Outcome Of Subarachnoid Hemorrhage Research Articles

Sex Differences in Outcome of Aneurysmal Subarachnoid Hemorrhage and Its Relation to Postoperative Cerebral Ischemia.

Whether there is a sex difference in the outcome of aneurysmal subarachnoid hemorrhage (aSAH) remains controversial, and clarifying the role of women in postoperative cerebral ischemic events can help us to understand its relationship with poor prognosis. Therefore, the purpose of this study was to elucidate the relationship between the three aspects of sex differences, postoperative cerebral ischemia, and poor prognosis after aSAH. A total of 472 patients admitted within 72h after aSAH between January 2018 and December 2022 were included. We systematically analyzed the characteristics of sex differences in aSAH and explored the relationship between delayed cerebral ischemia (DCI), surgery-related cerebral infarction (SRCI), and poor prognosis (modified Rankin Scale > 2). Compared with women, men were in worse condition and had more intracerebral hematoma (p = 0.001) on admission, whereas women were older (p < 0.001) and had more multiple aneurysms (p = 0.002). During hospitalization, men were more likely to experience emergency intubation (p = 0.036) and tracheotomy (p = 0.013). Women achieved functional independence at discharge at a similar rate to men (p = 0.394). Among postoperative complications, the incidence of DCI (22% vs. 12%, p = 0.01) and urinary tract infection (p = 0.022) was significantly higher in women. After adjusting for age, multivariable regression analysis showed that hypertension (odds ratio [OR] 2.139, 95% confidence interval [CI] 1.027-4.457), preoperative rerupture (OR 12.240, 95% CI 1.491-100.458), pulmonary infection (OR 2.297, 95% CI 1.070-4.930), external ventricular drainage placement (OR 4.382, 95% CI 1.550-12.390), bacteremia (OR 14.943, 95% CI 1.412-158.117), SRCI (OR 8.588, 95% CI 4.092-18.023), venous thrombosis (OR 5.283, 95% CI 1.859-15.013), higher modified Fisher grades (p = 0.003), and Hunt-Hess grades (p = 0.035) were associated with poor prognosis, whereas DCI (OR 1.394, 95% CI 0.591-3.292) was not an independent risk factor for poor prognosis. The proportion of patients who fully recovered from cerebral ischemia was higher in the DCI group (p < 0.001) compared with the SRCI group, and more patients were discharged with modified Rankin Scale > 2 in the SRCI group (p = 0.005). Women have a higher incidence of DCI, but there is no sex difference in outcomes after aSAH, and poor prognosis is associated with worse admission condition and perioperative complications. SRCI is a strong independent risk factor for poor prognosis, whereas DCI is not.

Impact of thyroid hormone replacement therapy on the course and functional outcome of aneurysmal subarachnoid hemorrhage

BackgroundThyroid hormones were reported to exert neuroprotective effects after ischemic stroke by reducing the burden of brain injury and promoting post-ischemic brain remodeling.ObjectiveWe aimed to analyze the value of thyroid hormone replacement therapy (THRT) due to pre-existing hypothyroidism on the clinical course and outcome of aneurysmal subarachnoid hemorrhage (SAH).MethodsSAH individuals treated between January 2003 and June 2016 were included. Data on baseline characteristics of patients and SAH, adverse events and functional outcome of SAH were recorded. Study endpoints were cerebral infarction, in-hospital mortality and unfavorable outcome at 6 months. Associations were adjusted for outcome-relevant confounders.Results109 (11%) of 995 individuals had THRT before SAH. Risk of intracranial pressure- or vasospasm-related cerebrovascular events was inversely associated with presence of THRT (p = 0.047). In multivariate analysis, THRT was independently associated with lower risk of cerebral infarction (adjusted odds ratio [aOR] = 0.64, 95% confidence interval [CI] = 0.41–0.99, p = 0.045) and unfavorable outcome (aOR = 0.50, 95% CI = 0.28–0.89, p = 0.018), but not with in-hospital mortality (aOR = 0.69, 95% CI = 0.38–1.26, p = 0.227).ConclusionSAH patients with THRT show lower burden of ischemia-relevant cerebrovascular events and more favorable outcome. Further experimental and clinical studies are required to confirm our results and elaborate the mechanistic background of the effect of THRT on course and outcome of SAH.

Association of Fluid Balance and Hemoglobin Decline With Neurological Outcome After Aneurysmal Subarachnoid Hemorrhage.

