular Disease, Henan Provincial People's Hospital, Zhengzhou, Henan, China.,Department of Cerebrovascular Disease, Zhengzhou University People's Hospital, Zhengzhou, China
| | - Tingyu Yi
- Department of Neurology, Zhangzhou Municipal Hospital of Fujian Province and Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Tianxiao Li
- Department of Cerebrovascular Disease, Henan Provincial People's Hospital, Zhengzhou, Henan, China .,Department of Cerebrovascular Disease, Zhengzhou University People's Hospital, Zhengzhou, China
| | - Liangfu Zhu
- Department of Cerebrovascular Disease, Henan Provincial People's Hospital, Zhengzhou, Henan, China
| | - Yucheng Li
- Department of Cerebrovascular Disease, Henan Provincial People's Hospital, Zhengzhou, Henan, China
| | - Zhaoshuo Li
- Department of Cerebrovascular Disease, Henan Provincial People's Hospital, Zhengzhou, Henan, China
| | - Meiyun Wang
- Department of Radiology, Henan Provincial People's Hospital, Zhengzhou, Henan, China
| | - Qiang Li
- Department of Cerebrovascular Disease, Henan Provincial People's Hospital, Zhengzhou, Henan, China
| | - Yingkun He
- Department of Cerebrovascular Disease, Henan Provincial People's Hospital, Zhengzhou, Henan, China
| | - Pengfei Yang
- Department of Neurosurgery, Naval Medical University Changhai Hospital, Shanghai, China
| | - Yongwei Zhang
- Department of Neurosurgery, Naval Medical University Changhai Hospital, Shanghai, China
| | - Zifu Li
- Department of Neurosurgery, Naval Medical University Changhai Hospital, Shanghai, China
| | - Yongxin Zhang
- Department of Neurosurgery, Naval Medical University Changhai Hospital, Shanghai, China
| | - Xiaofei Ye
- Department of Statistics, Naval Medical University, Shanghai, China
| | - Wenhuo Chen
- Department of Neurology, Zhangzhou Municipal Hospital of Fujian Province and Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Shouchun Wang
- Department of Neurology, The First Affiliated Hospital of Jilin University, Changchun, China
| | - Jianmin Liu
- Department of Neurosurgery, Naval Medical University Changhai Hospital, Shanghai, China
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Lattanzi S, Norata D, Divani AA, Di Napoli M, Broggi S, Rocchi C, Ortega-Gutierrez S, Mansueto G, Silvestrini M. Systemic Inflammatory Response Index and Futile Recanalization in Patients with Ischemic Stroke Undergoing Endovascular Treatment. Brain Sci 2021; 11:brainsci11091164. [PMID: 34573185 PMCID: PMC8468021 DOI: 10.3390/brainsci11091164] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 08/25/2021] [Accepted: 08/30/2021] [Indexed: 11/16/2022] Open
Abstract
Futile recanalization remains a significant challenge for endovascular treatment (EVT) of acute ischemic stroke (AIS). The inflammatory response that occurs after cerebral infarct plays a central role in stroke pathobiology that can influence the outcome of a recanalization procedure. The aim of this study was to evaluate the relationship between the systemic inflammatory response index (SIRI) and futile recanalization in patients with AIS. We retrospectively identified consecutive patients with ischemic stroke due to proximal arterial occlusion in the anterior circulation, who were treated with EVT and achieved near-complete or complete recanalization. Absolute neutrophil count (ANC), absolute monocyte count (AMC), and absolute lymphocyte count (ALC) were collected from admission blood work to calculate SIRI as ANC × AMC/ALC. The study outcome was futile recanalization, defined as poor functional status [modified Rankin scale (mRS) score ≥ 3] at 3 months despite complete or near-complete recanalization. A total of 184 patients were included. Futile recanalization was observed in 110 (59.8%) patients. Older patients (odds ratio (OR) = 1.07, 95% confidence interval (CI): 1.04–1.10, p < 0.001), higher admission National Institutes of Health stroke scale score (OR = 1.10, 95% CI: 1.02–1.19, p = 0.013), and higher admission SIRI (OR = 1.08, 95% CI: 1.01–1.17, p = 0.028) increased the risk of the poor outcome at 3 months despite complete or near-complete recanalization.
