经颅多普勒超声辅助动脉溶栓治疗急性缺血性卒中的临床研究

目的 观察应用经颅多普勒超声(TCD)辅助动脉接触性溶栓治疗急性缺血性卒中的临床疗效.方法 对北京军区总医院附属八一脑科医院自2010年8月至2011年4月收治的22例急性缺血性卒中患者(大脑中动脉闭塞13例,基底动脉闭塞9例)行动脉内超选择插管至闭塞动脉,注入重组人组织型纤溶酶原激活剂(rt-PA)20 mg进行接触性溶栓治疗,同时应用TCD对闭塞动脉进行低频(2 MHz)、低强度(0.25 W/cm2)超声辅助溶栓治疗.术后即刻及24h时复查头颅CT,观察动脉再通率、颅内出血率,并对术前术后美国国立卫生研究院卒中量表(NIHSS)评分及Barthel指数评分进行比较.结果 22例患者溶栓治疗后动脉再通率为77.27％(17/22),其中完全开通率为22.73％(5/22),部分开通率为54.55％(12/22);出现无症状性颅内出血3例(13.63％),均未发生症状性颅内出血;术后NIHSS评分及Barthel指数评分较术前明显提高,显示神经功能恢复良好.结论 对急性缺血性卒中患者在有效时间窗内应用低频TCD辅助小剂量rt-PA动脉接触性溶栓治疗,可显著提高闭塞动脉的再通率,明显减少颅内出血的发生,改善患者的预后,具有良好的临床疗效及安全性.     

rt-PA 动脉溶栓联合机械取栓治疗急性脑栓塞的临床疗效研究

目的：观察 rt-PA 动脉溶栓联合机械取栓治疗急性脑栓塞的临床疗效。方法回顾性分析 rt-PA 动脉溶栓联合机械取栓治疗的10例急性脑栓塞病例,采用 NIHSS 评分评估患者治疗前及治疗24 h 后的神经功能缺损程度,3月后采用改良 Rankin 量表（mRS）评估患者预后。结果治疗24 h 后患者 NIHSS 评分显著低于治疗前（P 〈0.01）,3月后 mRS 0~2分为90%。结论rt-PA 动脉溶栓联合机械取栓是治疗急性脑栓塞的一种有效方法。     

Dissolution of emboli in rats with experimental cerebral thromboembolism by recombinant human tissue plasminogen activator (TD-2061)

Tissue plasminogen activator (t-PA) is frequently administered clinically as thrombolytic therapy. We injected recombinant t-PA into rats with cerebral 125I-labeled blood clot emboli to evaluate the dissolutive effect of recombinant human single-chain t-PA (rt-PA; TD-2061) on such emboli and to examine the possibility of improving neurological damage in patients with cerebral thrombosis. When rt-PA was given intravenously at a dose of 350,000 IU/kg 2 minutes before embolization, radioactivity in the affected cerebral hemisphere decreased to 20% of that in the vehicle control 2 hours after embolization. A significant decrease in radioactivity in the cerebral hemisphere was also found on the administration of 700,000 IU/kg of rt-PA 30 or 60 minutes after embolization, but not when rt-PA was administered 2 minutes after embolization. Marked inhibition of abnormal behavior such as hemiplegia was seen on treatment with rt-PA 2 minutes before embolization, but not at all when rt-PA treatment was given 30 or 60 minutes after embolization. The findings suggest that rt-PA can dissolve blood clot emboli in cerebral vessels and that prompt thrombolytic therapy is important to minimize neurological dysfunction in cases of cerebral thromboembolism.     

