The letter to the editor titled \"Clinical severity of aneurysmal subarachnoid hemorrhage over time: systematic review\" provides a comprehensive and systematic examination of the changing clinical landscape of aSAH, emphasizing the importance of advancements in medical technology and treatment protocols. The review\'s methodological rigor ensures reliable findings, highlighting the positive trends in clinical outcomes due to improved diagnostic tools and early interventions. However, potential publication bias and the need for a more detailed analysis of specific medical innovations and regional variations are notable limitations. Despite these, the letter is a valuable contribution, offering insights that could guide future research and improve patient outcomes.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a severe event often complicated by cerebral vasospasm (CV). This study aimed to assess the efficacy and safety of clazosentan, an endothelin receptor antagonist, in reducing CV, delayed cerebral ischemia (DCI), and the need for rescue therapy in aSAH patients, while evaluating its impact on functional outcomes and mortality.
METHODS: We conducted a literature search across multiple databases to identify relevant studies evaluating the effects of clazosentan in aSAH patients. Both cohort studies and randomized controlled trials (RCTs) were included. The primary outcomes were vasospasm incidence, moderate to severe vasospasm, DCI, and the need for rescue therapy. Secondary outcomes included functional outcomes, mortality, and adverse events. The data were pooled as Risk ratios (R/R) with 95 % confidence intervals (CI) using RevMan 5.4 software.
RESULTS: A total of 11 studies, including 10 published and one unpublished, comprising 8,469 patients were included in the meta-analysis. Clazosentan significantly reduced the incidence of vasospasm (R/R = 0.49: 0.34-0.70), moderate to severe vasospasm (R/R = 0.53: 0.46-0.61), DCI (R/R = 0.70: 0.59-0.82), and the need for rescue therapy (R/R = 0.65: 0.52-0.83) compared to placebo. However, no significant improvement in functional outcomes or mortality rates was observed. Clazosentan was associated with increased rates of pulmonary adverse events (R/R = 1.89: 1.64-2.18), hypotension (R/R = 2.47: 1.79-3.42), and anemia (R/R = 1.49: 1.23-1.79) but no increased risk of hepatobiliary adverse events or cerebral hemorrhage.
CONCLUSIONS: Clazosentan demonstrates efficacy in reducing vasospasm, moderate to severe vasospasm, DCI, and the need for rescue therapy in aSAH patients, but does not significantly improve functional outcomes or mortality rates. While associated with specific adverse events, clazosentan may be a valuable adjunctive therapy in the management of aSAH, particularly in a high-risk population for vasospasm.

BACKGROUND: Vitamin D (VD) is one of the fat-soluble vitamins proposed to be associated with aSAH. According to the clinical evidence, this investigation explores the link between VD concentrations and clinical outcomes in aSAH patients.
METHODS: This systematic review was executed based on the PRISMA 2020 statement. Observational studies that evaluated the serum VD concentrations in aSAH patients were considered as included articles. Review articles, case reports, letters, commentaries, non-English papers, and conference abstracts were excluded. Five online databases-Scopus, PubMed, Web of Science, Embase, and Ovid-were searched up to November 23, 2023, and based on the Newcastle-Ottawa Scale, the risk of bias was assessed.
RESULTS: Out of 383 articles initially identified, eventually 7 studies were included in the systematic review. These studies were conducted between 2016 and 2023 and included a total of 333,907 patients. The varying results suggest that VD may impact clinical outcomes in aSAH patients.
CONCLUSIONS: This study highlights the complex association between VD concentration and the risk of aSAH. The observed inconsistencies in study outcomes suggest that the relationship between VD and aSAH is multifaceted and may be influenced by various factors, including study population, geographical location, and methodological approach.

