Outcome Of Subarachnoid Hemorrhage Research Articles

Rare Coding Variants in ANGPTL6 Are Associated with Familial Forms of Intracranial Aneurysm

Intracranial aneurysms (IAs) are acquired cerebrovascular abnormalities characterized by localized dilation and wall thinning in intracranial arteries, possibly leading to subarachnoid hemorrhage and severe outcome in case of rupture. Here, we identified one rare nonsense variant (c.1378A>T) in the last exon of ANGPTL6 (Angiopoietin-Like 6)-which encodes a circulating pro-angiogenic factor mainly secreted from the liver-shared by the four tested affected members of a large pedigree with multiple IA-affected case subjects. We showed a 50% reduction of ANGPTL6 serum concentration in individuals heterozygous for the c.1378A>T allele (p.Lys460Ter) compared to relatives homozygous for the normal allele, probably due to the non-secretion of the truncated protein produced by the c.1378A>T transcripts. Sequencing ANGPTL6 in a series of 94 additional index case subjects with familial IA identified three other rare coding variants in five case subjects. Overall, we detected a significant enrichment (p = 0.023) in rare coding variants within this gene among the 95 index case subjects with familial IA, compared to a reference population of 404 individuals with French ancestry. Among the 6 recruited families, 12 out of 13 (92%) individuals carrying IA also carry such variants in ANGPTL6, versus 15 out of 41 (37%) unaffected ones. We observed a higher rate of individuals with a history of high blood pressure among affected versus healthy individuals carrying ANGPTL6 variants, suggesting that ANGPTL6 could trigger cerebrovascular lesions when combined with other risk factors such as hypertension. Altogether, our results indicate that rare coding variants in ANGPTL6 are causally related to familial forms of IA.

Aneurysm Clipping and Outcome for Hunt & Hess Grade 4, 5 Subarachnoid Hemorrhage—A Literature Review

“Subarachnoid Hemorrhage is non-traumatic nasty bleeding into the subarachnoid area, the territory between the arachnoid and the piamater of the central nervous system showing prompt developing signs of neurological sequelae”. It is one among the neurological emergencies which is a very distressing cerebrovascular disease with complicated mechanisms that risks brain perfusion and its function, having higher morbidity and mortality rates. Its mortality rate is still ranged between 8.3% and 66.7%, with noticeable regional variations, beside recent advances in treatment approaches. The incidence of SAH among the population of 2 - 22.5/100,000 was reported with a minimum of 60% of aneurysm ruptures occurring amid ages of 40 and 60 years with 3:2 male:female ratio. The rupture risks for unruptured aneurysms are increased by the issues like present smokers, larger size of aneurysm, and amid young population. The surgical treatment decision should be contemplated upon factors such as aneurysm’s size, aneurysm’s location, patient’s illness history, and surgeon’s operative experiences. Latest technical progresses in imaging techniques, increased consideration of illness history, more awareness of incidences of aneurysms and use of micro neurosurgery, have raised the chance for detection of subarachnoid hemorrhage (SAH) and possible better outcomes with surgical management. Factors that may affect outcome include age, size and site of aneurysm, interval between ictus and surgery, CT Fisher Grade & Hunt and Hess Grading earlier to surgery, & Glasgow Coma Scale at the while of discharge. The studies here support the wide spread concept that surgical clipping of SAH for Hunt and Hess Grade 4, 5 SAH, which is also considered as poor Grade SAH stipulates an effective treatment if done earlier provides better outcome.

Desmopressin administration and rebleeding in subarachnoid hemorrhage: analysis of an observational prospective database.