Brain attack in Japan, now and future]

In Japan, all of the stroke center hospital equipped by high level diagnostic systems including MRI. Number of MRI is twice as that of U.S.A. Therefore, we can perform correct and effective treatment for ultra-acute cerebral infarction if rt-PA is permitted to clinical use for cerebral infarction. We are making Japan Standard Stroke Registry Study (JSSR Study) now, and already registered 2,740 acute stroke cases in 25 hospitals. Atherothrombotic embolism (artery to artery embolism) was found in 16.5% of the all atherothrombotic infarction. It suggests that diagnostic accuracy of our database is high level. Concerning with ultra acute thrombolysis, about 10,000 stroke patients per year are estimated to be treatable with rt-PA in Japan. Yamaguchi's study for acute cerebral infarction showed intra-arterial thrombolytic therapy using urokinase was significantly effective. Our JSSR Study also showed effectiveness of thrombolytic therapy using rt-PA or high dose urokinase in the patients with cerebral infarction treated within 6 hours. Therapeutic time windows for acute cerebral infarction using rt-PA is expected to be more longer by the newly developed free radical scavenger (edarabin). We must create evidence based medicine for Japanese stroke patients based on database system (JSSR).     

Intravenous thrombolysis in proximal middle cerebral artery occlusion

Subgroup analyses of data from an open-label study of intravenous recombinant tissue plasminogen activator (rt-PA) administered to stroke patients were performed. Clinical outcome and incidence of intracranial hemorrhage were evaluated in 20 patients diagnosed by transcranial Doppler ultrasound as having proximal middle cerebral artery (MCA) occlusion. Additionally early infarct signs and size of final infarction were assessed. A favorable outcome (mRS 0-2) was seen in 30% of all patients. The incidence of symptomatic intracranial hematoma (10%) in patients with proximal MCA occlusion was higher than the overall hemorrhage rate of intravenous rt-PA treatment, but comparable to the data on intra-arterial thrombolysis in this stroke subgroup. All patients except 1 developed ischemic infarction in the MCA territory. Intravenous rt-PA treatment within 3 h may also be effective in patients with proximal MCA occlusion. The risk of intracerebral hematoma does not seem to be greater than in intra-arterial thrombolysis.     

Transient global amnesia heralding basilar artery thrombosis

The cause of transient global amnesia (TGA) remains controversial. Focal cerebral ischemia, seizure, venous congestion, and migraine have all been proposed as underlying mechanisms. We describe a patient presenting with typical TGA who two days later developed a posterior circulation stroke due to basilar artery occlusion. He was treated successfully with intra-arterial thrombolytic therapy. Shortly thereafter, he had recurrent basilar artery thrombosis and jugular vein thrombosis, and was found to have a mucinous adenocarcinoma believed to be causing a hypercoagulable state. We believe this case supports the hypothesis that TGA can on occasion be caused by cerebral ischemia.     

Transient global amnesia heralding basilar artery thrombosis

The cause of transient global amnesia (TGA) remains controversial. Focal cerebral ischemia, seizure, venous congestion, and migraine have all been proposed as underlying mechanisms. We describe a patient presenting with typical TGA who two days later developed a posterior circulation stroke due to basilar artery occlusion. He was treated successfully with intra-arterial thrombolytic therapy. Shortly thereafter, he had recurrent basilar artery thrombosis and jugular vein thrombosis, and was found to have a mucinous adenocarcinoma believed to be causing a hypercoagulable state. We believe this case supports the hypothesis that TGA can on occasion be caused by cerebral ischemia.     

Acute ischaemic stroke in pregnancy: a severe complication of ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of sterility treatment. It is characterised by ovarian enlargement, ascites, electrolyte disturbance, hypovolaemia and haemoconcentration. A case of ischaemic stroke due to right middle cerebral artery (MCA) occlusion in a young female with OHSS after pharmacological treatment of sterility is reported. Left central hemiparesis occurred suddenly within a few days after the embryo transfer. Magnetic resonance imaging diffusion-weighted images showed infarction in the right basal ganglia and magnetic resonance angiography (MRA) revealed the occlusion of the M1 segment of the right MCA. The haemodilution and the anticoagulation therapy were effective. Twenty-four hours after the stroke onset, MRA showed MCA recanalisation. The neurological deficit resolved completely within 3 months. The patient delivered 2 healthy infants at term. This case emphasises that the recent advent of ovulation induction and reproductive techniques is a newly recognised cause of cerebral stroke in otherwise healthy females.     

