Endothelin and aneurysmal subarachnoid haemorrhage: a study of subarachnoid cisternal cerebrospinal fluid.

Endothelin (ET) is considered one of the most potent vasoconstrictor polypeptides; several experimental studies have suggested its possible role in the pathogenesis of arterial vasospasm after subarachnoid haemorrhage (SAH). Previously reported data on plasma and CSF levels of endothelin in patients with a diagnosis of SAH have been controversial. Cisternal endothelin CSF levels and the possibility that they could be related to vasospasm and other clinical patterns of SAH were investigated. CSF samples were obtained from 55 patients admitted after angiographic diagnosis of intracranial aneurysm. Levels of ET-1 and ET-3 were measured through radio-immunoassay technique. Twelve patients who had operations for unruptured aneurysms were considered control cases; 43 patients with SAH were classified according to: Hunt and Hess grading at admission, vasospasm grading, CT classification and timing of surgery. In all 55 patients ET-1 was measured, while positive levels of ET-3 were found only in 17 cases of 48. No linear correlation was found between cisternal CSF ET-1 levels when considering time of surgery, CT classification, Hunt and Hess grading at admission, and vasospasm grading. The results of ET-3 assay should be considered with great caution because of the low percentage of positive cases. Cisternal CSF levels of ET-1 and ET-3 are not directly related to the occurrence of arterial vasospasm after the aneurysm rupture, or to other major clinical patterns of SAH; however, ET-1 expression occurs either in paraphysiological (unruptured aneurysm) or in pathological conditions (SAH). It is suggested that ET may potentiate, or may be potentiated by, other factors playing a consistent pathophysiological role in the development of vasospasm.     

Vasopressin and oxytocin in CSF and plasma of patients with aneurysmal subarachnoid haemorrhage

Objective

Clinicopathological studies on patients succumbing to subarachnoid haemorrhage (SAH) demonstrated hypothalamic lesions. The implication of the hypothalamic neuropeptides arginine-vasopressin (AVP) and oxytocin (OXT) has not been linked to aneurysmal SAH yet. This study investigates AVP and OXT in CSF and plasma of patients with spontaneous aneurysmal SAH and their association with outcome.

Methods

CSF and plasma samples of 12 patients with aneurysmal SAH were prospectively studied for 2 weeks. AVP and OXT were measured by radioimmunoassay. Outcome was assessed on Glasgow-Outcome-Scale. Twenty-nine patients without neuropsychiatric disturbances served as controls. Differences in neuropeptide concentration time courses were assessed by regression models. Group comparisons were performed by Kruskal–Wallis and correlations by Spearman tests.

Results

Regression of CSF levels between patients with poor and good outcome revealed significantly lower levels of AVP in patients with poor outcome (p = 0.012) while OXT showed a trend towards lower levels (p = 0.063). In plasma, no significant differences between outcome groups were found. Group comparisons between poor outcome patients and controls revealed significant differences in CSF for AVP (p = 0.001) and OXT (p = 0.015). In plasma, AVP yielded significantly different results while OXT did not. No differences were found between the good outcome group and controls. Plasma and CSF concentrations showed no significant correlation.

Conclusion

Patients with poor outcome after aneurysmal SAH have lower AVP and OXT levels in CSF than patients with good outcome while neuropeptide levels in plasma failed to reflect differences in outcome. The data indicate hypothalamic damage as an aetiologic factor for outcome after aneurysmal SAH.     

Lower initial red blood cell count in cerebrospinal fluid predicts good functional outcome in patients with spontaneous subarachnoid haemorrhage

Background and purpose

Red blood cell (RBC) degradation after subarachnoid haemorrhage (SAH) negatively affects functional outcome. Although the detection of RBCs in the cerebrospinal fluid (CSF) is a widely available part of neurological routine diagnostics, the prognostic value as a biomarker remains unclear. This study was undertaken to investigate whether CSF RBC count correlates with established radiological markers of SAH volume and whether the CSF RBC count can predict functional outcome in SAH patients.

