Glycemic indices predict outcomes after aneurysmal subarachnoid hemorrhage: a retrospective single center comparative analysis.

Although hyperglycemia is associated with worse outcomes after aneurysmal subarachnoid hemorrhage (aSAH), there is no consensus on the optimal glucose control metric, acceptable in-hospital glucose ranges, or suitable insulin regimens in this population. In this single-center retrospective cohort study of aSAH patients, admission glucose, and hospital glucose mean (MHG), minimum (MinG), maximum (MaxG), and variability were compared. Primary endpoints (mortality, complications, and vasospasm) were assessed using multivariate logistic regressions. Of the 217 patients included, complications occurred in 83 (38.2%), 124 (57.1%) had vasospasm, and 41 (18.9%) died. MHG was independently associated with (p < 0.001) mortality, MaxG (p = 0.017) with complications, and lower MinG (p = 0.015) with vasospasm. Patients with MHG ≥ 140 mg/dL had 10 × increased odds of death [odds ratio (OR) = 10.3; 95% CI 4.6-21.5; p < 0.0001] while those with MinG ≤ 90 mg/dL had nearly 2× increased odds of vasospasm (OR = 1.8; 95% CI 1.01-3.21; p = 0.0422). While inpatient insulin was associated with increased complications and provided no mortality benefit, among those with MHG ≥ 140 mg/dL insulin therapy resulted in lower mortality (OR = 0.3; 95% CI 0.1-0.9; p = 0.0358), but no increased complication risk. While elevated MHG and MaxG are highly associated with poorer outcomes after aSAH, lower MinG is associated with increased vasospasm risk. Future trials should consider initiating insulin therapy based on MHG rather than other hyperglycemia measures.

Low total cholesterol and high density lipoprotein are independent predictors of poor outcomes following aneurysmal subarachnoid hemorrhage: A preliminary report.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) is devastating, with delayed cerebral ischemia (DCI) significantly contributing to the high morbidity and mortality rates. Cholesterol has been studied as a measure of nutritional status in other neurological pathologies, but reports examining cholesterol's effects on aSAH outcomes are sparse. This study aimed to elucidate the effect of low total cholesterol (TC) and high density lipoprotein (HDL) on mortality and DCI following aSAH. METHODS: We performed a retrospective cohort study at a quaternary academic medical center between June 2014 and July 2018. All patients had aSAH confirmed by digital subtraction angiography and had TC measured on admission. Primary outcomes were mortality and DCI. Secondary outcome was radiographic vasospasm. Univariate and multivariate logistic regressions were performed. RESULTS: There were 75 aSAH patients, with an average age of 58.7 ±â€¯1.7 (range: 14-89) and Hunt & Hess score of 2.8 ±â€¯0.1, included for analysis. Those with a low TC < 160 mg/dL had 3 times increased odds of DCI (OR = 3.4; 95 %CI: 1.3-9.0; p = 0.0175) and a nearly 5 times increased odds of death (OR = 4.9; 95 %CI: 1.1-18.3; p = 0.0339). Low HDL < 40 mg/dL was associated with 12 times increased odds of DCI (OR = 12.3; 95 %CI: 2.7-56.4; p = 0.0003) but no significant differences in death (p = 0.2205). In multivariate analysis, low TC was an independent risk factor for increased mortality (OR = 5.6; 95 %CI: 1.2-27.6; p = 0.0335) while low HDL was associated with increased risk for DCI (OR = 17.9; 95 %CI: 3.1-104.4; p = 0.0013). There was no effect of TC or HDL on radiographic vasospasm. CONCLUSIONS: Low TC and HDL are independent predictors of increased mortality and DCI, respectively, following aSAH. Low TC and HDL may be markers of poor overall health, in addition to having some pathophysiological effect on cerebral vasculature. These results may have practical implications for the improvement of aSAH prognostication and management.

Procedural Complications and Factors Influencing Immediate Angiographic Results after Endovascular Treatment of Small (<5 mm) Ruptured Intracranial Aneurysms.

