Insurance Status Is Associated with Treatment Allocation and Outcomes after Subarachnoid Hemorrhage

Objective

Subarachnoid hemorrhage (SAH) is a particularly devastating type of stroke which is responsible for one third of all stroke-related years of potential life lost before age 65. Surgical treatment has been shown to decrease both morbidity and mortality after subarachnoid hemorrhage. We hypothesized that payer status other than private insurance is associated with lower allocation to surgical treatment for patients with SAH and worse outcomes.

Design

We examined the association between insurance type and surgical treatment allocation and outcomes for patients with SAH while adjusting for a wide range of patient and hospital factors. We analyzed the Nationwide Inpatient Sample hospital discharge database using survey procedures to produce weighted estimates representative of the United States population.

Patients

We studied 21047 discharges, representing a weighted estimate of 102595 patients age 18 and above with a discharge diagnosis of SAH between 2003 and 2008.

Measurements

Multivariable logistic and generalized linear regression analyses were used to assess for any associations between insurance status and surgery allocation and outcomes.

Main Results

Despite the benefits of surgery 66% of SAH patients did not undergo surgical treatment to prevent rebleeding. Mortality was more than twice as likely for patients with no surgical treatment compared to those who received surgery. Medicare patients were significantly less likely to receive surgical treatment.

Conclusions

Nearly two thirds of patients with SAH don''t receive operative care, and Medicare patients were significantly less likely to receive surgical treatment than other patients. Bias against the elderly and those with chronic illness and disability may play a part in these findings. A system of regionalized care for patients presenting with SAH may reduce disparities and improve appropriate allocation to surgical care and deserves prospective study.     

尼莫地平对动脉瘤性蛛网膜下腔出血脑血管痉挛的临床疗效研究

目的:观察尼莫地平对动脉瘤性蛛网膜下腔出血脑血管痉挛的临床疗效及安全性,为临床治疗提供依据。方法:对我院2010年2月~2013年2月期间收治的92例动脉瘤性蛛网膜下腔出血患者进行随机分为观察组和对照组,每组46例。两组患者入院后均进行常规治疗,绝对卧床休息、镇静、给予氨甲环酸止血、脱水降颅压、防治感染及对症治疗。观察组在上述治疗基础上给予尼莫地平(德国拜尔公司)持续微泵静脉注射20 mg·d-1,连用14 d,后改为口服尼莫地平片40 mg,qid,至第21天,根据监测血压调整剂量。观察两组患者1个月内脑血管发病情况、CT评价情况,并进行对比分析。结果:两组患者治疗后,观察组有效率91.3%;对照组有效率73.91%。两组比较差异明显,观察组疗效明显优于对照组,具有统计学意义(P0.05)。两组患者在治疗期间,观察组发生脑血管痉挛4例,占8.7%;对照组发生脑血管痉挛26例,占56.52%,两组比较差异明显,具有统计学意义(P0.05)。结论:尼莫地平能够显著降低动脉瘤性蛛网膜下腔出血脑血管痉挛的发生率,对脑血管再出血具有积极防治作用,建议推广应用。     

终板造瘘对动脉瘤性蛛网膜下腔出血后慢性脑积水的影响

目的:探讨终板造瘘对动脉瘤性蛛网膜下腔出血后慢性脑积水的影响。方法:回顾性分析201例动脉瘤性蛛网膜下腔出血患者的临床资料,将所有患者按动脉瘤夹闭术中是否进行终板造瘘分为两组,随访6个月以上,评价其慢性脑积水的发生率。结果:所有患者慢性脑积水的总发生率为17.4%,终板造瘘组慢性脑积水的发生率7.8%,而单独夹闭组慢性脑积水的发生率为28.1%,显著高于终板造瘘组(P0.05)。在FisherⅠ-Ⅱ级中,终板造瘘组与单独夹闭组慢性脑积水的发生率分别为5.0%、7.7%,两组比较无统计学差异(P0.05);FisherⅢ-Ⅳ级中,终板造瘘组与单独夹闭组慢性脑积水的发生率分别为10.8%、40.3%,单独夹闭组显著高于终板造瘘组(P0.05);而Hunt-HessⅠ-Ⅱ级中,终板造瘘组与单独夹闭组慢性脑积水的发生率分别为7.0%、9.4%,两组比较无统计学差异(P0.05),Hunt-HessⅢ-Ⅳ级中终板造瘘与单独夹闭组慢性脑积水的发生率分别为11.3%、46.5%,单独夹闭组显著高于终板造瘘组(P0.05)。结论:终板造瘘可明显降低Hunt-HessⅢ-Ⅳ级、FisherⅢ、Ⅳ级动脉瘤性蛛网膜下腔出血后患者慢性脑积水的发生率,而对Hunt-HessⅠ-Ⅱ级、FisherⅠ-Ⅱ级的动脉瘤性蛛网膜下腔出血后患者慢性脑积水的发生率影响不明显。     