Intra-arterial tissue plasminogen activator for thrombosis complicating cerebral angiography in a 17-year-old girl

Few reports describe the use of intraarterial recombinant tissue plasminogen activator to treat intracranial thrombosis in children. A 17-year-old girl with a history of prior venous thrombosis developed a left middle cerebral artery thrombus during diagnostic cerebral angiogram. Therapy with intra-arterial tissue plasminogen activator was initiated. An immediate follow-up angiogram demonstrated recanalization, and diffusion-weighted magnetic resonance imaging 9 hours later showed no evidence of infarction. Following the angiogram, femoral artery thrombosis developed. Treatment with supratherapeutic levels of heparin, localized delivery of intra-arterial tissue plasminogen activator, embolectomy, danaparoid, and dipyridamole failed to re-establish perfusion to the lower leg, and below the knee amputation was required. Neurologic examination remained normal 1 year later. Cerebral damage was avoided with the use of emergency intra-arterial tissue plasminogen activator for cerebral artery thrombosis in this child.     

对rt-PA治疗脑梗塞中颈动脉粥样硬化影响的再讨论

目的人体组织纤维蛋白溶解酶原酶(t-PA)治疗不同病因脑梗塞的疗效的再探讨。方法以颈动脉和心脏Doppler超声和数字式血管造影(DSA)的检查结果为依据作分组对比分析rt-PA的治疗效果。结果rT-PA治疗后24h症状改善与预后有关。颈动脉粥样硬化性完全梗塞和严重狭窄组病例溶栓起效时间明显推迟(P＜0.05)。3个月后颈动脉完全梗塞组68.75%有严重神经系统后遗症。结论颈动脉粥样硬化性梗塞和严重狭窄是影响溶栓治疗预后的一个重要因素。     

MRI evaluation of treatment of embolic stroke in rat with intra-arterial and intravenous rt-PA

Using magnetic resonance imaging (MRI), we investigated treatment of a rat model of embolic stroke with rt-PA via intra-arterial (IA) and intravenous (IV) routes of administration. Rats were treated with rt-PA by either IA (n = 13) or IV (n = 13) routes at 3 h after stroke induction. Diffusion, perfusion, T2, and magnetization transfer MRI were performed prior to and at 1-3 and at 24 h after embolization. The IA treated group exhibited smaller lesion volumes than the IV treated group (p = 0.02). The relative areas with low ADCW and cerebral blood flow (CBF) after IA rt-PA intervention were significantly (p < or = 0.03) smaller than those in the IV treated group at 24 h after embolization. Significant differences (p < 0.02) between IA and IV treated groups in the relative area with high T2 and inverse of the apparent forward transfer rate of magnetization (kINV) in the ipsilateral hemisphere were also detected at 24 h after embolization. The IA treated group exhibited less intracerebral hemorrhage (27%) than the IV treated (64%) groups. Our data suggest that the beneficial effects of IA rt-PA treatment can be detected by changes in CBF, ADCW, T2, and kINV.     

尿激酶对非老年性脑梗死缺血半暗带相对弥散系数的影响简

目的评价尿激酶对非老年性急性脑梗死缺血半暗带相对弥散系数（rADC）的影响。方法80例18—59岁的急性脑梗死病人随机分为尿激酶组与重组人组织型纤溶酶原激活剂（rt—PA）组各40例,均进行动脉介入溶栓治疗,比较两组病人动脉溶栓手术前后rADC变化、血管再通、临床疗效及并发症情况。结果治疗前两组缺血半暗带内4个感兴趣点的rADC均不存在统计学差异（P〉0．05）,两组rADC从a-d点呈明显单调递增趋势（P〈0．05）;治疗后两组4个感兴趣点的rADC均高于治疗前,但差异均无统计学意义（P〉0．05）。两组的血管再通、临床疗效及并发症发生率差异亦均无统计学意义（P〉O．05）。结论尿激酶与rt—PA对非老年性急性脑梗死缺血半暗带rADC的影响无明显差异．尿激酶可在一定程度上替代rt—PA应用于该类病人。     