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Affiliation(s)
- Simona Lattanzi
- Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, 60020 Ancona, Italy; (D.N.); (S.B.); (C.R.); (M.S.)
- Correspondence: ; Tel.: +39-071-5964438
| | - Davide Norata
- Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, 60020 Ancona, Italy; (D.N.); (S.B.); (C.R.); (M.S.)
| | - Afshin A. Divani
- Department of Neurology, University of New Mexico, Albuquerque, NM 87131, USA;
| | - Mario Di Napoli
- Neurological Service, SS Annunziata Hospital, Sulmona, 67039 L’Aquila, Italy;
| | - Serena Broggi
- Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, 60020 Ancona, Italy; (D.N.); (S.B.); (C.R.); (M.S.)
| | - Chiara Rocchi
- Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, 60020 Ancona, Italy; (D.N.); (S.B.); (C.R.); (M.S.)
| | - Santiago Ortega-Gutierrez
- Departments of Neurology, Neurosurgery, and Radiology, University of Iowa, Iowa City, IA 52242, USA;
| | - Gelsomina Mansueto
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy;
- Clinical Department of Laboratory Services and Public Health—Legal Medicine Unit, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Mauro Silvestrini
- Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, 60020 Ancona, Italy; (D.N.); (S.B.); (C.R.); (M.S.)
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Su M, Zhou Y, Chen Z, Pu M, Li Z, Du H, Xu G. Cystatin C predicts futile recanalization in patients with acute ischemic stroke after endovascular treatment. J Neurol 2021; 269:966-972. [PMID: 34226965 DOI: 10.1007/s00415-021-10680-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 06/04/2021] [Accepted: 06/05/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND A previous study reported that cystatin C was related to acute ischemic stroke. The association between cystatin C and the clinical outcome in acute ischaemic stroke patients with successful recanalization after endovascular thrombectomy has rarely been reported. This study aimed to evaluate the association between cystatin C and futile recanalization in AIS patients who underwent endovascular thrombectomy. METHODS We carried out a retrospective study of acute ischaemic stroke patients with anterior circulation proximal arterial occlusion who achieved complete arterial recanalization after mechanical thrombectomy from May 2017 to April 2020. The patients with complete recanalization were divided into a useful recanalization group and a futile recanalization group according to their 3-month modified Rankin scale score. FR was defined as a modified mRS score of 3-6 at 3 months. Logistic regression analysis was used to identify the risk factors for FR. Receiver operating characteristic curves were used to assess the predictive value of cystatin C for FR. RESULTS Of 241 patients, 125 underwent futile recanalization and 116 underwent useful recanalization. Baseline serum cystatin C levels were higher in the futile recanalization group than in the useful recanalization group. After adjustment for potential confounding factors, multivariable adjusted regression models showed that cystatin C was an independent predictor of futile recanalization (odds ratio, 4.111 [95% CI 1.427-11.840], P = 0.009). Receiver operator characteristic (ROC) curve analysis indicated that the model combining cystatin C with other factors model effectively predicted unfavourable outcomes at 3 months (area under the curve = 0.782, p < 0.01). CONCLUSIONS A higher level of cystatin C is associated with unfavourable outcomes at 3 months in anterior circulation acute ischaemic stroke patients with endovascular thrombectomy.
