缺血性卒中静脉溶栓预后预测的研究进展

静脉溶栓是急性缺血性卒中最有效的治疗方法,但同时伴随着出血转化及预后不良风险
的增加。本文对急性缺血性卒中静脉溶栓预后不良的危险因素及相关预测模型进行综述,对不同预
后预测模型的特点及预测能力进行分析比较,以期帮助临床神经科医师在接诊急性缺血性卒中患者
时对于是否行静脉溶栓进行快速评判并指导决策。     

缺血性卒中患者静脉溶栓后不良预后危险因素的研究现状

急性缺血性卒中静脉溶栓的患者临床预后可受疾病严重程度、发病到溶栓的时间、脑小 血管病、血糖水平、中性粒细胞计数、血小板计数、溶栓后再灌注损伤及出血转化等多种因素的影响。 本文从流行病学、溶栓前后影响缺血性卒中静脉溶栓预后的危险因素及相关预测模型进行文献复习， 旨在加强对缺血性卒中患者静脉溶栓后不良预后危险因素及相关预测模型的认识，为其防治提供理 论依据和临床指导。     

缺血性卒中患者静脉溶栓后不良预后危险因素的研究现状

急性缺血性卒中静脉溶栓的患者临床预后可受疾病严重程度、发病到溶栓的时间、脑小
血管病、血糖水平、中性粒细胞计数、血小板计数、溶栓后再灌注损伤及出血转化等多种因素的影响。
本文从流行病学、溶栓前后影响缺血性卒中静脉溶栓预后的危险因素及相关预测模型进行文献复习,
旨在加强对缺血性卒中患者静脉溶栓后不良预后危险因素及相关预测模型的认识,为其防治提供理
论依据和临床指导。     

伴心房颤动的急性缺血性卒中静脉溶栓研究进展

心房颤动是急性缺血性卒中的独立危险因素,对静脉溶栓结局的影响尚不十分清楚。本文拟对伴心房颤动的急性缺血性卒中患者静脉溶栓有效性和安全性以及口服抗凝药的心房颤动患者发生急性缺血性卒中后静脉溶栓策略进行综述。     

溶栓后出血评分的临床应用及进展

静脉溶栓是治疗缺血性卒中有效的方法。出血转化是静脉溶栓后严重的并发症之一。溶 栓后出血评分是评估缺血性卒中患者溶栓后出血转化发生率的预测模型，它的3项评价指标分别为 卒中患者的血糖水平、卒中后临床严重程度及影像学数据。本文介绍了溶栓后出血评分的3项预测因 素与溶栓后出血转化的关系，并对该评分的临床应用及进展进行了综述。     

提高急性缺血性卒中静脉溶栓有效性和安全性的研究进展

重组组织型纤溶酶原激活剂(recombinant tissue plasminogen activator alteplase,rt-PA)是目前急性缺血性卒中时间窗内静脉溶栓最有效的治疗药物,然而,静脉溶栓也伴随着出血转化、症状性颅内出血风险的增加,导致患者预后不良,甚至死亡。因此,研究静脉溶栓治疗及预后的影响因素,提高静脉溶栓治疗的有效性及安全性,对急性缺血性卒中患者的预后有着重大意义。     

