床旁TCD监测对蛛网膜下腔出血后迟发性脑缺血价值研究

目的 探讨床旁经颅多普勒超声（transcranial Doppler,TCD）监测在蛛网膜下腔出血（subarachnoid hemorrhage,SAH）后预测和发现脑血管痉挛,减少迟发性脑缺血（delayed cerebral ischemia,DCI）发生 的价值。 方法 连续纳入2011年10月至2013年10月首都医科大学附属北京天坛医院神内重症监护病房 （intensive care unit,ICU）住院的完成床旁TCD监测的222例SAH患者。记录患者的临床及影像资料、治 疗及并发症。入院24小时内完成TCD基线监测,根据结果分成正常组85例、流速增快组14例、血 管痉挛组123例,比较患者抗血管痉挛强化治疗的使用率、DCI及不良预后［3个月后改良Rankin量表 （modified Rankin Scale,mRS）评分4～6分］的发生率和治疗改善率的差异。 结果 3组患者比较,血管痉挛组和血流增快组的GCS评分低、Hunt-Hess分级Ⅰ～Ⅲ级比例少、世界 神经外科医师联盟（World Federation of Neurosurgical Society,WFNS）分级Ⅰ～Ⅲ级比例少、改良Fisher 分级3～4级所占比例多、颅内血肿发生率多,差异均具有显著性（P <0.05）。血管痉挛组和流速增快 组患者DCI 发生率高于正常组（68.2%、35.7%、3.2%,P＜0.01）。TCD流速增快组和血管痉挛组患者给 予的抗血管痉挛加强治疗（70.6%、100%、4.1%）及脑脊液置换治疗（21.2%、7.1%、5.7%）多,临床缓 解率（56.5%、28.6%、10.6%）高（P＜0.01）。90天随访血管痉挛组和流速增快组预后不良高于正常组 （30.6%、21.4%、15.4%,P =0.031）。 结论 TCD结果异常的患者（血管痉挛组和血流增快组）发病后的病情重,出血量大,尽管给予加强 治疗,DCI的发生率及预后不良率仍高于正常组。床旁TCD监测能够筛查出DCI高危患者并评价治疗效 果,是防治DCI所需的有效检测工具。     

蛛网膜下腔出血后无迟发性脑缺血相关因素分析

目的 分析动脉瘤性蛛网膜下腔出血(aSAH)后无迟发性脑缺血(DCI)的相关因素,以期为DCI病人转出重症监护病房(ICU)提供临床依据.方法 选取2001-10 2011-06确诊的动脉瘤性蛛网膜下腔出血且入住重症监护病房患者153例,其中DCI组67例,非DCI组86例;分析蛛网膜下腔出血后无迟发性脑缺血的相关因素.结果 DCI组一般情况相比非DCI组显示:平均年龄、入院血糖＞6.1 mmol/L、后循环动脉瘤、脑室出血差异有统计学意义(P＜0.05);服用他汀类药物、GCS评分、WFNS Ⅰ～Ⅲ级、改良Fisher分级Ⅰ～Ⅱ级、TCD血管痉挛、血管造影血管痉挛差异有统计学意义(P＜0.001);单因素分析显示:年龄＞65岁,WFNS分级Ⅰ～Ⅲ级、改良Fisher分级1～2级、无颅内血肿和后交通动脉瘤与动脉瘤性蛛网膜下腔出血后无迟发性脑缺血相关(P＜0.05);多因素分析发现年龄＞65岁,WFNS Ⅰ～Ⅲ级,改良Fisher分级1～2级是未发生DCI的独立因素.结论 年龄＞65岁,WFNSⅠ～Ⅲ级和改良Fisher分级1～2级可作为病人转出ICU病房的依据.     

蛛网膜下腔出血后迟发性脑缺血的病理生理机制探讨

蛛网膜下腔出血(subarachnoid hemorrhage,SAH)是一种十分凶险的脑血管病,具有高死亡率、高致残率及高治疗难度的特点.迟发性脑缺血(delayed cerebral ischemia,DCI)是SAH后一种常见的并发症,一旦发生将严重影响患者预后.因此,明确DCI的病理生理机制对其预防和治疗具有至...     

