Aneurysmal Subarachnoid Hemorrhage Research Articles

Small Molecule Myeloperoxidase (MPO) Inhibition Prevents Delayed Cerebral Injury (DCI) After Subarachnoid Hemorrhage (SAH) in a Murine Model.

Delayed cerebral injury (DCI) after aneurysmal subarachnoid hemorrhage (SAH) is a preventable injury that would improve patient outcomes if an effective treatment can be developed. The most common long-term disability in patients with SAH is cognitive dysfunction. Contrary to the common theory that damage from DCI originates solely from ischemia caused by cerebral vasospasm, inflammation has been shown to be an important independent mediator of DCI. Neutrophil infiltration of the meninges is a critical step in developing late spatial memory deficits in a murine model of SAH and may serve as a surrogate marker for disease progression. Importantly, myeloperoxidase (MPO) null mice do not develop meningeal neutrophilia and are protected from spatial memory deficits. In this study, wildtype mice administered a single dose of the MPO inhibitor (MPOi) AZD5904 at peak neutrophil entry day have a higher percentage of neutrophils that remain in the meningeal blood vessel 6days after the hemorrhage suggesting neutrophil extravasation into the meninges is inhibited (79 ± 20 vs. 28 ± 24, p < 0.01). Interestingly, the intraperitoneal route of administration has a larger effect than the intrathecal route suggesting that MPO inhibition is best administered systemically not in the central nervous system. Second, mice administered AZD5904 intraperitoneal for 4 consecutive days starting 2days after the hemorrhage do not develop delayed spatial memory dysfunction (two-way analysis of variance, p > 0.001 F [2, 22] = 10.11). Systemic MPOi prevents neutrophil entry into the meninges and prevents spatial memory dysfunction. MPOi is a promising strategy for translation to patients with aneurysmal SAH.

Liberal or Restrictive Transfusion Strategy in Aneurysmal Subarachnoid Hemorrhage.

The effect of a liberal red-cell transfusion strategy as compared with a restrictive strategy in patients during the critical care period after an aneurysmal subarachnoid hemorrhage is unclear. We randomly assigned critically ill adults with acute aneurysmal subarachnoid hemorrhage and anemia to a liberal strategy (mandatory transfusion at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (optional transfusion at a hemoglobin level of ≤8 g per deciliter). The primary outcome was an unfavorable neurologic outcome, defined as a score of 4 or higher on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at 12 months. Secondary outcomes included 12-month functional independence as assessed with the Functional Independence Measure (FIM; scores range from 18 to 126) and quality of life as assessed with the EuroQolfive-dimension, five-level (EQ-5D-5L) utility index (scores range from -0.1 to 0.95) and a visual analogue scale (VAS; scores range from 0 to 100); on each assessment, higher scores indicate better health status or quality of life. A total of 742 patients underwent randomization at 23 centers. The analysis of the primary outcome at 12 months included 725 patients (97.7%). An unfavorable neurologic outcome occurred in 122 of 364 patients (33.5%) in the liberal-strategy group and in 136 of 361 patients (37.7%) in the restrictive-strategy group (risk ratio, 0.88; 95% confidence interval [CI], 0.72 to 1.09; P = 0.22). The mean (±SD) FIM score was 82.8±54.6 in the liberal-strategy group and 79.8±54.5 in the restrictive-strategy group (mean difference, 3.01; 95% CI, -5.49 to 11.51). The mean EQ-5D-5L utility index score was 0.5±0.4 in both groups (mean difference, 0.02; 95% CI, -0.04 to 0.09). The mean VAS score was 52.1±37.5 in the liberal-strategy group and 50±37.1 in the restrictive-strategy group (mean difference, 2.08; 95% CI, -3.76 to 7.93). The incidence of adverse events was similar in the two groups. In patients with aneurysmal subarachnoid hemorrhage and anemia, a liberal transfusion strategy did not result in a lower risk of an unfavorable neurologic outcome at 12 months than a restrictive strategy. (Funded by the Canadian Institutes of Health Research and others; SAHARA ClinicalTrials.gov number, NCT03309579.).

