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     

时间窗超过3h急性缺血性卒中患者动脉溶栓治疗观察

目的 评价时间窗超过3 h的急性缺血性卒中患者动脉溶栓治疗的疗效及影响因素.方法 选择法国南锡大学中心医院神经影像科自2008年1月至2009年1月收治的16例急性缺血性卒中患者(时间窗均达到或超过3 h,颈内动脉系统卒中时间窗不超过6 h,椎基底动脉系统卒中时间窗不超过24h.昏迷不超过6 h),行动脉内药物联合机械溶栓治疗,分析不同因素对疗效的影响.结果 7例患者闭塞血管达到完全再通,7例达到部分再通,另有2例闭塞血管未再通,再通率为87.5%.患者动脉溶栓后与溶栓前NIHSS评分比较明显降低.时间窗大于5 h的前循环系统闭塞患者溶栓前后NIHSS评分无改善,与时间窗较短患者相比较,出院时mRS评分明显较高.5例颈内动脉闭塞患者溶栓前后NIHSS评分无改善,与9例大脑中动脉闭塞患者、2例基底动脉闭塞患者相比预后较差.4例患者溶栓后24h出现症状性颅内出血,3例为颈内动脉闭塞,1例死亡.1例溶栓后发生血管再闭,但因侧支循环血流丰富,最终临床预后仍较好.结论 对于时间窗超过3 h大脑中动脉和基底动脉闭塞急性缺血性卒中患者,动脉溶栓可使闭塞血管达到较高的再通率,短期内使临床神经功能恢复,改善临床结局.临床应用动脉溶栓时应注意个体化选择性治疗,评价其疗效需结合时间窗、血管闭塞部位、侧支循环、并发症等因素,避免出血等并发症.     

时间窗超过3h急性缺血性卒中患者动脉溶栓治疗观察

目的 评价时间窗超过3 h的急性缺血性卒中患者动脉溶栓治疗的疗效及影响因素.方法 选择法国南锡大学中心医院神经影像科自2008年1月至2009年1月收治的16例急性缺血性卒中患者(时间窗均达到或超过3 h,颈内动脉系统卒中时间窗不超过6 h,椎基底动脉系统卒中时间窗不超过24h.昏迷不超过6 h),行动脉内药物联合机械溶栓治疗,分析不同因素对疗效的影响.结果 7例患者闭塞血管达到完全再通,7例达到部分再通,另有2例闭塞血管未再通,再通率为87.5%.患者动脉溶栓后与溶栓前NIHSS评分比较明显降低.时间窗大于5 h的前循环系统闭塞患者溶栓前后NIHSS评分无改善,与时间窗较短患者相比较,出院时mRS评分明显较高.5例颈内动脉闭塞患者溶栓前后NIHSS评分无改善,与9例大脑中动脉闭塞患者、2例基底动脉闭塞患者相比预后较差.4例患者溶栓后24h出现症状性颅内出血,3例为颈内动脉闭塞,1例死亡.1例溶栓后发生血管再闭,但因侧支循环血流丰富,最终临床预后仍较好.结论 对于时间窗超过3 h大脑中动脉和基底动脉闭塞急性缺血性卒中患者,动脉溶栓可使闭塞血管达到较高的再通率,短期内使临床神经功能恢复,改善临床结局.临床应用动脉溶栓时应注意个体化选择性治疗,评价其疗效需结合时间窗、血管闭塞部位、侧支循环、并发症等因素,避免出血等并发症.     

缺血性脑卒中的院前处理

脑卒中是致人类死亡的三大原因之一，也是成人致残的首位原因，其中缺血性脑卒中占所有卒中的80％以上。20世纪90年代以来，溶栓治疗、卒中单元和卒中病房使缺血性卒中治疗模式发生了划时代的改变。但这都有一个前提，即保证患者在溶栓时间窗内到医院并开始治疗。尽早识别脑卒中并使需要溶栓者在时间窗内得到最佳治疗已成为一个     

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。     

轻型脑梗死的溶栓治疗

循证医学证据表明溶栓治疗是当前急性脑梗死最有效的治疗方法,然而由于各种禁忌症,许多在时间窗内到达医院的急性脑梗死患者未能接受溶栓治疗。轻型卒中是最常见的原因之一。但近年来,越来越多的证据表明轻型卒中患者也可以受益于溶栓治疗。本文就轻型卒中的概念、病因、病理生理、治疗现状,特别是轻型卒中溶栓治疗的临床研究等进行综述。     