区域软脑膜侧支循环评分与Tan侧支循环评分预测前循环缺血性卒中静脉溶栓预后

目的筛查急性前循环缺血性卒中静脉溶栓预后相关影响因素,并探讨基于CTA的两种侧支循环评价量表对急性前循环缺血性卒中静脉溶栓预后的预测能力。方法连续纳入136例急性缺血性卒中患者,均予重组组织型纤溶酶原激活物静脉溶栓,采用基于CTA的区域软脑膜侧支循环评分(r LMC)和Tan侧支循环评分(Tan)评价侧支循环,发病后3个月采用改良Rankin量表评价预后(以病残或病死为主要结局指标)。单因素和多因素逐步法Logistic回归分析筛查急性前循环缺血性卒中静脉溶栓预后不良相关危险因素,受试者工作特征(ROC)曲线评价Tan评分对急性前循环缺血性卒中静脉溶栓预后的预测能力。结果最终纳入122例行静脉溶栓治疗的急性前循环缺血性卒中患者,Logistic回归分析显示,发病至静脉溶栓时间180~270 min(OR=0.309,95%CI:0.134~0.713;P=0.006)和Tan评分0~1分(OR=7.339,95%CI:2.072~25.994;P=0.002)是急性前循环缺血性卒中静脉溶栓预后不良的独立危险因素。Tan评分预测急性前循环缺血性卒中静脉溶栓预后的ROC曲线显示,曲线下面积为0.753(P=0.021)。结论发病至静脉溶栓时间180~270 min和Tan评分0~1分是急性前循环缺血性卒中静脉溶栓预后不良的独立危险因素。与rLMC评分相比,Tan评分是一种相对简单且预测能力较好的侧支循环评价量表。     

缺血性卒中静脉溶栓药物的发展和展望

正缺血性卒中是指由于脑的供血动脉狭窄或闭塞导致的脑组织坏死,可导致残疾或死亡,是我国居民主要死因之一。缺血性卒中的急性期治疗主要是溶栓和血管内治疗,目的是实现血管再通,恢复脑组织血流灌注[1]。国外有研究显示,约25%的急性缺血性卒中患者符合溶栓条件,10%～12%符合血管内治疗条件[2]。溶栓是急性缺血性卒中最主要的治疗方式。经过多年的研究,缺血性卒中静脉溶栓药物有了长足的发展,并显示出广阔的前景。     

炎症反应与急性缺血性脑卒中静脉溶栓后出血转化的研究进展

急性缺血性脑卒中是卒中最常见的形式之一，目前其主要的治疗方式是再灌注治疗，包 括静脉溶栓治疗和血管内治疗。急性缺血性卒中发病时间 6 h 内给予静脉溶栓可改善预后，然而静脉溶 栓同时也存在出血转化的风险，可能对患者早期神经功能改善和远期预后产生不利影响。目前的研究 认为，炎症反应主要参与急性缺血性脑卒中患者静脉溶栓后出血转化的生理病理机制。现对炎症反应 与静脉溶栓后出血转化的相关性风险预测因素进行综述，旨在为溶栓后出血转化的早期识别和预防提 供依据。     

建立中国急性缺血性卒中溶栓医疗质量持续改进体系

卒中是我国居民死亡的第一位杀手,也是成人致残的第一位原因。国内外发表的急性缺血性卒中临床指南均强调在时间窗内给予静脉重组组织型纤溶酶原激活剂(recombinanttissue plasminogen activator,rt-PA)溶栓是最有效的治疗方式,但由于溶栓意识匮乏、院前或院内延误等原因,许多急性缺血性卒中患者得不到rt-PA治疗或无法获得规范的溶栓治疗。对于急性缺血性卒中患者来说,在卒中症状发生后越早使用rt-PA溶栓治疗,其恢复良好神经功能的可能性越大(图1)。Lansberg     

