经颅多普勒超声检查对蛛网膜下腔出血后脑血管痉挛的诊断价值

目的探讨经颅多普勒超声(TCD)检查对蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)的诊断价值。方法应用TCD对30例SAH患者脑血流状况进行动态监测,并结合临床表现、头颅影像学资料进行分析。结果经TCD证实,本组17例(56.7%)发生CVS,其中10例无症状,7例出现CVS症状。头颅CTFisher分级中,Ⅲ、Ⅳ级SAH患者中CVS的发生率明显高于Ⅰ、Ⅱ级(均P<0.05)。结论TCD监测是早期发现SAH后CVS的一种敏感的检查手段。     

Cerebral vasospasm following aneurysmal subarachnoid hemorrhage

Cerebral vasospasm following aneurysmal subarachnoid hemorrhage is one of the most important causes of cerebral ischemia, and is the leading cause of death and disability after aneurysm rupture. There are two definitions of cerebral vasospasm: angiographic and clinical. Care must be exercised to be certain that it is clear which entity is being addressed. The diagnosis of the clinical syndrome is one of exclusion and can rarely be made with absolute certainty. The pathogenesis of cerebral vasospasm is poorly understood. Most current theories focus on the release of factors from the subarachnoid clot. More attention must be given to the role of endothelial damage and alterations in the blood-arterial wall barrier. The application of modern techniques for studying vascular smooth muscle which have been developed as a result of research in the areas of hypertension and atherosclerosis must be applied to the problem of cerebral vasospasm. A stress test to select patients with angiographic arterial narrowing who have adequate cerebral vascular reserve to undergo surgery should be developed. The optimal treatment of vasospasm awaits development of agents for blocking or inactivating spasmogenic substances or blocking arterial smooth muscle contraction. Rheological or hemodynamic manipulations to prevent or reverse ischemic consequences of vasospasm are relatively effective, but complicated and hazardous, and should be viewed principally as interim measures awaiting development of more specific therapies for the arterial narrowing.     

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。     

Mechanism of cerebral vasospasm following subarachnoid hemorrhage in monkeys.

This paper reviews our recent studies on the mechanism of cerebral vasospasm following subarachnoid hemorrhage (SAH) in monkeys. Middle cerebral artery (MCA) vasospasm was maximal at 7 days, resolving by 14 days, and absent at 28 days after SAH. Arterial fibrosis was not detected during vasospasm, although there was intimal hyperplasia with fibrosis 28 days after SAH. On scanning electron microscopy, smooth muscle cells from vasospastic arteries had corrugated cell membranes and appeared similar to cells contracted pharmacologically, suggesting that vasospastic smooth muscle is contracted. Morphometric analysis of arteries obtained 7 days after SAH showed no significant increases in arterial wall area of vasospastic arteries compared with normal MCAs. The results suggest vasospasm in monkeys is not due to hypertrophy, hyperplasia, or fibrosis in the arterial wall. Vasospasm may be mainly vascular smooth muscle contraction, which damages the arterial wall, leading to secondary structural changes in the arterial wall which occur after angiographic vasospasm.     

Prediction of symptomatic vasospasm after subarachnoid hemorrhage by rapidly increasing transcranial Doppler velocity and cerebral blood flow changes.

