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Ticking Brain: Circadian Rhythm as a New Target for Cerebroprotection. 滴答作响的大脑昼夜节律是大脑保护的新目标
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-16 DOI: 10.1161/STROKEAHA.124.046684
Shuaili Xu, Milan Jia, Jiaqi Guo, Jiachen He, Xi Chen, Yi Xu, Wenbo Hu, Di Wu, Chuanjie Wu, Xunming Ji

Circadian rhythm is a master process observed in nearly every type of cell throughout the body, and it macroscopically regulates daily physiology. Recent clinical trials have revealed the effects of circadian variation on the incidence, pathophysiological processes, and prognosis of acute ischemic stroke. Furthermore, core clock genes, the cell-autonomous pacemakers of the circadian rhythm, affect the neurovascular unit-composing cells in a nonparallel manner after the same pathophysiological processes of ischemia/reperfusion. In this review, we discuss the influence of circadian rhythms and clock genes on each type of neurovascular unit cell in the pathophysiological processes of acute ischemic stroke.

昼夜节律是在全身几乎所有类型细胞中观察到的一个主过程,它宏观调控着日常生理。最近的临床试验揭示了昼夜节律变化对急性缺血性中风的发病率、病理生理过程和预后的影响。此外,昼夜节律的细胞自主起搏器--核心时钟基因,在缺血/再灌注的相同病理生理过程后,会以非平行的方式影响神经血管单元组成细胞。在本综述中,我们将讨论昼夜节律和时钟基因在急性缺血性脑卒中病理生理过程中对各类神经血管单元细胞的影响。
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引用次数: 0
Addressing the Evidence Gap in Aneurysmal Subarachnoid Hemorrhage: The Need for a Pragmatic Randomized Trial Platform. 缩小动脉瘤性蛛网膜下腔出血的证据差距:需要一个务实的随机试验平台。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-25 DOI: 10.1161/STROKEAHA.124.048089
Hooman Kamel, Jose I Suarez, E Sander Connolly, Sepideh Amin-Hanjani, William T Mack, Sherry Hsiang-Yi Chou, Katharina M Busl, Colin P Derdeyn, Neha S Dangayach, Jordan E Elm, Jonathan Beall, Nerissa U Ko

Aneurysmal subarachnoid hemorrhage (aSAH) occurs less often than other stroke types but affects younger patients, imposing a disproportionately high burden of long-term disability. Although management advances have improved outcomes over time, relatively few aSAH treatments have been tested in randomized clinical trials (RCTs). One lesson learned from COVID-19 is that trial platforms can facilitate the efficient execution of multicenter RCTs even in complex diseases during challenging conditions. An aSAH trial platform with standardized eligibility criteria, randomization procedures, and end point definitions would enable the study of multiple targeted interventions in a perpetual manner, with treatments entering and leaving the platform based on predefined decision algorithms. An umbrella institutional review board protocol and clinical trial agreement would allow individual arms to be efficiently added as amendments rather than stand-alone protocols. Standardized case report forms using the National Institutes of Health/National Institute of Neurological Disorders and Stroke common data elements and general protocol standardization across arms would create synergies for data management and monitoring. A Bayesian analysis framework would emphasize frequent interim looks to enable early termination of trial arms for futility, common controls, borrowing of information across arms, and adaptive designs. A protocol development committee would assist investigators and encourage pragmatic designs to maximize generalizability, reduce site burden, and execute trials efficiently and cost-effectively. Despite decades of steady clinical progress in the management of aSAH, poor patient outcomes remain common, and despite the increasing availability of RCT data in other fields, it remains difficult to perform RCTs to guide more effective care for aSAH. The development of a platform for pragmatic RCTs in aSAH would help close the evidence gap between aSAH and other stroke types and improve outcomes for this important disease with its disproportionate public health burden.