Rebleeding remains a frequent and catastrophic event leading to poor outcome after subarachnoid hemorrhage (SAH). Reduced platelet function after the initial bleed is associated with higher risk of early rebleeding. Desmopressin (DDAVP) is a well-known hemostatic agent, and recent guidelines already suggest its use in individuals exposed to antiplatelet drugs. The authors hypothesized that DDAVP administration in patients with SAH at admission would be associated with lower risks of rebleeding. The authors performed an observational cohort study of patients enrolled in the Columbia University SAH Outcome Project between August 1996 and July 2015. The authors compared the rate of rebleeding between patients who were and those who were not treated with DDAVP. After adjustment for known predictors, logistic regression was used to measure the association between treatment with DDAVP and risks of rebleeding. Among 1639 patients with SAH, 12% were treated with DDAVP. The main indication for treatment was suspected exposure to an antiplatelet agent. The overall incidence of rebleeding was 9% (1% among patients treated with DDAVP compared with 8% among those not treated). After adjustment for antiplatelet use and known predictors, treatment with DDAVP was associated with a 45% reduction in the risks of rebleeding (adjusted OR 0.55, 95% CI 0.27-0.97). DDAVP was associated with a higher incidence of hyponatremia but not with thrombotic events or delayed cerebral ischemia. Treatment with DDAVP was associated with a lower risk of rebleeding among patients with SAH. These findings support further study of DDAVP as first-line therapy for medical hemostasis in patients with SAH.

Hypothesis on the Role of Cryptochromes in Inflammation and Subarachnoid Hemorrhage Outcome.

We have recently found that the temperature variability (TV) in the day–night cycle may predict the mean intracranial pressure in the following 24 h (ICP24) in subarachnoid hemorrhage (SAH) patients under multimodality monitoring, sedation, and hypothermia (<35°C). Specifically, we found that ICP24 = 6 (4 − TV) mmHg. TV is the ratio between the coefficient of variation of temperature during the nocturnal and the preceding diurnal periods. This result suggests that the circadian clock reflects brain plasticity mechanisms and its malfunctioning leads to deterioration of the neurologic status. The sleep–wake cycle is absent in these patients and their circadian clock can function properly only by environment light-independent mechanisms. One mechanism involves the circadian clock proteins named cryptochromes (CRYs). CRYs are highly preserved and widespread in the evolutionary tree, are expressed in different cell types in humans [type II CRYs, in two forms: human cryptochrome 1 and 2 (hCRY1 and hCRY2)], and in certain species, respond to blue light and play role in magnetoreception. Interestingly, SAH outcome seems to correlate with inflammation, and CRYs decrease inflammatory activity. Our hypothesis derived from these observations is that CRYs modulate the circadian oscillation of temperature even during therapeutic hypothermia and improve outcome in SAH through decrease in inflammation. A strategy to test this hypothesis is to measure periodically during the acute phase of high-grade SAH the level of CRYs in cerebrospinal fluid (CSF) and circulating white blood cells, and to correlate these levels with outcome, TV, ICP24, and pro- and anti-inflammatory markers in CSF and blood. If this hypothesis is true, the development of therapies targeting inflammation in SAH could take advantage of cryptochrome properties. It has been shown that blue light phototherapy increases the expression of CRYs in blood mononuclear cells in jaundiced neonates. Likewise, visual stimulus with flashing light improves Alzheimer’s disease features in experimental model and there is a prominent expression of CRYs in the retina. Remarkably, recent evidence showed that hCRY2 responds to electromagnetic fields, which could be one elusive mechanism of action of transcranial magnetic stimulation and a reason for its use in SAH.

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

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. 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. 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, AUCBNI 0.616, AUCWFNS 0.672, AUCHH 0.673, AUCVG 0.674, AUCHAIR 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 (AUCBNI 0.628, AUCmFish 0.654, AUCWFNS 0.736, AUCHH 0.749, AUCVG 0.711, AUCHAIR 0.739). 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.

Increased Plasma Galectin-3 Preceding the Development of Delayed Cerebral Infarction and Eventual Poor Outcome in Non-Severe Aneurysmal Subarachnoid Hemorrhage.