Impaired Blood Dendritic Cell Numbers and Functions after Aneurysmal Subarachnoid Hemorrhage

Previous Presentation

Portions of this study were presented at the Annual Congress of Société Française d’Anesthésie et de Réanimation in Paris, September 2012.

Background

Toll-like receptor (TLR) agonists are promising therapy for the prevention of nosocomial infections in critical ill patients. We aimed to analyze the TLR-reactivity of circulating dendritic cells (DC) as assessed by cytokine production after an ex vivo challenge with TLR agonists in aneurysmal subarachnoid hemorrhage (SAH) patients.

Methods and Findings

A single-center prospective observational study took place in one intensive care unit of a teaching hospital. Blood samples were harvested on days 2, 5 and 10 in 21 severe SAH patients requiring mechanical ventilation and 17 healthy controls. DC production of cytokines (Tumour Necrosis Factor, TNF-α; Interleukin, IL-12; and Interferon, IFN-α) was assessed by intracellular immunostaining on TLR-3, 4, 7/8 and 9 stimulations. SAH patients had decreased numbers of blood myeloid (mDCs) and plasmacytoid DCs (pDCs) on days 2, 5 and 10. Compared with the healthy controls, the frequency of mDCs producing TNF-α after TLR-3 stimulation was decreased in the SAH patients. The frequency of myeloid DCs producing IL-12 after TLR-3 and 4 stimulations was also decreased in the SAH patients. In contrast, the mDCs response to TLR-7/8 was not impaired in the SAH patients. The frequency of pDCs producing TNF-α⁺ and IFN-α⁺ on TLR-7/8 stimulation were reduced at all of the tested times in the SAH patients, whereas reactivity to TLR-9 was preserved. On day 2, the pDCs from non-survivor patients (n = 8) had a decreased ability to produce IFN-α on TLR-9 stimulation compared with the survivors.

Conclusions

These data suggest functional abnormalities of circulating pDCs and mDCs that could be important for immunomodulation after SAH.     

基于卒中登记的颅内动脉瘤致蛛网膜下腔出血的临床研究

目的:研究基于卒中登记的颅内动脉瘤致蛛网膜下腔出血(aneurysmal subarachnoid hemorrhage,a SAH)的颅脑血流动力学改变及其对诊断治疗的指导作用。方法:采用回顾性研究经卒中登记系统筛选出48例经DSA(digital subtraction angiography,DSA)确诊的a SAH,收集患者床旁经颅多普勒(transcranial Doppler,TCD)监测大脑中动脉(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),自身健侧作为正常对照,均采用血管内介入治疗,对其中符合脑血管痉挛(cerebral vasospasm,CVS)诊断标准的患者使用尼莫地平进行治疗,观察疗效。结果:与健侧相比,患侧PI、RI增大,Vd、Vm减小,其中以Vd减小较明显,与健侧相比有统计学差异(P0.01),Vs与健侧相比无统计学差异(P0.05)。CVS组与非CVS组相比Vm明显增加,有统计学差异(P0.001)。所有患者经水膨胀弹簧圈或支架预后均得到改善。结论:床旁实时TCD监测能反映a SAH脑血流变化,对CVS进行及时解除痉挛治疗,并为介入治疗提供参考依据,颅脑血流实时监测和介入治疗综合运用提高了a SAH患者的治疗效果。     