动脉瘤性蛛网膜下腔出血(aSAH)的发病率低于其他类型的中风,但患者年龄较轻,造成的长期残疾负担过重。虽然随着时间的推移,治疗方法的进步改善了预后,但在随机临床试验(RCT)中测试过的蛛网膜下腔出血治疗方法相对较少。从 COVID-19 中汲取的一个经验是,试验平台可以促进多中心 RCT 的高效执行,即使是在条件艰苦的复杂疾病中也不例外。aSAH 试验平台具有标准化的资格标准、随机化程序和终点定义,可以对多种目标干预措施进行永久性研究,治疗方法可根据预定义的决策算法进入或退出平台。总括性的机构审查委员会协议和临床试验协议将允许以修正案的形式而不是以独立协议的形式有效地添加单个臂。使用美国国立卫生研究院/美国国立神经疾病与中风研究所通用数据元素的标准化病例报告表以及各臂的一般方案标准化将为数据管理和监测带来协同效应。贝叶斯分析框架将强调频繁的中期检查,以便尽早终止无用的试验臂、共同控制、跨臂信息借用和适应性设计。方案制定委员会将协助研究人员并鼓励务实的设计,以最大限度地提高可推广性,减轻研究机构的负担,并以高效、经济的方式执行试验。尽管数十年来aSAH的临床治疗取得了稳步进展,但患者预后不佳的情况仍很普遍,而且尽管其他领域的RCT数据越来越多,但仍很难通过RCT来指导更有效的aSAH治疗。开发一个针对 aSAH 的务实 RCT 平台将有助于缩小 aSAH 与其他类型卒中之间的证据差距,并改善这种对公共卫生造成极大负担的重要疾病的预后。
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引用次数: 0
Recovery of Visuospatial Neglect With Standard Treatment: A Systematic Review and Meta-Analysis. 通过标准治疗恢复视觉空间疏忽:系统回顾与元分析》。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-17 DOI: 10.1161/STROKEAHA.124.046760
Margot Juliëtte Overman, Elena Binns, Elise T Milosevich, Nele Demeyere

Background: Visuospatial neglect is a common consequence of stroke and is characterized by impaired attention to contralesional space. Currently, the extent and time course of recovery from neglect are not clearly established. This systematic review and meta-analysis aimed to determine the recovery trajectory of poststroke neglect with standard treatment.

Methods: PsycInfo, Embase, and MEDLINE were searched for articles reporting recovery rates of neglect after stroke. Time since stroke was categorized into early (0-3 months), mid (3-6 months), and late (>6 months) recovery phases. Random-effects models for pooled prevalence were generated for each phase, and potential sources of heterogeneity were explored with metaregressions. Methodological quality of each study was assessed using the Joanna Briggs Institute checklist, with low-quality studies excluded in sensitivity analyses.

Results: The search captured 4130 articles including duplicates, and 111 full-text reviews were undertaken. A total of 27 studies reporting data from 839 stroke survivors with neglect were included for review. Meta-analyses indicated a recovery rate of 42% in the early phase, which increased to 53% in the mid-recovery phase. Additional recovery in the late phase was minimal, with an estimated 56% recovery rate. Heterogeneity of studies was high (I2>75%) in all 3 phases of recovery. Estimates were robust to sensitivity analyses. Metaregressions showed significantly greater recovery in studies that included patients with left-hemisphere lesions (β=0.275, P<0.05, I2=84%).

Conclusions: Most recovery from neglect occurs in the first 3 months, although additional gains can be expected up to 6 months poststroke. While a large proportion of patients recover from neglect, over 40% show persistent symptoms. Further research is needed on effective rehabilitation interventions, particularly focusing on patients most at risk of chronic visuospatial neglect.

Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42023388763.

