Enhanced cisternal drainage and cerebral vasospasm in early aneurysm surgery

Summary Enhanced cisternal drainage was performed following early aneurysm surgery in patients with Hunt and Kosnik grades I–III, to effect continuous wash-out of subarachnoid blood clots and reduce symptomatic vasospasm. Following extensive evacuation of the cisternal blood clots, the Liliequist's membrane was opened extensively and a third ventriculostomy was effected by opening the lamina terminals. The drainage effect was considered as poor, moderate or fair, depending on the average amount of CSF drainage/day. SAH was graded into 0–III depending on the severity of cisternal haematoma in the pre-operative CT. No symptomatic vasospasm occurred in patients with SAH grade I. In SAH grade II +III patients symptomatic vasospasm occurred in 78,60 and 42% of patients with a poor, moderate and fair drainage effect, respectively. Nine patients who developed symptomatic vasospasm were treated by hypertensive/hypervolemic therapy (HHT). The HHT was effective in 7 patients with fair and moderate CSF drainage and ineffective in 2 patients with poor a drainage effect. It seems, that enhanced post-operative cisternal drainage can reduce the incidence of symptomatic vasospasm and be of benefit to the outcome of early aneurysm surgery.     

Effect of cisternal drainage after early operation for ruptured intracranial aneurysms

The effect of postoperative cisternal drainage was assessed in 132 patients who underwent early surgery for ruptured aneurysms. Although the incidence of both cerebral vasospasm and mortality was low in the patients who had cisternal drainage, the incidence of hydrocephalus was significantly higher in these patients. Drainage has been recommended as a useful procedure because it has been shown to improve the prognosis through prophylaxis and relief of vasospasm and removal of bloodcontaminated cerebrospinal fluid. However, the results of this study indicate that extensive cerebrospinal fluid drainage may lead to hydrocephalus, which can be controlled by regulation of the drainage outflow and pressure.     

The effect of very early cisternal irrigation on basilar artery spasm after SAH in the rat model

Summary The authors have investigated the effect of very early irrigation of the cerebrospinal fluid (CSF) space in the haemorrhage rat model of vasospasm. Fifteen rats had basilar cistern irrigation with physiological saline for 3 hours after subarachnoid haemorrhage (SAH), and fifteen control rats had subarachnoid haemorrhage without irrigation of clot.The changes in basilar arteries diameters were determined by angiograms obtained from the rats. The post haemorrhage angiograms showed significant basilar artery spasm in both groups (P0.0005, t-test). However in the last angiogram the basilar artery diameter was found to have the same value measured before subarachnoid haemorrhage in the irrigation group whereas no obvious change was observed in the control group. In the irrigation group the mean diameter of the basilar artery in the last angiogram was 0.412 mm. (0.30 mm to 0.50 mm). None of the animals, treated by cisternal irrigation, showed angiographic vasospasm while the latter group did (P0.0005). Animals treated with physiological saline irrigation had a median clot grade of 0.40 (range grade 0 to 2); control rats had a median grade 2.86 (range grade 1 to 4, P<0.001, Mann-Withney U test), on the brain stem, indicating significant reduction of clot by lavage.In conclusion, performance of experimental physiological saline irrigation at a very early time after subarachnoid haemorrhage prevents the arteriographic and morphological changes of both acute and late vasospasms.     