动脉瘤性蛛网膜下腔出血的治疗进展与探讨

颅内动脉瘤破裂导致的自发性蛛网膜下腔出血是一种致残率以及病死率都非常高的一种疾病,其中动脉瘤性蛛网膜下腔出血Hunt-Hess和世界神经外科医师联盟Ⅳ、V级的患者为高分级颅内动脉瘤性蛛网膜下腔出血,这部分患者,无论采取何种治疗方案,预后仍较差。目前对高分级动脉瘤性蛛网膜下腔出血的治疗仍处于探索阶段,并没有形成统一的临床治疗指导规范或临床路径,其中是在采取保守治疗或者手术治疗的问题上存在较大争议,而在选择手术治疗时又存在手术时机的问题,并且随着显微颅内动脉瘤夹闭术的成熟以及颅内动脉瘤的血管内治疗材料和技术的迅速发展及治疗经验的积累,对于患者采取何种手术方式已成为近年来的争议热点,所以如何对这部分患者实施积极有效的治疗而改善其预后,已成为目前神经外科医生必须要解决的焦点问题。     

Antioxidant Therapy Against Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage

1. Approximately one-third of the morbidity and mortality due to aneurysmal subarachnoid hemorrhage (SAH) is caused by delayed ischemic neurological deficit (DIND) due to cerebral vasospasm.2. Compared to prolonged arterial constriction in other parts of the body, cerebral vasospasm is characterized by its long duration and refractoriness to vasodilators such as calcium antagonists.3. Whereas oxyhemoglobin (oxyHb) liberated into the CSF from the subarachnoid clot has been deemed the causative agent of vasoconstriction, the biochemical mechanisms whereby oxyHb elicits prolonged constriction of the cerebral arteries has remained elusive. Here, we suggest that oxyHb triggers the generation of reactive oxygen intermediates (ROI) within the CSF.4. Multiple lines of evidence indicate that the occurrence of vasospasm, namely, prolonged smooth muscle contraction, is due to the following intracellular events.5. First, hydroxyl radicals (OH*), the most reactive species of ROI, are generated within the cerebral arterial wall via the Fenton and Haber–Weiss reactions catalyzed by oxyHb. Second, subsequent peroxidative membrane damage in the arterial smooth muscle cell enhances the metabolism of phosphatidylcholine and phosphatidylethanolamine, leading to a rise in the intracellular level of diacylglycerol, an endogenous activator of protein kinase C.6. The prolonged arterial contraction that occurs during vasospasm is attributable primarily to the activation of protein kinase C, not to the Ca²⁺/calmodulin system. In this article, literature relevant to the above thesis is reviewed, and the rationale for the antioxidant therapy against cerebral vasospasm is discussed.     

The Association between Meteorological Parameters and Aneurysmal Subarachnoid Hemorrhage: A Nationwide Analysis

Prior research has suggested that regional weather patterns impact the risk of rupture of cerebral aneurysms, but the findings in the literature have been inconsistent. Furthermore, no nationwide analysis to date has examined the association between meteorological factors and the post-procedural outcomes of patients after the treatment for ruptured cerebral aneurysms. The purpose of this study was to use a nationwide sample to analyze the association between specific meteorological parameters—temperature, precipitation, sunlight, and humidity—and hospital admission rate for and outcome after aneurysmal subarachnoid hemorrhage. Patients were identified using the Nationwide Inpatient Sample (2001–2010): Those with an ICD-9 diagnosis code for subarachnoid hemorrhage and a procedural code for aneurysm repair were included. Climate data were obtained from the State of the Climate Report 2010 released by the National Climatic Data Center. Multivariate regression models were constructed to analyze the association between average state monthly temperature, precipitation, and percent possible sunlight, as well as relative morning humidity and both monthly hospital admission rate, adjusted for annual state population in millions, and in-hospital mortality. 16,970 admissions were included from 723 hospitals across 41 states. Decreased daily sunlight and lower relative humidity were associated with an increased rate of admission for ruptured cerebral aneurysms (p<0.001), but had no association with differential inpatient mortality. No significant changes in these observed associations were seen when multivariate analyses were constructed. This is the first nationwide study to suggest that decreased sunlight and lower relative humidity are associated with admission for ruptured cerebral aneurysms. While it has been postulated that external atmospheric factors may cause hormonal and homeostatic changes that impact the risk of rupture of cerebral aneurysms, additional research is needed to confirm and further understand these relationships.     