Methods

A total of 121 consecutive spontaneous SAH patients were retrospectively analyzed. CSF was collected from external ventricular drain as part of routine diagnostic procedures. We used multivariable binary logistic regression to investigate associations between CSF RBC counts and functional outcome 3 months after SAH or hospital survival. Good functional outcome was defined as modified Rankin Scale ≤ 2.

Results

Patients' age was 60 ± 14 years, and the median admission Hunt & Hess grade (H&H) was 4. CSF samples were collected 2 days after intensive care unit admission. High CSF RBC counts positively correlated with radiological measurements for SAH volume, for example, modified Fisher score (p = 0.002) and Hijdra ventricle score (p = 0.016). Multivariable regression analysis adjusted for age, H&H grade, modified Fisher and Hijdra scores showed that low CSF RBC counts predicted hospital survival (per 100,000 CSF RBCs: adjusted odds ratio [adjOR] = 0.74, 95% confidence interval [CI] = 0.61–0.89, p = 0.001) and good functional outcome after 3 months (per 100,000 CSF RBC: adjOR = 0.76, 95% CI = 0.60–0.96, p = 0.020).

Conclusions

CSF RBC counts correlate with radiographic scores quantifying SAH volume and may serve as an early independent biomarker for hospital survival and good functional 3-month outcome in patients requiring ventriculostomy after SAH.     

出血性脑卒中病人血浆和脑脊液β-内啡肽、GnRH、NO、CGRP的变化及意义

目的 探讨出血性脑卒中病人血浆和脑脊液β-内啡肽、促性腺激素释放激素（GnRH）、一氧化氮（NO）、降钙素基因相关肽（CGRP）的变化及意义。方法 选取2017年6月至2018年12月收治的高血压性脑出血（HICH）80例为HICH组,自发性蛛网膜下腔出血（SAH）52例为SAH组,以无神经系统疾病40例为对照组。检测血浆和脑脊液β-内啡肽、GnRH、CGRP、NO水平。结果 入院时,HICH组和SAH组血浆和脑脊液β-内啡肽、GnRH水平明显增高（P<0.05）,而血浆和脑脊液NO、CGRP水平明显降低（P<0.05）。入院后1、3、7、14、30 d,HICH组和SAH组血浆和脑脊液β-内啡肽、GnRH水平逐渐下降（P<0.05）。入院后1、3、7 d,HICH组、SAH组血浆和脑脊液NO、CGRP水平逐渐下降（P<0.05）,入院后14、30 d明显上升（P<0.05）。结论 β-内啡肽、GnRH、NO、CGRP参与HICH及SAH病人下丘脑应激反应,以SAH更明显。     

High ICP as trigger of proinflammatory IL-6 cytokine activation in aneurysmal subarachnoid hemorrhage

Abstract

Objective: There is a rising debate about the role of inflammation in the pathogenesis of complications after aneurysmal subarachnoid hemorrhage (SAH) such as intracranial hypertension (intracranial pressure, ICP >20 mmHg). This study aimed to analyse the origin of interleukin-6 (IL-6) in respect to ICP and cerebral metabolism in SAH patients.

Methods: Prospectively, IL-6 was measured in three compartments, the extracellular fluid (ECF) monitored by cerebral microdialysis (MD), cerebrospinal fluid (CSF) and plasma for 10 days after SAH (days 0–4, three times daily; days 5–10, two times daily). Patients were classified having intracranial hypertension (n=7) or normal ICP (n=17) during 10 days after bleeding. Glasgow outcome scale (GOS) was assessed after 3 and 6 months.