BACKGROUND AND PURPOSE: Increased transcranial Doppler velocities and regional cerebral perfusion defects have been well demonstrated in patients with subarachnoid hemorrhage, but the clinical significance of these changes has not been clearly defined, particularly in the presymptomatic stage of cerebral vasospasm. We have tested the hypothesis that a rapid, massive rise in Doppler velocity denotes progressive vasospasm by relating Doppler velocity increases to regional cerebral blood flow changes and to the subsequent clinical course. METHODS: Serial transcranial Doppler sonography was performed in 121 patients; 20 of these patients were selected for blood flow mapping on the basis of rapid increases (greater than 50 cm/sec/24 hr) in blood flow velocity. Cerebral blood flow was mapped by single-photon emission computed tomography using technetium-99m hexamethylpropyleneamine oxime. RESULTS: Ten of 15 patients studied before the onset of any deficit subsequently developed a focal neurological abnormality. In 14 of these 15 patients, and in a further five in which single-photon emission computed tomography was performed after the onset of a delayed neurological deficit, perfusion patterns were abnormal and correlated with sites of increased Doppler velocities. Four patients had zones of cerebral hypoperfusion but did not develop neurological deficit. CONCLUSIONS: Transcranial Doppler measurements can assist in identifying patients at risk of delayed ischemic deficit. Selection of patients for regional cerebral blood flow mapping studies and for prophylactic anti-ischemic therapy may be considered on this basis.     

蛛网膜下腔出血后脑血管痉挛的防治研究进展

蛛网膜下腔出血（SAH）后并发的脑血管痉挛（CVS）一直是临床较为棘手的问题,易引起继发性脑缺血,严重影响患者的预后。目前临床治疗SAH后CVS多以药物治疗为主,且取得一定的疗效。本文结合以往文献,就目前CVS的临床防治进行综述。     

蛛网膜下腔出血后迟发性脑血管痉挛与五羟色胺的关系

通过荧光分光方法测定了蛛网膜下腔出血(SAH)后迟发性脑血管痉挛(DCVS)时的病人及实验动物血清与脑脊液(CSF)中5—HT的含量。实验结果显示DCVS时病人及实验动物CSF中5—HT的含量处于很低水平,并且实验动物CSF中5—HT的含量在SAH后的第七天比出血后的第三天还要低。DCVS病人血清中5—HT含量也较正常对照组明显降低。本研究结果提示5—HT与DCVS的发生无明显关系。     

Doppler ultrasonography screening of poor-grade subarachnoid hemorrhage patients increases the diagnosis of deep venous thrombosis

Abstract

Background: Prophylactic anticoagulation greatly decreases the prevalence of deep venous thrombosis (DVT) in neurosurgical patients. Using Doppler ultrasonography (USG), recent studies demonstrate a 1% DVT detection rate following microsurgery or endovascular treatment for aneurysmal subarachnoid hemorrhage (aSAH). We hypothesize that reported statistics underestimate the DVT detection rate in this high risk cohort by accounting for only symptomatic thromboses. This study utilizes Doppler USG to examine the prevalence of DVT in a large population of aSAH patients and attempts to identify a high-risk subgroup within this cohort.

Methods: We retrospectively examined 178 aSAH patients who underwent screening lower extremity Dopplers (LEDs) and 57 who did not undergo screening LEDs. All received pharmacologic and mechanical DVT prophylaxis. We analysed DVT prevalence within these two groups and compared rates to the literature. We then segregated patients according to Hunt–Hess grade and determined DVT prevalence within subgroups.

Results: Patients who underwent LED screening demonstrated a 3.4% (6/178) DVT rate, compared to 0% (0/57) in the unscreened cohort. Our screening protocol yielded a thrombosis rate almost triple that reported in the literature (3.4% versus 1.2%). A significantly greater (p<0.05) percentage of screened Hunt–Hess III–V patients (6.5%, 6/93) had positive LEDs compared to Hunt–Hess I–II patients (0%, 0/85).

Conclusion: These data suggest that while pharmacologic prophylaxis lowers the prevalence of symptomatic DVTs in aSAH patients, the number of asymptomatic DVTs remains significant, particularly in patients with formidable neurological deficits. While a formal cost-effective analysis is warranted, our data suggest that screening high-risk patients may increase the diagnosis of asymptomatic DVTs and potentially prevent serious medical complications.     