BACKGROUND AND OBJECTIVE: There are technical challenges to complete occlusion of small (<5 mm) ruptured intracranial aneurysms (SRAs) using endovascular treatment (EVT). This study analyzed factors influencing immediate angiographic results in SRAs after EVT. MATERIAL AND METHODS: Intraoperative angiograms and medical records of 290 patients, who underwent EVT for SRAs at 2 stroke centers in China between January 2009 and October 2016, were retrospectively reviewed and evaluated. RESULTS: Immediate complete occlusion was achieved in 213 (73.4%) aneurysms. Aneurysms with a smaller aspect ratio, those less than 3 mm in size, irregular shape, small basal outpouching, multiple aneurysms, poorer Hunt and Hess grade, and location of communication arteries demonstrated higher rates of incomplete occlusion, although the differences were not statistically significant. Multivariate logistic regression analysis revealed that SRAs with parent artery stenosis greater than or equal to 50% and lobulation demonstrated a higher incidence of incomplete occlusion. Intra-procedural rupture occurred in 13 (6.1%) patients in the complete occlusion group, and 3 (3.9%) in the incomplete occlusion group (P = .467). Thromboembolic complications occurred in 3 (1.0%) patients, and 4 (1.9%) underwent decompressive craniotomy after EVT, all of whom were in the complete occlusion group. Nine (4.2%) patients in the complete occlusion group and 2 (2.6%) in the incomplete occlusion group (P = .733) experienced intraprocedural vasospasm, with corresponding morbidity and mortality rates of 15.0% and 2.1%, respectively. CONCLUSIONS: Proximal parent artery stenosis greater than or equal to 50% and lobulation were independent predictors of incomplete occlusion in patients with SRAs. Higher rates of intraprocedural rupture, thromboembolic complications, intraprocedural vasospasm, and mortality were found in the complete occlusion group; however, these differences were not statistically significant. Complete occlusion of SRAs may be achieved without additional mortality and perioperative complications.

Is Admission Lipoprotein-Associated Phospholipase A2 a Novel Predictor of Vasospasm and Outcome in Patients With Aneurysmal Subarachnoid Hemorrhage?

BACKGROUND: The relationships between lipoprotein-associated phospholipase A2 (Lp-PLA2) level, vasospasm, and clinical outcome of patients with aneurysmal subarachnoid hemorrhage (aSAH) are still unclear. OBJECTIVE: To identify the associations between admission Lp-PLA2 and vasospasm following subarachnoid hemorrhage and the clinical outcome of aSAH. METHODS: A total of 103 aSAH patients who had Lp-PLA2 level obtained within 24 h postbleeding were included. The relationships between Lp-PLA2 level, vasospasm, and clinical outcome were analyzed. RESULTS: Vasospasm was observed in 52 patients (50.49%). Patients with vasospasm had significantly higher Lp-PLA2 level than those without (P < .001). Both modified Fisher grade (P = .014) and Lp-PLA2 level (P < .001) were significant predictors associated with vasospasm. The Z test revealed that power of Lp-PLA2 was significantly higher than that of modified Fisher grade in predicting vasospasm (Z = 2.499, P = .012). At 6-mo follow-up, 44 patients (42.72%) had unfavorable outcome and 36 patients (34.95%) died. The World Federation of Neurosurgical Societies (WFNS) grade and Lp-PLA2 level were both significant predictors associated with 6-mo unfavorable outcome and mortality (all P < .001). The predictive values of Lp-PLA2 for unfavorable outcome and mortality at 6-mo tended to be lower than those of the WFNS grade, but the differences were not statistically significant (P = .366 and 0.115, respectively). Poor-grade patients having Lp-PLA2 > 200 µg/L had significantly worse 6-mo survival rate than poor-grade patients having Lp-PLA2 ≤ 200 µg/L (P = .001). CONCLUSION: The Lp-PLA2 might be useful as a novel predictor in aSAH patients. A total of 30 poor-grade patients; those with elevated Lp-PLA2 level have higher risk of 6-mo mortality compared to those without.

Cerebrospinal fluid untargeted metabolomic profiling of aneurysmal subarachnoid hemorrhage: an exploratory study.

