尼莫地平在aSAH治疗中的研究进展

<正>自发性蛛网膜下腔出血(subarachnoid hemo-rrhage,SAH)主要由颅内动脉瘤破裂引起,脑血管痉挛(cerebral vasospasm,CVS)、迟发性脑缺血(delayed cerebral ischaemia,DCI)是动脉瘤性SAH(aneurysmal SAH,a SAH)致残和死亡的主要原因~([1~3])。早期、积极预防这些并发症有助于改善患者预后。Meta分析表明,尼莫地平降低aSAH患者CVS、DCI、迟发性神经缺失发生率,明显改善患者预后~([3,4])。本文就尼莫地平在a SAH治疗中研究进展进行综述。     

CT灌注成像在动脉瘤性蛛网膜下腔出血中的 临床应用进展

正脑血管痉挛(cerebral vasospasm,CVS)和迟发性脑缺血(delayed cerebral ischemia,DCI)是动脉瘤性蛛网膜下腔出血(aneurysmal subarachnoidhemorrhage,a SAH)最常见的两大并发症。传统的观念认为,CVS是导致DCI的主要甚至唯一原因。但是,越来越多的证据表明,单纯用CVS无法完全解释DCI和预后不良。微循环障碍、微血栓形成、血液黏     

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。     

缺血修饰白蛋白评估动脉瘤性蛛网膜下腔出血患者迟发性脑缺血研究

目的探讨缺血修饰白蛋白(IMA)评估动脉瘤性蛛网膜下腔出血(a SAH)患者迟发性脑缺血(DCI)的价值及其与患者预后的关系。方法选取198例a SAH患者,根据有无DCI把患者分为DCI组和无DCI组,测定血清IMA,同时使用经颅多普勒(TCD)监测大脑中动脉的平均血流速度(VMCA),比较两组脑血管痉挛发生率和血清IMA。结果在7～10天时间段VMCA和血清IMA达到峰值,然后逐渐下降;在1～6天、7～10天、11～14天时间段,VMCA比较、血清IMA比较,差异均有统计学意义(P 0. 05)。DCI组的CVS发生率高于无DCI组,并且DCI组的血清IMA水平高于无DCI组,差异均有统计学意义(P 0. 05)。预后不良组的血清IMA[(64. 28±5. 94) U/ml]高于预后良好组[(45. 46±5. 72) U/ml],差异有统计学意义(P 0. 05)。结论血清IMA水平与脑血管痉挛及预后密切相关,它可在一定程度上反应a SAH后脑缺血情况,对血管痉挛相关的DCI评估有重要价值,并且有助于判断预后。     

CT灌注成像在动脉瘤性蛛网膜下腔出血中的应用

<正>动脉瘤性蛛网膜下腔出血(aneurysmal subarachnoid hemorrhage,a SAH)病死率高,致残率高^[1],主要原因包括脑血管痉挛(cerebral vasospasm,CVS)和迟发性脑缺血(delayed cerebral ischemia,DCI)^[2]。尽早诊断和治疗可降低aSAH的病死率和致残率。     

经颅多普勒对蛛网膜下腔出血导致血管痉挛的临床研究

目的研究实时床旁经颅多普勒(transcranial doppler,TCD)在蛛网膜下腔出血(subarachnoid hemorrhage,SAH)中对脑血管痉挛(cerebral vasospasm,CVS)的预警和治疗指导作用。方法采用前瞻性研究TCD实时监测180例CT确诊SAH患者大脑中动脉(middle cerebral artery,MCA)的动脉平均峰值流速(mean blood velocity,Vm)、搏动指数(pulsatility index,PI)、阻力指数(resistance index,RI)和血流频谱,自身健侧作为正常对照,对符合CVS诊断标准的使用尼莫地平进行治疗,观察疗效。结果与健侧相比,出血侧PI、RI增大,Vd、Vm减小,其中以Vd减小较明显,与健侧相比有显著差异意义(P0.01),Vs与健侧相比无显著差异(P0.05);CVS组与非CVS组相比Vm明显增加,差异有统计学意义(P0.001)。监测SAH后出现血管痉挛52例(28.89%),经尼莫地平治疗均获得缓解。结论采用TCD监测SAH患者脑血流变化,其对血流的监测为临床诊断和个性化治疗SAH后CVS提供参考依据,经TCD的预警和干预明显提高了SAH的疗效。     