Neurological Pupil Index and Intracranial Hypertension in Patients With Acute Brain Injury

Invasive intracranial pressure (ICP) is the standard of care in patients with acute brain injury (ABI) with impaired consciousness. The Neurological Pupil Index (NPi) obtained by automated pupillometry is promising for noninvasively estimating ICP. To evaluate the association between repeated NPi and invasive ICP values. This study is a secondary analysis of the Outcome Prognostication of Acute Brain Injury With the Neurological Pupil Index (ORANGE), a multicenter, prospective, observational study of patients with ABI performed from October 1, 2020, to May 31, 2022, with follow-up at 6 months after ABI. The ORANGE study was performed at neurologic intensive care units of tertiary hospitals in Europe and North America. In ORANGE, 514 adult patients receiving mechanical ventilatory support were admitted to the intensive care unit after ABI. Invasive ICP monitoring and automated pupillometry assessment every 4 hours during the first 7 days, considered as a standard of care. Association between ICP and NPi values over time, using bayesian joint models, with linear and logistic mixed-effects longitudinal submodels. The study included 318 adult patients (median [IQR] age, 58 [43-69] years; 187 [58.8%] male) who required intensive care unit admission, intubation, and mechanical ventilatory support due to acute traumatic brain injury (n = 133 [41.8%]), intracerebral hemorrhage (n = 104 [32.7%]), or aneurysmal subarachnoid hemorrhage (n = 81 [25.5%]) and had automatic infrared pupillometry used as part of the standard evaluation practice and ICP monitoring. A total of 8692 ICP measurements were collected, with a median (IQR) of 31 (18-37) evaluations per patient. The median (IQR) NPi and ICP for the study population were 4.1 (3.5-4.5) and 10 (5-14) mm Hg, respectively. In a linear mixed model, the mean change in the NPi value, as a continuous variable, was -0.003 (95% credible interval [CrI], -0.006 to 0.000) for each 1-mm Hg ICP increase. No significant association between ICP and abnormal NPi (<3; odds ratio, 1.01; 95% CrI, 0.99-1.03) or absent NPi (0; odds ratio, 1.03; 95% CrI, 0.99-1.06) was observed. Although an abnormal NPi could indicate brainstem dysfunction, in this large and heterogeneous population of patients, NPi values were not significantly associated overall with ICP values. Repeated NPi measurements may not be a sufficient replacement for invasive monitoring. ClinicalTrials.gov Identifier: NCT04490005.

Association between serum phosphate level and mortality of patients with aneurysmal subarachnoid hemorrhage.

Disorders of serum phosphate, including hyperphosphatemia and hypophosphatemia, have been confirmed to be related to the poor prognosis of specific critically ill patients. No study analyzes the relationship between continuous serum phosphate level and mortality from aneurysmal subarachnoid hemorrhage (aSAH). This study was performed to explore this relationship. aSAH patients were divided into four groups based on serum phosphate quartiles. Significant factors discovered in the univariate Cox regression were included in the multivariate Cox regression to explore the independent relationship between serum phosphate and mortality of aSAH. Kaplan-Meier survival analysis was performed to compare the difference in survival between the four groups. The 60-day mortality of overall aSAH patients was 20.7%. The mortality of the group with the 1st quartile (29.4%) and the 4th quartile (24.7%) had higher mortality than others (p = 0.028). Univariate Cox regression showed the 2nd quartile (p = 0.020) and 3rd quartile (p = 0.017) were associated with lower mortality risk than the 1st quartile. Compared with the 1st quartile, the 4th quartile was not associated with lower mortality risk (p = 0.458). After adjusting confounding effects, multivariate Cox regression showed only the 4th quartile was significantly associated with higher mortality risk (p = 0.009) than the 1st quartile. The unadjusted relationship between serum phosphate and mortality of aSAH is U-shaped. While high serum phosphate even within the normal range is independently related to the mortality of aSAH. Low serum phosphate may be just a marker for the severity of aSAH. Evaluating the initial serum phosphate is useful for risk stratification of aSAH.