经颅多普勒预测高改良Fisher分级蛛网膜下腔出血后迟发性脑缺血研究

目的 观察在高改良Fisher分级的蛛网膜下腔出血患者中双侧大脑中动脉血流速度比值（mean blood flow velocity ratio of the ipsilateral to contralateral middle cerebral arteries,I/C mBFV）对于迟发性脑 缺血（delayed cerebral ischemia,DCI）的预测价值是否高于大脑中动脉平均血流速度（mean blood flow velocity,mBFV）≥120 cm/s。 方法 回顾性连续收集2011年11月-2013年11月首都医科大学附属北京天坛医院NICU住院的改良 Fisher分级≥3级的蛛网膜下腔出血患者,所有患者均接受经颅多普勒（transcranial doppler sonography, TCD）检查。记录大脑中动脉mBFV及双侧I/C mBFV。终点事件为DCI。计算I/C mBFV和大脑中动脉 mBFV≥120 cm/s预测DCI的敏感性、特异性、阳性预测值及阴性预测值。 结果 共44例患者纳入研究,共18例患者发生了迟发性脑缺血,发生率为41%。以大脑中动脉 mBFV≥120 cm/s为标准时,TCD诊断的敏感性是77.8%,特异性是50%,阳性预测值53.8%,阴性预测 值为75%。以I/C mBFV≥1.5为标准时,TCD的敏感性是71.8%,特异性是41.7%,阳性预测值50%,阴 性预测值为71.4%。 结论 对于高Fisher分级的蛛网膜下腔出血的患者,TCD仍是预测迟发性脑缺血的有利工具。与I/C mBFV≥1.5为标准相比,mBFV≥120 cm/s的预测价值更高。     

经颅多普勒对动脉瘤夹闭术后迟发性脑缺血的早期预测研究

目的：观察经颅多普勒对破裂动脉瘤夹闭术后迟发性脑缺血的预测,并分析迟发性脑缺血发生的危险因素。方法回顾性分析46例因动脉瘤性蛛网膜下腔出血接受动脉瘤夹闭手术患者的临床资料,用受试者工作曲线分析经颅多普勒对迟发性脑缺血的预测情况。用Logistic多元回归分析迟发性脑缺血的可能危险因素。结果大脑中动脉平均血流速度为160 cm／s对迟发性脑缺血的预测准确率最高,敏感度为92．3％,特异度为42．4％。改良Fisher分级（OR＝3．27,P＝0．02）和大脑中动脉平均血流速度≥160 cm／s （OR＝10．24,P＝0．04）与迟发性脑缺血有显著统计学相关性。结论经颅多普勒可用于动脉瘤夹闭术后的早期动态监测。大脑中动脉平均血流速度≥160 cm／s和改良Fisher分级都是迟发性脑缺血发生的危险因素。     

血脂水平与动脉瘤性蛛网膜下腔出血后迟发性脑缺血的相关性

目的 探讨血脂水平与动脉瘤性蛛网膜下腔出血(aSAH)后迟发性脑缺血（DCI）的相关性。方法 回顾性分析2014年1月至2015年12月收治的74例aSAH的临床资料,采用多因素Logistic回归分析检验性别、年龄、动脉瘤位置、动脉瘤大小、世界神经外科医师联盟（WFNS）分级、改良Fisher分级、Hunt-Hess分级、治疗方式、总甘油三脂、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、脂蛋白(a)、载脂蛋白A、载脂蛋白B等因素与DCI的关系。结果 74例中,65例入院后检测血脂,20例出现DCI,45例未出现DCI,aSAH后DCI的发生率为30.8%。多因素Logistic回归分析显示高甘油三酯及改良Fisher分级是aSAH后DCI发生的独立危险因素。结论 及时检测aSAH患者的血脂水平和对患者进行改良Fisher分级对DCI的诊断治疗均有参考价值。     

蛛网膜下腔出血的脑血流速度检测

采用经颅多普勒超声，对３６例蛛网膜下腔出血病人和３０例正常对照者进行颅内主要动脉的血流速度检测，以观察其对ＳＡＨ的临床应用价值。结果发现６３．９％病人血流速度明显增高，１９．４％病人表现高阻力型频谱形态改变。     

蛛网膜下腔出血继发迟发性缺血性神经功能障碍患者TCD的动态观察

目的　研究蛛网膜下腔出血 (SAH)继发迟发性缺血性神经功能障碍 (DINDS)患者经颅多普勒(TCD)的动态变化。方法　应用TCD动态检查 2 3例SAH继发DINDS的患者 ,根据DINDS侧大脑中动脉(MCA)平均血流速度 (Vm)的改变分为流速增高组与流速正常组 ,并进行比较。结果　流速增高组DINDS侧MCA的Vm与脉动指数 (PI)均呈进行性增高并均高于对侧 (均P <0 0 1) ,且早于DINDS临床症状出现 (P <0 .0 1) ;流速正常组DINDS侧MCA的PI进行性增高并高于对侧 (P <0 0 1) ,同时Vm进行性减慢并低于对侧(P <0 0 1) ,早于DINDS临床症状出现 (P <0 .0 1)。结论　SAH继发迟发性脑血管痉挛 (DCVS)发生于脑底动脉 ,和其远端小动脉的TCD表现不同 ,两者的变化均早于临床症状出现。     

