rt-PA静脉溶栓治疗高龄急性缺血性脑卒中的研究进展

静脉溶栓治疗是急性缺血性脑卒中超早期治疗的首选方法,重组组织型纤溶酶原激活剂(rt-PA)是目前临床上广泛应用的静脉溶栓药物。既往静脉溶栓将80岁以上高龄患者排除在外,现年龄因素不再是应用排除标准。现对高龄缺血性脑卒中患者应用rt-PA静脉溶栓治疗有效性、时间窗、剂量、颅内出血并发症等相关研究进行综述,以对高龄患者应用rt-PA静脉溶栓治疗提供临床参考依据。     

rt-PA 静脉溶栓后颅内出血转化相关机制的研究进展

急性缺血性脑卒中是最常见的脑卒中类型,重组组织型纤溶酶原激活剂(Recombinant Tissue Plasminogen Activator,rt-PA)静脉溶栓是急性缺血性脑卒中有效的治疗方法,具有明确的循证学依据,美国国立神经疾病与卒中研究所(NINDS)、欧洲急性卒中协作研究(ECASS)及中国2014中国急性缺血性脑卒中诊治相关指南均加以推荐使用.rt-PA静脉溶栓后部分类型颅内出血,严重影响患者预后,增加患者的死亡及伤残率,是阻碍静脉溶栓实施的重要因素.因此,探讨rt-PA静脉溶栓后颅内出血转化的发病机制,具有重要意义.本文就溶栓后颅内出血转化的分类、rt-PA药理作用、不同类型出血转化发病机制加以综述.     

重组组织型纤溶酶原激活剂溶栓后特殊型出血性转化二例

虽然欧洲和美国大规模试验证明重组组织型纤溶酶原激活剂（rt-PA）在急性缺血性卒中患者中是有益的，但出血事件常常妨碍溶栓治疗在临床的应用。作者在用rt-PA溶栓治疗急性缺血性脑卒中的临床工作中，发现二种特殊的远部出血性转化（hemorrhagic transformation,HT），分析其特殊性，对将来临床溶栓治疗具有重要意义。     

rt-PA溶栓治疗急性缺血性脑卒中后脑出血的研究 进展

重组组织型纤溶酶原激活物（rt-PA）溶栓治疗急性缺血性脑卒中（AIS）后脑出血是溶栓治 疗中的严重并发症。rt-PA在局部溶栓的同时增加了机体出血风险，可能导致脑出血性转化（CHT），其发 病与纤溶酶原激活物抑制剂1（PAI1）和凝血酶激活的纤溶抑制物（TAFI）的基因多态性和生理差异有关。 体温、年龄、头颅CT或MRI的影像表现、血压和血糖等多种因素均是影响rt-PA 溶栓治疗AIS 后脑出血 的因素。在rt-PA 溶栓治疗中，针对不同生理状态和临床特征的AIS 患者进行预见性地监测和目的性地 护理具有重要的临床意义。     

rt-PA静脉溶栓治疗急性缺血性脑卒中的血压变化及对预后的影响

目的探讨重组组织型纤溶酶原激活剂(rt-PA)静脉溶栓治疗急性缺血性脑卒中(AIS)后的血压变化及对预后的影响。方法选取98例行rt-PA静脉溶栓治疗的AIS患者作为研究对象,根据溶栓后收缩压(SBP)下降与否分为观察组(58例,SBP下降)和对照组(40例,SBP未下降),对比两组静脉溶栓后2h及24h的血压值变化,分析溶栓后血压值变化与患者预后的相关性。结果观察组患者溶栓前及溶栓后24h的NIHSS评分均明显低于对照组,(P0.05)。观察组溶栓2h和溶栓24h后的SBP水平均显著低于对照组,(P0.05)。溶栓后2h SBP、溶栓后24h SBP、溶栓前NIHSS评分与患者预后呈负相关关系。对照组的颅内出血率、症状性颅内出血率和死亡率均显著高于观察组,(P0.05)。结论 rt-PA静脉溶栓治疗AIS具有确切疗效,溶栓后2h及24h的收缩压水平与患者预后密切相关,收缩压偏低者预后效果更好。     