To explore the relationship between fluid balance and hemoglobin decline with secondary infarctions and neurologic outcome in aneurysmal subarachnoid hemorrhage (aSAH) patients. Secondary analysis of the Earlydrain trial, a prospective randomized controlled study investigating prophylactic lumbar drain use in aSAH patients. Patients with aSAH treated in ICUs at 19 tertiary hospitals in Germany, Switzerland, and Canada. From January 2011 to January 2016, 287 patients were enrolled in the Earlydrain trial. Only files with complete information on both daily hemoglobin and balance values were used, leaving 237 patients for analysis. Investigation of fluid balance management and hemoglobin levels during the initial 8 days post-aSAH to establish thresholds for unfavorable outcomes and assess their impact on secondary infarctions and 6-month neurologic outcome on the modified Rankin Scale (mRS). Patients with unfavorable outcome after 6 months (mRS > 2) showed greater hemoglobin decline and increased cumulative fluid balance. A significant inverse relationship existed between fluid balance and hemoglobin decline. Thresholds for unfavorable outcome were 10.4 g/dL hemoglobin and 4894 mL cumulative fluid balance in the first 8 days. In multivariable analysis, fluid balance, but not fluid intake, remained significantly associated with unfavorable outcome, while the influence of hemoglobin lessened. Fluid balance but not hemoglobin related to secondary infarctions, with the effect being significant after inverse probability of treatment weighting. Transfusion was associated with unfavorable outcomes. Increased fluid balance influences hemoglobin decline through hemodilution. Fluid overload, rather than a slight decrease in hemoglobin levels, appears to be the primary factor contributing to poor outcomes in aSAH patients. The results suggest aiming for euvolemia and that a modest hemoglobin decline may be tolerated. It may be advisable to adopt a restrictive approach to transfusions, as they can potentially have a negative effect on outcome.

GPR30 improved subarachnoid hemorrhage induced blood-brain barrier dysfunction by activating PI3K/Akt and Nrf2/HO-1 pathways.

The blood-brain barrier (BBB) plays a critical role in the development and outcome of subarachnoid hemorrhage (SAH). This study focuses on the potential mechanism by which GPR30 affects the BBB after SAH. A rat SAH model was established using an intravascular perforation approach. G1 (GPR30 agonist) was administered to investigate the mechanism of BBB damage after SAH. Brain water content, western blotting, Evans blue leakage, and immunofluorescence staining were performed. Brain microvascular endothelial cells were induced by hemin to establish SAH model in vitro. By adding LY294002 (a PI3K blocker) and ZnPP IX (an HO-1 antagonist), the mechanism of improving BBB integrity through the activation of GPR30 was studied. In vivo, GPR30 activation improved BBB disruption, as evidenced by decreased cerebral edema, downregulated Albumin expression, and reduced extravasation of Evans blue and lgG after G1 administration in SAH rats. Moreover, SAH downregulated the levels of tight junction (TJ) proteins, while treatment with G1 reversed the effect of SAH. The protective effect of G1 on BBB integrity in vitro was consistent with that in vivo, as evidenced by G1 reducing the impact of hemin on TEER value, dextran diffusivity, and TJ protein levels in brain microvascular endothelial cells. In addition, G1 activated the PI3K/AKT and Nrf2/HO-1 pathways both in vivo and in vitro. Furthermore, the administration of LY294002 and ZnPP IX partially reversed the protective effect of G1 on BBB integrity in hemin-stimulated cells. These findings provide valuable insights for potential treatments for SAH. NEW & NOTEWORTHY We demonstrated that the activation of GPR30, at least partly through the PI3K/AKT and Nrf2/HO-1 pathways, alleviated BBB damage both in vivo and in vitro. This study introduced a novel therapeutic approach for protecting the BBB after SAH.