Results: Patient groups were comparable for age, WFNS and Fisher grade. Intracranial hypertension was associated with an inflammatory response, indicating activation of the inflammatory cascade in the brain (ECF) and systemic circulation with high IL-6 and C-reactive protein (CRP) plasma levels after SAH, the latter associated with unfavourable outcome. The data suggest the ECF but not the CSF as main origin of IL-6 in the systemic circulation in the presence of intracranial hypertension in SAH.

Discussion: Intracranial hypertension is associated with a strong activation of the inflammatory cascade in the brain and systemic circulation, and might be underestimated as proinflammmatory trigger in the pathogenesis of complications after SAH. Future therapies targeting anti-inflammatory response in plasma may help to reduce the inflammatory cascade responsible for development of intracranial hypertension.     

CT and clinical correlations in recent aneurysmal subarachnoid hemorrhage: a preliminary report of the Cooperative Aneurysm Study

Computed tomography was performed on 1,378 patients admitted within 3 days of subarachnoid hemorrhage (SAH) at 71 centers in a cooperative study. CT on the day of SAH (day 0) was abnormal in 95.8%. Intracranial blood was detected in 95.3% of patients on day 0, 90.5% on the first day after SAH (day 1), and 73.8% on day 3. CT was normal in only 1 of 284 patients in stupor or coma but was normal in 14.6% of 638 alert patients. In the first few days after SAH, CT is highly accurate, often obviating the need of CSF examinations. The interval from SAH until CT and the seriousness of the patient's condition are two factors that influence the results of CT.     

Determinants of Central Sympathetic Activation in Spontaneous Primary Subarachnoid Hemorrhage

Background

Subarachnoid hemorrhage (SAH) has been associated with pronounced acute sympathetic activation. The purpose of this investigation is to identify demographic, clinical, radiological, and anatomical features of SAH that relate to sympathetic activation.

Methods

Observational study of consecutive Grades 3?C5 SAH patients requiring ventriculostomy and undergoing endovascular aneurysmal obliteration. All patients underwent cerebrospinal fluid (CSF) sampling within 48?h of SAH onset, and samples were assayed for various catecholamine compounds and metabolites. Univariate analyses were performed to identify variables associated with catecholamine levels, and to correlate linearity among catecholamine compounds and metabolites. Variables demonstrating a possible association and variables of interest were entered into linear regression models to determine predictors of catecholamine elevations.

Results

Of the 102 patients, mean age was 58?years and 74% were female; 42% were Hunt?CHess (H/H) grade 4/5, 61% had a computed tomography (CT) score of 3/4, 57% had anterior cerebral or communicating artery (ACA/ACom) aneursysms, and 23% had aneurysms in the posterior circulation. In the univariate analysis, age, gender, H/H grade, CT score, and aneurysm location demonstrated various associations with catecholamine levels, and substantial positive correlations existed between the various catecholamine compounds and metabolites. Linear regression analyses revealed H/H grade to be an independent predictor of elevated CSF epinephrine (EPI), 3,4-dihydroxyphenylalanine (DOPA) and 3,4-dihydroxyphenyl acetic acid (DOPAC) levels, and of the norepinephrine/3,4-dihydroxyphenylglycol (NE/DHPG) ratio (p?p?p?Conclusions Central sympathetic activation relates to clinical severity and female gender. No definitive associations were found for age, hemorrhage amount, or aneurysm location.     

Increased cerebrospinal fluid concentrations of asymmetric dimethylarginine correlate with adverse clinical outcome in subarachnoid hemorrhage patients