PVI、CPP与动脉瘤性蛛网膜下腔出血后患者迟发性脑缺血的关系

目的 探讨血小板体积指数(PVI)、脑灌注压(CPP)与动脉瘤性蛛网膜下腔出血(aSAH)后患者迟发性脑缺血(DCI)的关系.方法 选择2016年1月至2018年2月枣庄市立医院诊治的198例aSAH患者,根据是否发生DCI将患者分为DCI组(61例)和NDCI组(137例).检测PVI和CPP,分析其对aSAH后DC...     

p38丝裂原活化蛋白激酶在实验性蛛网膜下腔出血后早期脑损伤中的作用

目的探讨p38丝裂原活化蛋白激酶(p38MAPK)在蛛网膜下腔出血(SAH)后早期脑损伤(EBI)中的作用。方法成年雄性SD大鼠随机分配至对照组、SAH组及p38MAPK干预组,每组18只。采用血管内穿刺法制作SAH模型,干预组于术前30 min经侧脑室注射p38MAPK特异性抑制剂SB203580,造模后24 h处死。观察各组大鼠脑含水量和神经功能评分,RT-PCR及免疫组化检测脑组织p38MAPK表达。结果与对照组相比,SAH组大鼠脑含水量(t=-196.35,P0.01)及p38 MAPK的mRNA水平(t=-24.75,P0.01)均明显升高,神经功能评分明显减低(t=201.08,P0.01)。与SAH组相比,干预组脑含水量(t=75.67,P0.01)及p38 MAPK的mRNA水平(t=9.43,P0.01)均明显下降,神经功能评分明显升高(t=-81.68,P0.01)。免疫组化示SAH组及干预组均有p38MAPK表达,但干预组较SAH组表达水平明显下降(t=-3.37,P0.01)。结论 p38 MAPK在EBI形成机制中起重要作用,有望成为防治EBI的药物作用新靶点。     

蛛网膜下腔出血后迟发性脑缺血患者血清可溶性凝集素样氧化型低密度脂蛋白受体-1水平的变化及其意义

目的 探讨蛛网膜下腔出血(SAH)后发生迟发性脑缺血(DCI)患者的血清可溶性凝集素样氧化型低密度脂蛋白受体-1(sLOX-1)水平的变化及其意义.方法 根据是否发生DCI将132例SAH患者分为DCI组(34例)和无DCI组(98例).采用酶联免疫吸附法检测患者的血清sLOX-1水平,并对结果进行分析.结果 DCI组患者血清sLOX-1水平[1325(313 ～ 2698) pg/ml]较无DCI组[757(128 ～ 1762) pg/ml]明显升高(P＜0.01).Logistic回归分析显示,血清sLOX-1水平升高是SAH患者发生DCI的独立危险因素(OR=2.362,95％CI:1.276～3.707,P＜0.05).结论 血清sLOX-1水平升高可作为预测SAH患者发生DCI的重要血清学标记物.     