Analysis of delayed cerebral ischemia incidence after treatment for aneurysmal subarachnoid hemorrhage in young adults: A cohort study

Background: This study aimed to analyze the incidence of delayed cerebral ischemia (DCI) and outcome stratified by age in patients who suffered aneurysmal subarachnoid hemorrhage. Methods: A cohort study with patients from Christ the Redeemer Hospital from 2014 to 2020, with 359 patients separated into 2 groups, 48 of them aged under 40 years and 311 aged 40 years or over. Results: In patients under 40 years of age, DCI was found in 81.3%, while in patients aged 40 or over, it was 61.4%. A relative risk of 1.32 (confidence interval: 1.12–1.55), with P = 0.013. After multivariate assessment, patients aged under 40 years were found to have a 27–39% higher risk of presenting DCI. Conclusion: We identified that age under 40 years is a risk factor for the occurrence of DCI.

Outcomes for older patients with subarachnoid haemorrhage who require admission to an Australian intensive care unit.

Advanced age is an independent risk factor for poor outcomes following aneurysmal subarachnoid haemorrhage (SAH). However, Australian data are lacking. Our aim was to evaluate outcomes for older patients admitted to an Australian intensive care unit for management of aneurysmal SAH. We conducted a single centre retrospective observational study looking at adult patients admitted with aneurysmal SAH to an Intensive Care Unit (ICU) over a 10-year period. Patients were grouped by age; <70 years, 70-79 years, ⩾80 years, and were of sufficient complexity to be unsuitable for our neurosurgical high-dependency unit. The primary outcome was in-hospital mortality. Secondary outcomes were ICU and hospital length of stay, and discharge destination. Of 372 patients admitted to ICU with aneurysmal SAH, 302 (82%) were younger (<70 years), 46 (12%) were septuagenarians and 24 (6%) were octogenarians. There were no differences between clinical or radiological grade of aneurysmal SAH between age cohorts. When compared to the patients younger than 70 years, there was increased odds of dying for those 70-79 and ⩾80 years (70-79: OR 1.98, 95% CI 0.93, 4.20 p = 0.077; ⩾80: OR 4.01, 95% CI 1.55, 10.35 p = 0.004). There were no associations between age and duration of admission. Only 6% of patients aged ⩾70 years were discharged home alive. It was uncommon for patients over 70 years of age who present with a SAH to be discharged home from hospital, and those aged ⩾80 are four times more likely to die in hospital than younger patients.

Intraoperative Hypotension and Postoperative Newly Developed Cerebral Infarction in Patients With Aneurysmal Subarachnoid Hemorrhage: A Retrospective Cohort Study.

To investigate the association between intraoperative hypotension and newly developed cerebral infarction in patients with aneurysmal subarachnoid hemorrhage (aSAH) undergoing aneurysm clipping or coiling. The patients who had emergent clipping/coiling procedures for aSAH under general anesthesia were included. The major exposure was mean arterial pressure (MAP) below different absolute or relative thresholds characterized by area under curve (AUC), duration, and time-weighted average (TWA) value. The outcome was newly developed cerebral infarction. The associations between MAP and newly developed cerebral infarction were adjusted by other risk factors. Odds ratio and 95% confidence interval were used to present the statistical difference. A total of 1205 patients were included in the analysis. Of these, 260 patients (21.6%) developed new cerebral infarctions assessed by computed tomography. Patients with newly developed cerebral infarction had higher incidence of modified Fisher Scale (mFS) score 3 to 4 (80.0 vs. 69.1%, p < 0.01) and longer duration of anesthesia (4.3 vs. 3.9 h, p < 0.01). In the multivariate model, the AUC-MAP (adjusted odds ratio: 1.00, 95% CI: 1.000 to 1.000, p = 0.02) and the TWA-MAP (adjusted odds ratio: 1.01, 95% CI: 1.001 to 1.024, p = 0.04) of 20% decrease from baseline were closely associated with the newly developed cerebral infarction. Mean arterial pressure decreased 20% from baseline value were independently associated with postoperative newly developed cerebral infarction in patients with aSAH.