Ocular Ultrasound as an Easy Applicable Tool for Detection of Terson's Syndrome after Aneurysmal Subarachnoid Hemorrhage

Introduction

Intraocular hemorrhage in patients suffering from aneurysmal subarachnoid hemorrhage is known as Terson''s syndrome and is an underestimated but common pathology. We therefore designed a prospective single-blinded study to evaluate the validity of ocular ultrasound compared to the gold standard indirect funduscopy in the diagnosis of Terson''s syndrome.

Material and Methods

Fifty-two patients (104 eyes in total) suffering from aneurysmal subarachnoid hemorrhage were enrolled in this study. Two investigators independently performed a single-blinded ocular ultrasound using a standard intensive care ultrasound system to detect an intraocular hemorrhage. Indirect funduscopy following iatrogenic mydriasis served as the gold standard for confirmation or exclusion of an intraocular hemorrhage. Statistical analyses were performed to evaluate the sensitivity and specificity, positive and negative predictive values of the method as well as the learning curve of ocular ultrasound.

Results

Indirect funduscopy detected Terson''s syndrome in 11 of 52 (21.2%) respectively in 21 of 104 (20.2%) eyes in patients suffering from subarachnoid hemorrhage. Sensitivity and specificity increased with the number of ocular ultrasound examinations for both investigators, reaching 81.8% and 100% respectively. Positive and negative predictive values were different for both investigators (63.6% vs. 100% positive and 100% vs. 95.7% negative) but were both correlated to the amount of intraocular hemorrhage. A low Glasgow Coma scale (p = 0.015) and high Hunt & Hess grade (p = 0.003) was associated with a higher rate of Terson''s syndrome.

Conclusions

Ocular ultrasound using standard ultrasound equipment has been confirmed as a reliable, easy-to-handle bedside screening tool for detecting Terson''s syndrome. Nevertheless funduscopy remains the gold standard to detect Terson''s syndrome.     

Copeptin as a Marker for Severity and Prognosis of Aneurysmal Subarachnoid Hemorrhage

Background

Grading of patients with aneurysmal subarachnoid hemorrhage (aSAH) is often confounded by seizure, hydrocephalus or sedation and the prediction of prognosis remains difficult. Recently, copeptin has been identified as a serum marker for outcomes in acute ischemic stroke and intracerebral hemorrhage (ICH). We investigated whether copeptin might serve as a marker for severity and prognosis in aSAH.

Methods

Eighteen consecutive patients with aSAH had plasma copeptin levels measured with a validated chemiluminescence sandwich immunoassay. The primary endpoint was the association of copeptin levels at admission with the World Federation of Neurological Surgeons (WFNS) grade score after resuscitation. Levels of copeptin were compared across clinical and radiological scores as well as between patients with ICH, intraventricular hemorrhage, hydrocephalus, vasospasm and ischemia.

Results

Copeptin levels were significantly associated with the severity of aSAH measured by WFNS grade (P = 0.006), the amount of subarachnoid blood (P = 0.03) and the occurrence of ICH (P = 0.02). There was also a trend between copeptin levels and functional clinical outcome at 6-months (P = 0.054). No other clinical outcomes showed any statistically significant association.

Conclusions

Copeptin may indicate clinical severity of the initial bleeding and may therefore help in guiding treatment decisions in the setting of aSAH. These initial results show that copeptin might also have prognostic value for clinical outcome in aSAH.     