Incidence of Rebleed Following Cerebrospinal Fluid (CSF) Drainage in Poor Grade Subarachnoid Hemorrhage: An Institutional Experience

Background: The outcome of poor grade subarachnoid hemorrhage (SAH) is dismal. Some of these patients need cerebrospinal fluid (CSF) drainage procedure for the hydrocephalus and intraventricular hemorrhage (IVH) which may precipitate rebleeding. However, aneurysmal rebleed following CSF drainage procedure is controversial. Objective: Our study aimed at analyzing the effect of CSF drainage procedure on aneurysmal rebleeding. Material and Methods: We retrospectively analyzed the records of all the consecutive patients diagnosed with poor grade aneurysmal SAH over three year period. Patients initially requiring either external ventricular drainage (EVD) or lumbar drain (LD) were included in the study group, and the rest (not requiring drainage) were included in the control group. Rebleeding was confirmed on computed tomography. The factors affecting rebleeding were analyzed. Results: Overall 194 patients with poor grade SAH were enrolled in the study (91 males: 103 females; mean age: 50.6 years). The study group had 91 patients (83 EVD and 8 LD) while 103 patients were in the control group. Posterior circulation aneurysms, poor grade SAH, hydrocephalus, and IVH were more common in the study group P &lt; 0.001. The rebleeding rate was 7.6% in the study group and 8.7% in the control group. On univariate analysis size &gt;1 cm, multiplicity, multilobularity, vasospasm, and CSF drainage were significant risk factors for rebleeding (P &lt; 0.001). On multivariate analysis aneurysm size &gt;1 cm, CSF overdrainage &gt;250 ml/day were significantly associated with risk of rebleeding. Conclusion: Ventricular drainage is essential to relieve acute hydrocephalus and drain IVH in SAH and we found no significant association between CSF drainage and rebleeding. However, rapid overdrainage of CSF can lead to aneurysm rupture, hence controlled controlled CSF drainage should be undertaken.

Impact of time to start of tranexamic acid treatment on rebleed risk and outcome in aneurysmal subarachnoid hemorrhage.

The ULTRA-trial investigated effectiveness of ultra-early administration of tranexamic acid (TXA) in subarachnoid hemorrhage (SAH) and showed that TXA reduces the risk of rebleeding without concurrent improvement in clinical outcome. Previous trials in bleeding conditions, distinct from SAH, have shown that time to start of antifibrinolytic treatment influences outcome. This post-hoc analysis of the ULTRA-trial investigates whether the interval between hemorrhage and start of TXA impacts the effect of TXA on rebleeding and functional outcome following aneurysmal SAH. A post-hoc comparative analysis was conducted between aneurysmal SAH patients of the ULTRA-trial, receiving TXA and usual care to those receiving usual care only. We assessed confounders, hazard ratio (HR) of rebleeding and odds ratio (OR) of good outcome (modified Rankin Scale 0-3) at 6 months, and investigated the impact of time between hemorrhage and start of TXA on the treatment effect, stratified into time categories (0-3, 3-6 and >6 h). Sixty-four of 394 patients (16.2%) in the TXA group experienced a rebleeding, compared to 83 of 413 patients (19.9%) with usual care only (HR 0.86, 95% confidence interval (CI): 0.62-1.19). Time to start of TXA modifies the effect of TXA on rebleeding rate (p < 0.001), with a clinically non-relevant reduction observed only when TXA was initiated after 6 h (absolute rate reduction 1.4%). Tranexamic acid treatment showed no effect on good outcome (OR 0.96, 95% CI: 0.72-1.27) with no evidence of effect modification on the time to start of TXA (p = 0.53). This study suggests that the effect of TXA on rebleeding is modified by time to treatment, providing a protective, albeit clinically non-relevant, effect only when started after 6 h. No difference in functional outcome was seen. Routine TXA treatment in the aneurysmal SAH population, even within a specified time frame, is not recommended to improve functional outcome.

Elevated cortical blood flow insufficiency volume as a predictor of adverse outcomes in aneurysmal subarachnoid hemorrhage: a large prospective quantitative computed tomography perfusion study

PurposeEarly hypoperfusion changes exist in patients with aneurysmal subarachnoid hemorrhage (aSAH). We aimed to investigate a readily obtainable quantitative computed tomography perfusion (CTP) parameter that could assist in quickly identifying patients at risk of delayed cerebral ischemia (DCI) and poor 90-day functional outcomes on admission. MethodsWe prospectively collected data between 2021.04 and 2022.12. Preoperative CTP data were post-processed using RAPID software. The cortical blood flow insufficiency (CBFI) was defined as Time-to-maximum > 4.0 s. Patients were categorized into four groups according to CBFI volume distribution. To minimize differences among the groups, we employed stabilized inverse probability of treatment weighting (sIPTW). The primary outcome was DCI and poor 90-day functional outcomes (modified Rankin Scale, 3–6) was the secondary outcome. Multivariable Cox or Logistic analysis were performed to estimate the association between CBFI volume and the study outcomes, both before and after sIPTW. ResultsAt baseline, the mean (SD) age of the 493 participants was 55.0 (11.8) years, and 299 (60.6%) were female. One hundred and seven participants with DCI and eighty-six participants with poor 90-day functional outcomes were identified. After sIPTW, CBFI volume demonstrated a significant association with DCI (Cox regression: Group 4 versus Group 1, HR 3.69, 95% CI 1.84–7.01) and poor 90-day functional outcomes (Logistic regression: Group 4 versus Group 1, OR 4.61, 95% CI 2.01–12.50). ConclusionIn this study, an elevated preoperative CBFI volume was associated with adverse outcomes in aSAH patients. More well-designed studies are needed to confirm this association.

