UNASSIGNED: The prevalence of intracranial aneurysms (IAs) and incidence of aneurysmal subarachnoid haemorrhage (aSAH) is higher in women than in men. Although several cardiometabolic and lifestyle factors have been related to the risk of IAs or aSAH, it is unclear whether there are sex differences in causal relationships of these risk factors.
UNASSIGNED: The aim of this study was to determine sex differences in causal relationships between cardiometabolic and lifestyle factors and risk of aSAH and IA.
UNASSIGNED: We conducted a sex-specific two-sample Mendelian randomization study using summary-level data from genome-wide association studies. We analysed low-density lipoprotein cholesterol, high-density lipoprotein cholesterol [HDL-C], triglycerides, non-HDL-C, total cholesterol, fasting glucose, systolic and diastolic blood pressure, smoking initiation, and alcohol use as exposures, and aSAH and IA (i.e. aSAH and unruptured IA combined) as outcomes.
UNASSIGNED: We found statistically significant sex differences in the relationship between genetically proxied non-HDL-C and aSAH risk, with odds ratios (ORs) of 0.72 (95% confidence interval 0.58, 0.88) in women and 1.01 (0.77, 1.31) in men (p-value for sex difference 0.044). Moreover, genetic liability to smoking initiation was related to a statistically significantly higher risk of aSAH in men compared to women (p-value for sex difference 0.007) with ORs of 3.81 (1.93, 7.52) and 1.12 (0.63, 1.99), respectively, and to a statistically significantly higher IA risk in men compared to women (p-value for sex difference 0.036) with ORs of 3.58 (2.04, 6.27) and 1.61 (0.98, 2.64), respectively. In addition, higher genetically proxied systolic and diastolic blood pressure were related to a higher risk of aSAH and IA in both women and men.
UNASSIGNED: Higher genetically proxied non-HDL-C was related to a lower risk of aSAH in women compared to men. Moreover, genetic liability to smoking initiation was associated with a higher risk for aSAH and IA in men compared to women. These findings may help improve understanding of sex differences in the development of aSAH and IA.

BACKGROUND: Insertion of an external ventricular drain (EVD) is a first-line treatment of acute hydrocephalus caused by aneurysmal subarachnoid haemorrhage (aSAH). Once the patient is clinically stable, the EVD is either removed or replaced by a permanent internal shunt. The optimal strategy for cessation of the EVD is unknown. Prompt closure carries a risk of acute hydrocephalus or redundant shunt implantations, whereas gradual weaning may increase the risk of EVD-related infections.
METHODS: DRAIN (Danish RAndomised Trial of External Ventricular Drainage Cessation IN Aneurysmal Subarachnoid Haemorrhage) is an international multicentre randomised clinical trial comparing prompt closure versus gradual weaning of the EVD after aSAH. The primary outcome is a composite of VP-shunt implantation, all-cause mortality, or EVD-related infection. Secondary outcomes are serious adverse events excluding mortality and health-related quality of life (EQ-5D-5L). Exploratory outcomes are modified Rankin Scale, Fatigue Severity Scale, Glasgow Outcome Scale Extended, and length of stay in the neurointensive care unit and hospital. Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, alpha 5%, power 80%), 122 participants are required in each intervention group. Outcome assessment for the primary outcome, statistical analyses, and conclusion drawing will be blinded. Two independent statistical analyses and reports will be tracked using a version control system, and both will be published. Based on the final statistical report, the blinded steering group will formulate two abstracts.
CONCLUSIONS: We present a pre-defined statistical analysis plan for the randomised DRAIN trial, which limits bias, p-hacking, and data-driven interpretations. This statistical analysis plan is accompanied by tables with simulated data, which increases transparency and reproducibility.
BACKGROUND: ClinicalTrials.gov identifier: NCT03948256. Registered on May 13, 2019.

