替罗非班辅助血管内治疗急性缺血性脑卒中的疗效评估研究进展

急性缺血性脑卒中（AIS）是脑组织缺血缺氧而引起神经功能损伤的临床综合征。抗血小板治疗是缺血性脑卒中预防及治疗的基础。目前,AIS血管内治疗主要方法有机械取栓、血栓抽吸、动脉溶栓、支架植入等,可有效改善血运及临床症状。但血管内治疗可能会损伤血管内皮细胞,导致血小板聚集及血栓形成。血管内治疗的围手术期使用抗血小板药物是降低手术期间和术后发生血栓形成、栓塞和缺血等并发症风险的常用治疗方法。近年来,有关AIS血管内治疗中抗血小板药物的应用,特别是血小板糖蛋白Ⅱb/Ⅲa（GPⅡb/Ⅲa）受体拮抗剂,使AIS血管内治疗的发展前景充满希望。目前,美国食品药品监督管理局发布的GPⅡb/Ⅲa受体拮抗剂有3种,分别为替罗非班、阿昔单抗和依替巴肽。替罗非班是国内临床中主要应用的GPⅡb/Ⅲa受体拮抗剂,GPⅡb/Ⅲa受体作为血小板聚集、血栓形成的最终通路,其拮抗剂通过直接与GPⅡb/Ⅲa受体结合,从而快速发挥抗血小板聚集的作用。替罗非班作为的新型抗血小板药物,在心血管疾病中的应用已经基本成熟,但是在脑血管疾病中的应用仍处于探索阶段,具体用法、用量及安全性仍有较多争议,且属于超说明书用药。该文就替罗非班在急性缺血性脑卒中血管内治疗中的应用及研究进展进行综述。     

Lack of improvement following endovascular therapy in patients with acute ischemic stroke

Background: Recent randomized trials have consistently demonstrated a clinical benefit of endovascular therapy (ET) over best medical therapy (including intravenous (IV) thrombolysis in eligible patients) or IV thrombolysis only in selected patients with acute ischemic stroke (AIS) due to proximal occlusion in the carotid territory. Previous study demonstrates that lack of improvement (LOI) at 24 hours is an independent predictor of poor outcome and death at 3 months in patients with AIS treated with IV alteplase. However, LOI at 24 hours following ET has not been studied systematically. The purpose of this study is to identify predictors of LOI at 24 hours in patients with AIS after ET as well as the relationship between LOI and unfavorable outcome at 3 months. Methods: A total of 98 consecutive patients with AIS treated with ET in two separate stroke centers from 2010 to 2014 were retrospectively reviewed. Data on demographics, preexisting vascular risk factors, occlusion site, pre- and post-treatment modified Treatment in Cerebral Ischemia (mTICI) classification, collaterals and National Institutes of Health Stroke Scale (NIHSS) score on admission as well as 24 hours after the endovascular procedurals were collected. LOI was defined as a reduction of 3 points or less on the NIHSS at 24 hours compared with baseline. A 3-month functional outcome was assessed using the modified Rankin scale (mRS). Unfavorable outcome was prespecified as a score of more than 2 on the mRS. The onset-to-reperfusion time (ORT) was defined as time to mTICI 2b or 3 or end of procedure. Long ORT was defined as time to reperfusion beyond 6 hours. Poor reperfusion was defined as mTICI ≦2a. The pretreatment collateral circulation extent was graded as poor (grades 0–1) or good (grades 2–4). Results: Among the 98 patients with AIS who were treated with ET, LOI was present in 48 (49%) subjects. Multivariate analysis indicated that poor collaterals (odds ratio [OR] 3.25; 95% confidence interval [CI]: 1.29–8.19; p = 0.012) and long ORT (OR 3.97, 95% CI: 1.66–9.54; p = 0.002) were independent predictors of LOI. LOI (OR 7.18, 95% CI: 2.39–21.61; p < 0.001) was independently associated with unfavorable outcome at 3 months. Conclusion: Among patients with AIS treated with ET, as an independent predictor of unfavorable outcome, LOI at 24 hours is associated with poor collaterals and long ORT.     