Whole Blood Gene Expression Profiles of Patients with a Past Aneurysmal Subarachnoid Hemorrhage

BackgroundThe pathogenesis of development and rupture of intracranial aneurysms (IA) is largely unknown. Also, screening for IA to prevent aneurysmal subarachnoid hemorrhage (aSAH) is inefficient, as disease markers are lacking. We investigated gene expression profiles in blood of previous aSAH patients, who are still at risk for future IA, aiming to gain insight into the pathogenesis of IA and aSAH, and to make a first step towards improvement of aSAH risk prediction.ConclusionsNo gene expression differences were present in blood of previous aSAH patients compared to controls, besides one differentially co-expressed gene network without a clear relevant biological function. Our findings suggest that gene expression profiles, as detected in blood of previous aSAH patients, do not reveal the pathogenesis of IA and aSAH, and cannot be used for aSAH risk prediction.     

Chronic Hydrocephalus after Experimental Subarachnoid Hemorrhage

Chronic communicating hydrocephalus is a significant health problem affecting up to 20% of survivors of spontaneous subarachnoid hemorrhage (SAH). The development of new treatment strategies is hampered by the lack of well characterized disease models. This study investigated the incidence of chronic hydrocephalus by evaluating the temporal profile of intracranial pressure (ICP) elevation after SAH, induced by endovascular perforation in rats. Twenty-five adult male Sprague-Dawley rats (260–320g) were subjected to either endovascular perforation or sham surgery. Five animals died after SAH induction. At 7, 14 and 21 days after surgery ICP was measured by stereotaxic puncture of the cisterna magna in SAH (n=10) and SHAM (n=10) animals. On day 21 T-maze test was performed and the number of alterations and latency to decision was recorded. On day 23, samples were processed for histological analyses. The relative ventricle area was evaluated in coronal Nissl stained sections. On day 7 after surgery all animals showed normal ICP. The absolute ICP values were significantly higher in SAH compared to SHAM animals on day 21 (8.26±4.53 mmHg versus 4.38±0.95 mmHg) but not on day 14. Observing an ICP of 10mmHg as cut-off, 3 animals showed elevated ICP on day 14 and another animal on day 21. The overall incidence of ICP elevation was 40% in SAH animals. On day 21, results of T-maze testing were significantly correlated with ICP values, i.e. animals with elevated ICP showed a lower number of alterations and a delayed decision. Histology yielded a significantly higher (3.59 fold increased) relative ventricle area in SAH animals with ICP elevation compared to SAH animals without ICP elevation. In conclusion, the current study shows that experimental SAH leads to chronic hydrocephalus, which is associated with ICP elevation, behavioral alterations and ventricular dilation in about 40% of SAH animals.     

动脉瘤性蛛网膜下腔出血后持续腰大池引流的时机探讨及分流依赖性脑积水的危险因素分析

摘要 目的：研究对比动脉瘤性蛛网膜下腔出血（aSAH）后不同时机开展持续腰大池引流的效果,并对分流依赖性脑积水（SDHC）的危险因素进行分析。方法：本院于2017年1月～2020年12月期间诊治的aSAH患者171例,将其纳入研究。将其按照持续腰大池引流时机不同分为A组（＜24 h）50例、B组（24～72h）84例以及C组（＞72 h）37例。观察三组头痛持续时间,双侧大脑中动脉（MAC）血流流速以及SDHC发生率,对aSAH后持续腰大池引流术后并发SDHC的影响因素进行单因素和多因素Logistic回归分析。结果：C组头痛持续时间长于A组和B组,MAC血流流速快于A组和B组,SDHC发生率高于A组和B组（均P＜0.05）;而A组和B组上述指标对比差异均不明显（均P＞0.05）,但是A组SDHC发生率更低。经单因素分析可得：aSAH持续腰大池引流术后并发SDHC和年龄、病变部位、中枢神经系统感染、改良Fisher分级及Hunt-Hess评分有关（均P＜0.05）。经多因素Logistic回归分析可得：年龄≥60岁、病变部位后循环、中枢神经系统感染、改良Fisher分级Ⅲ～Ⅳ级、Hunt-Hess评分Ⅲ～Ⅳ级及持续腰大池引流≥24 h均是aSAH持续腰大池引流术后并发SDHC的危险因素（均OR＞1,P＜0.05）。结论：以aSAH后＜24 h为时机开展持续腰大池引流术的效果较佳,SDHC发生率更低,其中年龄、病变部位、中枢神经系统感染、改良Fisher分级、Hunt-Hess评分、持续腰大池引流时机与aSAH持续腰大池引流术后并发SDHC的风险有关,临床工作中应针对上述因素制定相关措施,以期达到降低SDHC发生风险的目的。     