The role of ventricular and cisternal drainage in the early operation for ruptured intracranial aneurysms

Summary In a series of 177 patients with ruptured supratentorial aneurysms we studied retrospectively the results of early and delayed operation without aggressive removal of subarachnoid blood clots but ventricular and cisternal drainage. The early and delayed groups were comparable demographically and neurologically. The overall results for the early group were a good outcome in 65%, poor outcome in 10% and death in 24%, compared to 53, 20 and 27% respectively in the delayed group. Thus, patients with an early operation and CSF drainage had better results. Permanent ischaemic neurological deficits due to cerebral vasospasm accounted for the poor outcome in 10 and 21% of the patients in the early and delayed groups, respectively and rebleeding accounted for the poor outcome in 5 and 10% in the early and delayed groups respectively.The mean amount of haemoglobin in the cerebrospinal fluid from cisternal drainage was 6.4 g, corresponding to about 40 ml of whole blood, during the 12-day period after SAH. The level was higher in patients with larger subarachnoid clots or with symptomatic vasospasm than in those with smaller clots or without such vasospasm.Early operation combined with ventricular and cisternal drainage is considered to be a useful surgical method for patient with a ruptured aneurysm.     

HLA-type of cerebral vasospasm patients after aneurysmal subarachnoid hemorrhage

We studied human lymphocyte antigen (HLA) types in a group of 45 patients who had aneurysmal subarachnoid hemorrhage (SAH). A significantly increased frequency of HLA antigen A31 and a significantly decreased frequency of HLA antigen B40 were found. In patients with delayed ischemic neurological deficit (DIND) following aneurysmal SAH and HLA typing, HLA-Bw60 antigen showed significant increases; in patients who did not develop HLA-Aw33 and-Cw4 antigens showed significant. Among the patients with Fisher's Group 3 on CT, in particular, these antigens significantly increased when compared with controls from the same geographic area. These results suggest that HLA-Bw60 antigen plays a role as a predisposing factor of DIND resulting from vasospasm following aneurysmal SAH, and that HLA-Aw33 and-Cw4 exert protective influence against DIND.     

Management of cerebral vasospasm

Cerebral vasospasm is delayed narrowing of the large arteries of the circle of Willis occurring 4 to 14 days after aneurysmal subarachnoid hemorrhage (SAH). It is but one cause of delayed deterioration after SAH but, in general, is the most important potentially treatable cause of morbidity and mortality after SAH. Development of vasospasm is best predicted by the volume, location, persistence and density of subarachnoid clot early after SAH. Diagnosis is made by catheter angiography or, with less accuracy, by computed tomographic angiography, transcranial Doppler ultrasound or other methods. Treatment remains problematic because it is expensive, time-consuming, associated with substantial risk and largely ineffective. Treatment includes optimization of factors that affect cerebral blood flow and metabolism, systemic administration of nimodipine, hemodynamic therapy and pharmacologic and mechanical angioplasty.     

The effect of prostacyclin on cerebral vasospasm an experimental study

Summary Prostacyclin (PGI₂), a strong vasodilator of cerebral vessels and potent inhibitor of platelet aggregation, was infused intravenously into seven cats after induction of prolonged vasospasm by hourly application of oxyhaemoglobin solution into the subarachnoid space round the basilar artery. PGI₂, at a concentration of 50 ng/kg/min, was effective in releasing the vasospasm in the seven cats. It did not produce significant hypotension. This report gives our results and the probable mechanism of action of PGI, in cerebral vasospasm.     

辛伐他汀对蛛网膜下腔出血后迟发性脑血管痉挛的影响及作用机制

目的本研究拟观察辛伐他汀对蛛网膜下腔出血后迟发性脑血管痉挛的影响，并探讨其机制。方法随机将新西兰白兔36只均分为假手术组、自发性蛛网膜下腔出血（SAH）组和SAH＋辛伐他汀组（n=12）。假注血组动物行枕大池假穿刺假注血，其他2组受试动物行枕大池穿刺2次注血的方法，制作迟发性脑血管痉挛模型。于0～6d。经口给予SAH＋辛伐他汀组家兔辛伐他汀5mg／kg体重，其他动物给予等量的淀粉。所有受试动物在第1次穿刺后的第7天被处死，比较不同组间基底动脉内径、内径与血管壁厚度之比（D／T）的变化；并应用免疫组织化学、逆转录．聚合酶链反应（RT-PCR）的方法对家兔基底动脉的肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β和IL-6表达进行评价。结果与SAH组比较。SAH＋辛伐他汀组动物血管痉挛明显缓解（P〈0．05）、其血管壁促炎细胞因子TNF-α、IL-1β和IL-6表达显著减少（P〈0．05）。结论经口给予一定量的辛伐他汀（5mg／kg体重）能明显缓解蛛网膜下腔出血后迟发性脑血管痉挛，其作用机制可能与辛伐他汀的抗炎作用有关。     