A matricellular protein galectin-3 is involved in tissue injury and inflammation, but the role of galectin-3 remains unclear in aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to assess whether acute-stage galectin-3 levels were associated with the subsequent development of neurovascular events and outcome after SAH. This study included 83 consecutive patients diagnosed with aneurysmal SAH of resuscitated World Federation of Neurological Surgeons (WFNS) grades 1-3. Plasma galectin-3 levels were once measured on days 1-3 (the day after clipping or coiling). Fifteen patients had poor outcomes, which were associated with increasing age, female, pre-onset morbidity, worse WFNS grade, modified Fisher computed tomography scale, acute hydrocephalus, and higher galectin-3 levels compared with good outcomes. Multivariate analyses revealed that plasma galectin-3 was an independent determinant for poor outcome (odds ratio, 3.08; 95% confidence interval, 1.58-6.00; p=0.001). Among post-SAH neurovascular events occurring on day 4 and thereafter, delayed cerebral ischemia and infarction, but not angiographic vasospasm and shunt-dependent hydrocephalus, showed significantly higher plasma galectin-3 levels on days 1-3. The receiver operating characteristic curve indicated that plasma galectin-3 with a cutoff value of 3.30 or 3.48ng/ml predicted delayed cerebral infarction development or poor outcome (specificity, 62.5%, 70.6%; sensitivity, 90.9%, 73.3%, respectively). The findings suggest that plasma galectin-3 levels on days 1-3 would be a useful biomarker for predicting subsequent development of delayed cerebral infarction and eventual poor outcome and provide a new candidate, which may mediate between post-SAH early brain injury or inflammation and delayed cerebral infarction without vasospasm.

Clusterin, a New Cerebrospinal Fluid Biomarker in Severe Subarachnoid Hemorrhage: A Pilot Study.

Inflammation following subarachnoid hemorrhage (SAH) involves numerous mediators with biomarker properties. Preliminary studies indicated that clusterin, a multifunctional chaperon protein, was a potential biomarker in SAH. We aimed to clarify the status of clusterin in SAH. From 27 patients with severe SAH, 47 cerebrospinal fluid (CSF) samples were collected 0-3, 5-7, and 10-14 days after SAH. Control CSF was collected from 25 age- and sex-matched healthy control subjects undergoing spinal anesthesia for minor surgery. Clusterin concentrations were assayed using enzyme-linked immunosorbent assay and compared with inflammatory markers, imaging findings, and treatment outcome. In healthy control subjects, mean CSF clusterin level (1908.5 ng/mL ± 36.0) was significantly higher than in the patient group (P < 0.001). In the patient group, mean clusterin level was 741.1 ng/mL ± 759.2 0-3 days, 601.6 ng/mL ± 507.2 5-7 days, and 639.2 ng/mL ± 446.8 10-14 days after SAH. Clusterin level failed to differentiate between good (Glasgow Outcome Scale 4-5) and poor (Glasgow Outcome Scale 1-3) outcomes 0-3 days and 10-14 days after SAH (P= 0.238 and P= 0.225), but significantly higher levels of CSF clusterin were found 5-7 days after SAH in patients with good outcome (P= 0.017). There was a significant correlation between CSF clusterin level 5-7 days after SAH and Glasgow Outcome Scale at 3 months (correlation coefficient= 0.633). The best correlation was found for World Federation of Neurological Societies scale (correlation coefficient=-0.741). SAH is associated with immediate decrease in CSF clusterin concentrations. Clusterin level at one point was a good predictor of outcome, and it may serve as a biomarker.