眼跳潜伏期预测动脉瘤性蛛网膜下腔出血后迟发性脑缺血的研究

目的探讨眼跳潜伏期对动脉瘤性蛛网膜下腔出血(SAH)后迟发性脑缺血(DCI)的预测作用。方法回顾性选择2012年1月~2016年12月来我院接受治疗的SAH患者110例。根据患者入院后30天内有无并发迟发性脑缺血(DCI)分为并发DCI组(n=40)和未并发DCI组(n=70)。应用单因素、多因素非条件Logistic回归分析探讨影响SAH患者DCI发生的危险因素。结果眼跳频率、眼跳总时间、单次眼跳平均时间、眼跳总幅度、眼跳平均幅度、眼跳平均速度、眼跳潜伏期预测SAH后DCI发生的诊断界值分别为2.65次/s、1685.45 ms、39.03 ms、553.25°、8.05°、118.35°/s、375.42 ms。Hunt-Hess分级≥Ⅲ级、Fisher分级≥Ⅲ级、脑积水程度(中度、重度)、眼跳潜伏期≥375.42 ms会增加SAH后DCI发生风险(P0.05)。结论眼跳潜伏期可预测SAH后DCI发生。     

脑灌注压对动脉瘤性蛛网膜下腔出血后迟发性脑缺血的预测价值

目的探讨脑灌注压(CPP)对动脉瘤性蛛网膜下腔出血(aSAH)后迟发性脑缺血(DCI)发生的预测价值。方法纳入2016年1月至12月在我院就诊并进行CPP检测的50例aSAH患者,其中19例发生DCI。统计所有患者低于各CPP阈值的时间总比例,通过ROC曲线及二元logisctic回归分析比较CPP与DCI的相关性。结果 CPP低于50 mmHg、55 mmHg、60 mmHg、65 mmHg的时间比例对DCI的预测阈值分别为0.28%(AUC=0.778)、3.0%(AUC=0.756)、10.8%(AUC=0.749)、16.1%(AUC=0.718),经二元logistic回归分析显示均与DCI的发生相关(P0.05)。而CPP低于70 mmHg、75 mmHg、80 mmHg的时间比例对DCI的预测阈值分别为24.8%(AUC=0.697)、49.6%(AUC=0.686)、55.9%(AUC=0.672),经二元logistic回归分析显示均与DCI无相关性(P0.05)。结论 aSAH患者发生DCI的风险与CPP降低有关,而维持CPP在70 mmHg以上可能有助于预防DCI发生。     

脑灌注压对动脉瘤性蛛网膜下腔出血后迟发性脑缺血的预测价值

目的 探讨脑灌注压（CPP）对动脉瘤性蛛网膜下腔出血（aSAH）后迟发性脑缺血（DCI）发生的预测价值。方法 纳入2016年1月至12月在我院就诊并进行CPP检测的50例aSAH患者，其中19例发生DCI。统计所有患者低于各CPP阈值的时间总比例，通过ROC曲线及二元logisctic回归分析比较CPP与DCI的相关性。结果 CPP低于50 mmHg、55 mmHg、60 mmHg、65 mmHg的时间比例对DCI的预测阈值分别为0.28%（AUC=0.778）、3.0%（AUC=0.756）、10.8%（AUC=0.749）、16.1%（AUC=0.718），经二元logistic回归分析显示均与DCI的发生相关（P<0.05）。而CPP低于70 mmHg、75 mmHg、80 mmHg的时间比例对DCI的预测阈值分别为24.8%（AUC=0.697）、49.6%（AUC=0.686）、55.9%（AUC=0.672），经二元logistic回归分析显示均与DCI无相关性（P>0.05）。结论 aSAH患者发生DCI的风险与CPP降低有关，而维持CPP在70 mmHg以上可能有助于预防DCI发生。     

