rFⅦa在脑出血超早期治疗中的研究进展

长期以来,脑出血被公认为是病死率和致残率最高的脑血管急症,相对于缺血性脑卒中与蛛网膜下腔出血等的众多急性期治疗手段,脑出血却一直缺乏有效的治疗措施,传统的治疗主要是支持和对症处理,且效果始终不尽人意[1],脑出血的早期手术治疗仍然存在较大争议[2].近年来,重组人活性凝血因子Ⅶ(rFⅦa)超早期治疗脑出血成为1个新研究热点.各国学者围绕rFⅥa开展了一系列临床试验,以期望在传统的脑出血治疗上取得突破,且试验结果令人鼓舞,现将rFⅦa在脑出血超早期治疗中的进展综述如下.     

rFVIIa在脑出血超早期治疗中的研究进展

长期以来,脑出血被公认为是病死率和致残率最高的脑血管急症,相对于缺血性脑卒中与蛛网膜下腔出血等的众多急性期治疗手段,脑出血却一直缺乏有效的治疗措施,传统的治疗主要是支持和对症处理,且效果始终不尽人意[1],脑出血的早期手术治疗仍然存在较大争议[2]。近年来,重组人活性凝血因子VII(rFVIIa)超早期治疗脑出血成为1个新研究热点。各国学者围绕rFVIIa开展了一系列临床试验,以期望在传统的脑出血治疗上取得突破,且试验结果令人鼓舞,现将rFVIIa在脑出血超早期治疗中的进展综述如下。1rFVIIa的概述人凝血因子VII(FVII)是由肝脏…     

rFVⅡa在脑出血超早期治疗中的研究进展

长期以来，脑出血被公认为是病死率和致残率最高的脑血管急症，相对于缺血性脑卒中与蛛网膜下腔出血等的众多急性期治疗手段，脑出血却一直缺乏有效的治疗措施，传统的治疗主要是支持和对症处理，且效果始终不尽人意，脑出血的早期手术治疗仍然存在较大争议。近年来，重组人活性凝血因子VⅡ（rFVⅡa）超早期治疗脑出血成为1个新研究热点。各国学者围绕rFVⅡa开展了一系列临床试验，以期望在传统的脑出血治疗上取得突破，且试验结果令人鼓舞，现将rFVⅡa在脑出血超早期治疗中的进展综述如下。     

脑出血研究进展:中国学者海外报道

脑出血是全世界范围内的常见疾病,病死率和病残率均较高。近年关于脑出血相关病理生理学机制、神经保护、预防与治疗、预后和再出血风险研究取得部分突破,国内学者在脑出血领域的研究成果逐渐获得国际关注和认可。本文基于近5年我国学者在国外杂志发表的脑出血领域高质量临床研究,对我国脑出血病理生理学机制、神经保护、预防与治疗、预后和再出血风险等研究现状和进展进行概述。     

外科治疗脑出血:回顾与展望

脑内出血的发病率死亡率致残率均高,但研究不够充分,已有的随机化研究不能为外科治疗是否较优提供明确的依据。近年对于脑出血后的致病机理有了进一步的认识,外科治疗在脑出血的治疗中发挥着越来越重要的作用。微创手术清除脑内血肿广泛开展,取得了较好的疗效,有取代开颅手术的趋势。应进一步开展外科治疗脑出血及各种外科技术治疗脑出血的随机化研究,对微创手术中血肿液化剂的使用也应进一步研究。立体定向手术未来可能在清除血肿,局部应用药物拮抗继发性损害保护脑组织和神经移植中发挥巨大的作用。     

脑出血临床预防与治疗困惑及转化研究新策略

脑出血作为最重要的急性脑血管病之一,迄今尚缺乏有效治疗方法,因此迫切需要从脑出血发生与发展关键机制出发,凝练关键科学问题,开展基础与临床转化研究,为脑出血临床预防与治疗提供新策略。既往观点不能完全阐释脑出血的发生,借助现代基因测序技术有望丰富脑出血全新的发病机制。血肿和继发性脑组织损害是脑出血发展的关键环节,颅内血肿清除术理应是首选治疗方法,但还需要结合影像学等多学科手段,重视提高内源性神经保护作用等。     

