Subarachnoid hemorrhage rebleeding in the first 24 h is associated with external ventricular drain placement and higher grade on presentation: Cohort study

BackgroundRebleeding after aneurysmal subarachnoid hemorrhage (aSAH) confers a poor prognosis; however, risk factors and differential outcomes associated with early rebleeding in the first 24 h after symptom presentation are incompletely understood.MethodsA retrospective cohort study of all aSAH presenting to our institution between 2001 and 2016 was performed. Early rebleeding events were defined as clinical neurologic decline with radiographically confirmed acute intracranial hemorrhage within 24 h after symptom presentation. Univariate and multivariate logistic regression analyses were used to assess clinical associations, with a specific focus on baseline Glasgow Coma Score (GCS), World Federation of Neurosurgical Societies (WFNS), and modified Fisher scores.ResultsOf 471 aSAH cases, 33 (7%) experienced early rebleeding. Multivariate regression identified extraventricular drain (EVD) placement (OR = 2.16, P = 0.04) and WFNS 3–5 (OR = 2.69, P = 0.02) as significant predictors of early rebleeding. Good functional outcomes were observed in 8 patients with early rebleeding (24%), all of whom underwent aneurysm treatment. Higher SAH grade prior to rebleeding (WFNS 3–5) was significantly associated with increased odds of an unfavorable functional outcome (OR = 8.09, P < 0.01). Anticoagulation, aneurysm size and location were not significantly associated with either early rebleeding incidence or functional outcome.ConclusionsEarly rebleeding in aSAH is associated with unfavorable functional outcomes. EVD placement and higher SAH grade on presentation appear to be significantly and independently associated with increased risk of rebleeding within first 24 h, as well as unfavorable long-term functional outcome; however, the clinical benefit of hyper-acute aneurysm treatment requires further investigation.     

Association of cerebrospinal fluid advanced oxidation protein products levels with early brain injury and prognosis of aneurysmal subarachnoid hemorrhage: A preliminary prospective study

ObjectivesIn this study, we investigated the time course in the cerebrospinal fluid (CSF) advanced oxidation protein products (AOPPs) levels in patients with aneurysmal subarachnoid hemorrhage (aSAH), and ascertained the relationship between the levels of AOPPs and early brain injury (EBI), hydrocephalus and prognosis of patients with aSAH.MethodsWe measured the CSF AOPPs levels in 50 patients with aSAH at 1–3 d, 4–6 d, 7–9 d, and 10–12 d after hemorrhage. The modified Fisher grades, Hunt-Hess grades, CSF IL-6 levels, peripheral blood count of white blood cells, cerebral edema scores and hydrocephalus were used to assess the severity of brain injury. Modified Rankin Scale (mRS) scores were used to assess the prognosis. Patients with mRS scores greater than 2 were considered to have a poor outcome.ResultsCSF AOPPs levels were significantly higher in patients with aSAH with poor prognosis, compared to patients with good prognosis and peaked in the early stage. Among patients with aSAH, the levels of CSF AOPPs on days 1–3 were significantly correlated with modified Fisher grades, Hunt-Hess grades, CSF IL-6 levels, peripheral blood count of white blood cells, and cerebral edema scores. Also, in patients with hydrocephalus, early CSF AOPPs levels were significantly elevated. Levels of CSF AOPPs in aSAH patients on days 1–3, 4–6, and 7–9 were independently associated with poor prognosis at the 90-day follow-up, and the optimal area under the curve (AUC) values for CSF AOPPs levels were found on days 1–3.ConclusionsAOPPs may serve as the potential biomarker to assess the severity of EBI and prognosis in patients with aSAH.     