UNASSIGNED: The prevalence of intracranial aneurysms (IAs) and incidence of aneurysmal subarachnoid haemorrhage (aSAH) is higher in women than in men. Although several cardiometabolic and lifestyle factors have been related to the risk of IAs or aSAH, it is unclear whether there are sex differences in causal relationships of these risk factors.
UNASSIGNED: The aim of this study was to determine sex differences in causal relationships between cardiometabolic and lifestyle factors and risk of aSAH and IA.
UNASSIGNED: We conducted a sex-specific two-sample Mendelian randomisation study using summary-level data from genome-wide association studies. We analysed low-density lipoprotein cholesterol, high-density lipoprotein cholesterol [HDL-C], triglycerides, non-HDL-C, total cholesterol, fasting glucose, systolic and diastolic blood pressure, smoking initiation, and alcohol use as exposures, and aSAH and IA (i.e., aSAH and unruptured IA combined) as outcomes.
UNASSIGNED: We found statistically significant sex differences in the relationship between genetically proxied non-HDL-C and aSAH risk, with odds ratios (ORs) of 0.72 (95% confidence interval 0.58, 0.88) in women and 1.01 (0.77, 1.31) in men (P-value for sex difference 0.044). Moreover, genetic liability to smoking initiation was related to a statistically significantly higher risk of aSAH in men compared to women (P-value for sex difference 0.007) with ORs of 3.81 (1.93, 7.52) and 1.12 (0.63, 1.99), respectively, and to a statistically significantly higher IA risk in men compared to women (P-value for sex difference 0.036) with ORs of 3.58 (2.04, 6.27) and 1.61 (0.98, 2.64), respectively. In addition, higher genetically proxied systolic and diastolic blood pressure were related to a higher risk of aSAH and IA in both women and men.
UNASSIGNED: Higher genetically proxied non-HDL-C was related to a lower risk of aSAH in women compared to men. Moreover, genetic liability to smoking initiation was associated with a higher risk for aSAH and IA in men compared to women. These findings may help improve understanding of sex differences in the development of aSAH and IA.

UNASSIGNED: To investigate the correlation of serum changes and markers of brain injury (BI) in cerebrospinal fluid (CSF) with postoperative cognitive dysfunction (POCD) in patients with cerebral aneurysmal subarachnoid haemorrhage (aSAH).
UNASSIGNED: 120 patients diagnosed with aSAH were included. 3 months after surgery, these patients were divided into a normal cognition group and a cognitive dysfunction (CD) group relying on the Montreal Cognitive Assessment (MoCA) Scale.
UNASSIGNED: The correlations were analysed between the serological changes and the levels of BI markers, such as neurofilament-light (NF-L) protein, Ubisquitin C-terminal hydrolase L1(UCH-L1), Glial Fibrillary Acidic Protein (GFAP), and neuron specific enolase (NSE) in patients after surgery. Hunt-Hess grading standard was employed to determine the severity of aSAH in patients. The mean values of NF-L, UCH-L1, GFAP, and NSE were (8.2 ± 4.3) pg/mL, (0.7 ± 0.3) ng/mL, (2.2 ± 0.4) ng/mL, and (48.5 ± 10.9) ng/mL in patients with severe aSAH, which were remarkably higher than those in patients with mild aSAH [(3.5 ± 0.7) pg/mL, (0.5 ± 0.2) ng/mL, (1.3 ± 0.7) ng/mL, (30.7 ± 8.2) ng/mL]. The sensitivity, specificity, and accuracy of the combined prediction of four detections for POCD were 90.80%, 84.20%, and 82.80%, respectively, which were greatly higher than those of four independent predictions (p < 0.05). The combined prediction effect of the four items, with the area under the curve (AUC) of 0.938 and the 95% confidence interval (CI) of 0.851-0.926.
UNASSIGNED: BI markers NF-L, UCH-L1, GFAP, and NSE could be utilized as predictors of POCD in patients with aSAH, deserving a reference value.

BACKGROUND: Ruptured intracranial aneurysms resulting in subarachnoid haemorrhage can be treated by open surgical or endovascular treatment. Despite multiple previous studies, uncertainties on the optimal treatment practice still exists. The resulting treatment variation may result in a variable, potentially worse, patient outcome. To better inform future treatment strategies, this study aims to identify the effectiveness of different treatment strategies in patients with ruptured intracranial aneurysms by investigating long-term functional outcome, complications and cost-effectiveness. An explorative analysis of the diagnostic and prognostic value of radiological imaging will also be performed.
METHODS: This multi-centre observational prospective cohort study will have a follow-up of 10 years. A total of 880 adult patients with a subarachnoid haemorrhage caused by a ruptured intracranial aneurysm will be included. Calculation of sample size (N = 880) was performed to show non-inferiority of clip-reconstruction compared to endovascular treatment on 1 year outcome, assessed by using the ordinal modified Rankin Scale. The primary endpoint is the modified Rankin Scale score and mortality at 1 year after the initial subarachnoid haemorrhage. Patients will receive \'non-experimental\' regular care during their hospital stay. For this study, health questionnaires and functional outcome will be assessed at baseline, before discharge and at follow-up visits.
CONCLUSIONS: Despite the major healthcare and societal burden, the optimal treatment strategy for patients with subarachnoid haemorrhage caused by ruptured intracranial aneurysms is yet to be determined. Findings of this comparative effectiveness study, in which in-between centre variation in practice and patient outcome are investigated, will provide evidence on the effectiveness of treatment strategies, hopefully contributing to future high value treatment standardisation.
BACKGROUND: NCT05851989 DATE OF REGISTRATION: May 10th, 2023.

