Intravenous Magnesium Infusion for the Prevention of Symptomatic Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage

Objective

The study examined the difference in the incidence of symptomatic cerebral vasospasm with magnesium supplementation in aneurysmal subarachnoid hemorrhage (SAH) in a Korean population.

Methods

This retrospective analysis was performed in 157 patients diagnosed with aneurysmal SAH from January 2007 to December 2011 at a single center. Seventy patients (44.6%) received a combination treatment of nimodipine with magnesium and 87 patients (55.4%) received only nimodipine. A matched case-control study using propensity scores was conducted and 41 subjects were selected from each group. A dosage of 64 mmol/day of magnesium was administrated.

Results

The infusion of magnesium did not reduce the incidence of symptomatic cerebral vasospasm (n=7, 17.1%, p=0.29) compared with simple nimodipine injection (n=11, 26.8%). The ratios of good clinical outcome (modified Rankin scale 0-2) at 6 months were similar, being 78% in the combination treatment group and 80.5% in the nimodipine only group (p=0.79). The proportions of delayed cerebral infarction was not significantly lower in patients with combination treatment (n=2, 4.9% vs. n=3, 7.3%; p=0.64). There was no difference in the serum magnesium concentrations between the patients with symptomatic vasospasm and without vasospasm who had magnesium supplementation. No major complications associated with intravenous magnesium infusion were observed.

Conclusion

Magnesium supplementation (64 mmol/day) may not be beneficial for the reduction of the incidence of symptomatic cerebral vasospasm in patients with aneurysmal SAH.     

动脉瘤性SAH迟发性脑血管痉挛的多元因素分析

目的 探讨动脉瘤性蛛网膜下腔出血（SAH）继发脑血管痉挛的相关因素。方法 回顾性分析本院收治的54例动脉瘤性SAH病人的临床资料，判定脑血管痉挛程度，统计分析其相关因素。结果Fisher分级Ⅲ-Ⅳ级患者脑血管痉挛发生率（7014％，19／27）明显高于Fisher分级Ⅰ-Ⅱ级者（4414％，12／27）（P〈0．01）；Hunt—Hess分级Ⅲ-Ⅴ级患者脑血管痉挛发生率（75．0％，21／28）明显高于Hunt—Hess分级Ⅰ-Ⅱ级者（38．5％，10／26）（P〈0．05）；3d后手术患者的脑血管痉挛发生率（70．0％，21／30）明显高于3d内手术患者（41．7％，10／24）（P〈0．05）。结论SAH的Fisher分级〉Ⅱ级和Hunt—Hess分级〉Ⅱ级是颅内动脉瘤继发脑血管痉挛的危险因素。早期手术能降低脑血管痉挛的发生率。     

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。     

Significance of C-Reactive Protein and Transcranial Doppler in Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage

Objective

Cerebral vasospasm is a common and potentially devastating complication of aneurysmal subarachnoid hemorrhage (aSAH). Inflammatory processes seem to play a major role in the pathogenesis of vasospasm. C-reactive protein (CRP) constitutes a highly sensitive inflammatory marker. Elevation of serum CRP levels has been demonstrated in patients with aSAH. The purpose of the current study was to evaluate the possible relationship between CRP levels in the serum and transcranial Doppler (TCD) and the development of vasospasm in patients with aSAH.

Methods

A total of 61 adult patients in whom aSAH was diagnosed were included in the study from November 2008 to May 2011. The patients'' demographics, Hunt and Hess grade, Fisher grade, CT scans, digital subtraction angiography studies, and daily neurological examinations were recorded. Serial serum CRP measurements were obtained on days 1, 3, 5, 7, 9, 11 and 13 and TCD was measured on days 3, 5, 7, 9, 11 and 13. All patients underwent either surgical or endovascular treatment within 24 hours of their hemorrhagic attacks.

Results

Serum CRP levels peaked on the 3rd postoperative day. There were significant differences between the vasospasm group and the non-vasospasm group on the 1st, 3rd and 5th day. There were significant differences between the vasospasm group and the non-vasospasm group on the 3rd day in the mean middle cerebral artery velocities on TCD.

Conclusion

Patients with high levels of CRP on the 1st postoperative day and high velocity of mean TCD on the 3rd postoperative day may require closer observation to monitor for the development of vasospasm.     