Apelin对急性缺血性脑卒中静脉溶栓后出血性转化和生存率的影响

目的 检测脂肪细胞因子(Adipocyte factor, Apelin)在急性缺血性脑卒中(Acute ischemic stroke, AIS)的水平并分析其对静脉溶栓治疗(Intravenous thrombolytic therapy, ITT)后出血转化(Hemorrhagic transformation, HT)的预测及生存率的影响。方法 收集2017年2月-2019年2月接受静脉溶栓(Intravenous thrombolytic, IT)治疗的AIS患者185例，根据IT治疗后1周是否发生HT将其分为未出血转化(Non-hemorrhagic transformation, NHT)组(n=156)和HT组(n=29);采用酶联免疫吸附测定(Enzyme linked immunosorbent assay, ELISA)法检测患者外周血中Apelin、白介素(Interleukin, IL)-1β,IL-6、超氧化物歧化酶(Superoxide dismutase, SOD)、丙二醛(Malondialdehyde, MDA)水平；Logistic多因素回归分析影...     

急性缺血性脑卒中rt-PA静脉溶栓治疗

急性缺血性脑卒中的溶栓治疗是近年来国内外研究的热点,在适应证问题上存在较多争议。为此,本研究进行了双盲对照研究,共选取2005年10月至2008年6月发病的急性缺血性脑卒中患者125例,其中61例予以基因重组型人组织纤溶酶原激活剂（recombinant human tissue—type plasminogen activator,rt—PA）静脉溶栓治疗,并对患者进行TOAST分型,观察疗效及并发症。初步总结如下。     

轻型急性缺血性脑卒中患者静脉溶栓治疗的疗效分析

目的 探讨重组组织型纤溶酶原激活剂(rt-PA)治疗轻型急性缺血性脑卒中患者的疗效。方法 收集100例发病<4.5 h的轻型急性缺血性脑卒患者,随机分为溶栓组50例,未溶栓组50例; 溶栓组于入院后给予重组组织型纤溶酶原激活剂(rt-PA)静脉溶栓治疗,24 h后非心源性脑栓塞患者给予阿司匹林+氯吡格雷双联抗血小板聚集治疗,21d后改阿司匹林或氯吡格雷治疗,心源性脑栓塞患者给予抗凝治疗; 未溶栓组非心源性脑栓塞患者给予阿司匹林+氯吡格雷双联抗血小板聚集治疗,21d后改阿司匹林或氯吡格雷治疗,心源性脑栓塞患者给予抗凝治疗; 对所有患者入院时及治疗后第14 d、90 d分别进行NIHSS神经功能缺损评分及第90 d mRS评分,比较2组患者的疗效和预后。结果 入院时溶栓组及未溶栓组患者一般临床资料、NIHSS评分及mRS评分等比较无明显差异(P>0.05); 治疗后第14、90 d与未溶栓组患者比较,溶栓组患者的NIHSS评分及mRS评分显著降低,溶栓组患者的预后明显好于未溶栓组(P<0.05); 2组患者的颅内出血发生率、缺血性脑卒中复发率比较无明显差异(P均>0.05),且2组患者均无死亡。结论 rt-PA静脉溶栓治疗轻型急性缺血性脑卒中患者安全有效。     

阿替普酶静脉溶栓治疗急性脑梗死的疗效及安全性

目的研究重组组织型纤溶酶原激活物(rt-PA)静脉给药溶栓治疗急性脑梗死的临床效果。方法回顾性分析发病在4.5h内,具有溶栓指征的急性脑梗死患者105例,其中对照组56例仅给予抗血小板聚集、调脂稳定斑块等常规治疗方案,观察组49例给予rt-PA静脉溶栓治疗,24h后若无明显出血,开始给予脑梗死常规治疗。比较2组治疗后90d美国国立卫生院卒中量表(NIHSS)评分、Barthel指数(BI)评分及改良Rankin量表(mRS)评分改善情况,以评价rt-PA治疗急性脑梗死临床疗效。结果 2组治疗前NIHSS评分差异无统计学意义(P0.05),观察组溶栓后2h、24h、7d时NIHSS评分显著低于对照组(P0.05);观察组90d时mRS评分显示预后良好的患者较对照组明显增多,2组比较差异有统计学意义(P0.05);与对照组比较,观察组90d时Barthel指数评分明显升高(P0.05)。虽然观察组总体出血事件较对照组增高(P0.05);但2组症状性脑出血比较差异无统计学意义(P0.05)。结论发病4.5h以内,静脉给予rt-PA溶栓治疗急性脑梗死具有显著的临床疗效,且安全性较高,值得临床推广应用。     

Baseline Computed Tomography Changes and Clinical Outcome After Thrombolysis With Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke

