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.     

Intravenous Tissue Plasminogen Activator and Flow Improvement in Acute Ischemic Stroke Patients with Internal Carotid Artery Occlusion

BACKGROUND AND PURPOSE: It has been suggested that intravenous tissue plasminogen activator (TPA) would not lyse the large thrombus associated with internal carotid artery (ICA) occlusion and, therefore, would be ineffective in this setting. Vascular imaging, safety, and outcome of TPA therapy for ICA occlusion is not well described. Our goal was to determine the site of occlusion, early recanalization after TPA infusion, and its relationship to outcome. METHODS: We reviewed our database of all stroke patients treated with i.v. TPA between July 1997 and July 1999. We identified all cases with carotid occlusion suggested by transcranial Doppler (TCD) and angiography. Occlusion and recanalization were assessed by site including proximal ICA (prICA), terminal ICA (tICA), and middle cerebral artery (MCA). Baseline National Institutes of Health Stroke Scale (NIHSS) scores and follow-up Rankin scores were obtained. RESULTS: We treated 20 patients with carotid occlusion (age 63.9 +/- 10.8 years, 11 males, 9 females). Time to TPA infusion after stroke onset was 128 +/- 66 minutes. Baseline NIHSS scores were 16.4 +/- 5.4. Time to follow-up was 3.5 +/- 4.9 months (2 patients were lost to follow-up). Occlusion sites were prICA 40%, tICA 70%, and concurrent MCA 45%. Multiple sites were involved in 10/20 patients (50%). Among patients with pretreatment and posttreatment vascular imaging studies (n = 18), recanalization in the prICA and tICA was complete in 10%, partial in 16%, and none in 74%. MCA recanalization was complete in 35%, partial in 24%, and none in 41%. At follow-up, Rankin 0-1 was found in 8 patients (44%), Rankin 2-3 in 3 (17%), and Rankin 4-5 in 3 (17%). Mortality was 22% (n = 4) including 1 fatal intracerebral hemorrhage. Improvement was closely related to resumption of MCA flow (P < .01). CONCLUSIONS: Most patients did not recanalize their ICA occlusion after intravenous TPA therapy. However, recanalization of associated proximal MCA clot, found in 45% of our patients, or improved MCA collateral flow was strongly associated with good outcome.     

糖尿病性和非糖尿病性脑梗死患者血浆中纤溶酶原激活物及其抑制剂活性的动态观察

目的 :观察糖尿病性脑梗死 (diabeticischemicstroke ,DIS)和非糖尿病性脑梗死 (non diabeticischemicstroke ,NDIS)患者血浆中纤溶酶原激活物 (plasminogenactivator ,PA)及纤溶酶原激活物抑制剂 (plasminogenactivatorinhibitor ,PAI)的动态变化情况。方法 :应用底物发色法测定血浆中PA和PAI活性 ,以观察DIS和NDIS患者血浆PA和PAI活性的动态变化。结果 :NDIS患者血浆中PA活性在4～ 2 1d较非脑梗死患者升高 ;DIS患者的PA活性在 7h～ 2 1d较NDIS患者为低 ,但PAI活性在各组间无明显差异。结论 :DIS患者血浆中PA活性较NDIS患者降低 ,提示其存在纤溶系统激活的紊乱 ,并可能与DIS症状加重有关。     

Demonstration of Significant Resolution of Cerebral Sino-Venous Thrombosis Associated with Intravenous Recombinant Tissue Plasminogen Activator

BACKGROUND: Cerebral sino-venous thrombosis (CVT) is commonly treated with anticoagulant therapy. There are reports of response to endovascular thrombolysis with or without mechanical aspiration in patients with clinical deterioration. CASE: We present a 29-year-old man with acute onset of severe headache, found to have extensive CVT by magnetic resonance venography (MRV). His atypical presentation led to cerebral angiography that was complicated by global aphasia and right hemiparesis from left middle cerebral artery distribution ischemia. He received intravenous rt-PA (recombinant tissue plasminogen activator) within an hour of the procedure followed, 24 hours later, by intravenous heparin infusion with significant clinical improvement. The headache severity and CVT, on follow-up MRV, resolved significantly within 2 days. CONCLUSIONS: We demonstrate clinical and neuroimaging response to systemic rt-PA in CVT. Thrombolysis may have a role in CVT management with an extended therapeutic window.     

Outcomes of Endovascular Mechanical Thrombectomy and Intravenous Tissue Plasminogen Activator for the Treatment of Vertebrobasilar Stroke

Background and Purpose

Aggressive treatment of posterior-circulation occlusions is important due to the high rates of morbidity and mortality associated with these infarctions. A large administrative database was evaluated to determine the outcomes of mechanical thrombectomy and intravenous tissue plasminogen activator (IV-tPA) for the treatment of posterior-circulation (vertebrobasilar) strokes. Outcomes were compared across age groups.