Clinical Study of the Role of 64-Slice CT Cerebra Angiography in Aneurysmal Subarachnoid Hemorrhage

The objective of this study is to assess the clinical role of computed tomography angiography (CTA) in determining the etiology of aneurysmal subarachnoid hemorrhage (ASAH) and selecting the treatment options. A total of 452 patients with ASAH underwent a 64-slice CTA examination to determine the etiology and select the treatment strategies. Digital subtraction angiography (DSA) or clipping operation confirmed the detection from the CTA. The CTA results of 452 patients with ASAH were confirmed through the DSA or clipping operation and the CTA results of 451 cases were consistent with what were seen during the DSA or clipping operation. The treatment choices for 451 patients (99.8 %) were based on the CTA results. A total of 90 cases (19.9 %) underwent endovascular embolization and 362 cases (80.1 %) underwent clipping operation. The other one patient underwent endovascular embolization after the DSA examination due to insufficient information from the CTA. Also, there was one patient who was misdiagnosed in the CTA. In conclusion, a 64-slice CTA can accurately detect intracranial aneurysms and is helpful in choosing the best treatment option.     

Kallikrein 6 as a Serum Prognostic Marker in Patients with Aneurysmal Subarachnoid Hemorrhage

Background

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating condition that frequently causes death or significant disabilities. Blood tests to predict possible early complications could be very useful aids for therapy. The aim of this study was to analyze serum levels of kallikrein 6 (KLK6) in individuals with aSAH to determine the relevance of this protease with the outcome of these patients.

Methodology/Principal Findings

A reference interval for KLK6 was established by using serum samples (n = 136) from an adult population. Additionally, serum samples (n = 326) from patients with aSAH (n = 13) were collected for 5 to 14 days, to study the concentration of KLK6 in this disease. The correlation between KLK6 and S100B, an existing brain damage biomarker, was analyzed in 8 of 13 patients. The reference interval for KLK6 was established to be 1.04 to 3.93 ng/mL. The mean levels in patients with aSAH within the first 56 hours ranged from 0.27 to 1.44 ng/mL, with lowest levels found in patients with worse outcome. There were significant differences between patients with good recovery or moderate disability (n = 8) and patients with severe disability or death (n = 5) (mean values of 1.03 ng/mL versus 0.47 ng/mL, respectively) (p<0.01). There was no significant correlation between KLK6 and S100B.

Conclusions/Significance

Decreased serum concentrations of KLK6 are found in patients with aSAH, with the lowest levels in patients who died.     

Differential Regulation of Matrix-Metalloproteinases and Their Tissue Inhibitors in Patients with Aneurysmal Subarachnoid Hemorrhage

Background

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in vascular remodeling, (neuro)inflammation, blood-brain barrier breakdown and neuronal apoptosis. Proinflammatory mechanisms are suggested to play an important role during early brain injury and cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). This study aimed to analyze MMP-3, MMP-9, TIMP-1 and TIMP-3 in patients with SAH and their respective association with cerebral vasospasm (CVS).

Methods

Blood samples were collected in 20 SAH patients on days 1 to 7, 9, 11, 13 and 15 and 20 healthy age and gender matched volunteers. Serum MMPs and TIMPs were analyzed using enzyme-linked immunosorbent assay. Doppler sonographic CVS was defined as a mean blood flow velocity above 120 cm/sec in the middle cerebral artery. When discharged from hospital and at 6 month follow-up neurological outcome was evaluated using the Glasgow Outcome Score and the modified Rankin Scale.