INTRODUCTION: Despite advancements in medical and surgical therapies, clinical outcomes of aneurysmal subarachnoid hemorrhage (aSAH) continue to be poor. Currently, aSAH pathophysiology remains poorly understood. No aSAH biomarkers are commonly used in the clinical setting. This exploratory study used metabolomics profiling to identify global metabolic changes and metabolite predictors of long-term outcome using cerebrospinal fluid (CSF) samples of aSAH patients. METHODS AND METHODS: Gas chromatography time-of-flight mass spectrometry was applied to CSF samples collected from 15 consecutive high-grade aSAH patients (modified Fisher grade 3 or 4). Collected CSF samples were analyzed at two time points (admission and the anticipated vasospasm timeframe). Metabolite levels at both time points were compared and correlated with vasospasm status and Glasgow Outcome Scale (GOS) of patients at 1 year post-aSAH. Significance level was defined as p < 0.05 with false discovery rate correction for multiple comparisons. RESULTS: Of 97 metabolites identified, 16 metabolites, primarily free amino acids, significantly changed between the two time points. These changes were magnified in modified Fisher grade 4 compared with grade 3. Six metabolites (2-hydroxyglutarate, tryptophan, glycine, proline, isoleucine, and alanine) correlated with GOS at 1 year post-aSAH independent of vasospasm status. When predicting patients who had low disability (GOS 5 vs. GOS ≤4), 2-hydroxyglutarate had a sensitivity and specificity of 0.89 and 0.83 respectively. CONCLUSIONS: Our preliminary study suggests that specific metabolite changes occur in the brain during the course of aSAH and that quantification of specific CSF metabolites may be used to predict long-term outcome in patients with aSAH. This is the first study to implicate 2-hydroxyglutarate, a known marker of tissue hypoxia, in aSAH pathogenesis.

Endovascular treatment for cerebral vasospasm following aneurysmal subarachnoid hemorrhage: predictors of outcome and retreatment.

OBJECTIVE: Although endovascular therapy has been widely adopted for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH), its effect on clinical outcomes remains incompletely understood. The aims of this retrospective cohort study are to evaluate the outcomes of endovascular intervention for post-aSAH vasospasm and identify predictors of functional independence at discharge and repeat endovascular vasospasm treatment. METHODS: We assessed the baseline and outcomes data for patients with aSAH who underwent endovascular vasospasm treatment at our institution, including intra-arterial (IA) vasodilator infusion and angioplasty. Statistical analyses were performed to determine factors associated with good outcome at discharge (modified Rankin Scale 0-2) and repeat endovascular vasospasm treatment. RESULTS: The study cohort comprised 159 patients with a mean age of 52 years. Good outcome was achieved in 17% of patients at discharge (26/150 patients), with an in-hospital mortality rate of 22% (33/150 patients). In the multivariate analysis, age (OR 0.895; p=0.009) and positive smoking status (OR 0.206; p=0.040) were negative independent predictors of good outcome. Endovascular retreatment was performed in 34% (53/156 patients). In the multivariate analysis, older age (OR 0.950; p=0.004), symptomatic vasospasm (OR 0.441; p=0.046), initial treatment with angioplasty alone (OR 0.096; p=0.039), and initial treatment with combined IA vasodilator infusion and angioplasty (OR 0.342; p=0.026) were negative independent predictors of retreatment. CONCLUSION: We found a modest rate of functional independence at discharge in patients with aSAH who underwent endovascular vasospasm treatment. Older patients and smokers had worse functional outcomes at discharge. Initial use of angioplasty appears to decrease the need for subsequent retreatment.

Cerebral Vasospasm-Dependent and Cerebral Vasospasm-Independent Cerebral Infarctions Predict Outcome After Nonaneurysmal Subarachnoid Hemorrhage: A Single-Center Series with 250 Patients.