背景:视空间忽略是中风的常见后果,其特点是对对侧空间的注意力受损。目前,视空间忽略的恢复程度和时间进程尚未明确确定。本系统性综述和荟萃分析旨在确定脑卒中后忽视在标准治疗下的恢复轨迹:方法:在 PsycInfo、Embase 和 MEDLINE 中检索了报告中风后忽视恢复率的文章。中风后的恢复时间分为早期(0-3 个月)、中期(3-6 个月)和晚期(>6 个月)。每个阶段都生成了汇总患病率的随机效应模型,并通过元回归探讨了潜在的异质性来源。采用乔安娜-布里格斯研究所(Joanna Briggs Institute)的检查表对每项研究的方法学质量进行了评估,在敏感性分析中排除了低质量的研究:包括重复文章在内,共搜索到 4130 篇文章,并进行了 111 篇全文综述。共有 27 项研究报告了 839 名患有忽视的中风幸存者的数据,这些研究被纳入审查范围。元分析表明,早期恢复率为 42%,中期恢复率增至 53%。晚期的恢复率则微乎其微,估计为 56%。在所有三个恢复阶段,研究的异质性都很高(I2>75%)。估计值在敏感性分析中保持稳定。在包含左半球病变患者的研究中,元进展的恢复率明显更高(β=0.275,P2=84%):大多数患者在卒中后3个月内就能从忽视中恢复过来,但在卒中后6个月内还会有额外的恢复。虽然大部分患者都能从忽视中康复,但仍有超过 40% 的患者症状持续存在。需要进一步研究有效的康复干预措施,尤其是针对最有可能出现慢性视觉空间忽略的患者:URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier:CRD42023388763。
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引用次数: 0
Perfusion Abnormalities on 24-Hour Perfusion Imaging in Patients With Complete Endovascular Reperfusion. 完全血管内再灌注患者的 24 小时灌注成像异常。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-15 DOI: 10.1161/STROKEAHA.124.047441
Adnan Mujanovic, Anick Imhof, Shaokai Zheng, Eike I Piechowiak, Bettina L Serrallach, Thomas R Meinel, Tomas Dobrocky, Yasmin N Aziz, David J Seiffge, Martina Goeldlin, Marcel Arnold, Arsany Hakim, Roland Wiest, Jan Gralla, Eva A Mistry, Urs Fischer, Susanne Wegener, Johannes Kaesmacher

Background: Perfusion abnormalities in the infarct and salvaged penumbra have been proposed as a potential reason for poor clinical outcome (modified Rankin Scale score >2) despite complete angiographic reperfusion (Thrombolysis in Cerebral Infarction [TICI3]). In this study, we aimed to identify different microvascular perfusion patterns and their association with clinical outcomes among TICI3 patients.

Methods: University Hospital Bern's stroke registry of all patients between February 2015 and December 2021. Macrovascular reperfusion was graded using the TICI scale. Microvascular reperfusion status was evaluated within the infarct area on cerebral blood volume and cerebral blood flow perfusion maps obtained 24-hour postintervention. Primary outcome was functional independence (90-day modified Rankin Scale score 0-2) evaluated with the logistic regression analysis adjusted for age, sex, and 24-hour infarct volume from follow-up imaging.

Results: Based on microvascular perfusion findings, the entire cohort (N=248) was stratified into one of the 4 clusters: (1) normoperfusion (no perfusion abnormalities; n=143/248); (2) hyperperfusion (hyperperfusion on both cerebral blood volume and cerebral blood flow; n=54/248); (3) hypoperfusion (hypoperfusion on both cerebral blood volume and cerebral blood flow; n=14/248); and (4) mixed (discrepant findings, eg, cerebral blood volume hypoperfusion and cerebral blood flow hyperperfusion; n=37/248). Compared with the normoperfusion cluster, patients in the hypoperfusion cluster were less likely to achieve functional independence (adjusted odds ratio, 0.3 [95% CI, 0.1-0.9]), while patients in the hyperperfusion cluster tended to have better outcomes (adjusted odds ratio, 3.3 [95% CI, 1.3-8.8]).

Conclusions: In around half of TICI3 patients, perfusion abnormalities on the microvascular level can be observed. Microvascular hypoperfusion, despite complete macrovascular reperfusion, is rare but may explain the poor clinical course among some TICI3 patients, while a detrimental effect of hyperperfusion after reperfusion could not be confirmed.