Neutrophils extracellular traps myeloperoxidase and elastase predict cerebral vasospasms after aneurysmal subarachnoid hemorrhage

Neutrophils extracellular traps myeloperoxidase and elastase predict cerebral vasospasms after aneurysmal subarachnoid hemorrhage

Elevated serum and cerebrospinal fluid levels of Interleukin-4 related to poor outcome of Aneurysmal subarachnoid hemorrhage

Aneurysmal subarachnoid hemorrhage (aSAH) is a hemorrhagic cerebrovascular disease that seriously jeopardizes human life and health. Some studies have shown that although Interleukin-4 (IL-4) acts as an anti-inflammatory factor, IL-4 levels are elevated when the disease occurs. This study focuses on exploring the relationship between IL and 4 concentrations in the serum and cerebrospinal fluid (CSF) and poor outcome in patients with aSAH. This study was a prospective observational study and 210 aSAH patients who met the inclusion criteria were divided into two groups according to the mRS score at 3 months after discharge, and 210 healthy people were selected as controls. The IL-4 concentrations were quantitatively determined with enzyme-linked adsorption assay (ELISA). We can draw a conclusion that Serum and CSF IL-4 concentrations are generally elevated in patients with poor outcome(P < 0.05), and the CSF IL-4 concentration decreased gradually over the progress of time (P < 0.05). The IL-4 concentration in the CSF was positively correlated with age, platelet-lymphocyte ratio (PLR), C-reactive protein (CRP), Hunt-Hess grade, mRS score, and World Federation of Neurological Surgeons score (WFNS) (P < 0.0001). Additionally, IL-4 concentrations in the CSF were correlated with complications such as intracranial infection (P = 0.01), cerebral edema (P < 0.01), hydrocephalus (P = 0.02), and complications by DCI (P = 0.02). Elevated serum and CSF concentrations of IL-4 may associated with the outcome of aSAH and may be a candidate early biomarkers for outcome of aSAH.

Pain Assessment Following Opioid Administration in Aneurysmal Subarachnoid Hemorrhage Associated Headache

Background: Headache is a debilitating complication following an aneurysmal subarachnoid hemorrhage (aSAH). Despite its impact on morbidity and quality of life, limited evidence characterizes the effectiveness of opioids. Objective: The aim of this study was to evaluate opioid associated reduction in pain scores in patients with aSAH-associated headache. Methods: This is a retrospective study of adult patients with an aSAH, Hunt and Hess grades I – III, admitted to a neurosciences intensive care unit. Descriptive and inferential statistics were used to characterize headache treatment strategies and opioid associated reduction in pain scores. Results: Opioids were used in up to 97.6% of patients for the management of aSAH-associated headache. Median reduction in pain after opioid administration was −1 (IQR: -3-0). Correlation between opioid dose and change in pain scores was negligible (rs = .01). Overall, 68.8% of patients were discharged on an opioid analgesic with predictive factors being severe headache (OR 2.52; 1.04 – 6.14) and oral morphine milligram equivalents ≥60 mg per day during the hospital stay (OR 3.02; 1.22 – 7.47). Conclusions: Opioids were associated with a small reduction in pain when assessed via the NRS. An increased opioid dose did not correlate with a greater reduction in assessed pain scores. A high percentage of patients remained on opioids throughout hospitalization and were eventually discharged on an opioid. The impact of discharge opioid prescriptions and risk of opioid persistence creates a cause for concern. It is imperative that we seek improved pain management strategies for aSAH-associated headache.