Early Prediction of Delayed Ischemia and Functional Outcome in Acute Subarachnoid Hemorrhage

Diffusion tensor imaging (DTI) parameters are markers of cerebral lesion in some diseases. In patients with acute subarachnoid hemorrhage (SAH), we investigated whether DTI parameters measured at <72 hours might be associated with delayed cerebral ischemia (DCI) and with poor functional outcome at 3 months (modified Rankin Scale score ≥3). DTI was performed in a prospective cohort of 60 patients with nontraumatic SAH at <72 hours. Association of fractional anisotropy and apparent diffusion coefficient values at <72 hours with the occurrence of DCI and outcome at 3 months was evaluated with logistic regression models, adjusting for known predictors of prognosis. At <72 hours after SAH, fractional anisotropy values at the cerebellum were associated with DCI occurrence (78% less odds of DCI for each 0.1 increase in fractional anisotropy; P=0.019). Early apparent diffusion coefficient values were not associated with DCI. After adjusting for confounding variables, an increase of 10 U in apparent diffusion coefficient at the frontal centrum semiovale corresponded to 15% increased odds of poor outcome (P=0.061). DTI parameters at <72 hours post-SAH are independently associated with the occurrence of DCI and functional outcome. These preliminary results suggest the role of DTI parameters as surrogate markers of prognosis in nontraumatic SAH.

The Effect of Morbid Obesity on Subarachnoid Hemorrhage Prognosis in the United States.

The association between obesity and nontraumatic subarachnoid hemorrhage (SAH) patient outcome is unclear. The aim of this study was to determine the impact of morbid obesity (body mass index ≥40 kg/m2) on nontraumatic SAH outcomes. Using the Nationwide Inpatient Sample, we identified hospitalized, nontraumatic SAH patients who received their diagnoses from 2008 to 2013 and tested the effect of obesity on their mortality and clinical outcomes. Odds ratios were estimated with a mixed effects linear logistic model with adjustment for hospital clustering. All statistical testing was 2-sided, with a significance level of 5%. Out of 224,561 discharged patients with a diagnosis of nontraumatic SAH, 4714 (2.10%) were defined as morbidly obese. Patients with morbid obesity were younger (54.3 ± 0.44 vs. 59.5 ± 0.08 years; P < 0.001) and had longer length of stay (LOS) (13 ± 0.46 vs. 11.5 ± 0.06 days; P= 0.002). Morbid obesity was associated with significantly higher hospital costs (P < 0.001) and charges (P < 0.001). The risk of acute respiratory failure was higher in morbidly obese patients (odds ratio [OR] 1.49, 95% confidence interval [CI]: 1.3-1.71, P < 0.001). In a multivariate analysis of hospital mortality, obesity had a negative impact on mortality (OR 0.83, 95% CI: 0.74-0.92, P < 0.001). Overall, in-hospital mortality was associated with age, morbid obesity, LOS, clipping and coiling, and acute respiratory failure but not the symptomatic vasospasm. Morbid obesity is associated with increased LOS, hospital costs and charges and with acute respiratory failure. However, it is also associated with a decrease in hospital mortality.

Demographic and clinical predictors of multiple intracranial aneurysms in patients with subarachnoid hemorrhage

OBJECTIVE Pathophysiological differences that underlie the development and subsequent growth of multiple aneurysms may exist. In this study, the authors assessed the factors associated with the occurrence of multiple aneurysms in patients presenting with aneurysmal subarachnoid hemorrhage (SAH). METHODS Consecutive patients presenting with aneurysmal SAH between 1996 and 2012 were prospectively enrolled in the Subarachnoid Hemorrhage Outcome Project. Patients harboring 1, 2, or 3 or more aneurysms were stratified into groups, and the clinical and radiological characteristics of each group were compared using multivariate logistic regression. RESULTS Of 1277 patients with ruptured intracranial aneurysms, 890 had 1 aneurysm, 267 had 2 aneurysms, and 120 had 3 or more aneurysms. On multinomial regression using the single-aneurysm cohort as base case, risk factors for patients presenting with 2 aneurysms were female sex (relative risk ratio [RRR] 1.80, p < 0.001), higher body mass index (BMI) (RRR 1.02, p = 0.003), more years of smoking (RRR = 1.01, p = 0.004), and black race (RRR 1.83, p = 0.001). The risk factors for patients presenting with 3 or more aneurysms were female sex (RRR 3.10, p < 0.001), higher BMI (RRR 1.03, p < 0.001), aneurysm in the posterior circulation (RRR 2.59, p < 0.001), and black race (RRR 2.15, p = 0.001). Female sex, longer smoking history, aneurysms in the posterior circulation, BMI, and black race were independently associated with the development of multiple aneurysms in our adjusted multivariate multinomial model. CONCLUSIONS Significant demographic and clinical differences are found between patients presenting with single and multiple aneurysms in the setting of aneurysmal SAH. These predictors of multiple aneurysms likely reflect a predisposition toward inflammation and endothelial injury.