OBJECTIVE: The number of patients with nonaneurysmal subarachnoid hemorrhage (naSAH) has increased during the last decade. Data regarding infarctions in naSAH are still limited. The aim of this study was to identify the rate of cerebral vasospasm (CVS)-dependent and CVS-independent infarctions and their influence on clinical outcomes. METHODS: Between 1999 and 2015, 250 patients suffering from naSAH were analyzed retrospectively. A delayed infarction was analyzed whether it was associated with CVS (CVS-dependent infarction) or not (CVS-independent). RESULTS: A total of 36 patients (14%) had cerebral infarctions. CVS was detected in 54 patients (22%), and 15 (6%) of them developed infarctions (CVS-dependent). Infarctions without signs of CVS (CVS-independent) occurred in 21 patients (8%). Overall, 86% of the patients had favorable outcome. Patients without cerebral infarctions had the best outcome (91% favorable outcome, 5% mortality rate). Patients with CVS-independent infarctions (57%) as well as patients with CVS-dependent infarctions (53%) had a favorable outcome less often. The mortality rate was also significantly greater in patients with CVS-independent (19%) and CVS-dependent infarctions (33%). A further independent predictor was anticoagulative therapy, which increased during study period and was associated with nonperimesencephalic blood distribution. CONCLUSIONS: CVS-dependent and independent infarctions occur in naSAH and contribute to unfavorable outcomes. Whereas CVS-independent infarctions occur in any subgroup, CVS-dependent infarctions seem to be associated with blood pattern (Fisher 3). Anticoagulative therapy seems to be not only a predictor for worse outcome but also for nonperimesencephalic SAH. Accordingly, the proportion of perimesencephalic and nonperimesencephalic SAH changed during the study period (from 2.2:1 to 1:1.7).

Subarachnoid Hemorrhage in Advanced Age: Comparison of Patients Aged 70-79 Years and 80 Years and Older.

BACKGROUND: Clinical routine shows an increasing admission rate of elderly patients suffering from subarachnoid hemorrhage (SAH). OBJECTIVE: Aim of the study was to identify differences in outcome and prognostic factors to better anticipate clinical course and therefore treat this special subgroup better. METHODS: We retrospectively compared patients aged 70-79 and older than 80 years (80+). Patients were entered into a prospectively collected database. Between 1999 and June 2014, 191 patients aged ≥70 years suffered from SAH. We stratified between patients aged from 70 to 79 years (n = 138) and 80+ years (n = 53). Outcome was assessed by modified Rankin Scale 6 months after SAH. RESULTS: During the observation period, the rate of elderly patients increased from 9% to 24%. Patients aged 80+ years less often showed significant early hydrocephalus, cerebral vasospasm, and shunt dependence. A total of 51% of all patients were treated by coiling, whereupon also treatment modality had no influence on outcome. By comparing clinical outcomes, no significant differences could be detected. However, mortality rate was not significantly greater in patients 80+ years. Clinical status at time of admission statistically was a prognostic factor in elderly patients as well as the extent of blood clots and an early hydrocephalus. Patients aged 80+ years suffered less from severe cerebral vasospasm, which statistically was no prognostic factor for a favorable outcome in this group. CONCLUSIONS: Patients aged 80+ years with SAH also can achieve a favorable outcome. There was no difference in clinical outcome comparing both groups, but several pathophysiological mechanisms in elderly patients (especially 80+ years) seem to have a positive influence on typical complications after SAH, such as cerebral vasospasm, early hydrocephalus, and shunt dependence.

A Systematic and Meta-Analysis of Mortality in Experimental Mouse Models Analyzing Delayed Cerebral Ischemia After Subarachnoid Hemorrhage.