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Affiliation(s)
- Mouxiao Su
- Department of Neurology, The First School of Clinical Medicine, Jinling Hospital Southern Medical Universityt Jiangsu Province, 305 East Zhongshan Road, Xuanwu Distric, Nanjing, 210002, China.,Department of Neurology, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, Sichuan, 621000, China
| | - Ying Zhou
- Department of Radiology, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, Sichuan, China
| | - Zhonglun Chen
- Department of Neurology, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, Sichuan, 621000, China
| | - Mingjun Pu
- Department of Neurology, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, Sichuan, 621000, China
| | - Zhaokun Li
- Department of Neurology, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, Sichuan, 621000, China
| | - Hongcai Du
- Department of Neurology, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, Sichuan, 621000, China
| | - Gelin Xu
- Department of Neurology, The First School of Clinical Medicine, Jinling Hospital Southern Medical Universityt Jiangsu Province, 305 East Zhongshan Road, Xuanwu Distric, Nanjing, 210002, China. .,Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China.
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Natera-Villalba E, Cruz-Culebras A, García-Madrona S, Vera-Lechuga R, de Felipe-Mimbrera A, Matute-Lozano C, Gómez-López A, Ros-Castelló V, Sánchez-Sánchez A, Martínez-Poles J, Nedkova-Hristova V, Escribano-Paredes JB, García-Bermúdez I, Méndez J, Fandiño E, Masjuan J. Mechanical thrombectomy beyond 6 hours in acute ischaemic stroke with large vessel occlusion in the carotid artery territory: experience at a tertiary hospital. NEUROLOGÍA (ENGLISH EDITION) 2021; 38:236-245. [PMID: 34092537 DOI: 10.1016/j.nrleng.2020.08.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 08/04/2020] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION Thrombectomy in the carotid artery territory was recently shown to be effective up to 24 hours after symptoms onset. METHODS We conducted a retrospective review of a prospective registry of patients treated at our stroke reference centre between November 2016 and April 2019 in order to assess the safety and effectiveness of mechanical thrombectomy performed beyond 6 hours after symptoms onset in patients with acute ischaemic stroke and large vessel occlusion in the carotid artery territory. RESULTS Data were gathered from 59 patients (55.9% women; median age, 71 years). In 33 cases, stroke was detected upon awakening; 57.6% of patients were transferred from another hospital. Median baseline NIHSS score was 16, and median ASPECTS score was 8, with 94.9% of patients presenting > 50% of salvageable tissue. Satisfactory recanalisation was achieved in 88.1% of patients, beyond 24 hours after onset in 5 cases. At 90 days of follow-up, 67.8% were functionally independent; those who were not were older and presented higher prevalence of atrial fibrillation, greater puncture-to-recanalisation time, and higher NIHSS scores, both at baseline and at discharge. CONCLUSION In our experience, mechanical thrombectomy beyond 6 hours was associated with good 90-day functional outcomes. Age, NIHSS score, puncture-to-recanalisation time, and presence of atrial fibrillation affected functional prognosis. The efficacy of the treatment beyond 24 hours after onset merits study.
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Affiliation(s)
- E Natera-Villalba
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, Spain.
| | - A Cruz-Culebras
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - S García-Madrona
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - R Vera-Lechuga
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - A de Felipe-Mimbrera
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - C Matute-Lozano
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - A Gómez-López
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - V Ros-Castelló
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - A Sánchez-Sánchez
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - J Martínez-Poles
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - V Nedkova-Hristova
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - J B Escribano-Paredes