Results

MMP-9 was higher in SAH patients compared to healthy controls (p<0.001). Patients with CVS (n = 11) had elevated MMP-9 serum levels compared to patients without CVS (n = 9, p<0.05). Higher MMP-9 was observed in the presence of cerebral ischemia associated with cerebral vasospasm (p<0.05). TIMP-1 was increased in patients with SAH on day 4 (p<0.05). There was an imbalance of the MMP-9/TIMP-1 ratio in favor of MMP-9 in SAH patients, in particular those with CVS (p<0.001). MMP-3 and TIMP-3 were significantly lower in SAH patients throughout day 4 and day 7, respectively (p<0.05). We did not find an association between MMP-, TIMP levels and neurological outcome after 6 months.

Conclusions

MMP-3 and -9 are differentially regulated in SAH patients with both enzymes showing peak levels correlating with the development of CVS. The inhibitors TIMP-1 and -3 were low during the acute phase after SAH and increased later on which might suggest a preponderance of pro-inflammatory mechanisms.     

Association between S100B Levels and Long-Term Outcome after Aneurysmal Subarachnoid Hemorrhage: Systematic Review and Pooled Analysis

S100 calcium binding protein B (S100B), a well-studied marker for neurologic injury, has been suggested as a candidate for predicting outcome after subarachnoid hemorrhage. We performed a pooled analysis summarizing the associations between S100B protein in serum and cerebrospinal fluid (CSF) with radiographic vasospasm, delayed ischemic neurologic deficit (DIND), delayed cerebral infarction, and Glasgow Outcome Scale (GOS) outcome. A literature search using PubMed, the Cochrane Library, and the EMBASE databases was performed to identify relevant studies published up to May 2015. The weighted Stouffer’s Z method was used to perform a pooled analysis of outcome measures with greater than three studies. A total of 13 studies were included in this review. Higher serum S100B level was found to be associated with cerebral infarction as diagnosed by CT (p_adj = 3.1 x 10⁻⁴) and worse GOS outcome (p_adj = 5.5 x 10⁻¹¹). There was no association found between serum and CSF S100B with radiographic vasospasm or DIND. S100B is a potential prognostic marker for aSAH outcome.     

Circulating microRNA 132-3p and 324-3p Profiles in Patients after Acute Aneurysmal Subarachnoid Hemorrhage

Background

Aneurysmal subarachnoid hemorrhage (SAH) is a highly morbid and fatal condition with high rate of cognitive impairment and negative impact in quality of life among survivors. Delayed cerebral infarction (DCI) is one the major factors for these negative outcomes. In this study we compared the circulating microRNA profiles of SAH patients and healthy individuals, and the circulating microRNA profiles of SAH patients with and without DCI.

Methods

Peripheral blood samples on Day 7 after the onset of SAH were subjected to microarray analysis with Affymetrix miRNA 3.0 array and quantitative PCR analysis. SAH patients with (N = 20) and without DCI (N = 20) and Healthy controls (N = 20) were included for analyses.

Results

We demonstrated that 99 miRNAs were found to be dysregulated in the SAH patient group with DCI. 81 miRNAs were upregulated and 18 were downregulated. Findings from KEGG pathway analysis showed that miRNAs and target genes for axon guidance and TGF-beta signaling were involved, implying that the resulted differential miRNA expression pattern reflect the results of SAH instead of etiology of the disease. miR-132-3p and miR-324-3p showed distinctive upregulations in qPCR [miR-132: 9.5 fold (95%CI: 2.3 to 16.7) in DCI group and 3.4 fold (95%CI: 1.0 to 5.8) in Non-DCI group; miR-324: 4924 fold (95%CI: 2620 to 7228) in DCI group and 4545 fold (95%CI: 2408 to 6683) in non-DCI group]. However, there were no significant differences in fold changes between SAH patients with and without DCI [fold change ratios (mean+/-SD): 2.7+/-4.2 and 1.1+/-1.1 for miRNA-132 and miRNA-324].

Conclusion

Our study demonstrated that as compared to healthy control, miR-132 and miR-324 showed a upregulation in both SAH DCI and Non-DCI groups. However, the differences between the SAH DCI and non-DCI groups were not statistically significant.     