急性缺血性脑卒中血管内治疗21例临床分析

目的探讨急性缺血性脑卒中血管内治疗的方法、疗效和安全性。方法回顾性分析血管内治疗的大血管闭塞的急性缺血性脑卒中患者21例。10例为阿替普酶静脉溶栓后桥接血管内治疗,11例直接行血管内治疗。其中机械取栓12例,机械取栓+支架植入3例,单纯颈动脉支架植入3例,机械取栓+动脉溶栓1例,机械取栓+动脉溶栓+支架植入1例,单纯动脉溶栓1例。评估术中mTICI再通等级、并发症及术后随访第90天m RS评分,分析疗效与安全性。结果21例患者前循环卒中18例,后循环卒中3例。NIHSS评分平均15. 81±6. 44分。20例患者术后血管再通达mTICI 2 b-3级。术中并发出血1例,术后大量颅内出血1例,无症状少量颅内出血4例。术后高灌注综合征8例,其中4例行去骨瓣减压术,最终死亡5例(23. 81%)。术后随访第90天mRS评分0～2分8例。结论经充分评估并及时采取适宜的单一或多种血管内治疗方法对于大血管闭塞导致的急性缺血性脑卒中患者安全有效。     

急性缺血性脑卒中血管内治疗的临床研究进展

急性缺血性脑卒中发病率和致残率高,及早恢复血流有助于改善患者的预后,机械取栓因其时间窗相对宽以及血管再通率高而备受关注。机械取栓在医疗器械上经历了从MERCI取栓系统到Solitaire FR支架、Revive SE取栓器、3D支架取栓器和Penumbra系统等的改进,取栓成功率和90 d良好预后率（改良Ranking评分低于2分）逐渐得到提高。对取栓治疗失败的补救措施进行研究。而且对特殊人群（醒后卒中、儿童、高龄、妊娠）脑卒中的取栓应用也有成功使用的研究报道。总之,机械取栓能够有效开通急性闭塞的脑部大血管,从而及时恢复急性缺血脑组织的血液供应,达到改善急性缺血性脑卒中患者预后的效果。随着取栓医疗器械和技术的不断进步,效果越来越好。     

Association between stress hyperglycemia and outcomes in patients with acute ischemic stroke due to large vessel occlusion

Aims

This study aimed to evaluate the association between stress hyperglycemia ratio (SHR) and clinical outcomes at 90 days in acute ischemic stroke due to large vessel occlusion receiving endovascular treatment.

Methods

The RESCUE BT trial was a multicenter, randomized, double-blind, placebo-controlled clinical trial, consisting of 948 stroke patients from 55 centers in China. A total of 542 patients with glucose and glycated hemoglobin (HbA1C) values at admission were included in this analysis. SHR, measured by glucose/HbA1C, was evaluated as both a tri-categorical variable (≤1.07 vs. 1.08–1.29 vs. ≥1.30) and a continuous variable. The primary outcome was a favorable functional outcome (modified Rankin Scale [mRS] score ≤2) at 90 days. The secondary outcome included excellent functional outcome (mRS score ≤1) and safety outcomes, such as 90-day mortality and intracranial hemorrhage. The study was registered with Chictr.org.cn (ChiCTR-INR-17014167).

Results

Compared with patients in the lowest tertile of SHR, the highest tertile group had significantly lower odds of achieving favorable functional outcome of mRS score of 0–2 (adjusted odds ratio, 0.44; 95% confidence interval, 0.28–0.69; p < 0.001) and excellent clinical outcome of mRS score of 0–1 (adjusted odds ratio, 0.48; 95% confidence interval, 0.29–0.79; p = 0.004) at 90 days after adjusting for potential covariates. Similar results were observed after further adjustment for preexisting diabetes and Alberta Stroke Program Early Computed Tomography Score (ASPECTS).

Conclusion

Stress hyperglycemia ratio, as measured by the glucose/HbA1C, was associated with a decreased odds of achieving a favorable functional outcome in patients with acute large vessel occlusion stroke at 90 days.     

急性缺血性卒中血管内治疗筛选病例的研究进展

急性缺血性卒中发病率呈逐年上升趋势,并且具有很高的致残率和致死率。由于静脉阿替普酶溶栓治疗急性缺血性卒中的局限性,2015年以来5大临床前瞻随机双盲多中心临床研究证实新一代血管再通策略（主要是可回收支架）在大血管闭塞导致的急性缺血性卒中明显优于单独内科治疗,各国脑卒中指南也相应进行更新。本文围绕5大临床研究及欧洲、美国最新指南中关于筛选合适卒中患者进行机械取栓的研究进展综述如下。     

Hurdles in stroke thrombolysis: Experience from 100 consecutive ischemic stroke patients

Background:

Acute management of ischemic stroke involves thrombolysis within 4.5 h. For a successful outcome, early recognition of stroke, transportation to the hospital emergency department immediately after stroke, timely imaging, proper diagnosis, and thrombolysis within 4.5 h is of paramount importance.