Machine learning for predicting poor outcomes in aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis involving 8,445 participants

Machine learning for predicting poor outcomes in aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis involving 8,445 participants

Salivary Cortisol Levels as a Prognostic Outcome Marker in Patients with Acute Aneurysmal Subarachnoid Haemorrhage

The physiological stress response to aneurysmal subarachnoid haemorrhage (aSAH) may trigger not only beneficial effects. Production of corticosteroids and catecholamines can induce cerebral vasospasm. Cortisol secretion levels were used to assess physiological stress. However, the appropriate measurement method remains controversial. Our study aimed to establish the relationship between cortisol levels measured in the saliva of patients with aSAH, neurological status, and mortality rates. Our study included 128 patients with aSAH treated with endovascular embolization for cerebral aneurysm with a daily examination of the cortisol level in saliva at 08.00 AM and 08.00 PM until ICU discharge or death. Daily salivary cortisol levels, haemodynamic parameters (mean arterial pressure), neurological status, and the level of consciousness (GCS) were monitored. This study included 53 women and 75 men. The mean patient age was 64.2 years (range: 42–77 years). Eighteen (14.06%) patients died. Salivary cortisol levels were significantly higher in deceased patients, both in the morning (31.8 nmol/l for deceased patients vs. 16.8 nmol/l for patients discharged alive; p &lt; 0.001), and in the evening during the follow-up period (5.2 nmol/l for deceased patients vs. 3.6 nmol/l for patients discharged alive; p &lt; 0.001). We found a statistically significant correlation between an increase in morning salivary cortisol levels and neurological deterioration. Similar observations of evening cortisol levels were observed in only five patients. Measurement of salivary cortisol levels in patients with aSAH provides additional information about prognosis. Patients who die during the acute phase of aSAH have higher morning and evening salivary cortisol levels than those who survive. Patients who died demonstrated a progressive increase in salivary cortisol levels in the morning.

National trends in surgical treatment and clinical outcomes among patients with aneurysmal subarachnoid hemorrhage in the Republic of Korea.

In this study, changes in treatment methods and patient prognosis were analyzed using a Korean nationwide medical insurance information database. Patients with subarachnoid hemorrhage who received surgical treatment for cerebral aneurysm from 2005 to 2020 were included. The specific surgery type was classified using the surgical code and according to whether stents were used. Yearly trends in mortality rates and poor prognosis, using tracheostomy as proxy, were analyzed by a simple regression analysis. A multistep logistic regression analysis was performed to evaluate the risk factors of mortality and poor prognosis. Overall, 83,587 patients were included. Females were predominant (64.5%). Microsurgical clip usage rate decreased by approximately two-thirds from 78.8% in 2005 to 24.4% in 2020. Contrarily, endovascular treatment proportion gradually increased, and stent-assisted coil embolization rate surpassed microsurgical clip usage rate in 2020 (24.6% vs. 24.4%). In the multivariate analysis, endovascular treatment correlated positively with 3-month mortality (hazard ratio [HR]: 1.13, 95% confidence interval [CI]: 1.07-1.19, P<0.0001), although correlated negatively with poor prognosis (tracheostomy) (HR: 0.93, 95% CI: 0.89-0.98, P=0.0050). According to the treatment trend analysis, during the 16 years studied, for patients with subarachnoid hemorrhage due to ruptured cerebral aneurysm, the endovascular treatment rate increased rapidly and stent-assisted coil embolization rate surpassed that of microsurgical clip ligation. Diversification of treatment methods has led to a decrease in mortality and improved prognosis.