OBJECTIVE: Decompressive craniectomy (DC) remains a controversial intervention for intracranial hypertension among patients with aneurysmal subarachnoid haemorrhage (aSAH).
METHODS: We identified aSAH patients who underwent DC following microsurgical aneurysm repair from a prospectively maintained registry and compared their outcomes with a propensity-matched cohort who did not. Logistic regression was used to identify predictors of undergoing decompressive surgery and post-operative outcome. Outcomes of interest were inpatient mortality, unfavourable outcome, NIS-Subarachnoid Hemorrhage Outcome Measure and modified Rankin Score (mRS).
RESULTS: A total of 246 patients with aSAH underwent clipping of the culprit aneurysm between 01/09/2011 and 20/07/2020. Of these, 46 underwent DC and were included in the final analysis. Unsurprisingly, DC patients had a greater chance of unfavourable outcome (p < 0.001) and higher median mRS (p < 0.001) at final follow-up. Despite this, almost two-thirds (64.1 %) of DC patients had a favourable outcome at this time-point. When compared with a propensity-matched cohort who did not, patients treated with DC fared worse at all endpoints. Multivariable logistic regression revealed that the presence of intracerebral haemorrhage and increased pre-operative mid-line shift were predictive of undergoing DC, and WFNS grade ≥ 4 and a delayed ischaemic neurological deficit requiring endovascular angioplasty were associated with an unfavourable outcome.
CONCLUSIONS: Our data suggest that DC can be performed with acceptable rates of morbidity and mortality. Further research is required to determine the superiority, or otherwise, of DC compared with structured medical management of intracranial hypertension in this context, and to identify predictors of requiring decompressive surgery and patient outcome.

BACKGROUND: Despite aneurysmal subarachnoid haemorrhage (aSAH) patients often experiencing physical and mental disabilities impacting their quality of life (QoL), routine assessment of long-term QoL data and predictive tools are limited. This study evaluates the newly developed \"functional recovery expected after subarachnoid haemorrhage\" (FRESH) scores with long-term outcomes and QoL in European aSAH patients.
METHODS: FRESH, FRESH-cog, and FRESH-quol scores were retrospectively obtained from aSAH patients. Patients were contacted, and the modified Rankin Scale (mRS), extended short form-36 (SF-36), and telephone interview for cognitive status (TICS) were collected and performed. The prognostic and empirical outcomes were compared.
RESULTS: Out of 374 patients, 171 patients (54.1%) completed the SF-36, and 154 patients completed the TICS. The SF-36 analysis showed that 32.7% had below-average physical component summary (PCS) scores, and 39.8% had below-average mental component summary (MCS) scores. There was no significant correlation between the FRESH score and PCS (p = 0.09736), MCS (p = 0.1796), TICS (p = 0.7484), or mRS 10-82 months (average 46 months) post bleeding (p = 0.024), respectively. There was also no significant correlation found for \"FRESH-cog vs. TICS\" (p = 0.0311), \"FRESH-quol vs. PCS\" (p = 0.0204), \"FRESH-quol vs. MCS\" (p = 0.1361) and \"FRESH-quol vs. TICS\" (p = 0.1608).
CONCLUSIONS: This study found no correlation between FRESH scores and validated QoL tools in a European population of aSAH patients. The study highlights the complexity of reliable long-term QoL prognostication in aSAH patients and emphasises the need for further prospective research to also focus on QoL as an important outcome parameter.