蛛网膜下腔出血中神经炎症的研究进展

动脉瘤性蛛网膜下腔出血(subarachnoid hemorrhage,SAH)作为临床常见的一类疾病,有高病死率和致残率,尽管目前对于SAH病人的临床管理有所改善,病死率有所降低,但这一类病人的总体致残率和致死率仍然很高。在动脉瘤术后存活病人中,迟发性脑缺血(delayed cerebral ischemia,DCI)是病人致残甚至致死的主要原因之一,众多研究表明神经炎症是引起DCI的一个重要因素。本文回顾研究SAH的实验模型中,关于神经炎症的各种机制,以及目前针对神经炎症的各种临床药物试验。探讨机理研究在预防SAH后延迟性损伤和改善预后的作用。     

Whole-Brain Permeability Analysis on Admission Improves Prediction of Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage

PurposeTo evaluate the changes of blood-brain barrier permeability (BBBP) after aneurysmal subarachnoid hemorrhage (aSAH) and find out whether BBBP within 24 h after onset can further improve prediction of delayed cerebral ischemia (DCI).MethodsCT perfusion (CTP) was performed within 24 h after onset and in the DCI time window (DCITW). Whole brain average values of flow extraction product (mK^trans), qualitative and quantitative CTP parameters, and clinical data were compared between DCI and non-DCI groups. The changes of mK^trans were analysed using a Paired t test. Multivariate logistic regression analysis and ROC analyses were performed to identify predictors of DCI and evaluate the predictive performance.ResultsOne hundred and forty of 179 consecutive patients were included, 45 of whom (32%) developed DCI. mK^trans was higher in the DCI group both on admission and in the DCITW (P<0.001). mK^trans decreased significantly in the non-DCI group (P=0.003), but not in DCI group (P=0.285). Multivariate logistic regression analysis showed that mK^trans (OR=1.07, 95%CI: 1.03-1.11, P<0.001), World Federation of Neurosurgery Scale (OR=6.73, 95%CI: 1.09-41.41, P=0.040), Hunt-Hess grade (OR=0.16, 95%CI: 0.02-1.19, P=0.073), modified Fisher Score (OR=3.74, 95%CI: 1.30-10.75, P=0.014), and qualitative CTP (OR=4.31, 95%CI: 1.49-12.47, P=0.007) were independent predictors of DCI. The model with K^trans produced a larger AUC of 0.88 (95%CI: 0.81-0.95), with corresponding sensitivity and specificity of 84% and 86%, respectively.ConclusionBBBP measurement within 24 h after onset can improve the prediction of DCI. Early moderate BBB disruption may be reversible, whereas severe BBBP disruption indicates the risk of DCI.     

Lactate and Lactate Dehydrogenase in Cistern as Biomarkers of Early Brain Injury and Delayed Cerebral Ischemia of Subarachnoid Hemorrhage

Objective: The pathophysiology of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) has not been fully evaluated. The aim of this study was to evaluate the dynamics of lactate and lactate dehydrogenase (LDH) in carotid cisternal cerebrospinal fluid (CSF), and to discuss their effectiveness as markers of early brain injury (EBI) and DCI following aSAH. Patients and Methods: Among 91 consecutive aSAH patients treated between January 2012 and March 2019 at National Hospital Organization Beppu Medical Center, 19 patients (20.9%) were eligible for this retrospective study. Concentrations of lactate and LDH in carotid cisternal CSF within 14 days after onset of aSAH were evaluated. Results: Six of the 19 patients (31.6%) had a history of DCI. Both lactate and LDH levels in carotid cisternal CSF were significantly higher in the DCI group than in the non-DCI group on postbleeding day (PBD) 1-2, 3-4, and 5-6. Interestingly, neither lactate nor LDH levels in blood differed significantly between DCI and non-DCI groups on PBD 1-2. Conclusions: Lactate and LDH concentrations in carotid cisternal CSF may vividly reflect the EBI and may thus represent predictive biomarkers of DCI following aSAH.     