The dynamic changes of peripheral blood cell counts predict the clinical outcomes of aneurysmal subarachnoid hemorrhage

BackgroundAneurysmal subarachnoid hemorrhage (aSAH) is a serious type of hemorrhagic stroke. It is very important to predict the prognosis at early phase. In this work, we intend to characterize early changes in peripheral blood cells after aSAH and explore the association between peripheral blood cells and clinical outcomes after aSAH. MethodsaSAH patients admitted between December 2019 and September 2022 were enrolled. A retrospective observational study was performed. Total leukocytes, monocytes, neutrophils, erythrocytes, lymphocytes and platelets counts were recorded on the day of admission (day 1), day 3, day 5 and day 7. Statistical tests included Chi-square test, analysis of variance and multivariate logistic regression (MLR) models. 197 patients were analyzed. ResultsLeukocytes and neutrophils were higher in poor outcome groups from day 1 to day 7 and in delayed cerebral ischemia (DCI) groups from day 3 to day 7. Lymphocytes were higher at day 5 and day 7 in good outcome groups and no DCI groups. Neutrophil-to-lymphocyte ratio (NLR) was lower from day 3 to day 7 in good outcome groups and no DCI groups. Erythrocytes were higher from day 3 to day 7 in good outcome groups and no DCI groups. Lymphocytes were negatively related to poor outcomes on day 1 (OR = 0.457), indicating higher lymphocytes predicted good outcomes, Neutrophils were positively related to poor outcomes on day 3 (OR = 3.003) indicating higher neutrophils predicted poor outcomes. Lymphocytes were negatively related to DCI on day 5 (OR = 0.388) indicating higher lymphocytes predicted no DCI, Erythrocytes were negatively related to DCI on day 5 (OR = 0.335) and day 7 (OR = 0.204) indicating higher erythrocytes predicted no DCI. The improved ability of neutrophils, lymphocytes and erythrocytes to predict DCI or poor functional outcomes were revealed by ROC curve analysis. ConclusionsThe dynamic changes of peripheral blood cell counts were related to poor functional outcomes and DCI after aSAH. Elevated neutrophils, leukocytes, NLR, and decreased lymphocytes, erythrocytes were accompanied by DCI and poor outcome. Neutrophils, lymphocytes and erythrocytes counts could be beneficial to predict DCI and outcomes after aSAH.

The impact of regular aspirin use on aneurysm recanalization rates after endovascular coiling.

Intracranial aneurysms (IAs) pose a significant health risk, often leading to subarachnoid hemorrhage and severe neurological outcomes. Endovascular coiling has been a principal treatment method, but it comes with the challenge of high recanalization rates. Aspirin has recently emerged as a potential agent to reduce these rates. In this study, the authors aimed to investigate the impact of regular aspirin use on aneurysm recanalization rates following endovascular coiling in a 10-year single-institution study. A retrospective analysis was conducted on a dataset of 2236 aneurysms treated by a single neurosurgeon over a period of 10 years. The primary outcome measure was aneurysm recanalization, defined by a change in the Raymond-Roy Occlusion Classification of at least one grade. A total of 525 aneurysms were coiled, 109 of which involved patients who reported regular use of aspirin. The recanalization rate was significantly lower in the aspirin group (9.2%) compared with the control group (23.6%) (OR 0.33, 95% CI 0.15-0.66; p = 0.001). On analysis of the specific mechanisms of recanalization, aneurysm sac growth was less frequent in the aspirin group (5.5%) compared with the control group (18%) (OR 0.265, 95% CI 0.09-0.63; p = 0.002). Additionally, patients in the control group had a higher retreatment rate (18%) than patients in the aspirin group (5.5%) (OR 0.265, 95% CI 0.09-0.63; p = 0.002). Regular use of aspirin appears to be associated with reduced rates of aneurysm recanalization after endovascular coiling. However, caution is advised in interpretation of these results given the retrospective nature of this study. Further randomized controlled trials are needed to confirm these findings.