Characteristics of Blood Pressure Profiles After Endovascular Coiling as Predictors of Clinical Outcome in Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

Accurate identification of patients who will achieve a favorable outcome is almost impossible preoperatively or postoperatively in poor-grade (Hunt and Hess Grade IV and V) aneurysmal subarachnoid hemorrhage (SAH). Whether characteristics of blood pressure profiles during the first 24 hours after endovascular coiling could predict prognosis in poor grade patients was explored. Data were obtained retrospectively on all patients undergoing endovascular treatment with poor-grade SAH from November 2011 to June 2016. Blood pressure during the initial 24 hours was measured at 2-hour intervals after coil embolization. Studied features of mean systolic blood pressure (MSBP) and systolic blood pressure variability (SBPV) as well as demographics, medical history, clinical characteristics, and neurologic outcomes were documented. SBPV was determined as standard deviation and successive variation of systolic blood pressure. Logistic regression analysis was used to identify predictors of favorable outcome assessed on modified Rankin Scale score of 0 to2. The patients with favorable and unfavorable outcome were comparable with respect to systolic blood pressure on admission and MSBP after coiling. However, MSBP between 120 and 140 mm Hg was one of independent predictors of good outcomes at discharge (odds ratio 7.1; P= 0.002). SBPV-successive variation after embolization was associated with functional recovery (odds ratio 0.87; P= 0.011) in multivariate logistic analysis and mortality by Cox proportional hazard regression (hazard ratio, 1.10; P=0.001) at 6-month follow-up. Characteristics of blood pressure profiles after coiling appeared to be simple and convenient indexes for the prognosis of patients with poor-grade SAH.

Radiodensity of intraventricular hemorrhage associated with aneurysmal subarachnoid hemorrhage may be a negative predictor of outcome.

OBJECTIVE The presence, extent, and distribution of intraventricular hemorrhage (IVH) have been associated with negative outcomes in aneurysmal subarachnoid hemorrhage (SAH). Several qualitative scores (Fisher grade, LeRoux score, and Graeb score) have been established for evaluating SAH and IVH. However, no study has assessed the radiodensity within the ventricular system in aneurysmal SAH patients with IVH. Prior studies have suggested that hemorrhage with a higher radiodensity, as measured by CT Hounsfield units, can cause more irritation to brain parenchyma. Therefore, the authors set out to investigate the relationship between the overall radiodensity of the ventricular system in aneurysmal SAH patients with IVH and their clinical outcome scores. METHODS The authors reviewed the records of 101 patients who were admitted to their institution with aneurysmal SAH and IVH between January 2011 and July 2015. The following data were collected: age, sex, Glasgow Coma Scale (GCS) score, Hunt and Hess grade, extent of SAH (none, thin, or thick/localized), aneurysm location, and Glasgow Outcome Scale (GOS) score. To evaluate the ventricular radiodensity, the initial head CT scan was loaded into OsiriX MD. The ventricular system was manually selected as the region of interest (ROI) through all pertinent axial slices. After this, an averaged ventricular radiodensity was calculated from the ROI by the software. GOS scores were dichotomized as 1-3 and 4-5 subgroups for analysis. RESULTS On univariate analysis, younger age, higher GCS score, lower Hunt and Hess grade, and lower ventricular radiodensity significantly correlated with better GOS scores (all p < 0.05). Subsequent multivariate analysis yielded age (OR 0.936, 95% CI 0.895-0.979), GCS score (OR 3.422, 95% CI 1.9-6.164), and ventricular density (OR 0.937, 95% CI 0.878-0.999) as significant independent predictors (p < 0.05). A receiver operating characteristic curve yielded 12.7 HU (area under the curve 0.625, p = 0.032, sensitivity = 0.591, specificity = 0.596) as threshold between GOS scores of 1-3 and 4-5. CONCLUSIONS This study suggests that the ventricular radiodensity in aneurysmal SAH patients with IVH, along with GCS score and age, may serve as a predictor of clinical outcome.