Association between elevated cerebrospinal fluid D-dimer levels and delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage

Delayed cerebral ischaemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) is a major contributor to morbidity and mortality. It is currently not possible to reliably predict patients at risk of DCI after aSAH. The aim of this study was to quantify cerebrospinal fluid (CSF) D-Dimer and plasminogen levels and to investigate any association with development of DCI. Cerebrospinal fluid (CSF) samples collected from 30 patients within 72 h post-aSAH (n = 13 DCI and n = 17 non-DCI patients) were analysed. DCI was diagnosed when angiographic vasospasm was detected in the presence of new onset neurological deficit. Enzyme-linked immunosorbent assays were used to quantify D-dimer concentrations while western blotting was used to quantify plasminogen levels. Significant differences in CSF proteins between DCI and non-DCI cohorts were verified using Mann-Whitney test. Sensitivity and specificity of these proteins for detecting DCI was examined using a ROC curve and verified with a Fischer’s exact test. CSF levels of D-dimer within 72 h post aSAH were significantly elevated in DCI patients (54.29 ng/ml, 25.35–105.88 ng/ml) compared to non-DCI patients (26.75 ng/ml, 6.9–45.08 ng/ml) [p = 0.03]. In our sample population, D-dimer levels above 41.1 ng/ml had a sensitivity of 69.2% and specificity of 75% for predicting DCI. CSF levels of plasminogen (DCI: 0.50 signal-intensity/μl, 0.20–0.73 signal-intensity/μl, non-DCI: 0.28 signal-intensity/μl, 0.22–0.54 signal-intensity/μl) did not differ between the DCI and non-DCI cohort (p > 0.05). Our study suggests that elevated D-dimer in the first 72 h after aSAH may be a potential predictive biomarker for DCI.     

早期肠内营养在重型颅脑外伤去骨瓣减压术后患者中的应用

目的探讨早期肠内营养在重型颅脑损伤去骨瓣减压术后患者中的应用。方法对我院2013年1月至2014年6月57例重型颅脑外伤去骨瓣减压术后患者分为肠内营养组和肠外营养组,分别对两组患者的治疗7天后白蛋白及前白蛋白水平、重症监护室(intensive care unit,ICU)内感染并发症及28天死亡率的比较。结果早期肠内营养组中急性胃肠损伤(Acute gastrointestinal injury,AGI)分级Ⅰ级-Ⅱ级患者治疗7天后的前白蛋白水平较高(t=2.37,P=0.025,具有统计学意义),ICU感染并发症较少(χ2=7.636,P=0.06,具有统计学意义),28天死亡率低(χ2值4.667,P=0.031,具有统计学意义)。结论重型颅脑损伤开颅去骨瓣减压术后患者根据急性胃肠损伤分级,胃肠功能AGIⅠ级-Ⅱ级患者应尽早启动肠内营养。     

Continual Transcranial Doppler in the Monitoring of Hemodynamic Change following Aneurysmal Subarachnoid Hemorrhage

Aims: To analyze and compare the value of different treatment methods for acute aneurysmal subarachnoid hemorrhage (aSAH)‐related vasospasm. Cerebral hemodynamic variables’ changes were evaluated by transcranial Doppler (TCD) in aSAH patients within 14 days after onset. Methods: Thirty aSAH patients were enrolled in the study within 72 h after onset. Baseline CT and TCD were used for assessment. Patients were divided into three groups according to SAH severity and patients’ discretion: nonsurgical group, endovascular coiling, and neurosurgical clipping. TCD hemodynamic parameters were measured and Lindegaard index was calculated daily from onset to 14th day after SAH. The group mean cerebral blood velocity (MBFV) and Lindegaard index were compared using repeated measures analysis of variance (reANOVA). Least Significant Difference (LSD) test was used for post hoc comparison. All 30 patients were followed for 90 days after onset for outcome assessment. Results: The values of MBFV and Lindegaard index of anterior cerebral artery (ACA)/middle cerebral artery (MCA) from high to low is nonsurgical group, clipping and coiling (ACA: P= 0.0001/P= 0.006; MCA: P= 0.243/P= 0.317). Conclusions: These results indicate that both neurosurgical clipping and endovascular coiling management may relieve the severity of cerebral vasospasm in acute aSAH.     