Re-evaluating patient communication and care in angiographically negative subarachnoid hemorrhage: Balancing realism and optimism.

Angiographically negative subarachnoid hemorrhage (anSAH) has traditionally been considered a benign condition, mainly because of favorable outcomes in the acute stage in comparison to the often negative acute outcomes of aneurysmal subarachnoid hemorrhage. However, a growing body of research in recent years shows that anSAH often leads to cognitive impairments, emotional distress, and difficulties in resuming work or other daily life activities. Therefore, in this position paper, we call for a change in neurological care and a shift in patient communication, emphasizing the importance of addressing patient needs and fostering realistic expectations rather than solely focusing on the benign nature of the condition.

Ligation of cervical lymphatic vessels decelerates blood clearance and worsens outcomes after experimental subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) is characterized by the extravasation of blood into the subarachnoid space, in which erythrocyte lysis is the primary contributor to cell death and brain injuries. New evidence has indicated that meningeal lymphatic vessels (mLVs) are essential in guiding fluid and macromolecular waste from cerebrospinal fluid (CSF) into deep cervical lymph nodes (dCLNs). However, the role of mLVs in clearing erythrocytes after SAH has not been completely elucidated. Hence, we conducted a cross-species study. Autologous blood was injected into the subarachnoid space of rabbits and rats to induce SAH. Erythrocytes in the CSF were measured with/without deep cervical lymph vessels (dCLVs) ligation. Additionally, prior to inducing SAH, we administered rats with vascular endothelial growth factor C (VEGF-C), which is essential for meningeal lymphangiogenesis and maintaining integrity and survival of lymphatic vessels. The results showed that the blood clearance rate was significantly lower after dCLVs ligation in both the rat and rabbit models. DCLVs ligation aggravated neuroinflammation, neuronal damage, brain edema, and behavioral impairment after SAH. Conversely, the treatment of VEGF-C enhanced meningeal lymphatic drainage of erythrocytes and improved outcomes in SAH. In summary, our research highlights the indispensable role of the meningeal lymphatic pathway in the clearance of blood and mediating consequences after SAH.

Baseline and average platelet count can predict the outcome of patients with aneurysmal subarachnoid hemorrhage

BackgroundBaseline values and the change of platelet count (PLT) during disease were reported to be associated with prognosis of patients with cancer and intensive care treatment. We aimed to evaluate the association between PLT with the course and prognosis of aneurysmal subarachnoid hemorrhage (SAH). MethodsAdmission (AdmPLT) and the 14-days mean PLT (MeanPLT) values of 763 SAH patients treated between 01/2005 and 06/2016 were recorded and, for further analysis, divided into four categories: <150, 150–260, 261–400 and > 400 × 109/L. Primary endpoints were cerebral infarcts in follow-up computed tomography scans, in-hospital mortality and unfavorable outcome at 6-months follow-up defined as modified Rankin scale>3. Adverse events during SAH were assessed as secondary endpoints. ResultsHigher PLT values were independently associated with lower risk of cerebral infarction (MeanPLT: aOR = 0.65 per-PLT-category-increase, p = 0.001), in-hospital mortality (AdmPLT: aOR = 0.64, p = 0.017; MeanPLT: aOR = 0.23, p < 0.0001) and unfavorable outcome (AdmPLT: aOR = 0.70, p = 0.031; MeanPLT: aOR = 0.35, p < 0.0001). Moreover, individuals with poorer outcome were less prone to PLT increase during SAH (mean values: -+20.3 vs + 30.5 × 109/L for cerebral infarction; +9.3 vs + 32.8 × 109/L for in-hospital mortality; +14.4 vs + 31.1 × 109/L for unfavorable outcome). The following adverse events during SAH were related to AdmPLT and/or MeanPLT: non-aneurysm related secondary rebleeding, intracranial hypertension requiring conservative treatment or decompressive craniectomy, sepsis and acute kidney failure. ConclusionLow PLT at admission and their less prominent increase during SAH were strongly linked with poor outcome of SAH. Further analysis is required to clarify the background of this association and potential therapeutic implications.