青年卒中患者重组组织型纤溶酶原激活剂静脉溶栓治疗后临床预后不良的危险因素

目的探讨青年卒中患者重组组织型纤溶酶原激活剂(rt-PA)静脉溶栓治疗后临床预后不良的危险因素。方法回顾性、连续性纳入胜利油田中心医院2018年1月至2019年12月收治的首次发病并接受rt-PA静脉溶栓的青年卒中患者114例。根据发病90 d mRS评分,将青年卒中患者分为预后良好组(90 d mRS评分0~2分)和预后不良组(90 d mRS评分3~6分)。比较两组的基本资料并进行多因素回归分析。结果rt-PA静脉溶栓治疗后90 d,84例(73.7%)患者预后良好(预后良好组),30例(26.3%)患者预后不良(预后不良组)。预后不良组合并2型糖尿病、发病后合并意识障碍、溶栓24 h内脑出血、责任大血管闭塞的比例均明显高于预后良好组(均P<0.05);预后不良组入院时NIHSS评分明显高于预后良好组(P<0.05)。预后良好组入院时NIHSS评分明显高于90 d时(P<0.05)。预后良好组90 d mRS与入院时mRS的差值明显低于预后不良组(P<0.05)。多因素Logistic回归分析显示,患者发病后合并意识障碍(OR=0.06,95%CI:0.01~0.40)、责任大血管闭塞(OR=0.14,95%CI:0.03~0.72)是青年卒中rt-PA静脉溶栓治疗后临床预后不良的独立危险因素。结论青年卒中发病后合并意识障碍、责任大血管闭塞是青年卒中rt-PA静脉溶栓治疗后临床预后不良的独立危险因素。     

Dynamic change of coagulation and anticoagulation markers of patients with acute cerebral infarction during intravenous urokinase thrombolysis

BACKGROUND AND OBJECTIVE: The variations of blood coagulation and anticoagulation are of clinical importance in patients with acute cerebral infarction during intravenous urokinase (UK) thrombolysis. Although intravenous heparin is commonly used after thrombolytic therapy, few reports have addressed the relationship between the degree of anticoagulation and clinical outcomes, specifically the effect of thrombolytic agents on hemostasis. In this study, we dynamically monitored the activated partial thromboplastin time (APTT), the prothrombin time (PT), the thrombin time (TT) and the activated partial thromboplasmin time (APTT) in 56 patients with acute cerebral infarction during intravenous urokinase thrombolysis and analysed the relationship among the blood coagulation biomarkers (APTT, PT, TT, AT-III), as well as baseline patient characteristics and clinical outcomes. This allowed us to explore the valuable biomarkers for securing the thrombolysis regimen in clinical practice. METHODS: The levels of PT, APTT, TT and AT-III in peripheral blood of 56 patients with acute cerebral infarction and 50 normal controls were assayed by ELISA. Dynamic transformation of these markers at the baseline and the time points of the first, second, fourth, eighth, 12th, 24th, 48th, 72nd and 96th hour after intravenous UK thrombolysis was monitored serially. The relationship between the levels of these biomarkers and the clinical effectiveness and safety of urokinase thrombolysis was evaluated. RESULTS: The levels of PT, APTT, TT and AT-III in patients before intravenous UK thrombolysis were significantly lower than those in age- and sex-matched normal controls (all p<0.05). After treatment with UK, the levels of PT and APTT rose quickly during the first 4 hours (all p< 0.05), and then gradually recovered, reaching baseline at about the 48th hour. The activity of AT-III was slightly increased and showed fluctuations after UK infusion (p< 0.05), however the fluctuated range was not remarkable and lacked specificity. CONCLUSIONS: Dynamic monitoring of PT, APTT and TT can indicate coagulative and anticoagulative functions of patients with acute cerebral infarction during intravenous urokinase thrombolysis. Monitoring of these markers can be helpful both in regulating the infusion speed and the dosage of UK, as well as increasing the efficacy and safety of UK therapy. However, assay for AT-III might be unnecessary.     