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。     

急性缺血性脑卒中治疗的研究进展

急性缺血性脑卒中是一种临床上常见的高危疾病,是危害国民健康的重大疾病之一,快速识别并实施静脉溶栓或血管内治疗对急性缺血性卒中患者的预后至关重要,但尚未得到充分应用。出现发病时间不明的卒中是常见的临床情况,也是不宜行再灌注治疗的常见原因。更好地评估这部分患者的溶栓机会是一个非常值得重视和关注的问题。最新研究已经证明,在高级脑成像指导下,选择合适的患者行静脉溶栓治疗已经取得重大突破,本文将从未知发病时间卒中的概念和其病理生理学特点出发,结合静脉溶栓时间窗治疗的进展,探讨在影像学指导下静脉溶栓治疗未知发病时间卒中的可行性、安全性和有效性,并综述治疗和预防卒中的相关新兴药物研究应用进展,以期为临床提供参考。     

心房颤动对不同时间窗内急性缺血性脑卒中患者静脉溶栓疗效的影响

目的探讨急性缺血性脑卒中合并心房颤动患者不同时间窗内静脉溶栓的疗效差异。方法选取急性缺血性脑卒中行静脉溶栓治疗患者172例,根据发病-溶栓时间窗差异分为3组,时间窗分别为≤3.0 h(观察A组)、>3.0~4.5 h(观察B组)、>4.5 h(观察C组),对其中合并心房颤动者溶栓疗效进行评估分析。结果3组患者溶栓24 h后出血转化结果、溶栓3个月时神经功能结局良好率、病死率均无明显差异(P>0.05);溶栓时间窗>3 h者,心房颤动可显著增加患者发生PH型、HI型出血转化发生率,差异有统计学意义(P<0.05);单因素分析显示,合并心房颤动可造成溶栓时间窗≤4.5 h患者神经功能结局不良发生率增加,差异有统计学意义(P<0.05)。多因素分析显示,合并心房颤动与不同时间窗急性缺血性脑卒中患者静脉溶栓治疗后神经功能结局不良发生情况无明显相关性(P>0.05)。结论溶栓时间窗仍是影响急性缺血性脑卒中患者静脉溶栓疗效的重要因素,对于溶栓时间窗≤3.0 h者,合并心房颤动不会对溶栓疗效造成影响;对于发病-溶栓时间>3 h者,心房颤动可能造成患者溶栓后出血风险增加。     

血管诊断和急性卒中:行动、时机和决策

在急性缺血性卒中患者症状出现3 h内给予溶栓治疗被证实有效。依据6项静脉应用重组组织型纤溶酶原激活(rt-PA)的随机安慰剂对照试验研究数据分析,卒中患者越早给予rt-PA,获益越大,特别是在90 min时间窗内治疗。在90 min内给予rt-PA,患者良好结局的比值比为2．81,在91～180min为1．55(表1),这意味着患者在90min内治疗的成功几率是180min后开始治疗成功几     

前-后循环急性脑梗死静脉溶栓疗效比较及安全评价

目的探讨前-后循环急性脑梗死静脉溶栓疗效差异及安全性评价。方法对前-后循环急性脑梗死120例,其中前循环64例及后循环56例急性脑梗死进行rt-PA静脉溶栓治疗,比较两组间神经功能恢复情况;并通过Logistic回归分析影响急性脑梗死rt-PA静脉溶栓后出血风险的独立危险因素。结果两组患者经溶栓治疗后24h、2w神经功能较溶栓治疗前均有明显恢复(P<0.01),两组之间溶栓治疗后24h神经功能恢复差异无统计学意义,但两组之间溶栓治疗后2w神经功能恢复差异有统计学意义(P<0.05);Logistic回归分析表明高血压病、心房纤颤、糖尿病及吸烟增加rt-PA静脉溶栓出血风险。结论在急性脑梗死的rt-PA静脉溶栓治疗中,前循环疗效优于后循环,且高血压病、心房纤颤、糖尿病及吸烟影响rt-PA静脉溶栓疗效,有增加出血风险可能,从而影响患者日后生活质量。     