Admission Neutrophil to Lymphocyte Ratio for Predicting Outcome in Subarachnoid Hemorrhage

PurposeWe sought to evaluate the relationship between admission neutrophil-to-lymphocyte ratio (NLR) and functional outcome in aneurysmal subarachnoid hemorrhage (aSAH) patients.Material and methodsConsecutive patients with aSAH were treated at two tertiary stroke centers during a five-year period. Functional outcome was defined as discharge modified Rankin score dichotomized at scores 0-2 (good) vs. 3-6 (poor).Results474 aSAH patients were evaluated with a mean NLR 8.6 (SD 8.3). In multivariable logistic regression analysis, poor functional outcome was independently associated with higher NLR, older age, poorer clinical status on admission, prehospital statin use, and vasospasm. Increasing NLR analyzed as a continuous variable was independently associated with higher odds of poor functional outcome (OR 1.03, 95%CI 1.00-1.07, p=0.05) after adjustment for potential confounders. When dichotomized using ROC curve analysis, a threshold NLR value of greater than 6.48 was independently associated with higher odds of poor functional outcome (OR 1.71, 95%CI 1.07-2.74, p=0.03) after adjustment for potential confounders.ConclusionsHigher admission NLR is an independent predictor for poor functional outcome at discharge in aSAH patients. The evaluation of anti-inflammatory targets in the future may allow for improved functional outcome after aSAH.     

The association between fluid balance and outcomes after subarachnoid hemorrhage

Background

We sought to determine the association between early fluid balance and neurological/vital outcome of patients with subarachnoid hemorrhage.

Methods

Hospital admission, imaging, ICU and outcome data were retrospectively collected from the medical records of adult patients with aneurysmal SAH admitted to a level-1 trauma and stroke referral center during a 5-year period. Two groups were identified based on cumulative fluid balance by ICU day 3: (i) patients with a positive fluid balance (n?=?221) and (ii) patients with even or negative fluid balance (n?=?135). Multivariable logistic regression was used to adjust for age, Hunt-Hess and Fisher scores, mechanical ventilation and troponin elevation (>0.40?ng/ml) at ICU admission. The primary outcome was a composite of hospital mortality or new stroke.

Results

Patients with positive fluid balance had worse admission GCS and Hunt-Hess score, and by ICU day 3 had cumulatively received more IV fluids, but had less urine output when compared with the negative fluid balance group. There was no difference in the odds of hospital death or new stroke (adjusted OR: 1.47, 95%CI: 0.85, 2.54) between patients with positive and negative fluid balance. However, positive fluid balance was associated with increased odds of TCD vasospasm (adjusted OR 2.25, 95%CI: 1.37, 3.71) and prolonged hospital length of stay.

Conclusions

Although handling of IV fluid administration was not an independent predictor of mortality or new stroke, patients with early positive fluid balance had worse clinical presentation and had greater resource use during the hospital course.     

Best Motor Response Predicts Favorable Outcome for “True” WFNS Grade V Patients with Aneurysmal Subarachnoid Hemorrhage

BackgroundThe universal application of ultra-early surgery for World Federation of Neurological Societies (WFNS) grade V aneurysmal subarachnoid hemorrhage (aSAH) patients may lead to the increased implementation of unnecessary treatment. Therefore, this study aimed to refine the patient selection process for timely definitive treatment.MethodsFrom January 2011 to March 2020, a total of 517 aSAH patients were treated at our institution. Among these, 177 aSAH patients with WFNS grade V on admission were identified from our database. Patients with improved grades in response to the initial supportive treatment, with clinical or radiological signs of herniation, and with irreversible signs of brain damage such as bilaterally dilated pupils and global ischemia on follow-up CT scan were excluded. The outcome of definitive treatment for 54 patients without herniation who remained with WFNS grade V after the initial supportive treatment were analyzed to seek any factor for a favorable outcome (modified Rankin scale 0–2).ResultsAmong 54 patients, 19 (35.2%) had a favorable outcome after a definitive treatment. Multivariate logistic regression analysis showed that the best motor response (BMR) 4 on Glasgow Coma Scale was significantly associated with favorable outcomes (odds ratio, 3.76; 95% confidence interval, 1.09–13.0, p = 0.03). The positive predictive value of BMR 4 was 48.3%.ConclusionsAlbeit being simple, BMR 4 may facilitate the prompt aggressive treatment for patients with WFNS grade V including those with “true” grade V who do not have any clinical and radiological signs of herniation.     