Correlation between CT findings and subsequent development of cerebral infarction due to vasospasm in subarachnoid haemorrhage

Summary We have studied the correlations between computed tomograms (CT), clinical severity at the time of onset, and subsequent development of cerebral infarction due to vasospasm in 32 cases with subarachnoid haemorrhage secondary to rupture of cerebral aneurysms. It was found that the clinical severity could be judged by CT as shown by the amount of blood in subarachnoid space. Furthermore, it was possible to predict the subsequent occurrence of cerebral infarction by sequential findings of CT. A Hounsfield number of the high density area over 60 showed good correlation with the development of cerebral infarction.     

Severe delayed diffuse cerebral vasospasm and cerebral infarctions following spinal subdural hemorrhage

Background. We report a rare case of severe delayed cerebral vasospasm with cerebral infarctions after spinal subdural hemorrhage.Case report. A 56-year-old woman presented with an acute onset of paraplegia. MR-imaging revealed an extensive intraspinal hemorrhage reaching from T1 to L1. The hematoma was evacuated via a T8-laminectomy. At the 7^th postoperative day the patient developed visual disturbances. MR-scanning revealed extensive infarctions and cerebral angiography showed severe diffuse vasospasms.Interpretation. This case demonstrates that cerebral vasospasm may be caused by a spinal subdural hemorrhage, supporting the hypothesis that cerebral vasospasm may be triggered by factors from a remote site and that a direct contact of blood clots with the vessel is not mandatory.     

Effect of GSH on cerebral vasospasm in dogs

Reduced glutathinone (-glutamylcysteinglycine, GSH) is a scavenger for oxygen radicals and plays in important role in protection of cells from ischemia and from the harmful effects of free oxygen radicals. Free oxygen radicals due to cerebral vasospasm increase in both vasospasm and proliferative vasculopathy. This experiment was performed to determine whether GSH plays a role in cerebral vasospasm after subarachnoid hemorrhage by preventing the harmful effects of free oxygen radicals. In this study, GSH was administered intraarterially and intracisternally following vasospasm of the canine basilar artery. Less vasospasm was observed in the group treated with GSH intraarterially following subarachnoid hemorrhage than in the one treated with GSH intracisternally and in the control group. The arterial wall was investigated ultrastructurally. We evaluated the effect of the anti-oxidating substance through the activity of superoxide dismutase in the arterial wall. We compared the effect of glutathione reductase in the two groups treated with GSH intraarterially and intracisternally. Arterial degeneration was more prominent in the group in which GSH was used intracisternally, while the superoxide dismutase levels were low. In contrast, arterial degeneration was less in the other group in which GSH was used intraaterially, while the superoxide dismutase levels were high.     

Normovolaemic induced hypertension therapy for cerebral vasospasm after subarachnoid haemorrhage