Animal models are established to display the pathophysiological changes following subarachnoid hemorrhage (SAH). The aim of the present study was to determine case fatality in mouse delayed cerebral ischemia (DCI) models, to compare mortality in mouse DCI models to case fatality in human SAH patients, and to identify factors influencing mouse mortality. A systematic search of the PubMed database was performed to identify all studies that assessed mouse DCI models. Mortality rates and predictor variables were extracted and compared to the human case fatality after SAH as previously reported. Predictors for mouse mortality were identified through multivariate analysis. Forty-eight studies were included in the quantitative analysis. The mean overall mortality rate was 21% in mouse DCI models. However, the time period between induction of SAH and evaluation of mortality rates is a significant variable influencing the mortality rate in mouse SAH models. The experimental SAH model was the only significant predictor for mouse mortality after 48 h. In contrast, neither the genetic background nor the anesthetic changed the case fatality rate. Mouse mortality at 24, 48, and 72 h after experimental SAH in DCI models was significantly lower than human case fatality following aneurysmal SAH. The mean overall mortality rate in mouse DCI models is significantly lower than human case fatality following aneurysmal SAH. However, time between SAH induction and evaluation is a significant variable influencing the mortality rate in mouse SAH models. Further analyses will be required to establish whether and to which extent different DCI models affect mortality and reflect human pathophysiology.

Early NO-donor treatment improves acute perfusion deficit and brain damage after experimental subarachnoid hemorrhage in rats.

A lack of nitric oxide (NO) may be a possible factor in the pathogenesis of an acute decrease of cerebral blood flow (CBF) after subarachnoid hemorrhage (SAH). This study was conducted to investigate whether early therapy with an NO-donor can improve CBF and offer neuroprotection after experimental SAH in rats. Male Sprague-Dawley rats were subjected to SAH by the endovascular filament model and treated with 1.5µg/kg/min of intravenous sodium nitroprusside (SNP) or vehicle (n=10) starting 15min after induction of SAH until 180min thereafter. SNP caused a moderate decrease of arterial blood pressure and cerebral perfusion pressure. Conversely, CBF measured by laser-Doppler flowmetry increased significantly in SNP-treated animals. The rate of injured neurons in the hippocampal CA1-field was significantly reduced in SNP-treated animals (10.5±5%) compared to controls (14.2±7%), as well as the number of Caspase-3 positive neurons. Low-dose treatment with SNP can attenuate an early perfusion deficit after SAH and reduce neuronal damage in spite of a hypotensive side effect. This may reflect the reversal of an early NO-deficit. In the clinical setting, the moderate hypotensive effect may be welcome since SAH-patients frequently present with elevated blood pressure.

Is There an Influence of Routine Daily Transcranial Doppler Examination on Clinical Outcome in Patients After Aneurysmal Subarachnoid Hemorrhage?

BACKGROUND: Transcranial Doppler (TCD) is widely used as a daily routine method to detect vasospasm in patients after aneurysmal subarachnoid hemorrhage (aSAH); however, there are only limited data about the real benefit of this examination. Therefore, the clinical outcome of 2 cohorts with and without daily TCD after aSAH was assessed. METHODS: All patients included in this study received a standardized diagnostic and treatment protocol. Fifty patients admitted with aSAH from January 2013 to December 2013 received daily TCD measurements; 39 patients admitted from January 2014 to September 2014 received no TCD measurements. Data on clinical grade (Hunt and Hess grade), severity of bleeding (Barrow Neurological Institute grade), localization of aneurysm, and angiographic or clinically relevant vasospasm were collected prospectively. The Glasgow Outcome Scale, modified Rankin Scale, and the National Institute of Health Stroke Scale were used as clinical outcome parameters. RESULTS: Patient baseline characteristics and clinical data were comparable; treatment modality of the aneurysm was not different between the groups (P = 0.7756). No significant difference between the Hunt and Hess grade (P = 0.818) and the Barrow Neurological Institute grade (P = 0.1551) was observed. There was also no significance concerning the incidence of angiographic or clinically relevant vasospasm between both groups (P = 0.5842 and P = 0.7933). Glasgow Outcome Scale, mRS, and National Institute of Health Stroke Scale as the primary outcome parameters showed no significant difference in morbidity and mortality between both groups (mortality P = 0.8544). CONCLUSIONS: With the limitation of an explorative cohort study, the results indicate that routine TCD studies do not improve the overall outcome of patients after aSAH.

Outcome of Patients with Long-Lasting Cerebral Vasospasm After Subarachnoid Hemorrhage: Is Prolonged Treatment for Cerebral Vasospasm Worthwhile? A Matched-Pair Analysis.