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。     

Life-Threatening Anaphylactoid Reaction in an Acute Ischemic Stroke Patient With Intravenous rt-PA Thrombolysis, Followed by Successful Intra-Arterial Thrombolysis

An anaphylactoid reaction to recombinant tissue plasminogen activator (rt-PA) is an uncommon but fatal complication. A 39-year-old man was admitted within 1 hour of the onset of a right hemispheric stroke. He was not taking any specific medication, including angiotensin-converting enzyme (ACE) inhibitors. A systemic anaphylactoid reaction developed immediately after rt-PA infusion. However, the symptoms were improved after treatment with a steroid and antihistamine. Subsequent intra-arterial thrombolytic therapy resulted in complete recanalization and clinical improvement. To our knowledge, this is the first report of a life-threatening anaphylactoid reaction after rt-PA treatment followed by successful intra-arterial thrombolytic therapy in a patient who had not taken an ACE inhibitor.     

动脉内溶栓治疗急性缺血性脑卒中的临床分析

目的:探讨使用动脉内溶栓方法治疗急性缺血性脑卒中的效果。方法:回顾138例急性缺血性脑卒中患者,发病距接受治疗的时间为3～24h,采取超选择性动脉溶栓。结果:颈内动脉闭塞22例,大脑中动脉主干闭塞38例,大脑中动脉分支闭塞33例,大脑前动脉闭塞1例,椎基底动脉系统血管闭塞12支。脑血管造影未见异常32例。闭塞血管再通者,颈内动脉12例;大脑中动脉24例;大脑中动脉分支21例;椎基底动脉8例。8例患者因明显血管狭窄,治疗后予以球囊扩张,支架植入术。临床症状完全恢复或明显好转83例,溶栓后脑出血患者5例。结论:超选择动脉内溶栓是治疗急性缺血性脑卒中的有效方法。     

急性脑梗死超早期重组组织型纤溶酶原激活物溶栓治疗的临床研究

目的:探讨发病6h内急性脑梗死给予重组组织型纤溶酶原激活物(rt-PA)溶栓治疗的疗效及并发症,并分析预后相关因素。方法:共收集本院2001-2005年70例溶栓治疗的急性脑梗死病例,其中52例静脉溶栓,18例动脉溶栓,分析比较两组病例溶栓前后及3个月随访的ESS评分及Barthel指数结果;同时分析与预后相关的因素。结果:静脉和动脉溶栓组溶栓前及溶栓30min后ESS评分及Barthel指数迅速增加,溶栓前后分值有显著差异。1个月内颅内出血率为5.77%(静脉组)和16.67%(动脉组)。3个月时ESS评分及Barthel指数较溶栓后30min的评分有显著改善。结论:6h内动脉、静脉溶栓治疗均安全有效。     

Intra-arterial thrombolysis for acute angiographically proven occlusion in bifurcation of basilar artery. Case report

In a 52 year-old male patient with a past history of two strokes, an occlusion of the basilar cerebral artery in the area of bifurcation into the posterior cerebral arteries was angiographically confirmed. Following an intra-arterial application of rt-PA a partial revascularization of the occluded posterior arteries was observed. After an interval of 8 hours rt-PA was administered again, resulting in a complete recanalization of the arteries. The patient's neurological state was stabilized but not improved, despite a systematic anti-thrombotic treatment. His sudden death on the 23rd day of treatment was caused by pulmonary embolism. A postmortem examination indicated a complete patency of the Willis circle. The basilar artery was unchanged, while within the posterior cerebral arteries only a moderate thickening of the intima and a small dissection of the internal elastic membrane were found. There was no evidence of bleeding into the CNS. It was assumed that thrombolysis had resulted in a total revascularization of the occluded region and was uncomplicated. Ischemic changes within the nervous tissue had probably developed before the thrombolytic treatment, and were responsible for the lack of improvement. The patient's death due to pulmonary embolus in spite of the continued anticoagulant treatment, and his history of strokes in the young age, suggested the presence of some coagulation system abnormalities that could not be detected because of the thrombolytic and anticoagulant drugs administration.     