Summary We showed that normovolaemic induced hypertension therapy was effective in reducing ischaemic symptoms attributed to cerebral vasospasm in 41 patients after subarachnoid haemorrhage. By inducing hypertension to 25% to 50% above normal systolic arterial blood pressure, we observed that in 17 of 24 cases (71%) neurological deficits improved. In four cases of haemorrhagic infarction, the blood pressure rose to over 50% of systolic arterial pressure, and a low density area was confirmed on computerized tomography (CT) scan prior to vasospasm. Induced hypertension was therefore not considered when a low density area was revealed on CT scan.Restriction of fluid input is usually a factor in producing hypovolaemia after a neurosurgical operation. Intravascular volume expansion has been reported effective in reversing ischaemic deficits. However, according to Poiseuille's equation, increasing blood volume to a state of hypervolaemia can not enhance flow. The cerebral blood flow (CBF) was raised by increasing perfusion pressure, reducing viscosity, or increasing blood vessel diameter. Intravascular volume expansion elevates not only systemic arterial pressure, but also pulmonary artery wedge pressure over 18 mmHg and cardiac index over 2.2. Since pulmonary oedema and congestive heart failure may develop, one should monitor haemodynamic parameters with the Swan-Ganz catheter as a preventive measure.We emphasize that normovolaemic induced hypertension, maintaining haemodynamics subset 1 of the comparable haemodynamic subsets, is effective in raising perfusion pressure of CBF.     

Evaluation of cerebral vasospasm in patients with subarachnoid hemorrhage using single photon emission computed tomography

Cerebral vasospasm (CVS) occurs as a result of the breakdown in cerebral autoregulation mechanisms. Because cerebral vasospasm can occur after subrachnoid hemorrhage (SAH), it is important to evaluate borderline perfusion. Evaluation of borderline vascular insufficiency is important to reduce ischemic complications. In this study 25 patients with SAH were investigated by somatosensory evoked potentials (SEP), computed tomography (CT), digital subtraction angiography (DSA) and single photon emission computed tomography (SPECT) in order to predict borderline ischemic areas. Clinical grades were also correlated with these investigations. Thirteen patients had symptomatic vasospasm and 15 patients had angiographic vasospasm. SPECT showed hypoperfusion in 22 out of 25 patients. CT predicted CVS in 8 of these 22 patients. Our study shows that brain perfusion SPECT is a non-traumatic, non-invasive, non-allergic, inexpensive method for the prediction of cerebral vasospasm. We conclude that brain SPECT with Tc-99m HM-PAO is an accessible technique that can demonstrate varying degrees of regional tissue hypoperfusion in patients with delayed ischemic deficits due to CVS following SAH.     

去骨瓣减压对外伤性脑血管痉挛状态影响的研究

目的 通过对去骨瓣减压术后患者情况综合研究外伤性脑血管痉挛（CVS）的危险因素. 方法 对本院2010年3月至2011年3月收治的30例幕上急性硬膜外血肿合并外伤性蛛网膜下腔出血的脑疝患者,首先予经颅多普勒超声（TCD）检测,并予脑室穿刺行颅内压动态监测,再行去骨瓣减压术,术后连续7天行TCD及颅内压监测并作相关数据分析. 结果 18例发生CVS（占60％）,脑中线结构钟摆程度≥2cm的CVS发生率显著高于脑中线结构钟摆程度＜2cm;t-SAH积血Hijdra法计算6分以下20例中有9例（45％）、6以上10例中有9例（90％）发生CVS;脑疝至手术处理时间2小时以上3例中有3例（100％）、2小时以下27例中有15例（55.6％）发生CVS;手术进行硬膜下探查19例中有8例（50％）、未探查11例中有10例（90.9％）发生CVS;年龄＞50岁18例中有6例（33.3％）、＜50岁12例（40％）中有12例（100％）发生CVS. 结论 经血肿清除及去骨瓣减压术后的患者所发生的脑血管痉挛情况与患者术前术后脑中线结构钟摆程度、蛛网膜下腔出血量、脑疝至手术处理时间的长短、是否进行硬膜下探查、年龄等情况有关.     

动脉瘤性蛛网膜下腔出血后脑血管痉挛的低温治疗

脑血管痉挛(cerebral vasospasm,CVS)是导致动脉瘤性蛛网膜下腔出血(aneurysm subarachnoid hemorrhage,aSAH)患者死亡和残疾的主要原因之一.人们对SAH后CVS进行了广泛的研究,认为红细胞分解产物、血管内皮功能障碍以及分子机制在其发病起关键作用.目前对脑血管痉挛的治疗尚无确切治疗方法,近年来人们尝试应用低温治疗脑血管痉挛,现就SAH后CVS的病理生理机制和低温对于CVS的治疗进展作一综述.     