Retrospective imputation of Glasgow Outcome Scale scores at one month after aneurysmal subarachnoid hemorrhage

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a relatively rare, but devastating form of stroke. Fortunately, mortality rates have declined, but there is still a dearth of research on long-term survivorship, in part due to large amounts of missing data in longitudinal datasets. Clinical outcomes scale scores are often missing in the early post-hospital discharge period, due to regional and provider variations in the utilization of these tools in the outpatient setting. Yet, much of the data that is needed to calculate such scores may be available in the medical record. METHODS: Three experienced nurses used a decision tree protocol to impute 1-month Glasgow Outcome Scale (GOS) scores from medical record information in an existing database. Interrater reliability was evaluated, and the imputed scores were tested for associations with other demographic and clinical variables known to impact outcomes. RESULTS: Scores were imputed on 585 patients (72.8% female, mean age of 53 years, 53% African American). The majority of subjects had an imputed GOS score of 4 (n=301; 51.5%). Interrater agreement across the three nurses was estimated to be 0.72 (Fleiss’s Kappa, p &lt;0.0001). Age, stroke severity measures, employment, and prior history of hypertension or diabetes were associated with 1-month GOS scores. CONCLUSIONS: Using this decision tree protocol to derive follow-up outcome scores could be useful for unionization of large data sets, allowing greater trending of recovery over time. This type of data is needed to fill knowledge gaps and allow the development of effective interventions for recovery after aSAH.

Multi-targeted olink proteomics analyses of cerebrospinal fluid from patients with aneurysmal subarachnoid hemorrhage

BackgroundThe complexity of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) may require the simultaneous analysis of variant types of protein biomarkers to describe it more accurately. In this study, we analyzed for the first time the alterations of cerebrospinal fluid (CSF) proteins in patients with aSAH by multi-targeted Olink proteomics, aiming to reveal the pathophysiology of DCI and provide insights into the diagnosis and treatment of aSAH.MethodsSix aSAH patients and six control patients were selected, and CSF samples were analyzed by Olink Proteomics (including 96-neurology panel and 96-inflammation panel) based on Proximity Extension Assay (PEA). Differentially expressed proteins (DEPs) were acquired and bioinformatics analysis was performed.ResultsPCA analysis revealed better intra- and inter-group reproducibility of CSF samples in the control and aSAH groups. 23 neurology-related and 31 inflammation-relevant differential proteins were identified. In the neurology panel, compared to controls, the up-regulated proteins in the CSF of SAH patients predominantly included macrophage scavenger receptor 1 (MSR1), siglec-1, siglec-9, cathepsin C (CTSC), cathepsin S (CTSS), etc. Meanwhile, in the inflammation group, the incremental proteins mainly contained interleukin-6 (IL-6), MCP-1, CXCL10, CXCL-9, TRAIL, etc. Cluster analysis exhibited significant differences in differential proteins between the two groups. GO function enrichment analysis hinted that the differential proteins pertinent to neurology in the CSF of SAH patients were mainly involved in the regulation of defense response, vesicle-mediated transport and regulation of immune response; while the differential proteins related to inflammation were largely connected with the cellular response to chemokine, response to chemokine and chemokine-mediated signaling pathway. Additionally, in the neurology panel, KEGG enrichment analysis indicated that the differential proteins were significantly enriched in the phagosome, apoptosis and microRNAs in cancer pathway. And in the inflammation panel, the differential proteins were mainly enriched in the chemokine signaling pathway, viral protein interaction with cytokine and cytokine receptor and toll-like receptor signaling pathway.ConclusionsThese identified differential proteins reveal unique pathophysiological characteristics secondary to aSAH. Further characterization of these proteins and aberrant pathways in future research could enable their application as potential therapeutic targets and biomarkers for DCI after aSAH.

Reader Response: Predictive Model for Estimating the Risk of Epilepsy After Aneurysmal Subarachnoid Hemorrhage: The RISE Score.

Reader Response: Predictive Model for Estimating the Risk of Epilepsy After Aneurysmal Subarachnoid Hemorrhage: The RISE Score.

Author Response: Predictive Model for Estimating the Risk of Epilepsy After Aneurysmal Subarachnoid Hemorrhage: The RISE Score.