OBJECTIVE: Cerebral vasospasm (CVS) occurs regularly between days 3 and 12 after subarachnoid hemorrhage (SAH). Yet, some patients suffering from SAH have long-lasting cerebral vasospasm (LL-CVS, i.e., longer than 14 days). The outcome of these patients with a very long treatment is unknown. METHODS: Patients with SAH were entered into a prospectively collected database. In unconscious patients, CVS was treated until a reversal of CVS was confirmed by imaging. Outcome was assessed with the modified Rankin Scale (mRS; favorable [mRS 0-2] and unfavorable [mRS 3-6]) 6 months after SAH. Data were compared by matched pair analysis. RESULTS: Of 1126 patients, 106 had LL-CVS (9.4%). The mean of treatment was until day 20 (range, 15-42). Of these patients, more than 30% needed treatment longer than 21 days after SAH; 29% had a small intracerebral hematoma (ICH; <50 mL). Hydrocephalus that required external ventricular drainage was present in 81%. Outcomes were favorable in 60%, and 8% died. In the multivariate logistic regression analysis, risk factors for an unfavorable outcome were elderly patients, poor admission status, and the presence of small ICH. Compared with the matched control group, who had "regular-lasting" CVS, patients with LL-CVS had a significant better outcome (60% vs. 49%) and a significant lower mortality rate (8% vs. 27%). CONCLUSION: Patients with LL-CVS had a significant better outcome than patients with "regular-lasting" CVS. Risk factors for worse outcome of patients with LL-CVS were a worse admission status, elderly age, and the presence of small ICH. We recommend using an objective method to validate the reversal of CVS in unconscious patients.

Vasospasm on transcranial Doppler is predictive of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis.

OBJECT The impact of transcranial Doppler (TCD) ultrasonography evidence of vasospasm on patient-centered clinical outcomes following aneurysmal subarachnoid hemorrhage (aSAH) is unknown. Vasospasm is known to lead to delayed cerebral ischemia (DCI) and poor outcomes. This systematic review and meta-analysis evaluates the predictive value of vasospasm on DCI, as diagnosed on TCD. METHODS MEDLINE, Scopus, the Cochrane trial register, and clinicaltrials.gov were searched through September 2014 using key words and the terms "subarachnoid hemorrhage," "aneurysm," "aneurysmal," "cerebral vasospasm," "vasospasm," "transcranial Doppler," and "TCD." Sensitivities, specificities, and positive and negative predictive values were pooled by a DerSimonian and Laird random-effects model. RESULTS Seventeen studies (n = 2870 patients) met inclusion criteria. The amount of variance attributable to heterogeneity was significant (I(2) > 50%) for all syntheses. No studies reported the impact of TCD evidence of vasospasm on functional outcome or mortality. TCD evidence of vasospasm was found to be highly predictive of DCI. Pooled estimates for TCD diagnosis of vasospasm (for DCI) were sensitivity 90% (95% confidence interval [CI] 77%-96%), specificity 71% (95% CI 51%-84%), positive predictive value 57% (95% CI 38%-71%), and negative predictive value 92% (95% CI 83%-96%). CONCLUSIONS TCD evidence of vasospasm is predictive of DCI with high accuracy. Although high sensitivity and negative predictive value make TCD an ideal monitoring device, it is not a mandated standard of care in aSAH due to the paucity of evidence on clinically relevant outcomes, despite recommendation by national guidelines. High-quality randomized trials evaluating the impact of TCD monitoring on patient-centered and physician-relevant outcomes are needed.

Molsidomine for the prevention of vasospasm-related delayed ischemic neurological deficits and delayed brain infarction and the improvement of clinical outcome after subarachnoid hemorrhage: a single-center clinical observational study.