Obstructive Sleep Apnea is Associated with Improved Non-Traumatic Subarachnoid Hemorrhage Outcomes (P4.311)

Obstructive Sleep Apnea is Associated with Improved Non-Traumatic Subarachnoid Hemorrhage Outcomes (P4.311)

Predicting Outcome in Subarachnoid Hemorrhage (SAH) Utilizing the Full Outline of UnResponsiveness (FOUR) Score.

Existing scoring systems for aneurysmal subarachnoid hemorrhage (SAH) patients fail to accurately predict patient outcome. Our goal was to prospectively study the Full Outline of UnResponsiveness (FOUR) score as applied to newly admitted aneurysmal SAH patients. All adult patients presenting to Health Sciences Center in Winnipeg from January 2013 to July 2015 (2.5year period) with aneurysmal SAH were prospectively enrolled in this study. All patients were followed up to 6months. FOUR score was calculated upon admission, with repeat calculation at 7 and 14days. The primary outcomes were: mortality, as well as dichotomized 1- and 6-month Glasgow Outcome Scale (GOS) and modified Rankin Scale (mRS) values. Sixty-four patients were included, with a mean age of 54.2years (range 26-85years). The mean FOUR score upon admission pre- and post-external ventricular drain (EVD) was 10.3 (range 0-16) and 11.1 (range 3-16), respectively. There was a statistically significant association between pre-EVD FOUR score (total, eye, respiratory and motor sub-scores) with mortality, 1-month GOS, and 6-month GOS/mRS (p<0.05 in all). The day 7 total, eye, respiratory, and motor FOUR scores were associated with mortality, 1-month GOS/mRS, and 6-month GOS/mRS (p<0.05 in all). The day 14 total, eye, respiratory, and motor FOUR scores were associated with 6-month GOS (p<0.05 in all). The day 7 cumulative FOUR score was associated with the development of clinical vasospasm (p<0.05). The FOUR score at admission and day 7 post-SAH is associated with mortality, 1-month GOS/mRS, and 6-month GOS/mRS. The FOUR score at day 14 post-SAH is associated with 6-month GOS. The brainstem sub-score was not associated with 1- or 6-month primary outcomes.

Demographics and Short-Term Outcomes of Spontaneous Subarachnoid Hemorrhage in Young Adults.

Spontaneous subarachnoid hemorrhage (SAH) is a catastrophic disease with a high mortality. Although it is associated with poor prognosis in older patients, the socioeconomic consequences in younger patients with stroke may be more severe. We aimed to focus on the demographics and short-term outcomes of SAH in a population younger than 50 years. We retrospectively enrolled 1689 patients with a primary diagnosis of SAH from 1993 to 2010. We identified intergroup differences in clinical variables between the patients aged 18-49 years (n= 531) and those aged ≥50 years (n= 1158). The patients with SAH included 688 men and 1001 women (an overall male/female ratio of 1:1.45), of whom 31.4% were aged 18-49 years. Men comprised 53.5% of the younger patients and 34.9% of the older patients (P<0.01). The post-SAH sequela of hemiplegia was more common in the younger patients (P < 0.01), whereas the incidences of in-hospital mortality in the younger and older groups were 25.4% and 32.4%, respectively (P < 0.01). Adults younger than 50 years account for a significant portion of the population with SAH. There is a male predominance in this age group, probably related to early and substantial risk exposure. Although younger age imparts a higher probability of survival, it is also accompanied by a greater incidence of resultant sequelae. A better understanding of the age-related variability of SAH will assist in guidance for public health and adjustment of clinical management.