脑出血患者血压管理研究现状

脑出血急性期常伴血压升高,与患者预后不良相关。目前对脑出血降压目标和降压时机的推荐意见不尽相同。本文围绕脑出血急性期血压变化特征、血压升高与血肿扩大的关系、血压变异性与预后的关系,结合近年开展的几项强化降压治疗随机对照临床试验,对脑出血血压管理研究现状进行综述。     

早期康复指导对脑出血病人运动功能和生活能力的影响

随着现代康复医学的发展,康复治疗正日益受到重视,并被认为是脑出血治疗体系中不可缺少的部分。目前发达国家广泛采用早期康复训练来降低脑出血患者的致残率,提高患者的日常生活能力。由于我国康复治疗开展较晚,康复治疗一般在恢复期转入康复病房才开始,错过了最佳康复时机。我们对36例脑出血肢体偏瘫病人进行早期康复指导训练,取得良好效果。报道如下。     

植入异物法构建自发性脑出血实验动物模型

目前对于自发性脑出血的病理生理机制及治疗方法的研究大多基于动物试验。国内外不同实验室已经针对多种动物制作了实验性脑出血模型。根据其脑内移植的组织不同，分为缺血诱发脑出血、外伤导致脑出血、自发性脑出血和颅内植入异物导致脑出血4类。颅内植入异物导致脑出血根据植入异物的不同，又分为植入惰性物质导致的脑出血、植入生物制剂诱导脑出血、植入自体动脉血模拟脑出血3种。文章归纳总结实验性脑出血动物模型总类、制作方法和特点。     

脑出血微创穿刺血肿完全清除术及换代产品

微创穿刺抽吸术治疗脑出血在我国已开展数年,因创伤小,致残率低,备受专科大夫推崇。但因定位不准、血肿消除不彻底,影响了治疗效果。国内同类产品因设计方面的缺陷,     

European research priorities for intracerebral haemorrhage

Over 2 million people are affected by intracerebral haemorrhage (ICH) worldwide every year, one third of them dying within 1 month, and many survivors being left with permanent disability. Unlike most other stroke types, the incidence, morbidity and mortality of ICH have not declined over time. No standardised diagnostic workup for the detection of the various underlying causes of ICH currently exists, and the evidence for medical or surgical therapeutic interventions remains limited. A dedicated European research programme for ICH is needed to identify ways to reduce the burden of ICH-related death and disability. The European Research Network on Intracerebral Haemorrhage EURONICH is a multidisciplinary academic research collaboration that has been established to define current research priorities and to conduct large clinical studies on all aspects of ICH.     

Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) II: Design,Methods, and Rationale