背景:有人认为,尽管血管完全再灌注(脑梗塞溶栓治疗[TICI3]),但脑梗塞和救治后半影的灌注异常是临床预后不佳(改良Rankin量表评分>2)的潜在原因。本研究旨在确定不同的微血管灌注模式及其与 TICI3 患者临床预后的关系:方法:伯尔尼大学医院卒中登记处对 2015 年 2 月至 2021 年 12 月间的所有患者进行登记。采用TICI量表对大血管再灌注进行分级。根据干预后 24 小时获得的脑血容量和脑血流灌注图评估梗死区内的微血管再灌注状况。主要结果是功能独立性(90 天改良兰金量表评分 0-2 分),根据年龄、性别和 24 小时随访成像的梗死体积进行调整后,用逻辑回归分析进行评估:根据微血管灌注结果,整个组群(N=248)被分为 4 组:(1)正常灌注(无灌注异常;人数=143/248);(2)高灌注(脑血容量和脑血流量均高灌注;人数=54/248);(3)低灌注(脑血容量和脑血流量均低灌注;人数=14/248);(4)混合型(结果不一致,如脑血容量低灌注和脑血流量高灌注;人数=37/248)。与正常灌注组相比,低灌注组患者不太可能实现功能独立(调整后的几率比为0.3 [95% CI, 0.1-0.9]),而高灌注组患者的预后往往更好(调整后的几率比为3.3 [95% CI, 1.3-8.8]):结论:约有一半的 TICI3 患者可观察到微血管灌注异常。尽管大血管完全再灌注,但微血管灌注不足的情况并不多见,这可能是一些 TICI3 患者临床病程不佳的原因,而再灌注后过度灌注的有害影响则无法证实。
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引用次数: 0
Climbing the STAIRs to SPAN the Clinical Translation Gap: Recent Advances in Multicenter Preclinical Stroke Trials. 攀登 STAIRs,跨越临床转化差距:多中心临床前卒中试验的最新进展》(Climbing the STAIRs to SPAN the Clinical Translation Gap: Recent Advances in Multicenter Preclinical Stroke Trials.
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-01 Epub Date: 2024-03-06 DOI: 10.1161/STROKEAHA.124.045998
Renée J Turner, Tracy D Farr
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引用次数: 0
Cerebral Air Embolism: Radiologic and Pathologic Correlation. 脑空气栓塞:放射学与病理学相关性。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-01 DOI: 10.1161/STROKEAHA.124.048109
Shu Yoshihara, Shioto Suzuki, Kazuyo Yoshihara
{"title":"Cerebral Air Embolism: Radiologic and Pathologic Correlation.","authors":"Shu Yoshihara, Shioto Suzuki, Kazuyo Yoshihara","doi":"10.1161/STROKEAHA.124.048109","DOIUrl":"10.1161/STROKEAHA.124.048109","url":null,"abstract":"","PeriodicalId":21989,"journal":{"name":"Stroke","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of Carotid Siphon Calcification on the Course and Outcome of Patients With Aneurysmal Subarachnoid Hemorrhage. 颈动脉虹吸管钙化对动脉瘤性蛛网膜下腔出血患者病程和预后的影响
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-05 DOI: 10.1161/STROKEAHA.124.047594
Adrian Engel, Li Song, Laurèl Rauschenbach, Meltem Gümüs, Alejandro N Santos, Thiemo Florin Dinger, Marvin Darkwah Oppong, Yan Li, Oliver Gembruch, Yahya Ahmadipour, Philipp Dammann, Ulrich Sure, Ramazan Jabbarli

Background: Carotid siphon calcification (CSC) serves as a marker of atherosclerosis and therefore may influence the outcome after subarachnoid hemorrhage (aSAH). We aimed to analyze the impact of CSC on neurological outcomes, ischemia, and vasospasm.

Methods: A total of 716 patients with aSAH were treated between December 2004 and June 2016 in our central European tertiary neurovascular care center in Essen, Germany. CSC was recorded using the Woodcock scale (grades 0-3) on a computed tomography scan. Study end points included an unfavorable outcome at 6 months post-aSAH (modified Rankin Scale score ≥4), vasospasm, and early cerebral ischemia (72 hours) and delayed cerebral ischemia (delayed cerebral ischemia; >72 hours) in the follow-up computed tomography scans. The associations were adjusted for patients' baseline characteristics and secondary complications. Finally, within a subgroup analysis, patients with and without daily aspirin intake after endovascular aneurysm occlusion were compared.