Postprocedure Subarachnoid Hemorrhage after Endovascular Treatment for Acute Ischemic Stroke.

The rate of occurrence and associated outcomes of subarachnoid hemorrhage (SAH) in acute ischemic stroke patients following endovascular treatment is not well studied. We analyzed data from subjects treated with intravenous recombinant tissue plasminogen activator followed by endovascular treatment in the Interventional Management of Stroke III trial. The baseline and 24 (±6) hours postrandomization computed tomographic scans were interpreted centrally for presence, type, and location of intracranial hemorrhages (ICHs) including SAH. The primary outcome assessment was by modified Rankin scale (mRS) score at 3 months. Of these 323 subjects who underwent endovascular treatment, the patterns of postprocedure ICHs were as follows: none (n = 168), isolated SAH (type 1, n = 9), SAH with intraparenchymal hemorrhage (IPH) or other ICHs (type 2, n = 33), and IPH or other ICHs without SAH (n = 113). At 3 months, the rates of independent functional outcome (mRS 0-2) were lower among subjects with type 2 SAHs (odds ratio [OR] .2; 95% confidence interval [CI] .1-.8; P = .016), and IPH or other ICHs without SAH (OR .5; 95% CI .3-.9; P = .022) but not in subjects with type 1 SAH (OR .8; 95% CI .2-3.5; P = .810), after adjusting for age, baseline serum glucose levels, National Institutes of Health Stroke Scale score strata, and procedure related complications. The rates of independent functional outcome were lower among subjects with postprocedure type 2 SAHs but not in subjects with type 1 SAH.

Serum microRNAs are non-invasive biomarkers for the presence and progression of subarachnoid haemorrhage.

miRNAs are important regulators of translation and have been associated with the pathogenesis of a number of cardiovascular diseases including stroke and may be possible prognostic biomarkers. The purpose of the present study was to determine the expression levels of miRNAs in the sera of subarachnoid haemorrhage (SAH) patients and to evaluate their relationships with the severity and clinical outcome of SAH. Serum samples on day 3 after the onset of SAH were subjected to microarray analysis with Exqion miRCURYTM LNA array and quantitative PCR analysis. Serum samples from SAH patients (n=60) and healthy controls (n=10) were subjected to quantitative PCR analysis. The severities and clinical outcomes of the SAH patients were evaluated with the WFNS grade and the Modified Rankin Scale (mRS). Three miRNAs, miR-502-5p, miR-1297 and miR-4320 were significantly up-regulated in the sera of SAH patients when compared with the healthy controls. The serum miR-502-5p and miR-1297 levels were significantly higher in the patients with severe SAH and a poor outcome than in those with mild SAH and a good outcome (P<0.05). The areas under the receiver operating characteristic (ROC) curves (AUCs) of miR-502-5p, miR-1297 and miR-4320 to distinguish the SAH patients from the healthy controls were 0.958 (P<0.001), 0.950 (P<0.001) and 0.843 (P<0.001) respectively. Taken together, these results indicate that miR-502-5p and miR-1297 are potentially valuable indicators of the diagnosis, severity and prognosis of SAH, and miR-4320 was a potentially valuable indicator of the diagnosis of SAH.