The December 2003 report from the National Institute of Neurological Disorders and Stroke (NINDS) Workshop on priorities for clinical research in intracerebral hemorrhage (ICH) recommended clinical trials for evaluation of blood pressure management in acute ICH as a leading priority. The Special Writing Group of the Stroke Council of the American Heart Association in 1999 and 2007 emphasized the need for clinical trials to ensure evidence-based treatment of acute hypertensive response in ICH. To address important gaps in knowledge, we conducted a pilot study funded by the NINDS, Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) I Trial, during 2004–2008 to determine the appropriate level of systolic blood pressure (SBP) reduction. We now have initiated a multi-center, randomized Phase III trial, the ATACH II Trial, to definitively determine the efficacy of early, intensive, antihypertensive treatment using intravenous (IV) nicardipine initiated within 3 h of onset of ICH and continued for the next 24 h in subjects with spontaneous supratentorial ICH. The primary hypothesis of this large (N = 1,280), streamlined, and focused trial is that SBP reduction to ≤140 mm Hg reduces the likelihood of death or disability at 3 months after ICH, defined by modified Rankin scale score of 4–6, by at least 10% absolute compared to standard SBP reduction to ≤180 mm Hg. The ATACH II trial is a natural extension of numerous case series, the subsequent ATACH I pilot trial, and a preliminary, randomized, and controlled trial in this patient population funded by the Australian National Health and Medical Research Council. Both trials recently confirmed the safety and tolerability of both the regimen and goals of antihypertensive treatment in acutely hypertensive patients with ICH, as proposed in the present trial. The underlying mechanism for this expected beneficial effect of intensive treatment is presumably mediated through reduction of the rate and magnitude of hematoma expansion observed in approximately 73% of the patients with acute ICH. The Australian trial provided preliminary evidence of attenuation of hematoma expansion with intensive SBP reduction. The ATACH II trial will have important public health implications by providing evidence of, or lack thereof, regarding the efficacy and safety of acute antihypertensive treatment in subjects with ICH. This treatment represents a strategy that can be made widely available without the need for specialized equipment and personnel, and therefore, can make a major impact upon clinical practice for treating patients with ICH.

     

Trends in Surgical Management and Mortality of Intracerebral Hemorrhage in the United States Before and After the STICH Trial

Background  

The Surgical Trial in Intracerebral Hemorrhage (STICH) showed no overall benefit from early surgery compared with initial conservative treatment for intracerebral hemorrhage (ICH). We hypothesized that the STICH trial findings would lead to a reduction in the rates of surgery for ICH in the United States. Using a national hospital database, we determined trends in surgery for ICH before and after publication of STICH. We also determined trends in ICH mortality during the study period.     

Intensive Care Unit Admission for Patients in the INTERACT2 ICH Blood Pressure Treatment Trial: Characteristics,Predictors, and Outcomes

Background

Wide variation exists in criteria for accessing intensive care unit (ICU) facilities for managing patients with critical illnesses such as acute intracerebral hemorrhage (ICH). We aimed to determine the predictors of admission, length of stay, and outcome for ICU among participants of the main Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2).

Methods

INTERACT2 was an international, open, blinded endpoint, randomized controlled trial of 2839 ICH patients (<6 h) and elevated systolic blood pressure (SBP) allocated to receive intensive (target SBP <140 mmHg within 1 h) or guideline-recommended (target SBP <180 mmHg) BP-lowering treatment. The primary outcome was death or major disability, defined by modified Rankin scale scores 3–6 at 90 days. Logistic regression and propensity score analyses were used to determine independent associations.

Main Results

Predictors of ICU admission included younger age, recruitment in China, prior ischemic/undetermined stroke, high SBP, severe stroke [National Institute of Health stroke scale (NIHSS) score ≥15], large ICH volume (≥15 mL), intraventricular hemorrhage (IVH) extension, early neurological deterioration, intubation and surgery. Determinants of prolonged ICU stay (≥5 days) were prior antihypertensive use, NIHSS ≥15, large ICH volume, lobar ICH location, IVH, early neurological deterioration, intubation and surgery. ICU admission was associated with higher-risk major disability at 90-day assessment compared to those without ICU admission.

Conclusions

This study presents prognostic variables for ICU management and outcome of ICH patients included in a large international cohort. These data may assist in the selection and counseling of patients and families concerning ICU admission.