Increased blood coagulation is associated with poor neurological outcome in aneurysmal subarachnoid hemorrhage

Background and purposePatients with aneurysmal subarachnoid hemorrhage (aSAH) have demonstrated increased blood coagulation which is thought to contribute to delayed cerebral ischemia (DCI) and to a worse outcome. Therefore, we sought to determine whether this increased blood coagulation, detectable with rotational thromboelastometry (ROTEM), was associated with DCI and neurological outcome. MethodsWe conducted a prospective observational study of 60 consecutive adult aSAH patients. ROTEM's EXTEM and FIBTEM assays and D-dimer were analyzed at admission and post-bleed days (PBDs) 2–3, 4–5, 7–8, and 11–12. ROTEM's clot formation time (CFT) represents the stabilization of the clot, and the maximum clot firmness (MCF) the maximum clot strength. Glasgow Outcome Scale extended (GOSe) at three months determined the neurological outcome. ResultsDCI incidence was 41.7%. EXTEM-CFT was significantly shorter in patients with unfavorable neurological outcome (GOSe 1–4) on PBDs 4–5 and 7–8, p < 0.05, respectively. FIBTEM-MCF was significantly higher in patients with unfavorable neurological outcomes on PBD 4–5 (p < 0.05), PBD 7–8 (p < 0.05), and PBD 11–12 (p < 0.05). EXTEM-CFT decreased, and FIBTEM-MCF rose during the study period in all patients. Patients with unfavorable neurological outcome had a higher D-dimer at all studied time points, p < 0.05. No difference was found in the ROTEM parameters or D-dimer when assessing patients with and without DCI. ConclusionsPatients were in a state of increased blood coagulation after aSAH, with those with unfavorable neurological outcome being more coagulable than those with favorable outcome. However, increased blood coagulation was not associated with DCI.ClinicalTrials.gov, NCT03985176

Mapping geographic disparities in treatment and clinical outcomes of high-grade aneurysmal subarachnoid hemorrhage in the United States

Background and objectiveAlthough high-grade (Hunt and Hess 4 and 5) aneurysmal subarachnoid hemorrhage (aSAH) typically portends a poor prognosis, early and aggressive treatment has previously been demonstrated to confer a...

Factors Affecting Outcomes of Poor-Grade Subarachnoid Hemorrhage

Poor-grade subarachnoid hemorrhage (SAH) accounts for 20% of all SAH and is associated with poor outcomes. The first step in improving outcomes is to analyze the factors that contribute to poor outcomes. This was a multicenter, retrospective, observational, cohort study. Data fields included demographic, clinical, radiological, and outcome data for all spontaneous patients with SAH treated at 4 hospitals in Aomori Prefecture in Japan. Patients with modified Rankin Scale score 0-2 at discharge were defined as the good outcome group, and those with modified Rankin Scale score 3-6 were defined as the poor outcome group, and comparisons were made between the 2 groups. There were 329 eligible patients with poor-grade SAH, 41 with good outcome group, and 288 with poor outcome group. On multivariate analysis of the outcome, conservative treatment (P < 0.001), Fisher group 4 (P < 0.007), age ≥65 years (P= 0.011), and Hunt and Kosnik grade V on admission (P= 0.021) were significant factors contributing to a poor outcome. Nonelderly patients who are not in grade V and Fisher group 4 should undergo aneurysm treatment as soon as possible because they are more likely to have a good outcome, whereas elderly patients in grade V and Fisher group 4 are unlikely to benefit from aneurysm treatment at present. The development of a treatment for early brain injury may be important to improve the outcomes of patients with poor-grade SAH.

Dynamic changes of systemic inflammation response index and systemic immune-inflammation index are associated with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