Elevated cerebrospinal fluid (CSF) concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been found in patients with subarachnoid hemorrhage (SAH). In addition, CSF levels of ADMA are associated with the severity of vasospasm. However, the relation between CSF ADMA levels and the clinical outcome of SAH patients is still unclear. We hypothesized that elevated ADMA levels in CSF might be related to the clinical outcome of SAH patients. CSF ADMA levels were measured in 20 SAH patients at days 3–5, days 7–9 and days 12–14 after SAH onset using high-performance liquid chromatography. Cerebral vasospasm was assessed by transcranial Doppler ultra sonography. Clinical outcome at 2 year follow-up was evaluated using the Karnofsky Performance Status scale (KPS). CSF ADMA concentrations in all SAH patients were significantly increased at days 3–5 (p = 0.002) after SAH, peaked on days 7–9 (p < 0.001) and remained elevated until days 12–14 (p < 0.001). In subgroup analysis, significant increases of CSF ADMA levels were found in patients both with and without vasospasm. The KPS scores significantly correlated with CSF levels of ADMA at days 7–9 (correlation coefficient = −0.55, p = 0.012; 95% confidence interval −0.80 to −0.14). Binary logistic regression analysis indicated that higher ADMA level at days 7–9 predicted a poor clinical outcome at 2 year follow-up after SAH (odds ratio = 1.722, p = 0.039, 95% confidence interval 1.029 to 2.882). ADMA may be directly involved in the pathological process and future adverse prognosis of SAH.     

Effectiveness of papaverine cisternal irrigation for cerebral vasospasm after aneurysmal subarachnoid hemorrhage and measurement of biomarkers

Cisternal irrigation with thrombolytic agents was used to prevent post-SAH vasospasm, but its role remained inconclusive. To verify effectiveness of papaverine (PPV) in preventing vasospasm, we studied relationship between inflammatory biologic markers and vasospasm. This prospective study included 121 patients with clipped anterior circulation aneurysms that had ruptured, and 372 control patients. Patients were divided into three groups according to cisternal irrigation method: simple drain, papaverine group, and urokinase (UK) group. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined in CSF and serum on days 3 and 7 after SAH. The PPV group showed similar incidence of vasospasm with UK group, but lower incidence than the simple drain group. The levels of ICAM-1 and VCAM-1 were significantly higher in the SAH group than in the control group. CSF and serum levels were more elevated on day 7 than day 3, and the degree of elevation were more marked when measured in the CSF than in the serum. However, there was no statistical difference between measured levels of ICAM-1 and VCAM-1, and vasospasm development. PPV cisternal irrigation was similarly effective as UK at preventing vasospasm. Although neither PPV nor UK irrigation could reduce the concentration of adhesion molecules compared with simple drain, we found levels of ICAM-1 and VCAM-1 were specifically elevated in the CSF. Therefore, further research should focus on anti-inflammation as a therapeutic target against cerebral vasospasm and on the CSF as the optimum place where such inflammatory action practically brought about.     

L-dopa pharmacokinetics in plasma and cisternal and lumbar cerebrospinal fluid of monkeys

The pharmacokinetics of levodopa (L-dopa) in plasma and in cisternal and lumbar cerebrospinal fluid (CSF) were studied in Rhesus monkeys that were given 2- to 3-hour intravenous infusions of L-dopa. Steady-state L-dopa concentrations in cisternal CSF correlated well with plasma levels, and yielded a CSF:plasma ratio of 0.17. The disappearance of L-dopa from plasma and cisternal CSF compartments fits an open, two-compartment pharmacokinetic model. Although slower, the distribution and elimination half-lives for L-dopa from cisternal CSF (8.9 and 49.2 minutes, respectively) were of a similar magnitude to those from plasma (4.9 and 33.2 minutes, respectively). If cisternal CSF reflects brain extracellular fluid, then plasma pharmacokinetics of L-dopa are a reasonable approximation of those in the brain. In contrast to cisternal CSF, the disappearance of L-dopa from lumbar CSF fits an open, one-compartment model with an elimination half-life of 100 minutes. This indicates that the lumbar CSF compartment is unsuitable for investigation of the pharmacokinetics of L-dopa in the brain.     