Elevated blood viscosity is associated with delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage

ObjectivesDelayed cerebral ischemia (DCI) is a contributing factor for poor clinical outcome in aneurysmal subarachnoid hemorrhage (aSAH). Blood viscosity can reflect flow resistance and dehydration status. Our study aimed to analyze the association between blood viscosity and DCI in patients with aSAH.MethodsIn this retrospective cohort, systolic blood viscosity (SBV) and diastolic blood viscosity (DBV) were measured at admission in patients with aSAH. Receiver operating characteristic curve analysis was used to assess the predictive values of SBV and DBV for DCI after aSAH. Univariate and multivariate logistic regression was performed to analyze the association between blood viscosity and the development of DCI.ResultsA total of 470 patients with aSAH were included in this study, and 184 (39.1%) patients had DCI. Optimal cut-off values of DBV and SBV were presented as 12.05 (cP) and 3.75 (cP), respectively. In addition, DBV has higher predictable value of DCI than SBV (DBV: area under the curve [AUC] 0.793; standard error [SE] 0.026; 95% CI 0.722–0.864; P < 0.001, and SBV: AUC 0.702; SE 0.040; 95% CI 0.624-0.781; P < 0.001). In multivariate logistic regression analysis, elevated DBV was a predicting factor for development of DCI (odds ratio: 1.60; 95% confidence interval: 1.32-2.58; P = 0.037).ConclusionsBlood viscosity is associated with development of DCI in patients with aSAH. Especially, DBV has a higher predictive value for the occurrence of DCI than SBV. Elevated DBV is a potential predicting factor for the occurrence of DCI.     

Serum biomarkers and cerebral autoregulation as early warnings of delayed cerebral ischemia risk in patients after aneurysmal subarachnoid haemorrhage

BackgroundIdentifying patients at risk of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) remains challenging. This study aimed to evaluate the concentration of serum biomarkers along with cerebral autoregulation impairment on DCI.Methods55 patients suffering from aSAH were enrolled in the study. Serum S100 protein B (S100B) was tested both on the day of admission and over three consecutive days following the occurrence of aSAH. Cerebral autoregulation was assessed using a tissue oxygenation index (TOxa) based on near-infrared spectroscopy.ResultsChanges in serum S100B levels interacted with DCI status (presence vs. absence): F = 3.84, p = 0.016. Patients with DCI had higher S100B concentration level on day 3 than those without DCI (3.54 ± 0.50 ng/ml vs. 0.58 ± 0.43 ng/ml, p = 0.001). S100B concentration on day 3 following aSAH predicted DCI (AUC = 0.77, p = 0.006). Raised level of serum S100B on day 3 was related with higher TOxa, thus with impaired cerebral autoregulation (r_S = 0.52, p = 0.031). Multivariate logistic regression analysis showed that impaired cerebral autoregulation and elevated S100B concentration on day 3 increase the likelihood of DCI.ConclusionsTracking changes in the serum biomarkers concentration along with monitoring of cerebral autoregulation, may play a role in early detection of patients at risk of DCI after aSAH. These results need to be validated in larger prospective cohorts.     

左右侧大面积大脑中动脉供血区梗死继发心电图改变的预后研究

目的探讨左右侧大面积大脑中动脉(MCA)急性梗死继发心电图改变的预后。为临床早期评估及干预提供参考数据。方法选择兰州大学第二医院自2014年12月至2016年3月收治的54例急性MCA大面积脑梗死患者,按梗死部位分为左侧脑梗死组(n=20)和右侧脑梗死组(n=34),分别对两组患者入院时、1月、3月及6月时的美国国立卫生研究院卒中量表(NIHSS)评分、Barthel指数(BI)及改良Rankin(mRS)评分进行比较。结果左侧脑梗死组和右侧脑梗死组在1月内病死率比较,差异无统计学意义(χ~2=1.975,P0.05)。两组患者发病6月时BI评分比较,差异有统计学意义(t=-3.161,P0.05)。两组患者在1月、3月及6月时的NIHSS评分比较,无论是否继发心电图改变,差异均有统计学意义(P0.05)。结论不同侧大面积MCA梗死继发心电图改变的预后可能不同。