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - I García-Bermúdez
- Servicio de Radiología, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - J Méndez
- Servicio de Radiología, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - E Fandiño
- Servicio de Radiología, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - J Masjuan
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, Spain; Servicio de Neurología, Hospital Ramón y Cajal, Departamento de Medicina, Facultad de Medicina, Universidad de Alcalá, IRYCIS, Madrid, Spain
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Xu X, Gao W, Li L, Hao J, Yang B, Wang T, Li L, Bai X, Li F, Ren H, Zhang M, Zhang L, Wang J, Wang D, Zhang J, Jiao L. Annexin A1 protects against cerebral ischemia-reperfusion injury by modulating microglia/macrophage polarization via FPR2/ALX-dependent AMPK-mTOR pathway. J Neuroinflammation 2021; 18:119. [PMID: 34022892 PMCID: PMC8140477 DOI: 10.1186/s12974-021-02174-3] [Citation(s) in RCA: 150] [Impact Index Per Article: 37.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 05/12/2021] [Indexed: 02/07/2023] Open
Abstract
Background Cerebral ischemia–reperfusion (I/R) injury is a major cause of early complications and unfavorable outcomes after endovascular thrombectomy (EVT) therapy in patients with acute ischemic stroke (AIS). Recent studies indicate that modulating microglia/macrophage polarization and subsequent inflammatory response may be a potential adjunct therapy to recanalization. Annexin A1 (ANXA1) exerts potent anti-inflammatory and pro-resolving properties in models of cerebral I/R injury. However, whether ANXA1 modulates post-I/R-induced microglia/macrophage polarization has not yet been fully elucidated. Methods We retrospectively collected blood samples from AIS patients who underwent successful recanalization by EVT and analyzed ANXA1 levels longitudinally before and after EVT and correlation between ANXA1 levels and 3-month clinical outcomes. We also established a C57BL/6J mouse model of transient middle cerebral artery occlusion/reperfusion (tMCAO/R) and an in vitro model of oxygen–glucose deprivation and reoxygenation (OGD/R) in BV2 microglia and HT22 neurons to explore the role of Ac2-26, a pharmacophore N-terminal peptide of ANXA1, in regulating the I/R-induced microglia/macrophage activation and polarization. Results The baseline levels of ANXA1 pre-EVT were significantly lower in 23 AIS patients, as compared with those of healthy controls. They were significantly increased to the levels found in controls 2–3 days post-EVT. The increased post-EVT levels of ANXA1 were positively correlated with 3-month clinical outcomes. In the mouse model, we then found that Ac2-26 administered at the start of reperfusion shifted microglia/macrophage polarization toward anti-inflammatory M2-phenotype in ischemic penumbra, thus alleviating blood–brain barrier leakage and neuronal apoptosis and improving outcomes at 3 days post-tMCAO/R. The protection was abrogated when mice received Ac2-26 together with WRW4, which is a specific antagonist of formyl peptide receptor type 2/lipoxin A4 receptor (FPR2/ALX). Furthermore, the interaction between Ac2-26 and FPR2/ALX receptor activated the 5’ adenosine monophosphate-activated protein kinase (AMPK) and inhibited the downstream mammalian target of rapamycin (mTOR). These in vivo findings were validated through in vitro experiments. Conclusions Ac2-26 modulates microglial/macrophage polarization and alleviates subsequent cerebral inflammation by regulating the FPR2/ALX-dependent AMPK-mTOR pathway. It may be investigated as an adjunct strategy for clinical prevention and treatment of cerebral I/R injury after recanalization. Plasma ANXA1 may be a potential biomarker for outcomes of AIS patients receiving EVT. Supplementary Information The online version contains supplementary material available at 10.1186/s12974-021-02174-3.
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Affiliation(s)
- Xin Xu
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing, 100053, China. .,China International Neuroscience Institute (China-INI), 45 Changchun Street, Beijing, 100053, China.
| | - Weiwei Gao
- Department of Neurology, Tianjin Huanhu Hospital, 6 Jizhao Road, Tianjin, 300350, China.