Cerebral vasospasm in elderly patients treated by early operation for ruptured intracranial aneurysms

Summary Cerebral vasospasm in elderly patients was studied under strict criteria. A total of 145 patients, who had been operated on in the acute stage after subarachnoid haemorrhage, were classified into two age groups. Those aged 59 years or younger were in group 1 (76 cases, 52%), and those aged 60 years or older were in group 2 (69 cases, 48%). The severities of both the subarachnoid haemorrhage on computed tomography scan and the angiographic vasospasm were graded from 0 to IV. Close correlations were found in both groups for the angiographic vasospasm grades to the incidences of both symptomatic vasospasm and low-density areas on computed tomography scan. Angiographic vasospasm was observed in 95% of group 1 and in 91% of group 2 patients. The incidences of permanent symptomatic vasospasm were 14% in group 1 and 19% in group 2. Low-density areas on computed tomography occurred in 16% of group 1 and in 17% of group 2. Generally, the higher the clinical grades and/or the higher the subarachnoid haemorrhage grades, the more severe were the vasospasms. These tendencies were more apparent in subarachnoid haemorrhage grading. The mortality rates were 8% in group 1 and 17% in group 2. However, when both the clinical grades and the subarachnoid haemorrhage grades were analyzed, there were no significant differences between groups 1 and 2 in either the severity of vasospasm or in the outcome.It must be concluded that neither the angiographic vasospasm grades nor the incidence of symptomatic vasospasm are significantly effected by age.     

蛛网膜下腔出血后脑血管痉挛的研究进展

脑血管痉挛(cerebral vasospasm,CVS)是蛛网膜下腔出血(subaraachnoid hemorrhage,SAH)后一种常见的灾难性的并发症,其所致迟发性缺血性神经功能损害是造成患者致残和死亡的最主要原因.虽经多年研究,但其发病机制至今尚未完全阐明.一氧化氮、内皮素-1、血红蛋白氧化产物及炎症反应均被认为参与致病过程.针对这些发病机制的治疗措施目前仍处于研究阶段,预期会在今后的脑血管痉挛的防治中发挥重要作用.     

诱导型一氧化氮合成酶在迟发性血管痉挛中的作用

目的　以大鼠迟发性脑血管痉挛模型为基础研究诱导型一氧化氮合成酶 (iNOS)在迟发性血管痉挛发展中的作用。方法　 3 2只雄性SD大鼠随机分为实验组和对照组 ,实验组枕大池二次注血诱导迟发性脑血管痉挛 ,对照组枕大池注射生理盐水。第 8天行脑血管造影 ,枕大池抽取脑脊液测一氧化氮 (NO)浓度。逆转录 聚合酶链反应 (RT PCR )法和免疫组织化学法测定并评价iNOSmRNA和蛋白质在基底动脉、大脑中动脉和皮质中的表达。结果　颅内动脉血管减影提示对照组颈内动脉颅内段、大脑中动脉 (MCA)明显变细 ,大脑中动脉中段直径 (MD)与镫骨动脉中段直径 (SD)之比衡量大脑中动脉的管径显示实验组MCA管径较对照组MCA管径减少 3 0 %。对照组脑脊液中NO浓度为 (11.70± 2 .62 ) μmol/L ,实验组脑脊液中NO的浓度为(5 5 .67± 12 .84)μmol/L。iNOSmRNA和蛋白质表达于基底动脉、大脑中动脉和皮质 ,其中基底动脉表达最强。 结论　iNOS作为迟发性脑血管痉挛发展中的关键因素参与血管壁的迟发性损伤。     

Relation of cerebral vasospasm to operative findings of subarachnoid blood around ruptured aneurysms