C-反应蛋白与动脉瘤性蛛网膜下腔出血临床预后的关系

目的探讨动脉瘤性蛛网膜下腔出血(a SAH)血清C-反应蛋白(CRP)动态变化趋势及其与临床预后的关系。方法2014年1月至2015年8月前瞻性收集符合标准的a SAH 108例,发病72 h内行夹闭术(72例)或血管内栓塞(36例)。术后3个月采用GOS评分评估预后,4~5分为预后良好,1~3分为预后不良。入院时、术后1、3、5、7 d及出院当天,采集清晨空腹静脉血,检测血清CRP水平。采用多因素Logistic回归分析检验预后不良危险因素。结果 108例中,预后良好68例,预后不良40例。多因素Logistic回归分析显示,术后1、3 d血清CRP水平增高是a SAH不良预后的独立危险因素。受试者工作特征曲线分析结果术后3 d血清CRP水平[曲线下面积(AUC)=0.823]与术后1 d(AUC=0.861)相比,对不良预后的发生具有更好的预测价值。术后1 d血清CRP与入院时GCS评分、入院时Fisher评分和入院时Hunt-Hess分级均无明显相关性(P0.05)。术后3 d血清CRP水平与入院时GCS评分无明显相关性,但与入院时Fisher评分(r=0.28;P0.05)、入院时Hunt-Hess分级(r=0.42;P0.05)存在明显相关性。结论术后3 d血清CRP水平升高是a SAH不良预后的独立危险因素,能为不良预后的识别提供临床指导。     

Association of asymptomatic cerebral vasospasm with outcomes in survivors of aneurysmal subarachnoid hemorrhage

BackgroundCerebral vasospasm (cVSP) is a common complication in aneurysmal subarachnoid hemorrhage (aSAH) and is associated with worse outcomes. However, clinical significance of asymptomatic cVSP is poorly understood. We sought to determine the association of asymptomatic cVSP with functional outcome and hospital length of stay (LOS).MethodsWe performed a retrospective study of a prospectively collected cohort of patients with aSAH who survived hospitalization at an academic center between 2016 and 2021. We defined cVSP based on transcranial Doppler criteria. Multivariate logistic and multiple linear regression analyses were used to determine the association of asymptomatic cVSP with poor functional outcome (defined as modified Rankin scale 3-6 at 3 months after discharge) and hospital length of stay (LOS).ResultsThe cohort consisted of 201 aSAH patients with a mean age 54.9 years (SD 13.6) and 60% were female. One hundred nine patients (54%) experienced cVSP, of whom 43 patients (39%) were asymptomatic. Patients with asymptomatic cVSP were younger (mean 50.5 years [SD 10.6] vs 61 years [SD12.5]; p < 0.001) and had longer ICU LOS (median 13 days [IQR12-20] vs median 12 days [IQR9-15], p = 0.018) compared to those without cVSP. However, after adjusting with other variables asymptomatic cVSP was not associated with longer ICU or hospital LOS. Asymptomatic cVSP was not associated with poor outcome either (p = 0.14).ConclusionAsymptomatic cVSP, which was more common in younger patients, was neither associated with poor functional outcome nor hospital LOS.  Larger prospective studies are needed to assess the significance of asymptomatic cVSP on long-term outcomes.     