Effect of melatonin on cerebral vasospasm following experimental subarachnoid hemorrhage

OBJECT: The current study was undertaken to determine whether melatonin therapy reverses vasospasm and prevents apoptosis by inhibiting lipid peroxidation in an experimental subarachnoid hemorrhage (SAH) model. MATERIALS AND METHODS: The rabbits were divided into four groups as follows: Group 1, SAH + melatonin (5 mg/kg/i.p. BID) simultaneously with SAH (n = 6); Group 2, SAH + melatonin (5 mg/kg/i.p. BID) treated 2 hours after SAH (n = 6); Group 3, control group (n = 4); Group 4, SAH only (n = 6). Light microscopic examinations of the basilar arteries were performed to demonstrate the pathophysiological changes of the arterial wall with hematoxylin- eosin. Apoptosis: Immunohistology using the ApopTag Peroxidase In Situ Apoptosis Detection Kit was used to demonstrate apoptosis in a cross section of basilary arteries. Apoptotic index was calculated as the number of the immunoreactive nuclei per total number of endothelial cells, and expressed as a percentage. RESULTS: The results of measurements of diameters of the vessels between groups were significantly different (p = 0.028). While basilar arteries of the SAH only group showed 57% constriction, Groups 1 and 2 were calculated as 33 and 26% constriction, respectively, compared with the control group (p < 0.05). And also Groups 1 and 2 showed significant protection of apoptosis compared with Group 4. The difference between the four groups was tested by Kruskal-Wallis test and the significance between the two groups was tested by Mann- Whitney U-test. CONCLUSION: Melatonin with its strong antioxidant effect can prevent SAH-induced vasospasm and apoptosis of endothelial cells of vessels.     

Jugular bulb oximetry for prediction of vasospasm following subarachnoid hemorrhage

BACKGROUND: Cerebral vasospasm adversely impacts the outcome of those suffering aneurysmal subarachnoid hemorrhage (SAH). Prediction of vasospasm could improve outcomes. We hypothesized that preclinical vasospasm would be heralded by an increase in cerebral oxygen extractions (AVDO2) which could be detected by jugular bulb oximetry. A pilot study was conducted to address this hypothesis. METHODS: Fourteen consenting patients with aneurysmal SAH, undergoing early surgery, were entered into the study. Four patients were withdrawn from the study secondary to failure of catheters or religious belief. At the time of craniotomy, a jugular bulb catheter was placed. Post-operatively, arterial and jugular bulb blood samples were taken every 12 hours to calculate AVDO2. As this was an observational study, no change in management occurred based on measurements. RESULTS: Four of 10 patients had clinical vasospasm. These patients had a significant rise in AVDO2 approximately one day prior to the onset of neurologic deficits (P<0.001). Symptoms resolved along with a significant improvement in AVDO2 on instituting hypertensive, hemo-dilutional, and hypervolemic therapy in these patients. The six patients who did not exhibit clinical vasospasm did not demonstrate significant rise in AVDO2. CONCLUSIONS: Jugular bulb oximetry is simple and cost effective. Increases in AVDO2 using this technique were predictive of clinically evident vasospasm in the subsequent hours to days. This investigation supports a larger study to assess the utility of jugular bulb oximetry in predicting vasospasm in aneurysmal SAH.     

兔症状性脑血管痉挛模型的改进

目的完善单侧兔颈总动脉结扎后枕大池二次注血法致症状性脑血管痉挛（CVS）动物模型的血管形态学研究。方法实验兔随机分为单侧颈总动脉结扎后枕大池二次注血组（S-SAH组）与单纯枕大池二次注血组（SAH组）,每组各10只。比较两组神经功能改变,并分别于注血前、注血后（d1,d5）行基底动脉脑血管造影。结果各组均出现神经功能障碍,两组d5发生CVS数量与注血前比较均有显著性差异（P〈0.05）;各组同时间段CVS程度无显著差异（P〉0.05）。结论单侧兔颈总动脉结扎后枕大池二次注血法制作CVS动物模型方法可行,模型稳定,改良制作方法有助于提高成功率。     