OBJECTIVE: Intravenous recombinant tissue plasminogen activator (rt-PA) is the only therapy of proven value for patients with acute ischemic stroke (AIS). Controversy exists with regard to the prognostic significance of early computed tomography (CT) changes in patients receiving rt-PA for AIS. The authors retrospectively reviewed all cases of AIS who received intravenous rt-PA for AIS in University of South Alabama hospitals between January 1996 and May 1999. A neuroradiologist, blinded to clinical outcomes, reviewed all baseline CT scans for the presence of the following signs: hyperdense middle cerebral artery (HMCA), loss of gray-white differentiation (LGWD), insular ribbon sign (IRS), parenchymal hypodensity (PH), and sulcal effacement (SE). Modified Rankin Scale (mRS) score was recorded 90 days after thrombolysis, and clinical outcome was dichotomized as favorable (0-1) or unfavorable (2-6). The authors performed both univariate and multivariate analyses to investigate the relationship between early CT signs, baseline clinical variables, and functional outcome as measured by the 90-day mRS scores. Any one early CT finding was detected in 23(64%) patients. The frequency of specific findings were as follows: SE in 13 patients (36%), LGWD in 12 patients (33%), PH in 9 patients (25%), HMCA in 4 patients (11%), and IRS in 3 patients (8%) patients. There was no statistically significant association between the occurrence of these imaging findings and subsequent functional outcome after thrombolysis. The data suggest that the presence of subtle acute CT changes in AIS patients is not predictive of clinical outcome following administration of rt-PA as per National Institute of Neurological Disorders and Stroke protocol.     

Intravenous Recombinant Tissue Plasminogen Activator Thrombolysis in a Patient with Acute Ischemic Stroke Secondary to Aortic Dissection

Background

Acute ischemic stroke secondary to aortic dissection (AoD) is challenging in the era of thrombolysis owing to the diagnostic difficulty within a narrow time window and the high risk of complications.

Case Report

A 64-year-old woman with middle cerebral artery occlusion syndrome admitted to the emergency room within intravenous recombinant tissue plasminogen activator (rt-PA) time window. Her neurological symptoms improved during thrombolysis, but chest and abdominal pain developed. Repeated history-taking, physical examination, and imaging studies led to the timely diagnosis and surgical treatment of AoD, which produced a successful outcome.

Conclusions

Clinical suspicion is invaluable for the diagnosis of this rare cause of stroke. Considering the stroke mechanism and complications, the risks of thrombolysis might outweigh its benefits.     

高龄急性脑梗死患者重组组织型纤溶酶原激活剂静脉溶栓的疗效及安全性分析

目的 探讨高龄脑梗死患者接受标准剂量重组组织型纤溶酶原激活剂（r e c o m b i n a n t t i s s u e plasminogen activator,rt-PA）静脉溶栓治疗的疗效和安全性。 方法 对我院2011年1月～2013年12月连续收治入院的254例急性脑梗死患者的临床资料进行回顾性 分析,分为老龄溶栓组118例（60＜年龄≤80岁,rt-PA静脉溶栓治疗）;高龄溶栓组62例（年龄＞80岁, rt-PA静脉溶栓治疗）;高龄非溶栓组74例（年龄＞80岁,非rt-PA静脉溶栓治疗）。比较3组入院前的 一般情况,溶栓治疗前美国国立卫生研究院卒中量表（National Institutes of Health Stroke Scale,NIHSS） 评分,溶栓后出血转化率及治疗7 d内致死性出血率,治疗后90 d改良Rankin量表（modifed Rankin Scale,mRS）评分和90 d的病死率。 结果 老龄溶栓组、高龄溶栓组和高龄非溶栓组治疗前NIHSS评分（13.0±5.3、15.1±6.6、14.1±6.6; P =0.523）无显著差异,3组的急性期事件出血转化率分别为16.9%、20.9%和21.6%,P =0.675;3组 7 d内致死性出血的发生率分别为3.3%,9.6%,7.4%,P =0.20。90 d内的病死率分别为11.0%,22.6%, 16.2%,P =0.12。老龄溶栓组和高龄溶栓组治疗后90 d的mRS评分 0～2比值分别为56.8%和38.7%, 两组比值比（odds ratio,OR）为2.08;95%可信区间（confidence interval,CI）为1.11～3.86,P =0.021;两 组治疗后90 d mRS评分中位数比较：2 vs 3,P =0.025。高龄溶栓组和高龄非溶栓组90 d的mRS评分 0～2比值分别为38.7%和21.6%,OR 1.81,95%CI 0.80～4.06,P =0.098;90 d mRS评分中位数比较：3 vs 5,P =0.008。 结论 与未溶栓的高龄患者相比,急性缺血性卒中老龄和高龄患者接受rt-PA治疗不增加急性期 出血转化率和病死率。老龄组比高龄组rt-PA治疗获益大,高龄溶栓组比非溶栓组获益大。高龄组 rt-PA治疗可以改善患者90 d生活自理能力且不增加病死率。     