Effect of Clazosentan in Patients with Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis of Randomized Controlled Trials

Background

Cerebral vasospasm is the most important potentially treatable cause of mortality and morbidity following aneurysmal subarachnoid hemorrhage (aSAH). Clazosentan, a selective endothelinreceptor antagonist, has been suggested to help reduce the incidence of vasospasm in patients with aSAH. However, the results were controversial in previous trials. This meta-analysis attempts to assess the effect of clazosentan in patients with aSAH.

Methodology/Principal Findings

We systematically searched Pubmed, Embase, and the Cochrane Library from their inception until June, 2012. All randomized controlled trials (RCTs) related to the effect of clazosentan in aSAH were included. The primary outcomes included the incidence of angiographic vasospasm, new cerebral infarction (NCI), delayed ischemic neurological deficits (DIND), and vasospasm-related morbidity/mortality (M/M); the second outcomes included the occurrence of rescue therapy, all-cause-mortality, and poor outcome. 4 RCTs were included with a total of 2156 patients. The risk of angiographic vasospasm (relative risk [RR] = 0.58; 95% CI, 0.48 to 0.71), DIND (RR = 0.76; 95% CI, 0.62 to 0.92), and vasospasm-related M/M (RR = 0.80; 95% CI, 0.67 to 0.96) were statistically significantly reduced in the clazosentan group. Patients treated with clazosentan had a reduced occurrence of rescue therapy (RR = 0.62; 95% CI, 0.49 to 0.79). However, no statistically significant effects were observed in NCI (RR = 0.74; 95% CI, 0.52 to 1.04), mortality (RR = 1.03; 95% CI, 0.71 to 1.49), and poor outcome (RR = 1.12; 95% CI, 0.96 to 1.30).

Conclusions/Significance

Our pooling data supports that clazosentan is probably effective in preventing the occurrence of angiographic vasospasm, vasospasm-related DIND, vasospasm related M/M, and rescue therapy. However, no evidence lends significant supports to the benefits of clazosentan in decreasing the occurrence of NCI, mortality or improving the functional outcome.     

Tonic-Clonic Activity at Subarachnoid Hemorrhage Onset: Impact on Complications and Outcome

Objective

Tonic-clonic activity (TCA) at onset complicates 3% to 21% of cases of subarachnoid hemorrhage (SAH). The impact of onset TCA on in-hospital complications, including seizures, remains unclear. One study associated onset TCA with poor clinical outcome at 6 weeks after SAH, but to our knowledge no other studies have confirmed this relationship. This study aims to assess the impact of onset TCA on in-hospital complications, poor functional outcome, mortality, and epilepsy at 3 months.

Methods

Analysis of a prospective study cohort of 1479 SAH patients admitted to Columbia University Medical Center between 1996 and 2012. TCA within 6 hours of hemorrhage onset was identified based on accounts of emergency care providers or family witnesses.

Results

TCA at onset was described in 170 patients (11%). Patients with onset TCA were younger (P = 0.002), presented more often with poor clinical grade (55% vs. 26%, P<0.001) and had larger amounts of cisternal, intraventricular, and intracerebral blood than those without onset TCA (all, P<0.001). After adjusting for known confounders, onset TCA was significantly associated with in-hospital seizures (OR 3.80, 95%-CI: 2.43–5.96, P<0.001), in-hospital pneumonia (OR 1.56, 95%-CI: 1.06–2.31, p = 0.02), and delayed cerebral ischemia (OR 1.77, 95%-CI: 1.21–2.58, P = 0.003). At 3 months, however, onset TCA was not associated with poor functional outcome, mortality, and epilepsy after adjusting for age, admission clinical grade, and cisternal blood volume.

Conclusions

Onset TCA is not a rare event as it complicates 11% of cases of SAH. New and clinically relevant findings are the association of onset TCA with in-hospital seizures, pneumonia and delayed cerebral ischemia. Despite the increased risk of in-hospital complications, onset TCA is not associated with disability, mortality, and epilepsy at 3 months.