CSF lipocalin-2 increases early in subarachnoid hemorrhage are associated with neuroinflammation and unfavorable outcome

Lipocalin-2 mediates neuro-inflammation and iron homeostasis in vascular injuries of the central nervous system (CNS) and is upregulated in extra-CNS systemic inflammation. We postulate that cerebrospinal fluid (CSF) and blood lipocalin-2 levels are associated with markers of inflammation and functional outcome in subarachnoid hemorrhage (SAH). We prospectively enrolled 67 SAH subjects, serially measured CSF and plasma lipocalin-2, matrix metallopeptidase 9 (MMP-9), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) on post-SAH days 1-5 and assessed outcome by modified Rankin Scale (mRS) every 3 months. Unfavorable outcome is defined as mRS > 2. Twenty non-SAH patients undergoing lumbar drain trial were enrolled as controls. Lipocalin-2 was detectable in the CSF and significantly higher in SAH compared to controls (p < 0.0001). Higher CSF LCN2 throughout post-SAH days 1-5 was associated with unfavorable outcome at 3 (p = 0.0031) and 6 months (p = 0.014). Specifically, higher CSF lipocalin-2 on post-SAH days 3 (p = 0.036) and 5 (p = 0.016) were associated with unfavorable 3-month outcome. CSF lipocalin-2 levels positively correlated with CSF IL-6, TNF-α and MMP-9 levels. Higher plasma lipocalin-2 levels over time were associated with worse 6-month outcome. Additional studies are required to understand the role of lipocalin-2 in SAH and to validate CSF lipocalin-2 as a potential biomarker for SAH outcome.     

Inflammatory cytokine cascade released by leukocytes in cerebrospinal fluid after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) elicits an inflammatory response in the subarachnoid space, which is mediated by the release of various cytokines. To assess their involvement in post-hemorrhagic complications, we determined the source and time-course of the release of inflammatory cytokines and acute-phase proteins in cerebrospinal fluid (CSF) following SAH. Concentrations of interleukin (IL)- 1beta, IL-6, transforming growth factor-beta1 (TGF-beta1) and C-reactive protein (CRP) in CSF of 36 patients with SAH were measured by enzyme-linked immunoabsorbent assay (ELISA). Floating cells collected from the CSF were centrifuged four to six days after SAH, and examined immunohistochemically. Intracellular IL-1beta and IL-6 were examined by flow cytometric analysis. The molecular weight of TGF-beta1 in CSF of 30 patients was examined by Western blot analysis. The TGF-beta1 levels of patients who had undergone ventriculoperitoneal (VP) shunt (n = 19) was significantly higher than nonshunt group (n = 16). The CRP levels of VP shunt group was significantly higher than nonshunt group. IL-6 concentration was maximal within day 0-1 and it was secreted by neutrophils and monocytes. ELISA showed consistently low levels of IL-1beta, whereas a proportion of monocytes and lymphcytes were IL- 1beta-positive by flow cytometric analysis. TGF-beta1 levels were also maximal on day 0-1 according to ELISA, although it tended to be in the inactive form derived from platelets. A 25 kDa band of TGF-1 was detectable for at least 13 days after SAH, which may have been secreted in part by neutrophils and monocytes. CRP levels in CSF peaked on day 2-3. The present results suggest that leukocytes induced by SAH play an important role in post-hemorrhagic inflammation in the subarachnoid space by releasing IL-6 and TGF-beta1. The CRP and TGF-beta1 levels in CSF are strongly concerned with communicating hydrocephalus after SAH.     

Cerebrospinal fluid orexin in aneurysmal subarachnoid haemorrhage - a pilot study.