蛛网膜下腔出血后迟发性脑血管痉挛的发病机制和治疗进展

脑血管痉挛（cerebral vasospasm,CVS）是蛛网膜下腔出血（subarochnoid hemorrhage,SAH）最 严重的并发症,尤其是迟发性脑血管痉挛（delayed cerebral vasospasm,DCV）,一旦发生可能会出现 脑缺血甚至死亡等严重并发症。目前其发病机制尚不明确,多种因素如红细胞分解产物、一氧化氮 （nitric oxide,NO）、内皮素、自由基和脂质过氧化物等均是导致DCV的重要因素,而对于治疗DCV的方 法也在持续探索中,SAH后DCV仍是目前面临的一大难题。本文主要对SAH后CVS的发病机制及治疗进 展进行综述。     

蛛网膜下腔出血患者继发症状性脑血管痉挛的相关危险因素分析

目的 研究探讨动脉瘤性蛛网膜下腔出血（subarachnoid hemorrhage,SAH）继发症状性脑血管痉挛 （symptomatic cerebral vasospasm,SCVS）的相关危险因素,为SCVS的防治提供参考。 方法 回顾性分析96例SAH患者临床资料,对性别、年龄、高血压史、糖尿病史、Fisher分级等影响因 素进行统计学分析。 结果 96例患者中发生SCVS的患者共39例,单因素分析结果显示SCVS组与非SCVS组在年龄、高血 压、吸烟、脑室内积血、Hunt-Hess分级、Fisher分级、数字减影血管造影（digital subtraction angiography, DSA）显示血管痉挛程度、尼莫地平使用等方面差异有显著性;多因素Logistic回归分析结果显示：低 龄、高血压史、Fisher分级是发生SCVS的危险因素,其比值比（odds ratio,OR）分别为0.567、1.982和 2.713;而尼莫地平的使用是SCVS发生的保护因素,OR为0.799。 结论 SAH后SCVS是多种因素共同作用的结果,其中低年龄、高血压史、Fisher分级是SCVS的独立危 险因素,尼莫地平使用为保护因素。     

Intraarterial Nimodipine Infusion to Treat Symptomatic Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage

Objective

Cerebral vasospasm leading to cerebral ischemic infarction is a major cause of morbidity and mortality in the patients who suffer with aneurysmal subarachnoid hemorrhage. Despite adequate treatment, some patients deteriorate and they develop symptomatic vasospasm. The objective of the present study was to investigate the efficacy and clinical outcome of intraarterial nimodipine infusion on symptomatic vasospasm that is refractory to hemodynamic therapy.

Methods

We retrospectively reviewed the procedure reports, the clinical charts and the transcranial doppler, computed tomography and digital subtraction angiography results for the patients who underwent endovascular treatment for symptomatic cerebral vasospasm due to aneurysmal SAH. During the 36 months between Jan. 2005 and Dec. 2007, 19 patients were identified who had undergone a total of 53 procedures. We assessed the difference in the arterial vessel diameter, the blood flow velocity and the clinical outcome before and after these procedures.

Results

Vascular dilatation was observed in 42 of 53 procedures. The velocities of the affected vessels before and after procedures were available in 33 of 53 procedures. Twenty-nine procedures exhibited a mean decrease of 84.1 cm/s. We observed clinical improvement and an improved level of consciousness with an improved GCS score after 23 procedures.

Conclusion

Based on our results, the use of intraarterial nimodipine is effective and safe in selected cases of vasospasm following aneurysmal SAH. Prospective, randomized studies are needed to confirm these results.     

The Effectiveness of Lumbar Cerebrospinal Fluid Drainage to Reduce the Cerebral Vasospasm after Surgical Clipping for Aneurysmal Subarachnoid Hemorrhage

ObjectiveRemoval of blood from subarachnoid space with a lumbar drainage (LD) may decrease development of cerebral vasospasm. We evaluated the effectiveness of a LD for a clinical vasospasm and outcomes after clipping of aneurysmal subarachnoid hemorrhage (SAH).MethodsBetween July 2008 and July 2013, 234 patients were included in this study. The LD group consisted of 126 patients, 108 patients in the non LD group. We investigated outcomes as follow : 1) clinical vasospasm, 2) angioplasty, 3) cerebral infarction, 4) Glasgow outcome scale (GOS) score at discharge, 5) GOS score at 6-month follow-up, and 6) mortality.ResultsClinical vasospasm occurred in 19% of the LD group and 42% of the non LD group (p<0.001). Angioplasty was performed in 17% of the LD group and 38% of the non LD group (p=0.001). Cerebral infarctions were detected in 29% and 54% of each group respectively (p<0.001). The proportion of GOS score 5 at 6 month follow-up in the LD group was 69%, and it was 58% in the non LD group (p=0.001). Mortality rate showed 5% and 10% in each group respectively. But, there was no difference in shunt between the two groups.ConclusionLD after aneurysmal SAH shows marked reduction of clinical vasospasm and need for angioplasty. With this technique we have shown favorable GOS score at 6 month follow-up.     

