动脉瘤性蛛网膜下腔出血后脑血管痉挛的治疗

动脉瘤性蛛网膜下腔出血(aneurysmal subarachnoid hemorrhage,aSAH)占全部卒中的5%～15%,主要继发于囊状动脉瘤的破裂[1-2].本病的发病率为6～16/10万,平均为9/10万,最高的国家为日本及芬兰,是其他人群的两倍[3].该病的总体死亡率约30%～70%,10%～20%的患者出现严重的神经功能缺损[4].……     

Predictors of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Cardiac Focus

Background  

Myocardial injury after aneurysmal subarachnoid hemorrhage (aSAH) is associated with poor outcomes. Delayed cerebral ischemia (DCI) is also a complication of aSAH. We sought to determine whether (1) DCI could be predicted by demographics, aSAH severity/aneurysm location, or aSAH-associated myocardial injury (SAHMI), and (2) DCI is associated with increased mortality after aSAH.     

Treatment Options for Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage

Cerebral vasospasm occurs frequently after aneurysmal subarachnoid and contributes to delayed cerebral ischemia. In this article we address systematic problems with the literature on vasospasm and then review both established and experimental treatment options.     

Cerebral Vasospasm and Delayed Cerebral Ischemia in Intraventricular Hemorrhage

Background

Intracerebral hemorrhage (ICH) with intraventricular extension (IVH) is a devastating disease with a particular high mortality. In some aspects, IVH may resemble subarachnoid hemorrhage. The incidence and role of cerebral vasospasm in ICH with IVH are poorly understood. Here, we aimed to analyze the incidence and relationship of cerebral vasospasm to clinical characteristics, in-hospital mortality, and functional outcome at 3 months in patients suffering ICH with IVH.

Methods

Patients with ICH and IVH treated on a neurological intensive care unit were prospectively enrolled in a single-center observational study. Vasospasm was defined using established ultrasound criteria. Delayed cerebral ischemia (DCI) was defined as a new hypodensity on follow-up cranial CT. Functional outcome at 3 months was assessed using the modified Rankin Scale.

Results

129 patients with ICH and IVH were screened for the study. 62 patients entered the final analysis. The incidence of significant vasospasm was 37 %. A strong trend was found for the association between all cerebral vasospasm and DCI (P = 0.046). Early (up to 48 h) vasospasm was significantly associated with a DCI (P = 0.033). Overall mortality and outcome after 3 months did not differ between the groups.

Conclusion

Cerebral vasospasm seems to be a frequent complication after ICH with IVH and might be associated with DCI. Larger studies are warranted to confirm this hypothesis.     

Increased Cortisol Levels are Associated with Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Background  

Physiological reactions of the stress hormone cortisol include hyperglycemia, hypertension, and endothelium dysfunction. In patients with aneurysmal subarachnoid hemorrhage (SAH), hyperglycemia, hypertension, and endothelium dysfunction are associated with the occurrence of delayed cerebral ischemia (DCI). Therefore, the purpose of the present study was to investigate whether increased serum cortisol levels after aneurysmal SAH are associated with DCI occurrence.     

Delayed Cerebral Ischemia after Subarachnoid Hemorrhage

Delayed cerebral ischemia (DCI) is the most feared complication of aneurysmal subarachnoid hemorrhage (aSAH). It increases the mortality and morbidity associated with aSAH. Previously, large cerebral artery vasospasm was thought to be the sole major contributing factor associated with increased risk of DCI. Recent literature has challenged this concept. We conducted a literature search using PUBMED as the prime source of articles discussing various other factors which may contribute to the development of DCI both in the presence or absence of large cerebral artery vasospasm. These factors include microvascular spasm, micro-thrombosis, cerebrovascular dysregulation, and cortical spreading depolarization. These factors collectively result in inflammation of brain parenchyma, which is thought to precipitate early brain injury and DCI. We conclude that diagnostic modalities need to be refined in order to diagnose DCI more efficiently in its early phase, and newer interventions need to be developed to prevent and treat this condition. These newer interventions are currently being studied in experimental models. However, their effectiveness on patients with aSAH is yet to be determined.     