急性缺血性脑卒中时间窗内的动静脉溶栓分层治疗的对比研究

目的 通过对比急性缺血性脑卒中发病时间窗内（＜4.5 h）单纯静脉溶栓治疗与动静脉溶栓的分层治疗结局,从而为急性缺血性脑卒中的治疗寻求最佳方案.方法 分别选取湖北省中山医院2012年1月～2014年6月及湖北省新华医院2009年1月～2011年6月2.5年间的静脉溶栓时间窗内（＜4.5 h）的急性缺血性脑卒中病例,前者根据NIHSSS评分、3I-SS评分将急性缺血性脑卒中进行分层后采用静脉溶栓、动脉溶栓/机械溶栓,后者均采用时间窗内静脉溶栓治疗.结果 依据NIHSS评分/3I-SS评分对急性缺血性脑卒中时间窗内进行溶栓分层治疗较单纯的静脉溶栓治疗更能改善临床预后.另外,NIHSS评分/3I-SS评分对大/小血管病变的分类与经过血管检查（核磁MRA/DSA/TCD/超声）检查所发现大/小血管病变具备一定的特异性及敏感性.结论 急性缺血性脑卒中的溶栓的分层治疗,具备一定的科学性及可操作性,可更大限度发挥动/静脉溶栓治疗的优势,使两者优劣性互补,通过对患者/病变进行分层,能够更大限度使患者获益.     

Ultrasound in the treatment of ischaemic stroke

Intravenous alteplase (recombinant tissue plasminogen activator) has been shown to be beneficial within a short 3 h window after stroke. Ultrasound has a thrombolytic capacity that can be used for pure mechanical thrombolysis or improvement of enzyme-mediated thrombolysis. Mechanical thrombolysis with ultrasound needs high intensities at the clot (>2 W/cm2) that may have unwanted side-effects, whereas improvement of enzymatic thrombolysis can be done at the safer energy levels used in diagnostic ultrasound. Methods of improving enzymatic thrombolysis with ultrasound include intra-arterial delivery of thrombolytic agents with an ultrasound-emitting catheter and targeted and non-targeted non-invasive transcranial ultra sound delivery during intravenous thrombolytic infusion. Animal and clinical studies of sonothrombolysis have shown clot lysis and accelerated recanalisation of arterial occlusion has been seen in in vitro flow models, occluded peripheral and coronary arteries, and intracerebral arteries. Controlled clinical trials to test safety management and effectiveness of both strategies are in progress.     

急性脑梗死动静脉联合与单纯静脉溶栓治疗的疗效观察

目的观察急性脑梗死动静脉联合(IA/IV)与单纯静脉(IV)重组组织型纤溶酶原激活物(rtPA)溶栓治疗的临床疗效。方法对20例急性脑梗死患者分别进行IA/IV(10例)与IV(10例)溶栓治疗,治疗前后分别进行欧洲卒中量表评分(ESS)和Barthel指数(BI)评分,观察其疗效及不良反应。结果IA/IV组患者闭塞段血管均有效再通,其中8例完全再通,2例部分再通;ESS及BI评分均明显高于IV组(均P<0.01),临床总有效率IA/IV组为90%,明显优于IV组的30%(P<0.05)。结论IA/IV溶栓治疗急性脑梗死是一种安全、有效的治疗方法,效果优于IV溶栓治疗。     

Acute ischemic stroke management: medical management

The initial management of a patient with suspected stroke necessitates a rapid and focused evaluation. Establishing the time of symptom onset, performing a focused neurologic examination, and interpreting ancillary tests facilitates delivery of acute stroke therapies to eligible patients. This review emphasizes the fundamentals of urgent stroke evaluation and evidence-based acute ischemic stroke therapies. Results from randomized clinical trials of intravenous thrombolysis, glucose management, and blood pressure management in acute ischemic stroke patients will be highlighted. External ultrasound as an adjunct to intravenous thrombolysis and treatment of those patients that wake up with stroke symptoms will also be discussed.     

急性缺血性卒中静脉溶栓治疗研究新进展

随着静脉溶栓时间窗从3 h扩展到了9 h，研究重点也从时间窗理念扩展至组织窗理念。对 于发病时间不明、醒后卒中或者一定时间内的超时间窗患者，需完善相关神经影像学检查，权衡利弊 后决定是否静脉溶栓治疗。本文重点梳理了近年来根据组织窗寻找静脉溶栓获益患者的各种不同 筛选方法及静脉溶栓的药物选择，希望能为临床提供参考。