Author Response: Predictive Model for Estimating the Risk of Epilepsy After Aneurysmal Subarachnoid Hemorrhage: The RISE Score.

Editors' Note: Predictive Model for Estimating the Risk of Epilepsy After Aneurysmal Subarachnoid Hemorrhage: The RISE Score.

Editors' Note: Predictive Model for Estimating the Risk of Epilepsy After Aneurysmal Subarachnoid Hemorrhage: The RISE Score.

Outcome of Fourth Ventricular Hemorrhage in Ruptured Brain Aneurysms: Impact of Active Blood Clearance and Delayed Cerebral Ischemia Prevention.

Blood in the fourth ventricle is associated with poor outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). We investigated (1) the prognostic significance of the amount of blood in the fourth ventricle and (2) the influence of active blood clearance and delayed cerebral ischemia prevention (ABCD). We reviewed 817 consecutive aSAH patients admitted between January 1, 2009, and December 31, 2022, assessing blood amount in the fourth ventricle using a fourth ventricular hemorrhage scale (FVH): grade 1 (no or minimal blood), grade 2 (partially filled), grade 3 (completely filled/cast), and grade 4 (ballooning). Incidence of poor outcomes was evaluated using multivariate analysis before and after the introduction of ABCD (October 2015). Subsequently, a 1:1 matched-pairs analysis compared outcomes specifically between patients who underwent ABCD and matched controls receiving standard care. Neurological outcomes were evaluated at 6 months (independent modified Rankin scale). Before ABCD, poor outcomes occurred in 31/41 FVH grade 3 patients (76%; odds ratio (OR) 4.4) and in 38/41 FVH grade 4 patients (93%; OR 29.1). After ABCD, the incidence of poor outcomes decreased to 23/40 in FVH grade 3 patients (58%; P = .043; OR 1.3) and 31/41 in FVH grade 4 patients (76%; P = .017; OR: 3.6). The matched-pairs analysis also showed improvement in poor outcomes for FVH grade 4 patients who underwent ABCD compared with standard care (64% vs 89%, P = .024), but not for FVH grade 1 to 3 patients. No increase in the incidence of ventriculitis was seen in patients receiving ABCD treatment (P = .836). Ballooning fourth ventricular hemorrhage (grade 4 FVH) is a powerful predictor of poor outcomes after aSAH. With the introduction of ABCD, the prognosis of these patients improved considerably and 25% reached functional independence 6 months after aSAH.

Bi-directional effects between inflammatory molecules and intracranial aneurysm.

Although inflammation is closely associated with the pathogenesis of intracranial aneurysm (IA), detailed causal associations remain unclear. This study aimed to investigate the causality between circulating inflammatory molecules (IMs) and IA. The bi-directional Mendelian randomization (MR) analysis was conducted using two genome-wide association studies (GWAS) for inflammatory molecules (IMs) from Finnish and Icelandic populations, as well as GWAS datasets of IA cases and controls of European descent. Colocalization analysis was performed to validate MR associations. Subsequently, Venn analysis was conducted to identify the overlapped causalities. Integrating the findings from two MR models, RANTES was suggestively associated with IA (Finnish model: inverse variance-weighted odds ratio [ORIVW] (95% confidence interval [95% CI]), 0.86 (0.74-0.99); Icelandic model: 0.80 (0.68-0.94)) and aneurysmal subarachnoid hemorrhage (aSAH) (ORIVW (95% CI): 0.81 (0.68-0.95) and 0.80 (0.66-0.97) in Finnish and Icelandic models). IA and its subtypes were not associated with any of candidate IMs. However, colocalization analysis failed to identify significant evidence of shared genetic instruments between the exposures and outcomes, except for the MCP3-aSAH pair in the Icelandic model. No significant causality was identified between IMs and IA or their subtypes. RANTES is potentially associated with IA and aSAH. Further investigation is warranted to explore the role of IMs in IA development.