BACKGROUND: No standard has been established regarding timing and choice of strategy for discontinuation of external ventricular drainage (EVD) in patients with aneurysmal subarachnoid haemorrhage (aSAH), and little is known about the importance of clinical variables. A proportion of the patients who initially pass their discontinuation attempt return with delayed hydrocephalus and the need of a permanent shunt. Early differentiation between patients who need a shunt and those who do not would facilitate care. We conducted a retrospective analysis on patients with aSAH and an EVD to search significant differences in treatment and clinical variables between patients who received a permanent shunt during initial hospitalization or after readmission, and those who never received a shunt.
METHODS: We included 183 patients with aSAH who received an EVD over a 4-year period between 2015 and 2018 and divided them into three groups: those who received a shunt during primary admission, those who were readmitted for delayed hydrocephalus and received a shunt, and those who never needed a shunt. Between these groups, we compared selected clinical variables as well as outcome at discharge and after 6 months. Additionally, we assessed the ability of a shunt dependency score (SDASH) to predict the need for permanent drainage in the patients.
RESULTS: Of 183 included patients, 108 (59%) ultimately received a ventriculoperitoneal (VP) shunt. Of these, 89 (82%) failed discontinuation during the primary admission and received a permanent shunt before discharge from the neurosurgical department. The remaining 19 (18%) were discharged after successful discontinuation, but subsequently developed delayed hydrocephalus and were admitted for shunt placement a median of 39 (range: 18-235) days after ictus. Ninety-four patients were discharged after successful discontinuation of the EVD, consisting of those who never developed the need for a permanent shunt and the 19 who were readmitted with delayed hydrocephalus, corresponding to a 20% (19/94) readmittance rate. Clinical variables such as drainage volume or discontinuation strategy did not differ across the three groups of patients. The SDASH score failed to provide any clinically useful information regarding prediction of shunt placement.
CONCLUSIONS: In this study, clinical variables including use of the predictive score SDASH predicted neither the overall need for nor the timing of shunt placement after aSAH. The homogeneous distribution of data between the three different groups renders strong independent clinical predictive factors unlikely. Thus, attempts to predict a permanent shunt requirement from these variables may be futile in these patients.

UNASSIGNED: Aneurysmal Subarachnoid Haemorrhage (aSAH) is a vascular injury with significantly high mortality, especially when poorly managed. This study seeks to outline the experiences in setting up a neurovascular service in Lagos, Nigeria.
UNASSIGNED: A series of 45 patients were operated after aSAH over a period of 10 years. Patients consecutively were recruited following computed tomography angiography (CTA) diagnosis of aSAH. Clinical data were recorded on a predesigned form after obtaining informed consent; aSAH was classified using the WFNS classification, intraoperative findings were documented. Challenges in the management were analysed in a post-operative root cause analysis (RCA) review. Outcomes and factors responsible for the observed outcomes and actions taken were recorded.
UNASSIGNED: Forty-five patients were operated after aSAH was confirmed; there were 29 females and 16 males. (M:F 1:1.8), the age ranged from 14 to 76 years (mean 49.1±13.58). All the aneurysms were on the anterior circle of Willis, mainly on Anterior Communicating Artery aneurysm (18/48).Thirty-eight patients (84.4%) survived and were discharged within an average of 10 days after surgery. Lower GCS at presentation was associated with poor prognosis (p = 0.026); however, data analysis demonstrated that other factors (financial issues, lack of appropriate instrumentation and equipment, experience of the surgeon) played a significant role in determining the outcome.
UNASSIGNED: Aneurysmal Subarachnoid Haemorrhage (aSAH) is a challenging pathology and its management may be further burdened in resource constrained countries, as shown by the data analysed in this study from Lagos, Nigeria. Specialized and well-funded Neurovascular centres are needed to overcome the challenges faced and to improve care for aSAH patients in Nigeria.

General microvascular perfusion and its heterogeneity are pathophysiological features of delayed cerebral ischemia (DCI) that are gaining increasing attention. Recently, CT perfusion (CTP) imaging has made it possible to evaluate them radiologically using mean transit time (MTT) and its heterogeneity (measured by cvMTT). This study evaluates the effect of multimodal rescue therapy (intra-arterial nimodipine administration and elevation of blood pressure) on MTT and cvMTT during DCI in aneurysmal subarachnoid haemorrhage (aSAH) patients. A total of seventy-nine aSAH patients who underwent multimodal rescue therapy between May 2012 and December 2019 were retrospectively included in this study. CTP-based perfusion impairment (MTT and cvMTT) on the day of DCI diagnosis was compared with follow-up CTP after initiation of combined multimodal therapy. The mean MTT was significantly reduced in the follow-up CTP compared to the first CTP (3.7 ± 0.7 s vs. 3.3 ± 0.6 s; p < 0.0001). However, no significant reduction of cvMTT was observed (0.16 ± 0.06 vs. 0.15 ± 0.06; p = 0.44). Mean arterial pressure was significantly increased between follow-up and first CTP (98 ± 17 mmHg vs. 104 ± 15 mmHg; p < 0.0001). The combined multimodal rescue therapy was effective in addressing the general microvascular perfusion impairment but did not affect the mechanisms underlying microvascular perfusion heterogeneity. This highlights the need for research into new therapeutic approaches that also target these pathophysiological mechanisms of DCI.