脑梗死发生时间对动脉瘤性蛛网膜下腔出血患者临床结局的影响

目的探究脑梗死发生时间对动脉瘤性蛛网膜下腔出血患者(aSAH)临床结局的影响。方法纳入2010年3月至2016年6月来我院进行就诊的aSAH患者395例,其中发生早期脑梗死患者74例,迟发性脑梗死患者77例,两者并发患者29例。分析aSAH术后脑梗死患者临床特征;采用多因素Logistic回归分析术后脑梗死发生的独立危险因素和长期预后的独立危险因素。结果多因素Logistic回归分析显示Hunt～Hess≥Ⅲ级和手术夹闭术是早期脑梗死发生的独立危险因素(P0.05);Hunt～Hess≥Ⅲ级和血管痉挛是迟发性脑梗死发生的独立危险因素(P0.05);早期脑梗死是术后a SHA患者长期不良预后的独立危险因素(OR,2.43;95%CI,1.16～4.72;P0.001)。结论 Hunt～Hess≥Ⅲ级和手术夹闭术是aSAH患者术后并发早期脑梗死的独立危险因素,而Hunt～Hess≥Ⅲ级和血管痉挛则是迟发性脑梗死的独立危险因素。早期脑梗死比迟发性脑梗死更能预测aSAH患者术后的不良预后。     

Role of Endothelin-1 in Human Aneurysmal Subarachnoid Hemorrhage: Associations with Vasospasm and Delayed Cerebral Ischemia

Background

Endothelin-1 (ET-1) is a potent vasoconstrictor implicated in the pathogenesis of vasospasm and delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH) patients. The aim of this study was to investigate the relationship between cerebrospinal fluid (CSF) ET-1 levels and angiographic vasospasm and DCI.

Methods

Patients with aSAH were consented (n?=?106). Cerebral vasospasm was determined by angiography. DCI was determined by transcranial Doppler (TCD) results and/or angiogram results with corresponding clinical deterioration. CSF ET-1 levels over 14?days after the initial insult was quantified by ELISA. ET-1 analysis included a group-based trajectory analysis and ET-1 exposure rate during 24, 48, and 72?h prior to, as well as 72?h post angiography, or clinical deterioration.

Results

Trajectory analysis revealed two distinct groups of subjects with 56% of patients in the low ET-1 trajectory group (mean at day 1?=?0.31?pg/ml; SE?=?0.04; mean at day 14?=?0.41?pg/ml; SE?=?0.15) and 44% of patients in the high ET-1 trajectory group (mean at day 1?=?0.65?pg/ml; SE?=?0.08; mean at day 14?=?0.61?pg/ml; SE?=?0.06). Furthermore, we observed that ET-1 exposure rate 72?h before angiography and clinical spasm was a significant predictor of both angiographic vasospasm and DCI, whereas, ET-1 exposure after angiography and clinical spasm was not associated with either angiographic vasospasm or DCI.

Conclusion

Based on these results we conclude that ET-1 concentrations are elevated in a sub-group of patients and that the acute (72?h prior to angiography and clinical neurological deterioration), but not chronic, elevations in CSF ET-1 concentrations are indicative of the pathogenic alterations of vasospasm and DCI in aSAH patients.     

Correlation of Clinical Outcome with Pressure-, Oxygen-, and Flow-Related Indices of Cerebrovascular Reactivity in Patients Following Aneurysmal SAH

Background  

Impaired cerebrovascular reactivity (CR) has been reported to be associated with adverse outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, CR may be determined using different paradigms and it is unclear, which measurement method most suitable reflects the clinical course or is able to predict clinical deterioration.     

Prediction of cerebral infarction and patient outcome in aneurysmal subarachnoid hemorrhage: comparison of new and established radiographic,clinical and combined scores

Background and purpose

There are numerous grading scales to describe the severity of aneurysmal subarachnoid hemorrhage (aSAH) and to predict outcome. Historically, outcome measures are heterogeneous and the comparability of grading scales is therefore limited. We designed this study to compare radiographic, clinical and combined grading systems in aSAH.

Methods

Data from 423 consecutive patients with aSAH were analyzed. Modified Fisher (mFish), Barrow Neurological Institute (BNI), Hunt and Hess (HH), World Federation of Neurosurgical Societies (WFNS), VASOGRADE (VG) and HAIR scores were calculated from clinical and radiographic data or the combination of both. Outcome measures included the development of new cerebral infarction (CI) and functional patient outcome assessed by the modified Rankin scale.