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。     

蛛网膜下腔出血后脑血管痉挛与脑脊液免疫球蛋白的关系

检测４１例蛛网膜下腔出血病人脑脊液中免疫球蛋白Ｇ的含量，其中２２例为蛛网膜下腔出血后伴脑血管痉挛患者，其脑脊液中免疫球蛋白Ｇ含量为８３．０４±３１．７８ｍｇ／Ｌ，１９例不伴脑血管痉挛病人，脑脊液中免疫球蛋白Ｇ含最为：３０．７９±２２．１３ｍｇ／Ｌ；脑血管痉挛组脑脊液中免疫球蛋白Ｇ含量明显高于非脑血管痉挛组（Ｐ＜０．０１）。结果表明蛛网膜下腔出血后脑血管痉挛有免疫反应的存在。     

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.     

罂粟碱明胶微球治疗脑血管痉挛的实验研究

目的 研制罂粟碱明胶微球，探索微球药物控释系统治疗脑血管痉挛的可行性。方法 采用改良的双相乳化冷凝聚合法制备明胶微球。并将其与盐酸罂粟碱复合。观察微球分散度、粒径及外观形态；计算微球包封率、载药率及体外释药特性。将自体动脉血分二次注入枕大池制备兔蛛网膜下腔出血（SAH）模型，随后将罂粟碱明胶微球注入该模型兔的枕大池；第7天时，观察并计算基底动脉血管横截面积。结果 微球大小均匀，平均直径（18．36±3．56）μm，载药量为28．0％，包封率为93-3％，体外14d内药物缓释91．0％。兔的基底动脉横截面积：正常组为（0．91±0．19）mm^2，SAH模型组为（0.3l±0．44）mm^2，明胶微球（不含罂粟碱）组为（0．21±0．05）mm^2，罂粟碱明胶微球组为（0．71±0．11）mm^2；罂粟碱明胶微球与SAH模型组和明胶微球组间有明显差异（P〈0．05）。结论 在蛛网膜下腔早期注入罂粟碱缓释明胶微球对实验性脑血管痉挛有防治作用。     

Intraventricular Nicardipine for Refractory Cerebral Vasospasm after Subarachnoid Hemorrhage

Introduction  Delayed ischemic deficit from vasospasm is a leading cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage. Although several treatment modalities have been used to reverse the deleterious effects of vasospasm, alternative therapies are needed, as conventional therapies are often ineffective or contraindicated. Intrathecal nicardipine has been suggested for the prevention of vasospasm. We report our clinical experience with intraventricular nicardipine for refractory vasospasm in eight patients in whom conventional therapies were ineffective, contraindicated, or technically not feasible. Method  Retrospective case series performed at a tertiary care university hospital. Results  Eight patients (median Hunt-Hess grade = 2, median Fisher score = 4) with refractory vasospasm received intraventricular nicardipine (4 mg every 12 h) for a total of 5–17 days. One patient died in the intensive care unit. Seven patients had moderate to good outcomes with 6 being discharged to home (median Rankin Score = 2). Intraventricular nicardipine was well tolerated with minimal side effects. Conclusion  Our preliminary observations suggest that intraventricular nicardipine could be considered as a safe and effective treatment modality to treat vasospasm refractory to conventional management. A randomized, controlled trial to verify the efficacy and safety of intrathecal nicardipine in the prevention and treatment of cerebral vasospasm is warranted.     

Reduced Ipsilateral Hemispheric Cerebral Blood Flow at Admission is Predictive of Vasospasm with Infarction after Aneurysmal Subarachnoid Hemorrhage

Background and Purpose  Cerebral vasospasm (CV) with infarction causes a significant degree of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). We sought to determine if reduced cerebral blood flow (CBF) on Xenon CT within 48 h of the ictus was predictive of developing CV with infarction. Methods  This is a prospective study from 1999 to 2006 of 97 patients with aSAH who underwent Xenon CT within 48 h of their bleed. Demographic, clinical, radiographic, and angiographic parameters were investigated as potential risk factors for the development of CV with infarction. A binary logistic regression analysis was performed to determine the independent predictors of this endpoint. Results  A total of 97 patients with a mean age of 54 ± 12 years were studied. A total of 78 (80.4%) patients presented with a Fisher grade of 3 and 51 (52.6%) patients with a Hunt Hess score ≥3. CV with infarction was found in 33 (34%) patients. In univariate modeling, younger patients with a Fisher scale of 3 or a reduced ipsilateral mean hemispheric CBF had an association with developing CV with infarction. In binary logistic regression modeling, patients with lower initial hemispheric CBF’s were at a significant risk of CV with infarction in the ipsilateral hemisphere. Conclusions  Lower initial CBF at presentation is a risk factor for developing CV with infarction. These findings may help in early prediction of this entity and may have therapeutic implications in the future.     