The hypothalamus, a vital regulator of multiple physiologic functions, is the principal source of the neuropeptide orexin, which is thought to regulate the sleep-wake cycle. As hypothalamic damage may result from aneurysmal subarachnoid haemorrhage (SAH) and be associated with a depressed conscious level, we sought to investigate whether orexin levels reflected the severity of the ictus and were of any prognostic value in SAH. CSF orexin levels from 15 patients with aneurysmal SAH were analysed for up to 14 days. The correlation between orexin and GCS, WFNS grade, Fisher grade, GOS at 6 months and hydrocephalus were ascertained. Orexin levels in 5 patients with normal pressure hydrocephalus were used as controls. Patients with GCS less than 8 on admission had undetectable orexin whilst those with a GCS of 8 or greater had measurable orexin (p < 0.05). CSF orexin levels appear to correlate with conscious level and might be a valid indicator of hypothalamic injury. As some adverse sequelae of SAH are due to hypothalamic damage, pharmacological manipulation of orexinergic neuronal pathways could lead to exciting therapeutic options in the future.     

Brain natriuretic peptide and cerebral vasospasm in subarachnoid hemorrhage. Clinical and TCD correlations

BACKGROUND AND PURPOSE: Hyponatremia has been shown in association with cerebral vasospasm (CVS) following aneurysmal subarachnoid hemorrhage (SAH). In the past few years there has been increasing evidence that brain natriuretic peptide (BNP) is responsible for natriuresis after SAH. The purpose of the present study was to investigate the relationship between BNP plasma concentrations and CVS after aneurysmal SAH. METHODS: BNP plasma concentrations were assessed at 4 different time periods (1 to 3 days, 4 to 6 days, 7 to 9 days, and 10 to 12 days) in 19 patients with spontaneous SAH. BNP plasma levels were investigated with respect to neurological condition, SAH severity on CT, and flow velocities measured by means of transcranial Doppler. RESULTS: Thirteen patients had Doppler evidence of CVS; 7 of these had nonsymptomatic CVS. In 6 patients, CVS was severe and symptomatic, with delayed ischemic lesion on CT in 5 of these. CVS was severe and symptomatic in 6 patients, and delayed ischemic lesions were revealed on CT in 5 of these. BNP levels were found to be significantly elevated in SAH patients compared with control subjects (P=0.024). However, in patients without CVS or with nonsymptomatic CVS, BNP concentrations decreased throughout the 4 time periods, whereas a 6-fold increase was observed in patients with severe symptomatic CVS between the first and the third periods (P=0.0096). A similar trend in BNP plasma levels was found in patients with severe SAH compared with those with nonvisible or moderate SAH (P=0.015). CONCLUSIONS: In conclusion, our results show that BNP plasma levels are elevated shortly after SAH, although they increase markedly during the first week in patients with symptomatic CVS. The present findings suggest that secretion of BNP secretion after spontaneous SAH may exacerbate blood flow reduction due to arterial vasospasm.     

Predictors for cognitive impairment one year after surgery for aneurysmal subarachnoid hemorrhage

OBJECTIVE: To assess predictors for cognitive impairment one year after spontaneous subarachnoid hemorrhage (SAH). Evaluated predictors were the total amount of cisternal blood seen on computed tomography (CT) in the acute phase as measured by the Fisher grade, neurological grade at admission classified according to the Hunt and Hess scale, aneurysm site and patient's age, gender and education level. METHOD: 44 patients were operated by surgical clipping within 72 hours after CT verified aneurysmal SAH. After twelve months the remaining 42 patients were assessed by neuropsychological test, Beck Depression Inventory (BDI), the Glasgow Outcome Scale (GOS) and CT. Multiple regression analysis was conducted where predictor variables were independent factors and a global impairment index calculated for each patient was the dependent factor. RESULTS: The Fisher grade was the only independent predictor for neuropsychological impairment. Most patients had good neurological outcome as measured by the GOS and at the same time suffered from some degree of cognitive impairment at follow-up. Individual analysis of cognitive test scores showed mild to moderate dysfunction across multiple cognitive domains. Most frequent impairments were found in domains of memory, executive function and speed of information processing. Age below 50 years was associated with relatively better outcome. CONCLUSION: The severity of cognitive impairment one year post SAH is predicted by the volume of blood in the subarachnoid space as measured by the Fisher score.     