Methods

The United States Nationwide Inpatient Sample was used to evaluate the outcomes of patients treated for posterior-circulation acute ischemic stroke between 2006 and 2010. Patients who underwent endovascular mechanical thrombectomy and IV-tPA were selected. Primary outcomes were discharge status and mortality; secondary outcomes were length of stay, rate of intracranial hemorrhage, tracheostomy, and percutaneous endoscopic gastrostomy/jejunostomy tube placement. Outcomes were grouped according to age (i.e., <50, 50-64, and ≥65 years). Chi-squared test and Student''s t-test were used for comparisons of categorical and continuous variables, respectively.

Results

During 2006-2010 there were 36,675 patients who had discharge International Classification of Diseases (9th edition) codes indicating posterior-circulation strokes. Of these, 631 (1.7%) underwent mechanical thrombectomy and 1554 (4.2%) underwent IV-tPA. The in-hospital mortality rate for mechanical thrombectomy patients was significantly lower for those aged <50 years than for those aged 50-64 years (30.4% versus 47.4%, p<0.01) and those aged ≥65 years (30.4% versus 43.0%, p≤0.01). Age had no effect on the in-hospital mortality for IV-tPA patients, with an incidence of 22.7% for patients aged <50 years, compared to 25.4% for patients aged 50-64 years (p=0.46) and 23.0% for patients aged ≥65 years (p=0.92).

Conclusions

Patients requiring IV-tPA and/or mechanical thrombectomy for the treatment of posterior-circulation strokes suffer from high mortality rates. Increased age is associated with significantly higher mortality rates among posterior-circulation stroke patients who require mechanical thrombectomy.     

Cost-Effectiveness of Recombinant Tissue Plasminogen Activator in the Management of Acute Ischemic Stroke: A Systematic Review

Background and Purpose

This work was undertaken to review the current cost-effectiveness analysis data on thrombolysis by intravenous (IV) therapy with recombinant tissue plasminogen activator (rtPA) for acute ischemic stroke.

Methods

PubMed was searched for articles published between 1995 and 2008. The cost-effectiveness analysis data from eight eligible studies were reviewed, paying particular attention to their modeling assumptions and the quality of the source data.

Results

The reviewed studies were from six countries: USA (n=2), UK (n=2), Canada (n=1), Australia (n=1), Spain (n=1), and Denmark (n=1); most were performed from the healthcare-system and/or societal perspectives. IV rtPA was associated with an acceptable increase in short-term cost [range: US$ 36-236/patient; US$ 29,148-55,591/quality-adjusted life-years (QALYs)], and a net long-term cost saving that was higher from a societal perspective (range: -US$ 12,043 to -US$ 630/patient; -US$ 207,253 to -US$ 21,938/QALYs) than from a healthcare-system perspective (range: -US$ 5,811 to -US$ 5,415/patient; -US$ 41,137 to -US$ 4,662/QALYs).

Conclusions

IV rtPA seems to be a cost-effective strategy for the management of acute ischemic stroke, and might reduce the associated healthcare costs as well as patients'' disabilities. Further cost-effectiveness research and the development of a public health strategy are warranted to optimize the use of rtPA in Korea.     

重组组织型纤溶酶原激活剂静脉治疗轻型缺血性卒中患者的疗效分析

目的 观察轻型缺血性卒中患者重组组织型纤溶酶原激活剂（recombinant tissue plasminogen activator,rt-PA）静脉溶栓治疗的疗效及安全性。      

动脉内重组组织型纤溶酶原激活物局部溶栓治疗超早期脑梗死

目的：探讨动脉内重组组织型纤溶酶原激活物（rtPA）局部溶栓治疗超早期脑梗死的有效性和安全性。方法：收集有完整资料的动脉溶栓病例21例，用NIHSS评分评定溶栓的疗效，用改良Rankin量表评价溶栓治疗90d时的转归，并对溶栓治疗的再通率、有症状脑出血发生率和病死率进行分析。结果：动脉内局部溶栓转归良好的比例为42．9％，有症状脑出血发生率为9．5％，病死率为9．5％。57．1％的溶栓病例完全再通，38．1％的病例部分再通。溶栓后再通等级为Ⅲ级的患者预后良好的比例为58．3％，再通等级为Ⅱ级的患者预后良好的比例为25％。大脑前动脉和大脑中动脉闭塞患者的动脉溶栓后的转归良好，动脉溶栓可降低颈内动脉和基底动脉闭塞的病死率结论：动脉内rtPA局部应用溶栓治疗超早期急性脑梗死安全、有效，再通等级与闭塞部位和预后相关。     

Rectus Sheath Hematoma Following Intravenous Thrombolysis With Recombinant Tissue Plasminogen Activator for Cerebral Infarction: A Case Report

A 76-year-old Japanese man was admitted to our department because of aphasia and right hemiparesis. Brain magnetic resonance imaging showed cerebral infarction caused by occlusion of the left middle cerebral artery, and alteplase therapy was started. Thrombectomy was subsequently performed, resulting in recanalization. On day 4 after admission, he complained of epigastric pain when coughing. On day 8, contrast-enhanced computed tomography showed a left abdominal rectus sheath hematoma without extravasation. We carefully followed up the patient with conservative therapy, and the rectus sheath hematoma was ameliorated. Rectus sheath hematomas present as acute abdominal pain and are often misdiagnosed. Although several predisposing factors for rectus sheath hematomas have been identified, whether recombinant tissue-type plasminogen activator causes rectus sheath hematomas, remains unclear. This case highlights the need to consider a rectus sheath hematoma as a differential diagnosis of abdominal pain following treatment with recombinant tissue-type plasminogen activator.     