ObjectivesDelayed cerebral ischemia (DCI) is a factor contributing to poor outcome of aneurysmal subarachnoid hemorrhage (aSAH). Serial inflammatory response is known to affect the occurrence of DCI. The aim of this study was to evaluate associations of dynamic changes of various inflammatory markers with occurrence of DCI after aSAH. MethodsA total of 279 patients with interventional treatment for aSAH were enrolled, and dichotomized according to the occurrence of DCI. Various inflammatory markers, including systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and their dynamic changes were analyzed at four different time points. Receiver operating characteristic (ROC) curve analysis with area under the curve (AUC) and univariate, multivariate Cox regression analyses with hazard ratio (HR) and 95 % confidence interval (CI) were performed to identify predictors for DCI. ResultsDifferences of SII and SIRI values between DCI (+) and DCI (-) group were significantly higher at 5-7 days than at other time points (P < 0.001 and P < 0.001, respectively). SII and SIRI had higher predicting values for DCI occurrence than other inflammatory markers (AUC: 0.862, 95 % CI: 0.786–0.928; P < 0.001 and AUC: 0.851, 95 % CI: 0.769–0.913; P < 0.001, respectively). SII at 5–7 days (HR: 1.74, 95 % CI: 1.38–3.22, P = 0.020) and SIRI at 5–7 days (HR: 1.62, 95 % CI: 1.28–2.84, P = 0.035) were associated with occurrence of DCI. ConclusionsDynamic changes of SII and SII might be predictors of DCI occurrence in patients with aSAH.

Abstract TP19: Predictors of Outcome in Subarachnoid Hemorrhage in the Pediatric Population

Background: Studies describing outcomes of subarachnoid hemorrhage (SAH) in children are sparse. This study aims to describe outcomes and determinants of outcomes in pediatric patients with SAH. Methods: We reviewed all pediatric admissions with the primary diagnosis of SAH from the 2016-2020 National Inpatient Sample using International Classification of Disease Codes. Baseline characteristics of patients (age, gender, and associated comorbidities) were computed using descriptive statistics. Multivariable-adjusted logistic regression determined predictors of in-hospital mortality for children with SAH. Results: 1,310 weighted hospitalizations for SAH were identified during the 5-year study period. The median age was 11.8 years (95% CI, 11.0-12.5), 54.6% were male. Seizures (34.6%), intraparenchymal hematoma (21.7%), acute ischemic stroke (6.4%), brain tumors (0.7%), and arteriovenous (AV) malformations (6.1%) were identified as the most common associated neurologic disorders during index hospitalization. 320 patients (24.4%) were treated endovascularly and 480 (36.6%) were treated via open surgical approach to treat vascular pathologies (AV malformations, dural AV fistulas, and aneurysms). Median length of hospitalization was 9.7 days (95% CI, 8.2-11.2. A total of 61.8% were discharged home, 29.3% were discharged to a rehabilitation facility, and in-hospital mortality was 8.8%. Patient-level variables associated with higher odds of mortality were age (Odds Ratio [OR] 1.01, [95% CI 1.01-1.02], p&lt;0.001), higher NIS-Subarachnoid Hemorrhage Severity Score (NIS-SSS) (12.64 [4.21-37.95], p&lt;0.001), coagulopathy (5.72, [1.40-23.29], p=0.01), and liver dysfunction (69.02 [2.65 - &gt;999], p=0.01). Conclusion: Six of ten pediatric patients with SAH are discharged with excellent outcome with a 10% index hospitalization mortality. Underlying coagulopathy and liver dysfunction are the strongest risk factors for mortality

Abstract TP1: Changing Trends in the Epidemiology of Subarachnoid Hemorrhage: A Population-Based Study

Background: There are conflicting data on temporal trends in subarachnoid hemorrhage (SAH) incidence and outcomes. We examined trends from 1993-2020 in a long-running population-based stroke study conducted in the Greater Cincinnati Northern Kentucky (GCNK) region. Methods: Using a well-validated approach, we ascertained all incident nontraumatic SAHs among residents of the GCNK region in the following study periods; July 1993-June 94, calendar years 1999, 2005, 2010, 2015, and 2020. Potential cases were identified by ICD codes, abstracted, and then adjudicated by physicians. Aneurysmal SAH (aSAH) was defined as those with culprit aneurysms; cases with no available vessel imaging were considered aSAH if the hemorrhage volume was “massive” or if the patient died rapidly after onset. Incidence rates were compared over time using linear regression after normalizing to 2010 census demographics. The primary outcome assessed was unadjusted 30-day Case Fatality Rate (CFR), which was available through 2015. Results: We identified 518 SAH cases, of which 372 were aSAH (71.8%). Overall SAH incidence rate was stable over time, ranging from 8-10 cases per 100,000 person-years (Figure Panel A); however, the rate of aSAH showed a statistically significant decline, going from 7.2 cases/100,000 person-years in 1993 to 5.2 cases/100,000 person-years in 2020 (trend P =0.02). There was a nonsignificant increase in nonaneurysmal SAH ( P =0.09 for trend). Overall 30-day CFR declined significantly through 2015 ( P =0.006, Figure Panel B), driven predominantly by a decline in aSAH CFR (from 39.3% to 23.7%, trend P =0.04). Conclusion: We observed a significant decline in the incidence of aSAH from 1993-2020; however, overall SAH incidence was stable in the setting of numerically more nonaneurysmal SAHs. Further study is needed to understand the causes of this trend. 30-Day CFR has significantly improved both for overall SAH and for aSAH.