早期低脑血流量和高乳酸血症预测蛛网膜下腔出血后迟发性脑缺血的临床研究

目的 探讨早期低脑血流量和高乳酸血症对蛛网膜下腔出血(SAH)后迟发性脑缺血(DCI)的预测作用。方法 选择2010年1月-2014年12月来本院接受治疗的SAH患者90例; 根据患者有无DCI发生分为DCI发生组(n=35)和DCI未发生组(n=55); 根据病历信息及临床检查详细记录SAH患者的年龄、性别、体质量指数(BMI)、烟酒嗜好,高血压病、糖尿病史和现状、治疗方式,责任动脉瘤位置、血肿形成、脑积水、有无高乳酸血症、Hunt-Hess分级、Fisher分级等; 应用单因素、多因素非条件Cox回归分析预测SAH后DCI发生的危险因素。结果 90例SAH患者中35例(38.89%)发生DCI,55例(61.11%)未发生DCI。2组患者在性别、Fisher分级、Hunt-Hess分级、血肿形成、脑积水、有高乳酸血症、脑血流量(CBF)、脑血容量(CBV)、平均通过时间(MTT)、达峰时间(TTP)方面差异显著(P<0.05)。其中,DCI发生组在高乳酸血症患者比例方面显著高于DCI未发生组(P<0.05),在CBF方面显著低于DCI未发生组(P<0.05)。CBF、CBV、MTT、TTP的ROC曲线下面积分别为0.88、0.70、0.89、0.73,预测DCI最佳诊断界值分别为15.95 mL·100 g^-1·min^-1、1.77 mL·100 g^-1、9.62 s、11.48 s。 单因素、多因素Cox回归分析显示,有高乳酸血症、Hunt-Hess分级≥Ⅲ级、Fisher分级≥Ⅲ级、CBF<15.95 ml/100 g/min会增加SAH后DCI发生的风险(P<0.05)。结论 早期低脑血流量和高乳酸血症可预测SAH后DCI发生。     

Genetic determinants of cerebral vasospasm, delayed cerebral ischemia, and outcome after aneurysmal subarachnoid hemorrhage

Despite extensive effort to elucidate the cellular and molecular bases for delayed cerebral injury after aneurysmal subarachnoid hemorrhage (aSAH), the pathophysiology of these events remains poorly understood. Recently, much work has focused on evaluating the genetic underpinnings of various diseases in an effort to delineate the contribution of specific molecular pathways as well as to uncover novel mechanisms. The majority of subarachnoid hemorrhage genetic research has focused on gene expression and linkage studies of these markers as they relate to the development of intracranial aneurysms and their subsequent rupture. Far less work has centered on the genetic determinants of cerebral vasospasm, the predisposition to delayed cerebral injury, and the determinants of ensuing functional outcome after aSAH. The suspected genes are diverse and encompass multiple functional systems including fibrinolysis, inflammation, vascular reactivity, and neuronal repair. To this end, we present a systematic review of 21 studies suggesting a genetic basis for clinical outcome after aSAH, with a special emphasis on the pathogenesis of cerebral vasospasm and delayed cerebral ischemia. In addition, we highlight potential pitfalls in the interpretation of genetic association studies, and call for uniformity of design of larger multicenter studies in the future.     

Hemostasis and fibrinolysis in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: a systematic review

Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) has been associated with microthrombosis, which can result from activated hemostasis, inhibited fibrinolysis, or both. We systematically searched the PUBMED and EMBASE databases to identify hemostatic or fibrinolytic parameters that can be used for the prediction or diagnosis of DCI, or that inform on the pathogenesis of DCI and may serve as treatment targets. We included 24 studies that fulfilled predefined criteria and described 39 biomarkers. Only one study fulfilled predefined criteria for high quality. Since no parameter on admission was associated with DCI and in none of the included studies blood was drawn at the time of clinical deterioration, none of the studied parameters can presently be used for the prediction or diagnosis of DCI. Regarding the pathogenesis of DCI, it was shown that compared with patients without DCI those with DCI had higher levels of von Willebrand factor and platelet activating factor in plasma 5 to 9 days after aSAH, membrane tissue factor in cerebrospinal fluid 5 to 9 days after aSAH, and D-dimer in plasma 11 to 14 days after aSAH. Confirmation in high-quality studies is needed to investigate whether these parameters can serve as targets for new intervention studies.     

Timing of operation for poor-grade aneurysmal subarachnoid hemorrhage: Relationship with delayed cerebral ischemia and poor prognosis

Aims

To assess differences in the clinical prognosis between different treatment timings in poor-grade (Hunt and Hess grade 4–5) aneurysmal subarachnoid hemorrhage patients.

Methods

The treated 127 poor-grade aneurysmal subarachnoid hemorrhage patients were divided into three groups: early treatment within 2 days, treatment on days 3 to 10, and treatment for more than 10 days after the hemorrhage. Odd ratios with a 95% confidence interval were calculated in logistic regression for different timing strategies regarding delayed cerebral ischemia and poor prognosis at 3 months. Subgroup analyses were conducted to determine whether the different timing strategies affect the prognosis.