Antithrombotic strategy in stroke

Numerous randomised controlled trials have been devoted to antithrombotic strategy in stroke, thus making evidence-based recommendations possible. The use of antithrombotic drugs is crucial in the treatment of ischemic stroke though often limited by the inherent risk of intra-cerebral bleeding. In the prevention of stroke, the strategy depends on the underlying etiology: (i) antiplatelet drugs (with aspirin as first choice) in atherothrombotic stroke, and (ii) oral anticoagulants in cardioembolic stroke. In the acute treatment, the strategy depends on whether IV rt-PA can be performed; if rt-PA is available and approved, its use is recommended within 3 h of the onset of symptoms provided there is strict adherence to the inclusion and exclusion criteria. In all other cases, aspirin is the treatment of choice, associated with low dose LMWH in the event of restricted mobility. There is no evidence for efficacy of high dose heparin (or LMWH) in stroke, except in cerebral venous thrombosis.     

急性脑梗死超早期应用尿激酶动脉溶栓治疗四例

目的评价急性脑梗死超早期应用尿激酶动脉溶栓的疗效及安全性。方法应用尿激酶动脉溶栓治疗4例急性脑梗死患者,分析溶栓时间窗、尿激酶剂量、责任供血动脉再通情况与转归的关系等。结果例2大脑中动脉溶栓后症状完全缓解;例4颈内动脉溶栓后颈内动脉完全再通,但有皮层支梗死;例1、3大脑中动脉溶栓后部分再通。本文4例患者溶栓后2周神经功能缺损评分明显降低。结论急性脑梗死超早期应用尿激酶动脉溶栓治疗能明显提高责任供血动脉再通率,改善患者预后。动脉溶栓对大、中动脉急性闭塞性脑梗死患者疗效显著,对穿支动脉急性闭塞脑梗死患者疗效欠佳,有待进一步随机、双盲、大样本证实。     

rt-PA静脉窦注射结合血管内技术治疗重症颅内静脉窦血栓

目的 探讨重组组织血浆纤维蛋白溶酶原激活剂(rt-PA)静脉窦注射结合机械性血栓清除治疗重症颅内静脉窦血栓的效果.方法 11例重症颅内静脉窦血栓患者,共进行血管内介入治疗15次;其中机械性血栓清除结合rt-PA静脉窦局部注射14例次,单纯机械性血栓清除1次;应用AnsioJet导管清除血栓9次,球囊血栓清除5次,微导丝1次.进行2次血管内治疗者4例,进行1次血管内治疗7例.每次血管内治疗rt-PA用量0～15 mg,平均(9.4±4.5)mg.无介入治疗并发症发生.手术均在气管插管全麻下进行,患者介入治疗前、治疗中及治疗后均进行全身肝素化治疗.结果 本组11例患者接受血管内治疗时已发生意识障碍8例,其中6例已行气管捕管,2例已发生脑疝;GCS3～12分,平均(8.3±2.7)分.恢复优良8例,死亡3例.存活病例MRI/MRV随访10-32个月(平均21个月),静脉窦通畅6例,部分通畅2例.无静脉窦血栓复发病例.结论 重症颅内静脉血柃可危及病人的生命,常规治疗疗效差.溶栓药物局部应用结合机械性血栓清除可以快速使受累的静脉窦恢复通畅,是一种安全、有效的治疗方法.