Inflammatory cytokine cascade released by leukocytes in cerebrospinal fluid after subarachnoid hemorrhage

Abstract

Subarachnoid hemorrhage (SAH) elicits an inflammatory response in the subarachnoid space, which is mediated by the release of various cytokines. To assess their involvement in post-hemorrhagic complications, we determined the source and time-course of the release of inflammatory cytokines and acute-phase proteins in cerebrospinal fluid (CSF) following SAH. Concentrations of interleukin (IL)-1β, IL-6, transforming growth factor-β1 (TGF-β1) and C-reactive protein (CRP) in CSF of 36 patients with SAH were measured by enzyme-linked immunoabsorbent assay (ELISA). Floating cells collected from the CSF were centrifuged four to six days after SAH, and examined immunohistochemically. Intracellular IL-1β and IL-6 were examined by flow cytometric analysis. The molecular weight of TGF-β1 in CSF of 30 patients was examined by Western blot analysis. The TGF-β1 levels of patients who had undergone ventriculoperitoneal (VP) shunt (n = 19) was significantly higher than nonshunt group (n = 16). The CRP levels of VP shunt group was significantly higher than nonshunt group. IL-6 concentration was maximal within day 0-1 and it was secreted by neutrophils and monocytes. ELISA showed consistently low levels of IL-1β, whereas a proportion of monocytes and lymphcytes were IL-1β-positive by flow cytometric analysis. TGF-β1 levels were also maximal on day 0-1 according to ELISA, although it tended to be in the inactive form derived from platelets. A 25 kDa band of TGF-1 was detectable for at least 13 days after SAH, which may have been secreted in part by neutrophils and monocytes. CRP levels in CSF peaked on day 2-3. The present results suggest that leukocytes induced by SAH play an important role in post-hemorrhagic inflammation in the subarachnoid space by releasing IL-6 and TGF-β1. The CRP and TGF-β1 levels in CSF are strongly concerned with communicating hydrocephalus after SAH. [Neurol Res 2001; 23: 724-730]     

川芎嗪对实验性SAH后CVS防治作用的研究

目的研究兔症状性蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)与内皮素(ET)和一氧化氮(NO)的关系及川芎嗪的保护作用.方法采用双侧颈动脉结扎和枕大池二次注血制成兔SAH模型,观察SAH前后动物进食量和神经功能改变,用放射免疫方法和硝酸还原酶法分别测定血液和脑脊液中ET和NOx-含量,以氢清除法测定局部脑血流量(rCBF).结果SAH后大部分动物进食量有不同程度的下降,所有动物均有不同程度的神经功能障碍和rCBF下降.SAH后血液和脑脊液中ET含量增加,NOx-含量下降(P＜0.01).上述变化随出血时间延长和出血量的增大而增加.川芎嗪治疗组上述变化均有不同程度的改善.结论双侧颈动脉结扎后枕大池二次注血可制成可靠的兔症状性SAH后CVS的动物模型.兔SAH后ET和NO含量的改变与CVS的发生密切相关,并进而导致临床症状的恶化.川芎嗪可通过抑制SAH后ET和NO的变化而对CVS的发生和发展起到防治作用.     

Elevated concentrations of sphingosylphosphorylcholine in cerebrospinal fluid after subarachnoid hemorrhage: A possible role as a spasmogen

This study investigates the role of sphingosylphosphorylcholine (SPC) in the mechanisms underlying cerebral vasospasm after subarachnoid hemorrhage (SAH). The levels of SPC were measured in cerebrospinal fluid (CSF) of patients with SAH and also in an experimental canine model. CSF samples were collected from 11 patients with SAH, and from dogs that had received an injection of SPC into the cisterna magna to examine SPC kinetics in the CSF. SPC was assayed using solid-phase extraction and triple quadrupole mass spectrometry. The SPC concentrations in SAH patients on days 3, 8, and 14 after the onset of SAH were significantly higher than those in normal CSF. In the canine model, rapid dilution of SPC in CSF was observed. In combination with data from previous studies, these results suggest that SPC is involved in the development of cerebral vasospasm. Rapid dilution of SPC in CSF suggests that SPC is released into CSF at higher concentrations than those measured in the present study.     