Results

Patients who received the treatment on days 3 to 10 were prone to develop delayed cerebral ischemia and poor prognosis at 3 months. Postponing treatment in patients older than 55 years or diagnosed with an intraventricular hematoma on the initial computed tomography scan may lead to poor prognosis, with the early intervention group as a reference.

Conclusions

Early intervention in poor-grade aneurysmal subarachnoid hemorrhage is suggested to be implemented. The treatment on 3 to 10 days harbored the highest risk of poor prognosis; patients might benefit more from early intervention, especially for ones older than 55 years or diagnosed with an intraventricular hematoma.     

The role of the microcirculation in delayed cerebral ischemia and chronic degenerative changes after subarachnoid hemorrhage

The mortality after aneurysmal subarachnoid hemorrhage (SAH) is 50%, and most survivors suffer severe functional and cognitive deficits. Half of SAH patients deteriorate 5 to 14 days after the initial bleeding, so-called delayed cerebral ischemia (DCI). Although often attributed to vasospasms, DCI may develop in the absence of angiographic vasospasms, and therapeutic reversal of angiographic vasospasms fails to improve patient outcome. The etiology of chronic neurodegenerative changes after SAH remains poorly understood. Brain oxygenation depends on both cerebral blood flow (CBF) and its microscopic distribution, the so-called capillary transit time heterogeneity (CTH). In theory, increased CTH can therefore lead to tissue hypoxia in the absence of severe CBF reductions, whereas reductions in CBF, paradoxically, improve brain oxygenation if CTH is critically elevated. We review potential sources of elevated CTH after SAH. Pericyte constrictions in relation to the initial ischemic episode and subsequent oxidative stress, nitric oxide depletion during the pericapillary clearance of oxyhemoglobin, vasogenic edema, leukocytosis, and astrocytic endfeet swelling are identified as potential sources of elevated CTH, and hence of metabolic derangement, after SAH. Irreversible changes in capillary morphology and function are predicted to contribute to long-term relative tissue hypoxia, inflammation, and neurodegeneration. We discuss diagnostic and therapeutic implications of these predictions.     

促红细胞生成素对迟发型脑血管痉挛抑制作用的实验研究

目的研究全身应用重组人促红细胞生成素(rHuEPO)对蛛网膜下腔出血后(SAH)迟发型脑血管痉挛(DCVS)的抑制作用。方法清洁级雄性wistar大鼠40只随机分为四组:空白组、SAH组、SAH+rHuEPO组、SAH+安慰剂组。采用枕大池2次注血法建立蛛网膜下腔出血模型。注血后7d取血,采用酶联免疫吸附法(ELISA)检测测血浆中内皮素-1(ET-1)含量,原位细胞凋亡检测法(TUNEL)检测颞叶神经元凋亡情况,通过测定基底动脉血管横截面积判断脑血管痉挛情况。结果实验显示SAH后第7dSAH+rHuEPO组基底动脉横截面积比SAH组和SAH+安慰剂组相比明显变大(P<0.01);血浆ET-1浓度SAH+rHuEPO组与SAH组和SAH+安慰剂组相比明显减少(P<0.01);TUNEL染色显示SAH+rHuEPO组皮质神经元凋亡程度较SAH组和SAH+安慰剂组显著减轻。结论早期全身应用rHuEPO可以有效预防SAH后迟发型脑血管痉挛,并有脑保护作用,部分与rHuEPO能抑制ET-1的产生有关。     

CT perfusion and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis

Delayed cerebral ischemia (DCI) is at presentation a diagnosis per exclusionem, and can only be confirmed with follow-up imaging. For treatment of DCI a diagnostic tool is needed. We performed a systematic review to evaluate the value of CT perfusion (CTP) in the prediction and diagnosis of DCI. We searched PubMed, Embase, and Cochrane databases to identify studies on the relationship between CTP and DCI. Eleven studies totaling 570 patients were included. On admission, cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time-to-peak (TTP) did not differ between patients who did and did not develop DCI. In the DCI time-window (4 to 14 days after subarachnoid hemorrhage (SAH)), DCI was associated with a decreased CBF (pooled mean difference −11.9 mL/100 g per minute (95% confidence interval (CI): −15.2 to −8.6)) and an increased MTT (pooled mean difference 1.5 seconds (0.9–2.2)). Cerebral blood volume did not differ and TTP was rarely reported. Perfusion thresholds reported in studies were comparable, although the corresponding test characteristics were moderate and differed between studies. We conclude that CTP can be used in the diagnosis but not in the prediction of DCI. A need exists to standardize the method for measuring perfusion with CTP after SAH, and optimize and validate perfusion thresholds.