| | - Lei Li
- Department of Neurosurgery & Neurology, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin, 300052, China
| | - Jiheng Hao
- Department of Neurosurgery, Liaocheng People's Hospital, 67 Dongchang West Road, Liaocheng, 252000, China
| | - Bin Yang
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing, 100053, China.,China International Neuroscience Institute (China-INI), 45 Changchun Street, Beijing, 100053, China
| | - Tao Wang
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing, 100053, China.,China International Neuroscience Institute (China-INI), 45 Changchun Street, Beijing, 100053, China
| | - Long Li
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing, 100053, China.,China International Neuroscience Institute (China-INI), 45 Changchun Street, Beijing, 100053, China
| | - Xuesong Bai
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing, 100053, China.,China International Neuroscience Institute (China-INI), 45 Changchun Street, Beijing, 100053, China
| | - Fanjian Li
- Department of Neurosurgery & Neurology, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin, 300052, China
| | - Honglei Ren
- Department of Neurosurgery & Neurology, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin, 300052, China
| | - Meng Zhang
- Department of Neurosurgery, Liaocheng People's Hospital, 67 Dongchang West Road, Liaocheng, 252000, China
| | - Liyong Zhang
- Department of Neurosurgery, Liaocheng People's Hospital, 67 Dongchang West Road, Liaocheng, 252000, China
| | - Jiyue Wang
- Department of Neurosurgery, Liaocheng People's Hospital, 67 Dongchang West Road, Liaocheng, 252000, China
| | - Dong Wang
- Department of Neurosurgery & Neurology, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin, 300052, China
| | - Jianning Zhang
- Department of Neurosurgery & Neurology, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin, 300052, China
| | - Liqun Jiao
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing, 100053, China. .,China International Neuroscience Institute (China-INI), 45 Changchun Street, Beijing, 100053, China. .,Department of Interventional Neuroradiology, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing, 100053, China.
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49
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Cheng Z, Geng X, Rajah GB, Gao J, Ma L, Li F, Du H, Ding Y. NIHSS Consciousness Score Combined with ASPECTS is a Favorable Predictor of Functional Outcome post Endovascular Recanalization in Stroke Patients. Aging Dis 2021; 12:415-424. [PMID: 33815874 PMCID: PMC7990364 DOI: 10.14336/ad.2020.0709] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 07/09/2020] [Indexed: 12/29/2022] Open
Abstract
Although revascularization rates after endovascular thrombectomy for large vessel acute ischemic stroke (AIS) are high (71%), only 46% of patients achieve functional independence at 90 days. The present study was designed to explore a new method for predicting the functional prognosis of AIS patients after endovascular recanalization. A total of 200 anterior circulation stroke patients who received endovascular therapy were enrolled. Logistic regression analysis of clinical characteristics on functional independence were performed. The predictive power of sub-items in National Institute of Health stroke scale (NIHSS) and the combination of NIHSS consciousness and Alberta Stroke Program Early CT Score (ASPECTS) on functional independence were assessed by Receiver Operating Characteristic (ROC) curves and the latter was compared with 3 previously published prediction models by AUC (the area under ROC curve). The AUC for the NIHSS consciousness score to predict functional independence was higher than whole NIHSS and other sub-items (0.716 v 0.705, 0.586, 0.573, 0.552 and 0.559). Low NIHSS consciousness score, high ASPECTS score, short time from onset to recanalization, and high rate of successful recanalization were demonstrated to be significantly associated with the functional independence (OR 0.697, 2.226, 0.994 and 28.643). The prediction power of the combination was significantly better than NIHSS and ASPECTS alone (AUC 0.793 v 0.705 and 0.752). Compared with 3 other prediction models, the combination was found to be the strongest predictor for functional independence (AUC 0.793 v 0.791, 0.671 and 0.564). NIHSS which has been shown to be a strong predictor of functional outcomes after endovascular recanalization is largely dependent on the consciousness component. NIHSS consciousness score combined with ASPECTS appears to be a favorable predictor of functional independence. These findings may have broad reaching effects for isolated centers around the world without advanced imaging for triage and prognostication.
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Affiliation(s)
- Zhe Cheng
- Department of Neurology and Stroke Center, Luhe Hospital, Capital Medical University, Beijing, China.
| | - Xiaokun Geng
- Department of Neurology and Stroke Center, Luhe Hospital, Capital Medical University, Beijing, China.
- China-America Institute of Neuroscience, Luhe Hospital, Capital Medical University, Beijing, China.
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA.
| | - Gary B Rajah
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA.
- Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, New York, USA.