Timing of Computed Tomography and Prediction of Vasospasm after Aneurysmal Subarachnoid Hemorrhage

Background  The initial noncontrast computed tomography (CT) study of the head after an aneurysmal subarachnoid hemorrhage (SAH) is used to predict the risk of developing vasospasm. Changes in the extent of subarachnoid blood seen on CT images occur as a function of time after SAH, but there is no consensus on the time interval during which this study needs to be completed. Methods  Clinical and radiological information on adult SAH patients were reviewed. Patients were grouped based on the time elapsed from ictus to the initial head CT study. The amount of subarachnoid blood on CT was graded using the Hijdra sum score (HSS) and the modified Fisher scale (MFS). The relationship between the initial CT grading score and the risk of angiographic vasospasm was assessed for each group. Results  A total of 224 consecutive patients were identified (145 females, 65%). Initial CT was performed within 24 h of the event in 163 (Group 1, 73%) and after 24 h in 61 patients (Group 2, 27%). A total of 54 patients (24%) developed angiographic vasospasm. A statistically significant association between the extent of subarachnoid blood and subsequent development of vasospasm was observed only if the initial CT imaging study was performed within 24 h of aneurysmal rupture (P = 0.0001 and 0.02 for HSS and MFS, respectively). Conclusions  We propose that only CT scans obtained within 24 h of a subarachnoid bleeding event should be used to estimate the risk of vasospasm.     

不同浓度氧合血红蛋白对大鼠蛛网膜下腔出血后迟发性脑血管痉挛的影响

目的 观察不同浓度氧合血红蛋白对大鼠蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后迟发性脑血管痉挛(delayed cerebral vasospasm,DCV)的影响.方法 将24只大鼠分为三组,对照组(8例)、动脉血SAH组(8例)、静脉血SAH组(8例),分别用枕大池二次注血法将0.3...     

脑血管痉挛大鼠脑微区血流量和血浆内皮素1观察

应用非开颅大鼠蛛网膜下腔出血(SAH)模型,观察24h内脑微区血流量和颅内血清内皮素1(ET1)动态变化,并测量基底动脉(BA)管径。发现SAH后脑微区血流量迅速降低,1h达最低值,24h内无明显恢复趋势。SAH后1h开始至24h血浆ET1浓度显著增高。SAH后0.5h BA管径明显缩小。结果提示SAH后ET1的增多与脑血管痉挛及其缺血性脑损害的产生有关。     

动脉瘤夹闭术可能缩短急性动脉瘤性蛛网膜下腔出血相关脑血管痉挛持续时间

目的   比较不同治疗方法对动脉瘤性蛛网膜下腔出血（aneurysmal subarachnoid hemorrhage,aSAH）后的血流动力学变化,并分析对aSAH后血管痉挛的影响。 方法  连续选取2008年4月～2009年10月首都医科大学附属北京天坛医院神经病学中心急诊入院的45例发病在72?h内的aSAH患者,收集基线资料、计算机断层扫描（computed tomography,CT）、经颅多普勒超声（transcranial Doppler,TCD）及90?d改良Rankin量表评分。根据患者接受的治疗分为保守组、填塞组和夹闭组。使用TCD连续测定14?d之内大脑中动脉及大脑前动脉血流速度,计算Lindegaard指数,比较3组的处理平均血流速度、Lindegaard指数及血管痉挛持续时间。 结果  大脑前动脉/大脑中动脉的平均血流速度及Lindegaard指数由高到低依次为保守组、夹闭组及填塞组［大脑前动脉：平均血流速度为（74.60±5.84）cm/s、（70.00±5.24）cm/s、（65.70±6.03）cm/s,P=0.0001;Lindegaard指数分别为3.87±0.32、3.82±0.31、3.65±0.36,P=0.006;大脑中动脉：平均血流速度分别为（101.2±9.1）cm/s、（87.0±6.2）cm/s、（76.2±9.2）cm/s,P=0.004;Lindegaard指数分别为5.50±0.65、4.15±0.46、3.81±0.55,P=0.005］。夹闭组患者脑血管痉挛持续时间较保守组短［（3.30±1.87）d vs?（7.29±2.23）d,P=0.035］。保守组患者90?d预后较差（P=0.028）。 结论  神经外科夹闭术和血管内动脉瘤填塞术均能缓解急性aSAH后脑血管痉挛的严重程度;外科夹闭术可缩短脑血管痉挛持续时间。