蛛网膜下腔出血后迟发性脑血管痉挛的临床研究

为了探讨蛛网膜下腔出血（ＳＡＨ）后迟发性脑血管痉挛（ＤＣＶＳ）的临床规律，本文对６１例ＳＡＨ住院病人的脑动脉造影（ＣＡＧ）、ＣＴ及临床资料进行了回顾研究，结果如下：１、ＳＡＨ并ＤＣＶＳ的主要病因为颅内动脉瘤破裂，ＤＣＶＳ发生与颅内动脉瘤所在的部位及大小无明显关系．ＤＣＶＳ时轻度痉挛略多于重度痉挛．２、ＣＴ见基底池存在明显的高密度影时，能预示ＤＣＶＳ的发生。３、ＤＣＶＳ常与脑内血肿、脑室出血、脑积水或脑梗塞同时存在。４、ＳＡＨ再发出血，尤其是近期再发出血，可能产生或加重ＤＣＶＳ．５、ＤＣＶＳ的发生及程度与临床病情严重程度有关，ＤＣＶＳ的程度越重，临床病情也越重。６、ＤＣＶＳ的主要体征为意识障碍，近半数的病人有神经示位体征。     

中药川芎嗪对蛛网膜下腔出血后脑血管痉挛的实验研究

目的观察川芎嗪（TMP）对蛛网膜下腔出血后脑血管痉挛（CVS）的治疗效果。方法制备能够连续造影的兔CVS动物模型，将其随机分为TMP组、尼莫地平组和对照组，每组13只，各组分别注入TMP 60mg／kg、尼莫地平0．1mg／kg及等量生理盐水，观察各组动物的神经功能状态变化，并应用脑血管造影、经颅多普勒（TCD）及电镜技术，了解药物对急、慢性CVS的治疗效果。结果CVS急性期静脉注射TMP、尼莫地平30min后，基底动脉口径分别由（57．17±11．40）％、（58．0±10．90）％扩大到（80.16±14.22）％、（90．0±11.38）％（均P〈0．01）。在CVS慢性期，动脉口径扩张不明显（P〉0．05），但TCD检测基底动脉的平均血流速度则分别由（57.92±10．54）cm／s、（61.61±11.49）cm／s下降到（36．58±10.39）cm／s、（33.67±7.57）cm／s（均P〈0.01）；形态学研究显示：对照组基底动脉内皮细胞、平滑肌细胞及神经细胞的损害程度明显重于实验组。结论①TMP能够缓解CVS，明显改善CVS后的神经系统功能损害症状。②TMP与尼莫地平对CVS同样具有良好的治疗效果，但TMP60mg／kg对脑组织、血管组织的保护作用优于尼莫地平0.1mg／kg。     

蛛网膜下腔出血性脑血管痉挛动物模型的制作

蛛网膜下腔出血引起的脑血管痉挛是导致蛛网膜下腔出血患者不良预后的主要原因之一,其发生机制至今尚未完全明了。因此,建立一种理想的蛛网膜下腔出血性脑血管痉挛动物模型将对脑血管痉挛发生机制及临床防治的研究起到巨大的推动作用。文章介绍了各种蛛网膜下腔出血性脑血管痉挛动物模型的制作方法、优缺点及应用范围,但目前尚无一种用于研究蛛网膜下腔出血后症状性脑血管痉挛的理想模型。     

盐酸法舒地尔对蛛网膜下腔出血后血管痉挛的实验研究

目的通过建立大鼠蛛网膜下腔出血（SAH）模型,探讨盐酸法舒地尔对蛛网膜下腔出血后血管痉挛的缓解作用和神经保护作用,并与尼莫地平对比,观察疗效。方法通过枕大池二次注血法建立大鼠SAH模型,观察基底动脉和海马神经元形态变化,测量基底动脉管径和管壁厚度,计算海马CA1区神经元密度,检测基底动脉内皮型一氧化氮合成酶（eNOS）的表达。结果各组模型大鼠的基底动脉均出现血管痉挛,海马CA1区正常神经元数目明显减少,多数神经元发生变性,基底动脉的eNOS表达明显减弱。但注射法舒地尔组与其他模型组相比能较大程度的缓解以上变化,具有统计学差异（P〈0.05）,且优于尼莫地平。结论法舒地尔可以有效缓解SAH后的迟发性脑血管痉挛,具有神经保护作用,其缓解迟发性脑血管痉挛作用和神经保护作用与动脉壁产生的一氧化氮（NO）有关。     

Role of single photon emission computed tomography and transcranial Doppler ultrasonography in clinical vasospasm.