Abstract TP429: Association Between Perioperative Management and Outcome in Aged SAH Patients

Background and purpose: The outcomes of subarachnoid hemorrhage (SAH) in aged patients are more severe than those in non-aged patients. There are few reports about the relationship between the age and the effect of perioperative care for SAH patients. We performed a nationwide survey in Japan to determine the relationship between perioperative care and SAH outcomes in aged and non-aged patients. Methods: We analyzed 17,343 subarachnoid hemorrhage (SAH) patients treated with clipping or coiling in 579 hospitals who participated in the J-ASPECT study. Data between 2010 and 2013 were obtained from the Japanese Diagnosis Procedure Combination Database. We stratified patients into two groups according to their age (aged group &gt;75 y.o., n=3885; non-aged group &lt; 75 y.o., n=13,458) and analyzed the association between perioperative care and poor outcome (modified Rankin Scale score 3-6 at the time of discharge). With respect to perioperative care, we evaluated time from onset to surgery (days), treatment (clipping or coiling), and drugs delivered after surgery (fasudil hydrochloride, ozagrel sodium, cilostazol, statin, EPA, edaravone). Results: In the non-aged group, coiling (OR=0.84; P&lt;0.01) and treatment with fasudil hydrochloride (OR=0.59; P&lt;0.01), statin (OR=0.83; P&lt;0.01), and EPA (OR=0.83; P&lt;0.01) significantly improved the outcomes and cilostazol treatment tended to improve the outcomes (OR=0.91; P=0.07). In both groups, edaravone treatment was associated with poor outcome (aged group: OR=2.34, P&lt;0.01; non-aged group: OR=2.33, P&lt;0.01). Although no factor that could improve outcome in the aged group was identified, JCS scores less than 30, coiling (OR=0.80; P=0.03), and EPA treatment (OR=0.74; P=0.02) were statistically significant prognosis improvement factors. Conclusion: Coiling and treatment with fasudil hydrochloride, statins, and EPA improved outcomes of non-aged patients. Although perioperative care did not improve the outcome of aged SAH patients, in cases of relatively mild SAH, perioperative care had the potential to improve the outcome.

3 mm以下の破裂小型動脈瘤によるくも膜下出血の特徴と治療成績

3 mm以下の破裂小型動脈瘤によるくも膜下出血の特徴と治療成績

Beta Blockade and Clinical Outcomes in Aneurysmal Subarachnoid Hemorrhage.

Background:Aneurysmal subarachnoid hemorrhages are frequently complicated by hypertension and neurogenic myocardial stunning. Beta blockers may be used for management of these complications. We sought to investigate sympathetic nervous system modulation by beta blockers and their effect on radiographic vasospasm, delayed cerebral infarction, discharge destination and death.Methods:Retrospective chart review of 218 adults admitted to the ICU between 8/2004 and 9/2010 was performed. Groups were identified relevant to beta blockade: 77 were never beta blocked (No/No), 123 received post-admission beta blockers (No/Yes), and 18 were continued on their home beta blockers (Yes/Yes). Records were analyzed for baseline characteristics and the development of vasospasm, delayed cerebral infarction, discharge destination and death, expressed as adjusted odds ratio.Results:Of the 218 patients 145 patients developed vasospasm, 47 consequently infarcted, and 53 died or required care in a long-term facility. When compared to No/No patients, No/Yes patients had significantly increased vasospasm (OR 2.11 (1.06-4.16)). However, these patients also had significantly fewer deaths or need for long term care (OR 0.17 (0.05-0.64)), with decreased tendency for infarcts (OR 0.70 (0.32-1.55)). When compared to No/No patients, Yes/Yes patients demonstrated a trend toward increased vasospasm (OR 1.61 (0.50-5.29)) that led to infarction (OR 1.51 (0.44-5.13)), but with decreased mortality or need for long term care in a facility (OR 0.13 (0.01-1.30)).Conclusion:Post-admission beta blockade in aneurysmal subarachnoid hemorrhage patients was associated with increased incidence of vasospasm. However, despite the increased occurrence of vasospasm, beta blockers were associated with improved discharge characteristics and fewer deaths.