Abstract 16: Integrin α9β1 and VCAM-1 Interaction Promotes Neutrophil Hyperactivation and Cognitive Decline Following Subarachnoid Hemorrhage

Background: Integrin α9β1 is a transmembrane glycoprotein that is highly expressed on neutrophils and mediates transendothelial migration via vascular cell adhesion molecule-1 (VCAM-1). Neutrophils are major contributors to cerebral thrombosis and oxidative stress following subarachnoid hemorrhage (SAH); however, the mechanism by which neutrophil integrin α9 contributes to SAH pathogenesis is unclear. Here, we evaluated the mechanistic role of neutrophil integrin α9 in the post-SAH sensorimotor and cognitive recovery. Methods: SAH was induced by filament perforation in neutrophil-specific α9 -/- (α9 fl/fl Mrp8Cre +/- ) mice and littermate controls. Cognitive recovery (Y-maze, Barnes maze, and novel object recognition test) and sensorimotor recovery (modified neurological severity score, corner, and cylinder test) were performed for up to 4-weeks. Unbiased RNA sequencing (RNA-seq) was used to evaluate the potential mechanisms by which neutrophil integrin α9-VCAM-1 interactions promote SAH. Computational modeling, docking, virtual screening, and cell-free assays were used to identify small-molecule inhibitors of the integrin α9-VCAM-1 interactions. Results: Experimental SAH resulted in increased levels of neutrophil integrin α9 which was concomitant with neutrophil hyperactivation. Post-SAH neutrophil-specific α9 -/- mice exhibited improved sensorimotor and cognitive recovery, along with reduced plasma elastase and MPO levels and brain neutrophil infiltration. Mechanistically, integrin α9/VCAM-1 interactions promote neutrophil hyperactivation, extracellular signal-regulated kinase (ERK) phosphorylation, and endothelial cell apoptosis. RNA-seq data revealed that α9/VCAM-1 interactions promotes gene expression related to neutrophil inflammation, exocytosis, NF-κB signaling, and chemotaxis. Virtual screening and cell-free assay identified macitentan as a potent inhibitor of integrin α9-VCAM-1 interactions. In vitro, macitentan treatment decreased neutrophil adhesion to VCAM-1 and macitentan treatment at a dose of 5 mg/kg resulted in improved SAH outcomes. Conclusion: The results of this study describe a previously unrecognized pathway involving integrin α9 and VCAM-1 in the pathogenesis of SAH.

Schizandrin A attenuates early brain injury following subarachnoid hemorrhage through suppressing neuroinflammation.

Early brain injury (EBI) is the vital factor in determining the outcome of subarachnoid hemorrhage (SAH). Schizandrin A (Sch A), the bioactive ingredient extracted from Schisandra chinensis, has been proved to exert beneficial effects in multiple human diseases. However, the effect of Sch A on SAH remains unknown. The current study was designed to explored role and mechanism of Sch A in the pathophysiological process of EBI following SAH. A total of 74 male C57BL/6 J mice were subjected to endovascular perforation to establish the SAH model. Different dosages of Sch A were administrated post-modeling. The post-modeling assessments included neurological test, brain water content, RT-PCR, immunofluorescence, Nissl staining. Oxygenated hemoglobin was introduced into microglia to establish a SAH model in vitro. Sch A significantly alleviated SAH-induced brain edema and neurological impairment. Moreover, application of Sch A remarkably inhibited SAH-induced neuroinflammation, evidenced by the decreased microglial activation and downregulated TNF-α, IL-1β and IL-6 and expression. Additionally, Sch A, both in vivo and in vitro, protected neurons against SAH-induced inflammatory injury. Mechanismly, administration of Sch A inhibited miR-155/NF-κB axis and attenuated neuroinflammation, as well as alleviating neuronal injury. Our data suggested that Sch A could attenuated EBI following SAH via modulating neuroinflammation. The anti-inflammatory effect was exerted, at least partly through the miR-155/NF-κB axis, which may shed light on a possible therapeutic target for SAH.