Results: Increasing grades of CSC were associated with lower rates of vasospasm in the anterior circulation. Severe CSC (grade 3) was independently related to the risk of an unfavorable outcome (adjusted odds ratio [aOR], 4.06 [95% CI, 1.98-8.33]; P<0.001) and early cerebral ischemia (aOR, 1.58 [95% CI, 1.03-2.43]; P=0.035) but not delayed cerebral ischemia (aOR, 1.08 [95% CI, 0.67-1.73]; P=0.763). In the aspirin subgroup analysis, the negative effect of severe CSC on functional outcome remained significant only in aSAH cases without aspirin (aOR, 5.47 [95% CI, 2.38-12.54]; P<0.001). In contrast, there was no association between severe CSC and unfavorable outcomes among individuals with daily aspirin intake (aOR, 0.84 [95% CI, 0.59-4.21]; P=0.603).

Conclusions: Our data suggest CSC as a cerebrovascular risk factor resulting in higher rates of early cerebral ischemia and unfavorable outcomes after aSAH. However, by increasing arterial stiffness, CSC might lower the probability of vasospasm, which could explain the missing link between CSC and delayed cerebral ischemia. Additionally, aspirin intake seems to potentially mitigate the negative impact of CSC on aSAH outcome. Further investigations are needed to confirm the observations from the present study.

背景:颈动脉虹吸管钙化(CSC)是动脉粥样硬化的标志物,因此可能影响蛛网膜下腔出血(aSAH)后的预后。我们旨在分析 CSC 对神经系统预后、缺血和血管痉挛的影响:2004年12月至2016年6月期间,我们在德国埃森的中欧三级神经血管治疗中心共治疗了716名蛛网膜下腔出血患者。在计算机断层扫描中使用伍德考克量表(0-3级)记录CSC。研究终点包括急性脑缺血后6个月的不良预后(改良Rankin量表评分≥4分)、血管痉挛、随访计算机断层扫描中的早期脑缺血(72小时)和延迟性脑缺血(延迟性脑缺血;>72小时)。这些关联已根据患者的基线特征和继发性并发症进行了调整。最后,在一项亚组分析中,对血管内动脉瘤闭塞后每天服用阿司匹林和未服用阿司匹林的患者进行了比较:结果:CSC等级越高,前循环血管痉挛发生率越低。严重 CSC(3 级)与不利预后的风险独立相关(调整后比值比 [aOR],4.06 [95% CI,1.98-8.33];PP=0.035),但与延迟性脑缺血无关(aOR,1.08 [95% CI,0.67-1.73];P=0.763)。在阿司匹林亚组分析中,严重CSC对功能预后的负面影响仅在未服用阿司匹林的aSAH病例中保持显著(aOR,5.47 [95% CI,2.38-12.54];PP=0.603):我们的数据表明,CSC是一个脑血管风险因素,会导致更高的早期脑缺血率和不利的aSAH后预后。然而,通过增加动脉僵化,CSC 可能会降低血管痉挛的概率,这可以解释 CSC 与延迟性脑缺血之间缺失的联系。此外,摄入阿司匹林似乎有可能减轻CSC对急性脑缺血结局的负面影响。要证实本研究的观察结果,还需要进一步的研究。
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引用次数: 0
Stroke: Strong and Strengthening. 中风:强身健体。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-08 DOI: 10.1161/STROKEAHA.124.048145
Argye E Hillis
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引用次数: 0
Stroke Literature Synopsis (Clinical). 中风文献概要(临床)。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-26 DOI: 10.1161/STROKEAHA.124.048527
Kalliopi Mavromati, Terence J Quinn
{"title":"<i>Stroke</i> Literature Synopsis (Clinical).","authors":"Kalliopi Mavromati, Terence J Quinn","doi":"10.1161/STROKEAHA.124.048527","DOIUrl":"https://doi.org/10.1161/STROKEAHA.124.048527","url":null,"abstract":"","PeriodicalId":21989,"journal":{"name":"Stroke","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to: Prevention of Vascular Contributions to Cognitive Impairment and Dementia: The Role of Physical Activity and Exercise. 更正:预防血管对认知障碍和痴呆症的影响:体力活动和锻炼的作用。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-26 DOI: 10.1161/STR.0000000000000474
{"title":"Correction to: Prevention of Vascular Contributions to Cognitive Impairment and Dementia: The Role of Physical Activity and Exercise.","authors":"","doi":"10.1161/STR.0000000000000474","DOIUrl":"https://doi.org/10.1161/STR.0000000000000474","url":null,"abstract":"","PeriodicalId":21989,"journal":{"name":"Stroke","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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