Results

Cerebral infarction and unfavorable outcome were predicted by radiographic, clinical and combined measures (each with P ≤ 0.001). Clinical (HH, WFNS) and combined (VG, HAIR) scores had superior predictive power for CI compared with mFish grading but not BNI [area under the curve (AUC)_mFish 0.612, AUC_BNI 0.616, AUC_WFNS 0.672, AUC_HH 0.673, AUC_VG 0.674, AUC_HAIR 0.638]. Predictive performances of clinical gradings (HH, WFNS) for patient outcome were superior to radiographic measures and of similar quality or better than combined systems (AUC_BNI 0.628, AUC_mFish 0.654, AUC_WFNS 0.736, AUC_HH 0.749, AUC_VG 0.711, AUC_HAIR 0.739).

Conclusions

Knowledge of the merits and limitations of clinical, radiographic and combined scores is necessary in routine clinical practice. The new combined grading systems (HAIR, VG) showed no superiority compared with the established clinical measures (WFNS, HH) in predicting CI and unfavorable patient outcome.     

Results of surgery for aneurysmal subarachnoid haemorrhage in northern Norway: a retrospective study with special focus on timing of surgery in a rural area

OBJECTIVES: This study reports data on time consumption before aneurysm surgery and the results of treatment in northern Norway. MATERIAL AND METHODS: A total of 279 cases were identified and included in our analysis of time span from bleeding to arrival at our department. Fifty-one patients were treated conservatively, either because of bad clinical condition or because angiography revealed no aneurysm. The remaining 228 patients were operated and included in our analysis of outcome after early aneurysm surgery. RESULTS: Among all 279 patients with aneurysmal subarachnoid haemorrhage (SAH), median time from ictus to arrival at the university hospital was 1 (0-30) day. Forty-one per cent arrived at the day of bleeding and 86% within the first 3 days after bleeding. Among the 228 patients who underwent surgical aneurysm repair, median time from bleeding to operation was 2 (0-33) days. Early aneurysm surgery (< 72 h) was performed in 146 patients (64%). Fifty patients (22%) underwent intermediate surgery (days 4-10) and 32 patients (14%) were operated later (day 11 or later). A significant association was found between Hunt and Hess (HH) grade and Glasgow Outcome Scale (GOS) score (P < 0.001). CONCLUSIONS: Most patients suffering aneurysmal SAH in northern Norway undergo early aneurysm surgery and the outcome is comparable with that obtained in other Scandinavian centres. Initial Hunt and Hess grade is a major determinant for outcome in aneurysmal subarachnoid haemorrhage.     

Sodium Variability and Probability of Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage

ObjectivesVasospasm is a well-known complication of aneurysmal subarachnoid hemorrhage (aSAH) that generally occurs 4–14 days post-hemorrhage. Based on American Heart Association guidelines, the current understanding is that hyponatremic episodes may lead to vasospasm. Therefore, we sought to determine the association between repeated serum sodium levels of aSAH patients and its relationship to radiographic vasospasm.Materials and methodsA single-center retrospective analysis from 2007–2016 was conducted of aSAH patients. Daily serum sodium levels were recorded up to day 14 post-admission. Hyponatremia was defined as a serum sodium value of < 135 mEq/L. We evaluated the relationship to radiologic vasospasm, neurologic deterioration, functional status at discharge, and mortality. A repeated measures analysis using a mixed-effect regression model was performed to assess the interindividual relationship between serum sodium trends and outcomes.ResultsA total of 271 aSAH patients were included. There were no significant differences in interindividual serum sodium values over time and occurrence of radiographic vasospasm, neurologic deterioration, functional, or mortality outcomes (p = .59, p = .42, p = .94, p = .99, respectively) using the mixed-effect regression model. However, overall mean serum sodium levels were significantly higher in patients who had neurologic deterioration, poor functional outcome (mRS 3-6), and mortality.ConclusionsSerum sodium level variations are not associated with subsequent development of cerebral vasospasm in aSAH patients. These findings indicate that serum sodium may not have an impact on vasospasm, and avoiding hypernatremia may provide a neurologic, functional and survival benefit.     