Update on stroke

PURPOSE OF REVIEW: This review highlights some advances in the areas of epidemiology, therapy, and imaging of acute stroke. RECENT FINDINGS: Studies published in 2003 provided new insights into the epidemiology of stroke. The African American Antiplatelet Stroke Prevention Study found that traditional stroke risk factors are still undiagnosed and undertreated, particularly in minorities. Cohort studies have identified incident silent infarcts as risk factors for stroke and history of type I diabetes as a risk factor for death in patients with acute stroke. Cervical artery dissection, on the other hand, seems to have a benign course. Imaging has become an important tool for understanding the pathophysiology of stroke, as demonstrated in recent publications. New studies have shown the prognostic value of magnetic resonance imaging: it can predict the volume of ischemic tissue that will progress to infarction and detects cerebral microbleeds - a risk factor for intracranial hemorrhage. Computed tomographic scanning may have a role in selecting patients for thrombolysis, particularly when validated scales are used. Despite the barriers to the use of tissue plasminogen activator in the treatment of patients with stroke, data published this year show that it is a safe medication when used routinely in community and university hospitals. In addition to thrombolysis, other general medical measures, such as glucose control and adequate attention to nutritional status, can help improve the outcome of patients with stroke. SUMMARY: In acute stroke, recognition and modification of risk factors continue to be challenging tasks. Treatment of acute stroke should involve thrombolysis and attention to medical conditions that may influence outcome. New applications of magnetic resonance imaging and computed tomography may help guide stroke therapy.     

Catastrophic Multiple Microbleeds Caused by Infective Endocarditis Following Intravenous Thrombolysis and Endovascular Thrombectomy

Ischemic stroke is one of the most common complications of infective endocarditis (IE). IE must be considered as one of the causes of acute ischemic stroke (AIS) with emergent large vessel occlusion (ELVO), but early diagnosis of IE is difficult. AIS with ELVO must be treated using endovascular thrombectomy (EVT), with or without intravenous thrombolysis (IVT). IVT for AIS due to IE is not well established and remains controversial because of the risk of intracranial hemorrhage. A 42-year-old man suffered from right hemiparesis and disorientation, and AIS with ELVO was diagnosed. EVT with IVT was successfully performed and recanalization was achieved, but catastrophic multiple cerebral microbleeds appeared after treatment. EVT without IVT could be chosen for AIS caused by IE to avoid hemorrhagic complications. Hypointense signal spots on T2*-weighted magnetic resonance imaging (MRI) and susceptibility-weighted MRI could facilitate early diagnosis of IE.     

Treatment of arterial and venous brain ischemia. Experts' recommendations: stroke management in the intensive care unit

With thrombolysis, intravenous alteplase (0.9 mg/kg body weight, maximum 90 mg), with 10% of the dose given as a bolus followed by a 60-minute infusion, is recommended within 4.5 hours of onset of ischemic stroke. When indicated, intravenous thrombolysis must be initiated as soon as possible. It is possible to use intravenous alteplase in patients with seizures at stroke onset, if the neurological deficit is related to acute cerebral ischemia. Intravenous alteplase can be discussed for use on a case-by-case basis, according to risk of bleeding, in selected patients under 18 years and over 80 years of age, although for the current European recommendations this would be an off-label use. In hospitals with a stroke unit, intravenous thrombolysis is prescribed by a neurologist (current French labelling) or a physician having the French certification for neurovascular diseases (outside the current French labelling). The patient must be monitored in the stroke unit or in case of multiple organ failure in an intensive and critical care unit. In hospitals without a stroke unit, thrombolysis must be decided by the neurologist from the corresponding stroke unit via telemedicine. It is recommended to perform brain imaging 24 hours after thromboysis. Intra-arterial thrombolysis can be contemplated on a case-by-case basis after multidisciplinary discussion within a 6-hour time window for patients with acute middle cerebral artery or carotid occlusions, and within a larger time window for patients with basilar artery occlusion, because of their very poor spontaneous prognosis. Mechanical thrombectomy can also be contemplated in the same situations. With antiplatelet agents, it is recommended that patients receive aspirin (160 mg-325 mg) within 48 hours of ischemic stroke onset. When thrombolysis is performed or contemplated, it is recommended to delay the initiation of aspirin or other antithrombotic drugs for 24 hours. The use of antiplatelet agents that inhibit the glycoprotein IIb/IIIa receptor is not recommended. Urgent anticoagulation using heparin, low-molecular-weight heparins or danaparoid with the goal to treat ischemic stroke patients is not recommended. Secondary prevention by anticoagulation can be used, immediately or within the first days, after minor ischemic stroke or TIA in patients with a high risk for cardioembolism, if uncontrolled hypertension is absent. In patients with large infarcts and a high risk for cardioembolism, the timing for initiating anticoagulation must be decided on a case-by-case basis. In patients with anticoagulation who had an ischemic stroke, the decision to temporarily stop or maintain anticoagulation must be made on a case-by-case basis, depending on thromboembolic risk, level of anticoagulation at stroke onset and estimated risk of hemorrhagic transformation. It is not recommended to use neuroprotective agents in ischemic stroke patients. Patients with cerebral venous thrombosis must be treated with therapeutic doses of heparin, even in case of concomitant intracranial hemorrhage related to cerebral venous thrombosis. If the patient's status worsens despite adequate anticoagulation, thrombolysis may be used in selected cases. The optimal administration route (local or intravenous), thrombolytic agent (urokinase or alteplase) and dose are unknown. There is currently no recommendation with regard to local thrombolytic therapy in patients with dural sinus thrombosis. Urgent blood transfusions are recommended to reduce hemoglobin S to <30% in patients with sickle cell disease and acute ischemic stroke.     