Aim:

To analyze the obstacles for thrombolysis in acute stroke patients.

Materials and Methods:

The study was conducted in a tertiary care center in South India. A total of hundred consecutive patients of acute ischemic stroke who were not thrombolysed, but otherwise fulfilled the criteria for thrombolysis were evaluated prospectively for various factors that prevented thrombolysis. The constraints to thrombolysis were categorized into: i) Failure of patient to recognize stroke symptoms, ii) patient''s awareness of thrombolysis as a treatment modality for stroke, iii) failure of patient''s relative to recognize stroke, iv) failure of primary care physician to recognize stroke, v) transport delays, vi) lack of neuroimaging and thrombolysis facility, and vii) nonaffordability.

Results:

The biggest hurdle for early hospital presentation is failure of patients to recognize stroke (73%), followed by lack of neuroimaging facility (58%), nonaffordability (56%), failure of patient''s relative to recognize stroke (38%), failure of the primary care physician to recognize stroke (21%), and transport problems (13%). Awareness of thrombolysis as a treatment modality for stroke was seen only in 2%.

Conclusion:

Considering the urgency of therapeutic measures in acute stroke, there is necessity and room for improvement to overcome various hurdles that prevent thrombolysis.     

Endovascular treatment for ischemic stroke beyond the time window: A meta-analysis

Currently, endovascular treatment has been proven to be effective when conducted within 6 hours of symptom onset. However, when patients have symptoms for more than 6 hours, have a daytime-unwitnessed stroke (DUS) or wake up with a stroke (wake-up stroke, WUS), the safety and efficacy of endovascular treatment need to be further elucidated. Therefore, we performed a systematic review and meta-analysis to compare the clinical outcomes of endovascular treatment in patients with ischemic stroke beyond the time window with that ≤6 hours. PubMed, EMBASE, and Ovid MEDLINE were searched from inception to November 2018. The following outcomes were evaluated by a random-effects model: efficacy outcomes, that is, functional independence and successful recanalization, and safety outcomes, that is, symptomatic intracranial hemorrhage and mortality. Subgroup analyses were also performed to examine whether patient or study characteristics were associated with the outcomes. Nine observational studies, including 5192 patients (1414 patients with extended time windows [ETWs]; 3778 patients ≤6 hours), were eligible for analysis. The overall analysis demonstrated that the functional independence was worse in patients with ETWs vs those ≤6 hours (OR, 0.78; 95% CI, 0.68-0.90, P = .0006). However, subgroup analysis showed that there was no significant difference in functional independence between the two groups when patients were selected for a perfusion mismatch by imaging (OR, 1.00; 95% CI, 0.70-1.43, P = 1.000). Therefore, compared with a window ≤6 hours, endovascular treatment with ETWs for ischemic stroke may not result in poor outcomes when patients are typically selected by perfusion techniques.     

Predictors of outcome after acute ischemic stroke

The aim of this study was to determine which variables should be the predictors for clinical outcome at discharge and sixth month after acute ischemic stroke. METHODS: Two hundred and sixty-six consecutive patients, each with an acute ischemic cerebrovascular disease, were evaluated within 24 h of symptom onset. We divided our patients into two groups; 1 - Independent (Rankin scale RS < or = 2) and, 2 - Dependent (RS>3) and death. Baseline characteristics, clinical variables, risk factors, infarct subtypes and radiologic parameters were analyzed. RESULTS: Canadian Neurological Scale (CNS) on admission <6.5 [odds ratio (OR) 22] and posterior circulation infarction (OR 4.2) were associated with a poor outcome at discharge from hospital whereas only a CNS score <6.5 (OR 14) was associated with a poor outcome at 6 months. CONCLUSIONS: Severity of neurologic deficit is the most important indicator for clinical outcome in acute ischemic stroke both at short-term and at sixth month, whereas posterior circulation infarction also predicts a poor outcome at discharge.     