Organic psychiatric disorders after aneurysmal SAH: outcome and associations with age,bleeding severity,and arterial hypertension

OBJECTIVES: The Lindqvist & Malmgren's system was used to describe the outcome of organic psychiatric disorders (OPDs) after aneurysmal subarachnoid hemorrhage (aSAH) and their associations with age, bleeding severity, and pre-existing arterial hypertension (preAH). MATERIAL AND METHOD: OPDs were diagnosed at 3, 6, and 12 months after aSAH in a prospective cohort study (n=63). Reaction level (RLS85), World Federation of Neurological Surgeons Committee SAH scale (WFNS), Fisher, and hydrocephalus grades were assessed at admission. RESULTS: At 3/6/12 months, 60/49/38% had an Astheno-emotional disorder (AED), 4/5/5% had emotional-motivational blunting disorder (EMD) and 19/19/16% had Korsakoffs amnestic disorder (KAD). AED was associated with preAH, whereas EMD/KAD, but not AED, was associated with a higher mean age, worse median RLS85 levels, WFNS grades, and Fisher grades. CONCLUSIONS: OPDs were diagnosed in 59% of the patients at 12 months after aSAH. AED, the most common OPD, had the highest recovery rate and was associated with preAH. Use of organic psychiatric diagnoses for evaluation of outcome after aSAH and other brain injuries is encouraged.     

Safety of early rehabilitation in patients with aneurysmal subarachnoid hemorrhage: A retrospective cohort study

ObjectiveTo investigate the safety and efficacy of early rehabilitation in patients with aneurysmal subarachnoid hemorrhage (aSAH) patients.MethodsOne hundred eleven patients with aSAH admitted between April 2015 and March 2019, were retrospectively evaluated. The early rehabilitation program was introduced in April 2017 to actively promote mobilization and walking training for aSAH patients. Therefore, patients were divided into two groups (The conventional group (n = 55) and the early rehabilitation group (n == 56). Clinical characteristics, mobilization progression, and treatment variables were analyzed. Complications (rebleeding, symptomatic cerebral vasospasm, hydrocephalus, disuse complications,) and a modified Rankin Scale (mRS) at 90 days were compared in two groups. Factors associated with favorable outcomes (mRS≤2) at 90 days were also assessed.ResultsThe early rehabilitation group had a significantly shorter span to first walking (9 vs. 5 days; P = 0.007). The prevalence of complications was not significantly increased in the early rehabilitation group. Approximately 40% of patients in both groups had pneumonia and urinary tract infections but significantly reduced antibiotic-administration days (13 vs. 6 days; P < 0.001). mRS at 90 days also showed significant improvement in the early rehabilitation group (3 vs. 2; P=0.01). Multivariate logistic regression analysis of favorable outcomes associated that the administration of the early rehabilitation program has a significant independent factor (odds ratio, 3.03; 95% confidence interval, 1.1-8.37).ConclusionsEarly rehabilitation for patients with aSAH can be feasible without increasing complication occurrences. The early rehabilitation program with active mobilization and walking training reduced antibiotic use and was associated with improved independence.     

Spontaneous Elevation of Blood Pressure After SAH: An Epiphenomenon of Disease Severity and Demand,But Not a Surrogate for Outcome?

Background

Spontaneous blood pressure increase is frequently observed after aneurysmal subarachnoid hemorrhage (aSAH). These episodes of spontaneous blood pressure alterations are usually tolerated under the assumption of an endogenous response to maintain cerebral perfusion. The relevance of blood pressure variability and its relationship to disease severity and outcome, however, remain obscure.

Methods

A total of 115 consecutive patients with aSAH were included for this retrospective analysis of a continuously collected data pool. Demographics, initial clinical severity of aSAH (HH°, mFS), treatment modality, clinical course, and outcome (development of DCI, cerebral infarction, and GOS after 3 months) were recorded. Hemodynamic information—recorded automatically with a frequency of 1/15 min—was analyzed for spontaneous blood pressure increase (SBI) and endogenous persistent hypertension (EPH) after exclusion of iatrogenic factors and relevant co-medication. Subgroup analysis included stratification for day 0–3, 4–14, and 14–21.