Safety and efficacy of thrombolytic therapy in postoperative cerebral infarctions

Acute ischemic stroke is a common and devastating complication of many surgical procedures. If diagnosed early, however, there are reasonably safe and effective treatment options. Although IV rtPA is the most well studied means of recanalization after ischemic stroke, it should be avoided within 14 days of a surgical procedure in favor of other locally directed techniques that carry a significantly lower risk of bleeding at the surgical site. Only in rare circumstances, when these newer modalities are not available and the surgery is minor, should IV rtPA be considered in postoperative patients. The treatment of choice for carefully selected patients with postoperative strokes is IAT with either rtPA or urokinase. IAT may be attempted up to 6 hours after an acute ischemic stroke and may be assisted by mechanical clot disruption/embolectomy in an attempt to improve recanalization rates. In patients who have had a recent craniotomy or any surgery where surgical site bleeding is expected to be massive or difficult to control or where small amounts of bleeding could be life threatening, IAT should be avoided. In these patients, and in patients who present greater than 6 hours but less than 8 hours after their stroke, mechanical thrombolysis/embolectomy may emerge as the only viable treatment option.     

Thrombolysis for ischemic stroke in patients with old microbleeds on pretreatment MRI

BACKGROUND: Old asymptomatic microbleeds (MBs) visualized on T2-weighted MRI are indicative of microangiopathy. They may be a marker of increased risk of intracerebral hemorrhage (ICH) following thrombolysis. However, data regarding this potential risk are limited. METHODS: A retrospective analysis of pretreatment T2-weighted MRI was performed in consecutive stroke patients who received intravenous tissue plasminogen activator (tPA). We aimed to assess the impact of MBs on the risk of cerebral bleeding. The frequency and location of MBs were assessed and compared with the location of ICH after thrombolysis. RESULTS: Forty-four patients were studied. MBs were present on pretreatment MRI in 8 cases (18.2%). At day 1, symptomatic ICH occurred in none of 8 patients with MBs versus 1 of 36 patients without (NS). At day 1, ICH occurred in 3 of 8 patients with MBs versus 10 of 36 patients without (NS). At day 7, symptomatic ICH occurred in 1 of 8 patients with MBs versus 2 of 36 patients without (NS). At day 7, ICH occurred in 5 of 8 patients with MBs versus 12 of 36 patients without (NS). No ICH occurred at the site of an MB. ICH occurred within the ischemic area in all patients who bled. CONCLUSIONS: Our study suggests that stroke patients with a small number of MBs on pretreatment MRI could be treated safely with thrombolysis. Larger prospective studies are needed to address the predictive value of detection of MBs with regard to the risk of tPA-induced ICH.     