实验性糖尿病大鼠脑缺血纤溶酶原激活物和纤溶酶原激活物抑制剂活性测定

目的 :了解糖尿病大鼠脑缺血 /再灌注后纤溶系统的变化。方法 :糖尿病和正常大鼠于脑缺血 1h再灌注 1、2、5、11、2 3h后 ,用发色底物法测定脑组织中PA和PAI的活性。结果 :糖尿病大鼠脑梗死体积增大、再灌注时血流恢复显著降低 ;脑缺血后 ,正常组和糖尿病组PAI活性无变化 ,PA活性增高 ;再灌注 5h ,正常大鼠PA活性和PA/PAI比值增高。结论 :大鼠脑缺血 /再灌注后PA活性和PA/PAI增高 ,且呈动态变化 ;糖尿病大鼠实际的应激促纤溶功能降低     

重组组织型纤溶酶原激活剂治疗心源性脑栓塞的疗效与安全性分析

目的 探讨重组组织型纤溶酶原激活剂（recombinant tissue plasminogen activator,rt-PA）治疗心源性脑栓塞的有效性与安全性。 方法 采用回顾性分析方法,非连续性选取北京积水潭医院2007年1月～2011年12月间发病4.5～12 h内的（前循环梗死发病4.5 h内,后循环12 h内）心源性脑栓塞患者45例,其中接受rt-PA溶栓治疗的22例患者为溶栓组,接受常规二级预防的23例作为对照组。收集患者牛津郡社区卒中项目（Oxfordshire Community Stroke Project,OCSP）分型、危险因素、既往史、用药史和神经功能缺损情况。比较两组患者基线（治疗前）、24 h、90 d神经系统功能缺损情况、预后良好的比例及两组间梗死后出血转化（hemorrhagic transformation,HT）的发生率以及90 d患者死亡率。 结果 两组患者基线美国国立卫生研究院卒中量表（National Institutes of Health Stroke Scale,NIHSS）评分及OCSP分型差异均无显著性。发病24 h后,溶栓组NIHSS改善分值［4.5（－1.5,8）］较对照组［0（0,3）］差异具有显著性（P=0.04）。溶栓组早期改善百分比（54.55%）高于对照组（34.78%）,但差异无显著性。发病90 d,溶栓组NIHSS改善分值［9（7,11）］较对照组［3.5（2,4.75）］差异具有显著性（P＜0.01）。溶栓组预后良好百分比（22.7%～36.4%）较对照组（17.4%～26.1%）升高,但差异无显著性。溶栓组和对照组HT患者均为4例,其中症状性出血转化（symptomatic intracranial hemorrhage,sICH）每组各3例,溶栓组4例HT患者均无糖尿病病史,对照组4例患者均有糖尿病病史,6例sICH患者收缩压均大于140 mmHg。发病90 d,两组患者死亡例数均为3例,6例死亡患者入院时NIHSS分值普遍偏高,且梗死类型以完全前循环梗死（total anterior circulation infarct,TACI）为主。 结论 rt-PA用于治疗心源性脑栓塞能够改善发病24 h、90 d的神经功能缺损程度,使用rt-PA相对安全。     

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.     

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。     

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。     

急性缺血性脑卒中rt-PA静脉溶栓后出血性转化的特殊类型

目的溶栓后出血性转化(hemorrhagic transformation,HT)是重组组织型纤维蛋白溶酶原激活剂(rt-PA)治疗急性缺血性脑卒中的一个重要安全指标。HT有不同的亚型,而不同亚型的预后也不尽相同。我们对急性缺血性脑卒中患者rt-PA静脉溶栓后出现的特殊型HT进行分析。方法对发病3zh内的98例缺血性卒中患者用rt-PA(剂量0．6 mg/kg,最大剂量5 0 mg)进行静脉溶栓治疗,溶栓前后行头颅CT、MRI或数字减影血管造影(DSA)检查判断是否有HT,并判定这种HT与责任病灶的关系。结果溶栓后经CT或MRI检查发现4种特殊的远端HT类型,1例发生蛛网膜下腔出血(SAH),1例梗死部位的对侧出现明显占位效应的脑实质出血,1例出现梗死灶对侧的侧脑室出血,1例出现梗死部位对侧的腔隙性出血。这4例患者所引起的4类HT在临床上均为无症状,预后好。结论对急性缺血性脑卒中的溶栓治疗要坚持动态观和平衡观,对症状性出血性转化的诊断要慎重,充分考虑HT的分型和程度,从而正确判断HT对预后的影响。