OBJECT Delayed ischemic neurological deficits (DINDs) and cerebral vasospasm (CVS) are responsible fora poor outcome in patients with aneurysmal subarachnoid hemorrhage (SAH), most likely because of a decreased availability of nitric oxide (NO) in the cerebral microcirculation. In this study, the authors examined the effects of treatment with the NO donor molsidomine with regard to decreasing the incidence of spasm-related delayed brain infarctions and improving clinical outcome in patients with SAH. METHODS Seventy-four patients with spontaneous aneurysmal SAH were included in this post hoc analysis. Twenty-nine patients with SAH and proven CVS received molsidomine in addition to oral or intravenous nimodipine. Control groups consisted of 25 SAH patients with proven vasospasm and 20 SAH patients without. These patients received nimodipine therapy alone. Cranial computed tomography (CCT) before and after treatment was analyzed for CVS-related infarcts. A modified National Institutes of Health Stroke Scale (mNIHSS) and the modified Rankin Scale (mRS) were used to assess outcomes at a 3-month clinical follow-up. RESULTS Four of the 29 (13.8%) patients receiving molsidomine plus nimodipine and 22 of the 45 (48%) patients receiving nimodipine therapy alone developed vasospasm-associated brain infarcts (p < 0.01). Follow-up revealed a median mNIHSS score of 3.0 and a median mRS score of 2.5 in the molsidomine group compared with scores of 11.5 and 5.0, respectively, in the nimodipine group with CVS (p < 0.001). One patient in the molsidomine treatment group died, and 12 patients in the standard care group died (p < 0.01). CONCLUSIONS In this post hoc analysis, patients with CVS who were treated with intravenous molsidomine had a significant improvement in clinical outcome and less cerebral infarction. Molsidomine offers a promising therapeutic option in patients with severe SAH and CVS and should be assessed in a prospective study.

[Content of C-reactive protein in patients in an acute period of a ruptured intracranial aneurysm].

A content of C-reactive protein (CRP) in the blood serum was determined in 36 patients in acute period of a ruptured intracranial arterial aneurysm (AA). It was significantly more, than in a control group, and have exceeded 10 mg/I in 1 - 4th day of the disease. The level of CRP have had differ, depending on severity of cerebral vasospasm (CVS), determined in accordance to the ultrasound investigation data. In a pronounced CVS in majority of patients the level of CRP in the blood serum have had exceed 10 mg/l, and have secured elevated in a spinal liquor on the 7 - 10th day of the disease, differing from this index in patients with moderately pronounced CVS or without it. In patients with severe invalidization or those, who have died, the level of CRP was trust-worthy higher.

Haptoglobin phenotype predicts the development of focal and global cerebral vasospasm and may influence outcomes after aneurysmal subarachnoid hemorrhage.

Cerebral vasospasm (CV) and the resulting delayed cerebral ischemia (DCI) significantly contribute to poor outcomes following aneurysmal subarachnoid hemorrhage (aSAH). Free hemoglobin (Hb) within the subarachnoid space has been implicated in the pathogenesis of CV. Haptoglobin (Hp) binds free pro-oxidant Hb, thereby modulating its harmful effects. Humans can be of three Hp phenotypes: Hp1-1, Hp2-1, or Hp2-2. In several disease states, the Hp2-2 protein has been associated with reduced ability to protect against toxic free Hb. We hypothesized that individuals with the Hp2-2 phenotype would have more CV, DCI, mortality, and worse functional outcomes after aSAH. In a sample of 74 aSAH patients, Hp2-2 phenotype was significantly associated with increased focal moderate (P = 0.014) and severe (P = 0.008) CV and more global CV (P = 0.014) after controlling for covariates. Strong trends toward increased mortality (P = 0.079) and worse functional outcomes were seen for the Hp2-2 patients with modified Rankin scale at 6 wk (P = 0.076) and at 1 y (P = 0.051) and with Glasgow Outcome Scale Extended at discharge (P = 0.091) and at 1 y (P = 0.055). In conclusion, Hp2-2 phenotype is an independent risk factor for the development of both focal and global CV and also predicts poor functional outcomes and mortality after aSAH. Hp phenotyping may serve as a clinically useful tool in the critical care management of aSAH patients by allowing for early prediction of those patients who require increased vigilance due to their inherent genetic risk for the development of CV and resulting DCI and poor outcomes.