Thrombolytic therapy for acute ischemic stroke]

In this paper, results of the recent clinical trials were reviewed, and problems in treating patients with thrombolysis were discussed. Data generated from randomized controlled trials over the past few years have shown that acute intervention can improve neurological outcome in patients with ischemic stroke. Intravenous recombinant tissue plasminogen activator has become established as an acute treatment for stroke. Intra-arterial thrombolysis is a developing modality for the treatment of the acute stroke that shows promise in restoring cerebral arterial supply. However, thrombolysis have not approved yet in any forms in Japan. Under this circumstance, thrombolysis should be carried out in GCP-compatible clinical trials, so far. The overall results of a clinical trial cannot necessarily generalized to all patients in the trial and all similar future patients. A difference between settings of a clinical trial and of general practice should be also noted. Early recognition of stroke symptoms and immediate transfer to a suitable treatment facility should bring thrombolysis to a larger number of stroke victims. Finally, successful treatment is due in part to selecting patients who are not at increased risk for intracranial hemorrhage based on clinical and imaging features, and therefore rapid in-hospital triage protocols are mandatory.     

Intra-arterial thrombolysis for perioperative stroke after open heart surgery

Recent major surgery is an exclusion criterion for thrombolysis. Six patients with acute ischemic stroke underwent intra-arterial thrombolysis after recent open heart surgery without clinically significant bleeding complications, although one patient developed a small, asymptomatic cerebellar hemorrhage. Intra-arterial thrombolysis may be an option for patients with cerebral embolism in the perioperative period.     

Hinweis auf zerebrale Mikroblutungen in der MRT Vergleichende histologische Befunde und mögliche klinische Bedeutung

Increased use of gradient echo T2*-weighted gradient echo sequences in magnetic resonance imaging (MRI) of patients suffering from primary ICH called attention to foci of signal loss which were suggested to represent remnants of cerebral microbleeds. In a post mortem correlative MR and histopathological study we provide support for this notion. We found areas of signal loss on gradient echo T2*-weighted sequences in 7 out of 11 brains of patients who had died of intracerebral hematoma. Histopathologically, these areas represented hemosiderin deposits indicating previous extravasation of blood. To provide data about the prevalence of these MRI findings in a healthy elderly population a subgroup of participants of the Austrian Stroke Prevention Study was analyzed. We detected foci of signal loss on gradient echo T2*-weighted sequences in 18 out of 280 volunteers (6.4%). MR-based evidence of previous microbleeds may indicate a potentially higher risk of suffering from intracerebral bleeding which could have therapeutic implications for the treatment of acute stroke and for secondary prevention. This hypothesis will have to be tested in future prospective trials.     

脑小血管病影像总负荷与急性脑梗死静脉溶栓远期预后的相关性研究

目的研究CSVD影像学总负荷与急性脑梗死静脉溶栓远期预后的相关性。方法回顾性连续收集我院2018年1月-2020年1月收治的发病4.5 h之内经重组组织型纤溶酶原激活剂(rt-PA)静脉溶栓的急性脑梗死患者124例,收集患者的一般基线资料,发病48 h之内行头颅MRI检查,根据Staals等的评分标准,评估患者CSVD影像学总负荷评分为0~4分,通过电话随访评估患者90 d mRS评分,根据mRS评分将患者分为预后良好组(mRS:0~2分)和预后不良组(mRS:3~5分),比较2组患者的一般资料及影像学CSVD评分有无差异。结果124例脑梗死静脉溶栓患者远期预后基线资料的单因素分析发现预后良好患者82例(66%),预后不良患者42例(34%),静脉溶栓早期有出血转化患者10例,其中HI-1型8例,PH-1型2例,2组出血转化差异无统计学意义(P>0.05),无死亡患者。2组患者基线资料比较显示溶栓前NIHSS评分、溶栓前舒张压水平、高密度脂蛋白胆固醇水平、既往房颤病史、既往心衰病史、既往脑梗死病史、TOSTA分型、CSVD影像总负荷两组间差异有统计学意义(P<0.05)。其余资料比较两组间差异无统计学意义(P>0.05)。多因素Logistic回归分析结果显示溶栓前NIHSS评分(OR=1.241,95%CI 1.125~1.370,P<0.001)、高CSVD总评分(OR=2.393,95%CI 1.493~3.873,P<0.001)是影响脑梗死静脉溶栓预后的独立危险因素;CSVD不同影像表现中WMH中重度(OR=2.560,95%CI 1.158~5.662,P<0.020)和腔隙性脑梗死(OR=5.030,95%CI 1.579~16.044,P<0.006)是预后的独立危险因素。结论急性脑梗死静脉溶栓患者CSVD影像总负荷评分较高者与90 d不良预后相关,影像学表现为腔隙性脑梗死及中重度的WMH是不良预后的独立危险因素。