急性缺血性脑卒中血管内治疗后 症状性颅内出血的预测因素

目的 探讨急性缺血性脑卒中血管内治疗后症状性颅内出血的预测因素。方法 选取2014年1月-2017年12月因急性缺血性脑卒中至本院就诊并进行血管内治疗的患者,记录其一般情况与凝血功能,观察其治疗效果与不良反应,采用Logistic回归分析颅内出血的影响因素。结果 血管内治疗颅内出血概率为16.09%。发生颅内出血的患者平均年龄(64.46±15.47)岁,饮酒率28.57%,高血压患病率71.43%,糖尿病患病率42.86%,溶栓前抗血小板聚集药使用率64.26%,溶栓前NIHSS评分(15.63±6.84)分,溶栓前血小板计数(182.05±52.49)×10⁹/L,溶栓前INR(1.09±0.16),溶栓前收缩压(145.79±12.40)mmHg,均高于未出血组; 进一步logistic回归分析显示年龄OR=1.75(0.82～2.08),饮酒OR=0.99(0.47～1.65),高血压病OR=4.29(3.74～5.63),溶栓前NIHSS评分OR=2.81(1.46～3.26),溶栓前收缩压OR=1.45(1.15～1.93)为血管内治疗后颅内出血的危险因素(P<0.05)。结论 年龄、饮酒、高血压病、NIHSS评分溶栓前收缩压为血管内治疗颅内出血的危险因素。     

Mechanical thrombectomy: Determining the proportion of eligible acute ischemic stroke patients in the cohort of single academic stroke center

Background and purpose

Mechanical thrombectomy (MT) is now well-established treatment method for selected patients with acute ischemic stroke (AIS) and efforts are being made to incorporate it into the systems of stroke care. Our objective is to assess the number of AIS individuals eligible for MT in the cohort of single academic stroke center.

Association of serum albumin to globulin ratio with outcomes in acute ischemic stroke

Background

Serum albumin to globulin ratio (A/G) has been widely used as a representative biomarker for assessing inflammation and nutrition status. However, in patients with acute ischemic stroke (AIS), the predictive value of serum A/G has rarely been reported. We aimed to evaluate whether serum A/G is associated with prognosis in stroke.

Methods

We analyzed data from the Third China National Stroke Registry. The patients were categorized into quartile groups according to the serum A/G at admission. Clinical outcomes included poor functional outcomes (modified Rankin Scale [mRS] score of 3–6 or 2–6) and all-cause mortality at 3 months and1 year. Multivariable logistic regressions and Cox proportional hazards regressions were used to evaluate the association of serum A/G with the risk of poor functional outcomes and all-cause mortality.

Results

A total of 11, 298 patients were included in this study. After adjustment for confounding factors, patients in the highest serum A/G quartile had a lower proportion of mRS score 2–6 (odds ratio [OR], 0.87; 95% confidence interval [CI], 0.76–1.00) and mRS score 3–6 (OR, 0.87; 95% CI, 0.73–1.03) at 3 months follow-up. At 1 year follow-up, there was a significant association between higher serum A/G and mRS score 3–6 (OR, 0.68; 95% CI, 0.57–0.81). We also found that the highest serum A/G was related to decreased risk of all-cause mortality (hazard ratio [HR], 0.58; 95% CI, 0.36–0.94) at 3 months follow-up. Similar results were found at 1-year follow-up.

Conclusions

Lower serum A/G levels were associated with poor functional outcomes and all-cause mortality at 3 months and 1-year follow-up in patients with acute ischemic stroke.     

Local intraarterial tirofiban after formation of anterograde flow in patients with acute ischemic stroke: Preliminary experience and short term follow-up results

Objective

Despite the risk of intracranial hemorrhage, combination therapy with intravenous recombinant tissue plasminogen activator and intraarterial mechanical thrombolysis can be effective for treatment of acute ischemic stroke. We investigated the feasibility and safety of intraarterial tirofiban following formation of anterograde flow after mechanical thrombolysis in acute ischemic stroke.

Methods

We analyzed data from consecutive patients with acute ischemic stroke, who underwent treatment with intraarterial thrombolysis. All patients were evaluated immediately and 7 days later by computed tomography scanning and magnetic resonance imaging scanning with magnetic resonance angiography. For clinical outcome analysis, we followed up the NIHSS score and modified Rankin Scale score during a period of 3 months.