This report presents our experience with Transcranial Doppler (TCD) ultrasonography and Single Photon Emission Computed Tomography (SPECT) in the assessment of patients with aneurysmal subarachnoid haemorrhage (SAH). It was designed to evaluate clinical vasospasm with both TCD and SPECT and determine their diagnostic value. Twenty-eight consecutive patients were examined with both TCD and SPECT, performed within 24 hours of each other. They had a total of 45 TCDs and 46 SPECT scans. Eight patients (29%) developed clinical vasospasm, noted from day 2 to day 11 post subarachnoid haemorrhage; these patients underwent TCDs and SPECT scans when the diagnosis of vasospasm was made. Twenty patients (71%) did not demonstrate clinical vasospasm throughout their hospital stay and underwent TCDs and SPECT scans within the first 2 weeks of their SAH, mostly between day 2 and day 10, the period of greatest risk for vasospasm. TCD and SPECT sensitivity for clinical vasospasm was 100% and 50% respectively, their specificity was only 20% and 60%. TCD sensitivity for symptomatic vasospasm was found to be excellent, whereas SPECT was not found to be as useful. We conclude that TCD is the preferred method in the evaluation of patients with subarachnoid haemorrhage.     

Effect of vardenafil on cerebral vasospasm following experimental subarachnoid hemorrhage in rats

We examined the effects of the phosphodiesterase 5 (PDE-5) inhibitor vardenafil on cerebral vasospasm in an experimental rat subarachnoid hemorrhage (SAH) model. Thirty-two albino Wistar rats were divided into five groups: G1, no experimental intervention; G2, administered subarachnoid physiological saline after sham surgery; G3, subjected to SAH; G4, subjected to SAH and administered low-dose (0.5 mg/kg) vardenafil treatment; and G5, subjected to SAH and administered high-dose (5 mg/kg) vardenafil treatment. For animals in G3, G4 and G5, SAH was induced by an injection of autologous non-heparinized blood into the cisterna magna. Immediately after SAH, for animals in G4 and G5, vardenafil was administered by gavage at intervals of 8 hours for 2 days. The rats were then decapitated, and basilar arteries and blood samples were taken for biochemical and histopathological examination. Malonyldialdehyde values in G2 (p = 0.004) and G3 (p = 0.002) were significantly higher than those in G1. G4 and G5 had significantly lower values than G2 and G3 (p = 0.014, G4 v. G2; p = 0.005, G4 v. G3; p = 0.005, G5 v. G2; p = 0.002, G5 v. G3). Total antioxidant capacity (TAC) values in G3 were significantly lower than those in G1 (p = 0.041). TAC values in G4 and G5 were significantly higher than those in G3 (p = 0.043). Mean luminal diameter in G3 was significantly smaller compared with G1 and G2 (p = 0.002), but larger in G4 (p = 0.002) and G5 (p = 0.001) compared with G3. Mean luminal diameter was also significantly larger in G5 than in G2 (p = 0.008) and G4 (p = 0.038). Mean wall thickness in G2 (p = 0.015) and G3 (p = 0.002) was significantly thicker compared with G1. Wall thickness was significantly thinner in G4 and G5 compared with G2 and G3 (p = 0.008, G4 v. G2; p = 0.001, G4 v. G3; p = 0.005, G5 v. G2; p = 0.001, G5 v. G3). Our results confirm that vardenafil may induce vasodilatation and provide potential benefits in SAH therapy by preventing vasospasm.