     

去铁胺干预对大鼠ICH后水通道蛋白4表达变化的影响

目的 观察水通道蛋白4（AQP4）在脑出血（ICH）模型组及去铁胺（DFO）干预组的表达变化及作用。方法 采用自体血ICH模型．应用免疫组化及RT-PCR方法观察不同组别及时间段AQP4的表达。结果 AQP4阳性细胞主要分布于脑内星形细胞足突与毛细血管接触区。AQP4蛋白表达在ICH模型组及DFO干预组均较假手术组明显增高且以第7天最高．DFO干预组第7及第14天AQP4蛋白表达较同期ICH模型组显著降低。AQP4 mRNA表达在所有ICH组及DFO干预第3及第7天组较假手术组显著增高且以第3天最高，ICH组第14与第7天AQP4 mRNA表达无显著差别。DFO干预各组与同期ICH模型组相比AQP4 mRNA表达显著降低，且DFO干预各组较前一时间点AQP4 mRNA表达呈显著下降趋势，DFO干预第14天组AQP4 mRNA表达与对照组无差别。AQP4蛋白表达与AQP4 mRNA表达呈正相关关系。结论 AQP4在ICH后水肿的形成及消退中可能起重要作用．DFO可能对于预ICH后水肿形成有一定作用。     

Admission glucose level and clinical outcomes in the NINDS rt-PA Stroke Trial

BACKGROUND: Hyperglycemia during acute ischemic stroke may augment brain injury, predispose to intracerebral hemorrhage (ICH), or both. METHOD: To analyze the relationship between admission glucose level and clinical outcomes from acute ischemic stroke, the authors performed multivariate regression analysis with the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator (rt-PA) Stroke Trial data. Neurologic improvement was defined as improvement on the NIH Stroke Scale by 4 or more points from baseline to 3 months, or a final score of zero. Favorable outcome was defined as both Glasgow Outcome score of 1 and Barthel Index 95 to 100 at 3 months. Symptomatic ICH was defined as CT-documented hemorrhage temporally related to clinical deterioration within 36 hours of treatment. Potential confounding factors were controlled, including acute treatment (rt-PA or placebo), age, baseline NIH Stroke Scale score, history of diabetes mellitus, stroke subtype, and admission blood pressure. RESULTS: There were 624 patients enrolled within 3 hours after stroke onset. As admission glucose increased, the odds for neurologic improvement decreased (odds ratio [OR] = 0.76 per 100 mg/dL increase in admission glucose, 95% CI 0.61 to 0.95, p = 0.01). The relation between admission glucose and favorable outcome depended on admission mean blood pressure (MBP): as admission MBP increased, the odds for favorable outcome related to increasing admission glucose levels progressively decreased (p = 0.02). As admission glucose increased, the odds for symptomatic ICH also increased (OR = 1.75 per 100 mg/dL increase in admission glucose, 95% CI 1.11 to 2.78, p = 0.02). Admission glucose level was not associated with altered effectiveness of rt-PA. CONCLUSIONS: In patients with acute ischemic stroke, higher admission glucose levels are associated with significantly lower odds for desirable clinical outcomes and significantly higher odds for symptomatic ICH, regardless of rt-PA treatment. Whether this represents a cause and effect relationship remains to be determined.     

Update on intracerebral haemorrhage

Intracerebral haemorrhage (ICH) is a common and serious disease. About 1 to 2 out of 10 patients with stroke have an ICH. The mortality of ICH is higher than that of ischaemic stroke. Only 31% are functionally independent at 3 months. Only 38% of the patients survive the 1^st year. The cost of ICH is high. Hypertension is the major risk factor, increasing the risk of ICH about 4x. Up to half of hypertensive patients who suffer a ICH are either unaware of their hypertension, non-compliant with the medication or fail to control periodically their blood pressure levels Microbleeds and white matter changes are MRI markers of the risk of ICH. ICH has 3 main pathophysiological phases: arterial rupture and haematoma formation, haematoma enlargement and peri-haematoma oedema. Up to 40% of the haematomas grow in the first hours post-rupture. ICH growth is associated with early clinical deterioration. Two randomised clinical trials (RCTs) demonstrated that treatment with rFVIIa limited haematoma growth and improved outcome, but was associated with a increase in thromboembolic complications. Ventricular drainage with thrombolytics might improve outcome for patients with intraventricular bleeding. A large RCT and meta-analysis failed to show a benefit of surgery over conservative treatment in acute ICH. Received in revised form: 28 November 2005     