Summary An investigation was carried out in 28 patients in order to evaluate the relationship between angiographically documented vasospasm, amount of subarachnoid blood found at surgery around ruptured intracranial aneurysms, and delayed ischaemic deficits. Angiography was performed at time intervals ranging between 5 and 17 days, and surgery not later than 21 days following subarachnoid haemorrhage. The absence of subarachnoid clots was associated in ten patients, with no or minor vasospasm and no or mild neurological deficits. Thin clots were found in eight patients; one of them had no vasospasm, six had minor vasospasm, and one showed severe vessel narrowing. Major clinical signs were absent in these cases. All ten patients with thick clots developed severe vasospasm, and eight of them severe neurological signs.The important aetiological role of local subarachnoid clots in determining vasospasm is emphasized in view of surgical timing.     

经椎动脉内持续注射盐酸法舒地尔治疗脑血管痉挛

目的 在活体动物模型中持续椎动脉内注射盐酸法舒地尔,观察其在不同时间点对蛛网膜下腔出血(SAH)引起的迟发性脑血管痉挛(CVS)的防治作用,并和静脉内给药对比.方法 将日本大耳白兔随机分为椎动脉7 d给药组、椎动脉5 d给药组、静脉给药组及对照组.枕大池2次注血法建立蛛网膜下腔出血模型,椎动脉给药组经微量注射泵分别于不同时间点开始给予盐酸法舒地尔或5%葡萄糖溶液,静脉给药组经耳缘静脉滴注盐酸法舒地尔,注血前及第5、7天各组均行脑血管造影及血管彩色超声检查,测算基底动脉内径变化的比例和血流峰值速度的变化.7 d时处死兔取基底动脉,行光镜、电镜检查,观察其病理改变.结果　动、静脉给药各组均对蛛网膜下腔出血引起的基底动脉痉挛有显著保护作用.在第5天,静脉给药组与椎动脉5 d给药组的保护作用差异无统计学意义(15.43±4.82)%比(10.37±6.92)%,但与椎动脉7 d给药组差异有统计学意义(2.02±6.21)%;在第7天,椎动脉5 d组与7 d组的保护作用差异无统计学意义(2.60±6.42)%比(0.44±5.12)%,但与静脉给药组差异有统计学意义(8.40±4.28)%.同时用血管彩色超声对各组基底动脉峰值流速进行监测,并行光镜、电镜等病理检查,也支持上述结果　.结论　脑血管痉挛动物模型中椎动脉内持续注射盐酸法舒地尔对蛛网膜下腔出血引起的脑血管痉挛的保护作用优于静脉内给药.

Abstract：

Objective To investigate and compare the effects of continuous intravertebral artery (CIV) injection of fasudil hydrochloride with intravenous injection of fasudil hydrochloride as well as control agents in treating delayed cerebral vasospasm ( CVS ) following subarachnoid hemorrhage (SAH).Methods Forty healthy Japanese white rabbits were selected and randomly divided into 4 groups: 7-day (continual CIV injection of fasudil hydrochloride after the first injection of blood for 7 days), 5-day (CIV injection of fasudil hydrochloride for 5 days on the 3rd day after the first injection), intravenous treatment (iv), and controls. There were 28 rabbits that underwent 84 cerebral angiographies. The basal artery was obtained, and its pathological changes were observed under the light and electron microscopies. Results Severe CVS occurred in the control group on the 5th and 7th day. CVS due to SAH was significantly alleviated after intravertebral artery and intravenous injection. The difference between the intravenous and intravertebral artery groups was significant on the 7th day but not on the 5th day. There was no significant difference in the preventive effect between the 5-day and 7-day groups, but this effect differed from the iv group, which was supported by the pathological examinations. Conclusion The effect of CIV injection of fasudil hydrochloride in treating delayed CVS due to SAH at different time points was better than intravenous administration.