Shunt-Dependent Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage: The Role of Intrathecal Interleukin-6

Object

Aneurysmal subarachnoid hemorrhage (SAH) has been reported to induce an intrathecal inflammatory reaction reflected by cytokine release, particularly interleukin-6 (IL-6), which correlates with early brain damage and poor outcome. The present study examines intrathecal IL-6 production together with clinical parameters, as a predictor of posthemorrhagic shunt dependency.

Methods

Among 186 SAH patients admitted between July 2010 and December 2012, 82 received external ventricular drainage due to acute hydrocephalus. In these patients, cerebrospinal fluid (CSF) concentrations of IL-6 were measured within the first 14 days after SAH. Patients whose IL-6 values were not determined regularly and those who did not survive until discharge were excluded. The peak value of IL-6, ventricular infection during the hospital stay, microbial CSF culture, patient’s age and sex, Hunt and Hess grade, and aneurysm location were assumed as predictive for shunt dependency.

Results

Sixty-nine patients were included, 24 of whom underwent shunt surgery. Peak IL-6 values of ≥10,000 pg/ml were significantly associated with a higher incidence of shunt dependency (p = 0.009). Additional risk factors were aneurysm location on the anterior cerebral artery and its branches or in the posterior circulation (p = 0.025), and age ≥60 years (p = 0.014). In a multivariate analysis, IL-6 ≥10,000 pg/ml appeared to be the only independent predictor for shunt dependency (p = 0.029)

Conclusion

CSF IL-6 values of ≥10,000 pg/ml in the early post-SAH period may be a useful diagnostic tool for predicting shunt dependency in patients with acute posthemorrhagic hydrocephalus. The development of shunt-dependent posthemorrhagic hydrocephalus remains a multifactorial process.     

Clipping or coiling of ruptured cerebral aneurysms and shunt-dependent hydrocephalus

Background  Hydrocephalus may develop either early in the course of aneurysmal subarachnoid hemorrhage (SAH) or after the first 2 weeks. Because the amount of SAH is a predictor of hydrocephalus, the two available aneurysmal treatments, clipping or coiling, may lead to differences in the need for cerebrospinal fluid (CSF) diversion, as only surgery permits clot removal. Methods  Hospital and University Hospitals Consortium (UHC) databases were used to retrieve data on all patients admitted to our hospital with aneurysmal SAH during the last 4 years. The incidence of permanent ventricular shunt (VS) according to treatment modality used was evaluated. Results  One hundred eighty-eight patients were admitted with aneurysmal SAH. Coiling was performed on 48 (26%) and clipping on 135 (73.8%) patients. Fifty-six (31%) patients required CSF diversion. External ventricular drain was placed in 30 (22.2%) clipped and 13 (27.1%) coiled patients (p=0.5), and VS in 6 patients of the two treatment groups (4.4 versus 12.5%, respectively; p=0.08). Patients requiring VS had longer UHC-expected hospital length of stay (LOS), as well as observed ICU and hospital LOS, compared to patients with temporary or no CSF diversion (24±14 versus 15±8, 20.5±9 versus 11±7, and 30±13 versus 16±11 days, respectively; p≤0.01). In a logistic regression model, VS was independently associated with rebleeding, external ventricular drain placement, coiling, and UHC-expected LOS (odds ratios, 95% confidence interval 12.1, 2.3–62.6, 6.9, 1.6–30, 6.25, 1.3–29, and 1.1, 1.02–1.14, respectively). Conclusions  One-third of patients admitted with aneurysmal SAH require temporary or permanent CSF diversion. Permanent shunting was found to be associated with coiling in our patient population.