New era for management of primary hypertensive intracerebral hemorrhage

This discussion focuses on recent reports relevant to improved understanding and future directions in the management of intracerebral hemorrhage (ICH). Prevention is possible with adequate treatment of hypertension; microbleeds, apolipoprotein genotype, and cholesterol treatment have been examined in relation to ICH risk. Hematoma products, matrix metalloproteinases, inflammatory markers, and means to attenuate injury have also received attention. The multifaceted character of perihematomal edema has been further defined but evidence for perihematomal ischemia remains elusive. New data on acute blood pressure reinforces the need for a clinical trial. With the lack of efficacy found in the International Surgical Trial in Intracerebral Hemorrhage (ISTICH), a landmark surgical trial, emphasis is shifting to minimally invasive and catheter/ thrombolytic-based technologies for clot evacuation. On the medical side, activated factor VII has been shown to control hemorrhage growth. Looking forward, stem cell therapies for ICH are under investigation and some outcome studies are shedding new rays of hope.     

盐源山蛭注射液治疗脑出血的实验研究

目的 :探索纯化的盐源山蛭注射液促进血肿吸收的作用及其作用机理。方法 :采用定量胶源酶注入大鼠尾状核建立脑出血模型 ,观察盐源山蛭注射液对鼠脑内血肿容积、脑水含量、血浆 F。 a活性、 AT- 活性、 D- D含量及组织病理变化的影响。 BWC采用称重法 ,酶活性测定采用发色底物法 ,D- D含量测定采用 EL IAS测定。结果 :(1)盐源山蛭注射液治疗后 6 d、 10 d的脑内血肿明显缩小 ;使治疗后 3d、 6 d的 BWC明显减轻。 (2 )盐源山蛭注射液能抑制脑出血后 F。 a活性的升高 ,不影响 AT- 活性 ,增加纤溶活性。 (3)盐源山蛭注射液能加快脑出血后的病理组织修复。结论 :(1)盐源山蛭注射对大鼠脑出血后脑内血肿有治疗作用 ;(2 )作用机制可能为 :拮抗凝血形成的稳定因素 ,激活内源性纤溶系统 ,促进胶质细胞增生 ,改善微循环     

Coagulopathy Disproportionately Predisposes to Lobar Intracerebral Hemorrhage

Background

Anticoagulation increases the risk of intracerebral hemorrhage (ICH), yet whether different underlying disease processes are equally affected is unknown. We tested the hypothesis that coagulopathy, measured by admission international normalized ratio (INR), disproportionately increases the risk for lobar hemorrhages.

Methods

Patients with primary ICH were enrolled into a registry between December 2006 and February 2012 with prospective data acquisition and systematic follow up. Logistic regression was used to test whether lobar versus deep ICH location was independently associated with INR, and then whether INR had an influence on mortality. Spearman’s correlation coefficient was used to test for an association between INR and hematoma volume separately in the lobar and deep ICH groups.

Results

221 patients were studied. Patients with lobar ICH were older (71 vs. 62 years old, p < 0.001) and more likely to have prior ICH (10 vs. 0 %, p < 0.001). INR >1.4 was observed on admission more frequently in lobar versus deep ICH (19 vs. 8 %, p = 0.02). Lobar ICH location was independently associated with INR >1.4 (OR: 2.51, 95 % CI: 1.03–6.14, p = 0.043). ICH volume correlated with INR in lobar ICH (p = 0.009), but not deep ICH (p = 0.8). Death at 1 month was independently associated with INR >1.4 (OR: 7.6, 95 % CI: 2.4–24.1, p = 0.001) after correction for the ICH Score.

Conclusions

Abnormal coagulation occurs disproportionally in lobar versus deep ICH, and is associated with larger ICH volumes and higher mortality. These findings suggest a unique risk interaction between coagulopathy and underlying brain pathology due to cerebral amyloid angiopathy.