Results

SBI and EPH incidence varied from 17 to 84% depending on detection threshold (15–35 mmHg) and time period under scrutiny. Incidence of blood pressure increase correlated with disease severity upon admission (p < 0.05), but the anticipated association with outcome was not observed. SBI and EPH were more likely to occur between day 4 and 14 (p < 0.001), but only early occurrence (day 0–3) was associated with higher incidence of DCI (p < 0.05). Persistent blood pressure elevation between day 4 and 21 was associated with fewer DCI. However, no influence of spontaneous upregulation on clinical outcome after three months was observed.

Conclusions

Spontaneous hemodynamic upregulation is a frequent phenomenon after aSAH. Our data support the hypothesis that spontaneous blood pressure alterations reflect an endogenous, demand-driven response correlating with disease severity. Early alterations may indicate an aggravated clinical course, while later upregulation in particular—if permitted—does not translate into a higher risk of unfavorable outcome.

     

血清尿酸与动脉瘤性蛛网膜下腔出血患者Hunt-Hess分级及短期预后相关性研究

目的探讨血清尿酸（SUA）与动脉瘤性蛛网膜下腔出血（aSAH）Hunt-Hess（H-H）分级及短期预后之间的相关性。 方法回顾性分析武警医学特色中心脑科中心自2012年1月至2018年12月收治的293例aSAH患者的临床资料，搜集纳入患者的H-H分级、SUA水平、性别、年龄、高血压病史及出院时GOS评分等资料。根据入院时SUA水平、病情的轻重（H-H分级）、转归分别进行分组，分析SUA与aSAH患者H-H分级及短期预后之间的关系，以及影响aSAH患者入院H-H分级不同的因素。 结果3组aSAH患者不同SUA水平的H-H分级比较，差异具有统计学意义（χ²=10.790，P=0.005）。Logistic回归分析显示，SUA的不同是造成H-H分级不同的独立危险因素（P<0.05）。不同SUA水平患者的预后良好率比较，差异均具有统计学意义（P<0.05）。入院H-H 4~5级与H-H 1~3级的预后良好率比较，差异具有统计学意义（P<0.05）。 结论aSAH患者入院时SUA水平不同，其H-H分级也不同，SUA的不同是造成H-H分级不同的独立危险因素，SUA水平差异一定程度提示aSAH患者短期预后不同。     

Preventing Vasospasm Improves Outcome After Aneurysmal Subarachnoid Hemorrhage: Rationale and Design of CONSCIOUS-2 and CONSCIOUS-3 Trials

Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is a frequent but unpredictable complication associated with poor outcome. Current vasospasm therapies are suboptimal; new therapies are needed. Clazosentan, an endothelin receptor antagonist, has shown promise in phase 2 studies, and two randomized, double-blind, placebo-controlled phase 3 trials (CONSCIOUS-2 and CONSCIOUS-3) are underway to further investigate its impact on vasospasm-related outcome after aSAH. Here, we describe the design of these studies, which was challenging with respect to defining endpoints and standardizing endpoint interpretation and patient care. Main inclusion criteria are: age 18–75 years; SAH due to ruptured saccular aneurysm secured by surgical clipping (CONSCIOUS-2) or endovascular coiling (CONSCIOUS-3); substantial subarachnoid clot; and World Federation of Neurosurgical Societies grades I–IV prior to aneurysm-securing procedure. In CONSCIOUS-2, patients are randomized 2:1 to clazosentan (5 mg/h) or placebo. In CONSCIOUS-3, patients are randomized 1:1:1 to clazosentan 5, 15 mg/h, or placebo. Treatment is initiated within 56 h of aSAH and continued until 14 days after aSAH. Primary endpoint is a composite of mortality and vasospasm-related morbidity within 6 weeks of aSAH (all-cause mortality, vasospasm-related new cerebral infarction, vasospasm-related delayed ischemic neurological deficit, neurological signs or symptoms in the presence of angiographic vasospasm leading to rescue therapy initiation). Main secondary endpoint is extended Glasgow Outcome Scale at week 12. A critical events committee assesses all data centrally to ensure consistency in interpretation, and patient management guidelines are used to standardize care. Results are expected at the end of 2010 and 2011 for CONSCIOUS-2 and CONSCIOUS-3, respectively.