Results

Sixteen patients underwent treatment. The mean baseline NIHSS score was 16.1 ± 4.4 points. 75.1% of patients showed angiographic improvement; 43.8% and 31.3% had complete and partial recanalization, respectively. 53.3% and 56.3% showed clinical improvement and favorable outcome at 24 h and 3 months, respectively. One patient had symptomatic intracranial hemorrhage.

Conclusions

Our results suggest that administration of local intraarterial tirofiban after anterograde flow formation is a viable treatment strategy for patients of acute ischemic stroke for reducing the risk of reocclusion after intraarterial thrombolysis.     

血清小而密低密度脂蛋白与急性缺血性脑卒中及预后的关系

目的探讨血清小而密低密度脂蛋白(sdLDL)与急性缺血性脑卒中(AIS)发生及预后的相关性。方法测定338例AIS患者(AIS组)和103例排除脑血管疾病患者(对照组)的血清sdLDL水平。AIS组患者根据临床常用的TOAST分型标准进行分型,并根据有无sdLDL异常进行分组,90 d后采用mRS评分评价患者的预后。结果与对照组相比,AIS组异常sdLDL发生率较对照明显增高,其中大动脉粥样硬化型卒中(LAA)亚组异常sdLDL所占比率较对照组明显升高,差异有统计学意义(均P<0.05)。在AIS组内,sdLDL异常亚组中男性、高血压和冠心病比率,总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、三酰甘油(TG)水平及90 d mRS评分、90 d NIHSS评分均显著高于sdLDL正常亚组(均P<0.05)。与预后良好组患者比较,预后不良组患者中男性、异常sdLDL所占比率明显偏高(均P<0.05),但高血压、高血脂、冠心病、心房纤颤及同型半胱氨酸血症所占的比率无明显统计学差异。行多因素Logistic回归分析显示,男性(OR=0.82,P<0.05)、冠心...     

Factors influencing hemorrhagic transformation in ischemic stroke: a clinicopathological comparison

As hemorrhagic transformation (HTr) is a frequent complication and can worsen the outcome of acute ischemic stroke, our aim was to assess the risk factors of HTr. Using the database of our neuropathological laboratory, 245 consecutive acute ischemic stroke patients were analyzed. An exploratory logistic regression procedure was carried out to find the best multiple model identifying the factors associated with HTr. The autopsy revealed ischemic infarct in 175 (71%) and ischemic infarct with HTr in 70 (29%) patients. Mean age was 71.5 ± 11.4 years (mean ± SD) and 74.8 ± 10.2 years (mean ± SD), respectively. The multiple model confirmed age in case of embolic stroke, and diabetes mellitus and infarct size as independent risk factors of HTr. It seems that not serum glucose level but diabetes mellitus in the case history is an independent predictor of HTr.     

Risk factors and outcomes of childhood ischemic stroke in Taiwan

In this retrospective study, we reviewed the charts and collected clinical and radiographic data on children (age range, 1 month to 18 years) with symptoms and radiographic confirmation of ischemic stroke for the period of January 1996 to July 2006. Ninety-four children were enrolled. Eighty-eight had arterial ischemic stroke and six had sinovenous thrombosis. Twenty-nine percent of the children had seizures. Twenty-six percent had diffuse neurological signs and 76% had focal neurological signs. Risk factors included vascular disease (33%), infection (27%), metabolic disorders (18%), trauma (11%), prothrombotic states (13%), cardiac disease (10%), and mitochondrial disease (6%). Ten percent (n=9) had no identifiable cause. Twenty-two percent of the children had more than one risk factor. Anterior territory (70%) was more involved than posterior territory (18%) in arterial ischemic stroke. Unilateral infarctions were more common on the left side (51%) than on the right (24.5%). Neurological deficits were present in 45% (n=34/75) of the children; the most frequent deficit was motor impairment (24%). Seven children (9%) died in the acute stage. There were 12 children (16%) who had recurrent stroke and 8 children (8/12) who had underlying vascular disease. The vascular disease included moyamoya disease (5), CNS lupus (1) and ill-defined vasculopathy (2). The etiology pattern in Taiwan was different from that in Western countries. Vascular disease was a significant risk factor for recurrence in childhood ischemic stroke.