- Department of Neurosurgery, Munson Medical Center, Traverse City, MI, USA.
| | - Jie Gao
- Department of Neurology and Stroke Center, Luhe Hospital, Capital Medical University, Beijing, China.
| | - Linlin Ma
- Department of Neurology and Stroke Center, Luhe Hospital, Capital Medical University, Beijing, China.
| | - Fenghai Li
- Department of Neurology and Stroke Center, Luhe Hospital, Capital Medical University, Beijing, China.
| | - Huishan Du
- Department of Neurology and Stroke Center, Luhe Hospital, Capital Medical University, Beijing, China.
| | - Yuchuan Ding
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA.
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50
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Natera-Villalba E, Cruz-Culebras A, García-Madrona S, Vera-Lechuga R, de Felipe-Mimbrera A, Matute-Lozano C, Gómez-López A, Ros-Castelló V, Sánchez-Sánchez A, Martínez-Poles J, Nedkova-Hristova V, Escribano-Paredes JB, García-Bermúdez I, Méndez J, Fandiño E, Masjuan J. Mechanical thrombectomy beyond 6hours in acute ischaemic stroke with large vessel occlusion in the carotid artery territory: Experience at a tertiary hospital. Neurologia 2021; 38:S0213-4853(20)30298-X. [PMID: 33551125 DOI: 10.1016/j.nrl.2020.08.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 07/06/2020] [Accepted: 08/04/2020] [Indexed: 11/29/2022] Open
Abstract
INTRODUCTION Thrombectomy in the carotid artery territory was recently shown to be effective up to 24hours after symptoms onset. METHODS We conducted a retrospective review of a prospective registry of patients treated at our stroke reference centre between November 2016 and April 2019 in order to assess the safety and effectiveness of mechanical thrombectomy performed beyond 6hours after symptoms onset in patients with acute ischaemic stroke and large vessel occlusion in the carotid artery territory. RESULTS Data were gathered from 59 patients (55.9% women; median age, 71 years). In 33 cases, stroke was detected upon awakening; 57.6% of patients were transferred from another hospital. Median baseline NIHSS score was 16, and median ASPECTS score was 8, with 94.9% of patients presenting>50% of salvageable tissue. Satisfactory recanalisation was achieved in 88.1% of patients, beyond 24hours after onset in 5 cases. At 90 days of follow-up, 67.8% were functionally independent; those who were not were older and presented higher prevalence of atrial fibrillation, greater puncture-to-recanalisation time, and higher NIHSS scores, both at baseline and at discharge. CONCLUSION In our experience, mechanical thrombectomy beyond 6hours was associated with good 90-day functional outcomes. Age, NIHSS score, puncture-to-recanalisation time, and presence of atrial fibrillation affected functional prognosis. The efficacy of the treatment beyond 24hours after onset merits study.
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Affiliation(s)
- E Natera-Villalba
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, España.
| | - A Cruz-Culebras
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, España
| | - S García-Madrona
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, España
| | - R Vera-Lechuga
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, España
| | - A de Felipe-Mimbrera
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, España
| | - C Matute-Lozano
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, España
| | - A Gómez-López
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, España
| | - V Ros-Castelló
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, España
| | - A Sánchez-Sánchez
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, España
| | - J Martínez-Poles
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, España
| | - V Nedkova-Hristova
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, España
| | - J B Escribano-Paredes
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, España
| | - I García-Bermúdez
- Servicio de Radiología, Hospital Universitario Ramón y Cajal, Madrid, España
| | - J Méndez
- Servicio de Radiología, Hospital Universitario Ramón y Cajal, Madrid, España
| | - E Fandiño
- Servicio de Radiología, Hospital Universitario Ramón y Cajal, Madrid, España
| | - J Masjuan
- Servicio de Neurología, Unidad de Ictus, Hospital Universitario Ramón y Cajal, Madrid, España; Servicio de Neurología, Hospital Ramón y Cajal, Departamento de Medicina, Facultad de Medicina, Universidad de Alcalá, IRYCIS, Madrid, España
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