     

Midline Shift is Unrelated to Subjective Pupillary Reactivity Assessment on Admission in Moderate and Severe Traumatic Brain Injury

Background

Early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH) is defined as brain injury occurring within 72 h of aneurysmal rupture. Although EBI is the most significant predictor of outcomes after aSAH, its underlying pathophysiology is not well understood. We hypothesize that EBI after aSAH is associated with an increase in peripheral inflammation measured by cytokine expression levels and changes in associations between cytokines.

Methods

aSAH patients were enrolled into a prospective observational study and were assessed for markers of EBI: global cerebral edema (GCE), subarachnoid hemorrhage early brain edema score (SEBES), and Hunt–Hess grade. Serum samples collected at ≤ 48 h of admission were analyzed using multiplex bead-based assays to determine levels of 13 pro- and anti-inflammatory cytokines. Pairwise correlation coefficients between cytokines were represented as networks. Cytokine levels and differences in correlation networks were compared between EBI groups.

Results

Of the 71 patients enrolled in the study, 17 (24%) subjects had GCE, 31 (44%) subjects had SEBES ≥ 3, and 21 (29%) had HH ≥ 4. IL-6 was elevated in groups with GCE, SEBES ≥ 3, and HH ≥ 4. MIP1β was independently associated with high-grade SEBES. Correlation network analysis suggests higher systematic inflammation in subjects with SEBES ≥ 3.

Conclusions

EBI after SAH is associated with increased levels of specific cytokines. Peripheral levels of IL-10, IL-6, and MIP1β may be important markers of EBI. Investigating systematic correlations in addition to expression levels of individual cytokines may offer deeper insight into the underlying mechanisms related to EBI.

     

Systemic Inflammation Response Index and Systemic Immune-inflammation Index for Predicting the Prognosis of Patients with Aneurysmal Subarachnoid Hemorrhage

ObjectivesInflammatory response plays a pivotal role in the progress of aneurysmal subarachnoid hemorrhage (aSAH). As novel inflammatory markers, systemic inflammation response index (SIRI) and systemic immune-inflammation (SII) index could reflect clinical outcomes of patients with various diseases. The aim of this study was to ascertain whether initial SIRI and SII index were associated with prognosis of aSAH patients.MethodsA total of 680 patients with aSAH were enrolled. Their prognosis was evaluated with modified Rankin Scale (mRS) at 3 months, and unfavorable clinical outcome was defined as mRS score of 3-6. Receiver operating characteristic (ROC) curve analysis was performed to identify cutoff values of SIRI and SII index for predicting clinical outcomes. Univariate and multivariate regression analyses were performed to explore relationships of SIRI and SII index with prognosis of patients.ResultsOptimal cutoff values of SIRI and SII index to discriminate between favorable and unfavorable clinical outcomes were 3.2 × 10⁹/L and 960 × 10⁹/L, respectively (P < 0.001 and 0.004, respectively). In multivariate analysis, SIRI value ≥ 3.2 × 10⁹/L (odds ratio [OR]: 1.82, 95% CI: 1.46–3.24; P = 0.021) and SII index value ≥ 960 × 10⁹/L (OR: 1.68, 95% CI: 1.24–2.74; P = 0.040) were independent predicting factors for poor prognosis after aSAH.ConclusionsSIRI and SII index values are associated with clinical outcomes of patients with aSAH. Elevated SIRI and SII index could be independent predicting factors for a poor prognosis after aSAH.