Early Computed Tomography Hypodensity Predicts Hemorrhage After Intravenous Tissue Plasminogen Activator in Acute Ischemic Stroke

Parenchymal hypodensity is a proposed risk factor for hemorrhage after recombinant tissue plasminogen activator (TPA) thrombolysis for ischemic stroke. In Buffalo, NY, and Houston, TX, the authors reviewed 70 patients who were treated with intravenous TPA for acute middle cerebral artery (MCA) stroke. Two observers blinded to clinical outcome analyzed initial noncontrast head computed tomography (CT) scans. Basal ganglia CT hypodensity was quantitated in Hounsfield units (HUs). Contralateral-ipsilateral difference in density was calculated using the asymptomatic side as a control. Ictus time to TPA averaged 2.5 hours. Six patients developed symptomatic intraparenchymal hematomas (2 fatal). The hemorrhage group had more severe basal ganglia hypodensity (mean 7.5 +/- 1.4, range 6-10 HU) than the nonhemorrhage group (2.2 +/- 1.4, range 0-9 HU) (P < .0001). The hemorrhage group had hypodensity of > 5 HU; the nonhemorrhage group had hypodensity of < or = 4 HU, except 1 patient with hypodensity of 9 HU. In predicting hemorrhage, the positive predictive value of hypodensity > 5 HU was 86%; the negative predictive value was 100%. Prethrombolysis NIH Stroke Scale (NIHSS) deficit (P = .0007) and blood glucose (P = .005) were also higher in the hemorrhage group. Age, gender, smoking, hypertension, and ictus time to TPA infusion did not differ between the 2 groups. Logistic regression indicated that basal ganglia hypodensity was the best single predictor of hemorrhage. Hypodensity and NIHSS score together predicted all cases of hemorrhage. The authors conclude that basal ganglia hypodensity quantified by CT may be a useful method of risk stratification to select acute MCA stroke patients for thrombolytic therapy.     

个体化静脉溶栓治疗的研究进展

缺血性卒中严重影响着人类的生活。静脉重组组织型纤溶酶原激活剂（intravenou s
recombinant tissue plasminogen activator,rt-PA）溶栓治疗是目前被循证医学证明缺血性卒中急性期唯
一有效的方法。然而,在临床实施中,存在一些问题,如时间窗问题、伴随意识障碍问题、年龄问题、
剂量问题等等,提示在规范的基础上需进行个体化治疗,从而提高溶栓的有效性和安全性。本文就
静脉溶栓中涉及个体化方案临床研究的最新进展做一综述。     

rt-PA治疗急性脑梗死的临床研究

目的探讨重组组织型纤溶酶原激活剂(rt-PA)治疗急性脑梗死的有效性和安全性。方法选择发病6 h内的急性脑梗死患者5 0例,采用rt-PA(5 0 mg/例)静脉溶栓,其中1 O％剂量5 min内静脉推注,余90%剂量60～90 min内静脉滴注。评定患者治疗前、治疗24 h及21 d时的神经功能缺损程度评分(NIFISS),21 d、90 d日常生活能力评分(ADL)及90 d综合生活能力(改良Rankin评分,mRS)。结果治疗后24 h及21 d的NIHSS评分与治疗前比较差异均有统计学意义(P均＜0．01)。随访3个月,mRS为0～3分者33例(66%);脑出血者7例(14%),其中症状性脑出血3例(6%);死亡13例(26%)。在发病4．5 h内进行溶栓治疗的41例患者中有25例(60%)获得良好预后(mRS为0～1分),在4．5～6 h内进行溶栓治疗的9例患者中只有3例(33%)获得良好预后。13例心源性脑梗死患者仅有5例(38%)获得良好预后。结论在排除心源性脑梗死的情况下,采用rt-PA 50 mg/例治疗发病4．5 h内的脑梗死患者,能够改善神经功能,恢复生活能力。