Plasma Endothelin-1 as Screening Marker for Cerebral Vasospasm After Subarachnoid Hemorrhage

Background

Cerebral vasospasm complicating subarachnoid hemorrhage causes ischemic stroke and worsens the neurological outcome. The potential role of endothelin-1 in vasospasm pathogenesis may provide therapeutic opportunities. A recent meta-analysis however, did not support the use of endothelin antagonists. Apart from clinical assessment, transcranial Doppler and interval angiography, there are no sensitive screening markers for evolving vasospasm. We investigate the ability of serial measurement of endothelin-1 to predict the development of vasospasm following subarachnoid hemorrhage.

Methods

Endothelin-1 levels in cerebrospinal fluid and blood were measured daily in 20 patients admitted to the ICU with subarachnoid hemorrhage from days 1 to 10 following the inception bleed. In addition to clinical assessment, patients had daily transcranial Doppler. Digital subtraction angiography was performed on the suspicion of vasospasm based upon clinical or transcranial Doppler assessment. Neuron-specific enolase and SB100 were measured in blood as comparative biomarkers of neurological injury.

Results

Mean plasma endothelin-1 on day 5, was 4.2 mcg/L (CI 3.1–5.8) in patients with vasospasm compared to 2.5 mcg/L (CI 1.5–4.0) in those without vasospasm (P = 0.047). There were no time-related differences in cerebrospinal fluid endothelin-1, plasma NSE, or SB100 for patients with and without vasospasm.

Conclusions

In patients with subarachnoid hemorrhage and vasospasm, endothelin-1 is significantly higher in plasma than in CSF on day 5. Neither NSE nor SB100 is associated with the development of vasospasm. Measurement of serial plasma endothelin-1 concentration is a potential screening marker of vasospasm.     

Intra-arterial Dantrolene for Refractory Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage

Background

Intravenous dantrolene has been used to prevent and treat cerebral vasospasm. We report a case of refractory cerebral vasospasm treated with intra-arterial dantrolene after aneurysmal subarachnoid hemorrhage.

Methods

A 56-year-old woman suffered a diffuse subarachnoid hemorrhage from a ruptured anterior communicating artery aneurysm which was successfully treated with coil embolization. She subsequently developed bilateral severe angiographic vasospasm which was treated with intra-arterial vasodilators. However, owing to the recurrence of vasospasm, intra-arterial dantrolene followed by balloon angioplasty was used.

Results

There was moderate improvement of the severe vasospasm in bilateral A1 segments of the anterior cerebral arteries after microcatheter-based intra-arterial infusion of 30?ml (1?mg/ml) dantrolene. Patient??s hemodynamic parameters were monitored during and after the procedure and no significant changes were seen after dantrolene infusion. A follow up cerebral angiogram after 1?day demonstrated the persistence of therapeutic effect.

Conclusion

Intra-arterial dantrolene induced a sustained improvement in cerebral vasospasm secondary to ruptured aneurysm. No significant side effects were observed during or after the infusion of the drug.     

Efficacy of Cilostazol in Prevention of Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis

Objectives

Cilostazol, a selective inhibitor of phosphodiesterase 3, may reduce symptomatic vasospasm and improve outcome in patients with aneurysmal subarachnoid hemorrhage considering its anti-platelet and vasodilatory effects. We aimed to analyze the effects of cilostazol on symptomatic vasospasm and clinical outcome among patients with aneurysmal subarachnoid hemorrhage (aSAH).

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。     

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。     

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.     

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 Association Between Serum Macrophage Migration Inhibitory Factor and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Neurotoxicity Research - Inflammatory processes have long been implicated in the development of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). Macrophage...     

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.     

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...     

Milrinone as a Rescue Therapy for Symptomatic Refractory Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage

Introduction  

Delayed ischemic neurological deficit associated to cerebral vasospasm is the most common cause of sequelae and death that follows the rupture of an aneurysm. The objective of this study was to evaluate the safety and efficacy of intra-arterial Milrinone in patients with symptomatic refractory cerebral vasospasm.