Application of lumbar drainage in vasospasm after spontaneous subarachnoid hemorrhage and prevention of late cerebral infarction.

Cerebral vasospasm, especially delayed cerebral ischemia following subarachnoid hemorrhage (SAH) is the most important complication that effects mortality and morbidity of patients with intracranial aneurysms. The presence of cerebral vasospasm has been correlated with an increase in mortality in the first 2 weeks after SAH. Despite clinical studies and research, the etiopathogenesis of cerebral vasospasm is not understood exactly and there is not yet an effective therapy. The aim of our study was to investigate the effect of application of lumber drainage on vasospasm and delayed cerebral infarction following SAH and to examine the incidence of complications. Patient groups were determined by retrospective screening of 70 patients who underwent a surgical operation at the Osmangazi University Medical Faculty Department of Neurosurgery between 2009 and 2013 after a diagnosis of ruptured aneurysmal SAH. After the application of lumbar drainage, the complications and mortality after aneurysm surgery was significantly decreased and correlated with the amount of hemorrhagic cerebrospinal fluid drainage.

Genetic variation in soluble epoxide hydrolase: association with outcome after aneurysmal subarachnoid hemorrhage.

OBJECT: Patients with aneurysmal subarachnoid hemorrhage (SAH) are at high risk for delayed cerebral ischemia (DCI) and stroke. Epoxyeicosatrienoic acids (EETs) play an important role in cerebral blood flow regulation and neuroprotection after brain injury. Polymorphisms in the gene for the enzyme soluble epoxide hydrolase (sEH), which inactivates EETs, are associated with ischemic stroke risk and neuronal survival after ischemia. This prospective observational study of patients with SAH compares vital and neurologic outcomes based on functional polymorphisms of sEH. METHODS: Allelic discrimination based on quantitative real-time polymerase chain reaction was used to differentiate wild-type sEH from K55R heterozygotes (predictive of increased sEH activity and reduced EETs) and R287Q heterozygotes (predictive of decreased sEH activity and increased EETs). The primary outcome was new stroke after SAH. Secondary outcomes were death, Glasgow Outcome Scale score, and neurological deterioration attributable to DCI. RESULTS: Multivariable logistic regression models adjusted for age at admission and Glasgow Coma Scale scores revealed an increase in the odds of new stroke (OR 5.48 [95% CI 1.51-19.91]) and death (OR 7.52 [95% CI 1.27-44.46]) in the K55R group, but no change in the odds of new stroke (OR 0.56 [95% CI 0.16-1.96]) or death (OR 3.09 [95% CI 0.51-18.52]) in patients with R287Q genotype, compared with wild-type sEH. The R287Q genotype was associated with reduced odds of having a Glasgow Outcome Scale score of ≤ 3 (OR 0.23 [95% CI 0.06-0.82]). There were no significant differences in the odds of neurological deterioration due to DCI. CONCLUSIONS: Genetic polymorphisms of sEH are associated with neurological and vital outcomes after aneurysmal SAH.

To look beyond vasospasm in aneurysmal subarachnoid haemorrhage.

Delayed cerebral vasospasm has classically been considered the most important and treatable cause of mortality and morbidity in patients with aneurysmal subarachnoid hemorrhage (aSAH). Secondary ischemia (or delayed ischemic neurological deficit, DIND) has been shown to be the leading determinant of poor clinical outcome in patients with aSAH surviving the early phase and cerebral vasospasm has been attributed to being primarily responsible. Recently, various clinical trials aimed at treating vasospasm have produced disappointing results. DIND seems to have a multifactorial etiology and vasospasm may simply represent one contributing factor and not the major determinant. Increasing evidence shows that a series of early secondary cerebral insults may occur following aneurysm rupture (the so-called early brain injury). This further aggravates the initial insult and actually determines the functional outcome. A better understanding of these mechanisms and their prevention in the very early phase is needed to improve the prognosis. The aim of this review is to summarize the existing literature on this topic and so to illustrate how the presence of cerebral vasospasm may not necessarily be a prerequisite for DIND development. The various factors determining DIND that worsen functional outcome and prognosis are then discussed.