The effectiveness of target temperature management (TTM) in poor-grade aneurysmal subarachnoid hemorrhage (aSAH) remains a topic of debate. In order to assess the clinical efficacy of TTM in patients with poor-grade aSAH, we conducted a systematic review and meta-analysis. This research was registered in PROSPERO (CRD42023445582) and included all relevant publications up until October 2023. We compared the TTM groups with the control groups in terms of unfavorable outcomes (modified Rankin scale [mRS] score > 3), mortality, delayed cerebral ischemia (DCI), cerebral vasospasm (CVS), and specific complications. Subgroup analyses were performed based on country, study type, follow-up time, TTM method, cooling maintenance period, and rewarming rate. Effect sizes were calculated as relative risk (RR) using random-effect or fixed-effect models. The quality of the articles was assessed using the methodological index for non-randomized studies scale. Our analysis included a total of 5 clinical studies (including 1 randomized controlled trial) and 219 patients (85 in the TTM group and 134 in the control group). Most of the studies were of moderate quality. TTM was found to be associated with a statistically significant improvement in mortality (mRS score 6) rates compared with the control group (RR = 0.61, 95% confidence interval [CI]: 0.40-0.94, p = 0.026). However, there was no statistically significant difference in unfavorable outcomes (mRS 4-6) between the TTM and control groups (RR = 0.94, 95% CI: 0.71-1.26, p = 0.702). The incidence of adverse events, including DCI, CVS, pneumonia, cardiac complications, and electrolyte imbalance, did not significantly differ between the two groups. In conclusion, our overall results suggest that TTM does not significantly reduce unfavorable outcomes in poor-grade aSAH patients. However, TTM may decrease mortality rates. Preoperative TTM may cause patients to miss the opportunity for surgery, although it temporarily protects the brain. Furthermore, the incidence of adverse events was similar between the TTM and control groups.

Background/Objective: Sex-related differences among patients with aneurysmal subarachnoid hemorrhage (aSAH) and their potential clinical implications have been insufficiently investigated. To address this knowledge gap, we conduct a comprehensive systematic review and meta-analysis. Methods: Sex-specific differences in patients with aSAH, including mortality, delayed cerebral ischemia (DCI), and functional outcomes were assessed. The functional outcome was dichotomized into favorable or unfavorable based on the modified Rankin Scale (mRS), Glasgow Outcome Scale (GOS), and Glasgow Outcome Scale Extended (GOSE). Results: Overall, 2823 studies were identified in EMBASE, MEDLINE, PubMed, and by manual search on 14 February 2024. After an initial assessment, 74 studies were included in the meta-analysis. In the analysis of mortality, including 18,534 aSAH patients, no statistically significant differences could be detected (risk ratio (RR) 0.99; 95% CI, 0.90-1.09; p = 0.91). In contrast, the risk analysis for DCI, including 23,864 aSAH patients, showed an 11% relative risk reduction in DCI in males versus females (RR, 0.89; 95% CI, 0.81-0.97; p = 0.01). The functional outcome analysis (favorable vs. unfavorable), including 7739 aSAH patients, showed a tendency towards better functional outcomes in men than women; however, this did not reach statistical significance (RR, 1.02; 95% CI, 0.98-1.07; p = 0.34). Conclusions: In conclusion, the available data suggest that sex/gender may play a significant role in the risk of DCI in patients with aSAH, emphasizing the need for sex-specific management strategies.

UNASSIGNED: Cerebral vasospasm (CV) is a common complication of aneurysmal subarachnoid hemorrhage (aSAH), leading to increased morbidity and mortality rates. Endovascular therapy, particularly intra-arterial vasodilator infusion (IAVI), has emerged as a potential alternative treatment for CV.
UNASSIGNED: A systematic review and meta-analysis were conducted to compare the efficacy of endovascular therapy with standard treatment in patients with CV following aSAH. The primary outcomes assessed were in-hospital mortality, discharge favorable outcome, and follow-up favorable outcome. Secondary outcomes included major infarction on CT, ICU stay duration, and total hospital stay.
UNASSIGNED: Regarding our primary outcomes of interest, patients undergoing intervention exhibited a significantly lower in-hospital mortality compared to the standard treatment group, with the intervention group having only half the mortality risk (RR = 0.49, 95% CI [0.29, 0.83], p = 0.008). However, there were no significant differences between the two groups in terms of discharge favorable outcome (RR = 0.99, 95% CI [0.68, 1.45], p = 0.963) and follow-up favorable outcome (RR = 1.09, 95% CI [0.86, 1.39], p = 0.485). Additionally, there was no significant difference in major infarction rates (RR = 0.79, 95% CI [0.34, 1.84], p = 0.588). It is important to note that patients undergoing endovascular treatment experienced longer stays in the ICU (MD = 6.07, 95% CI [1.03, 11.12], p = 0.018) and extended hospitalization (MD = 5.6, 95% CI [3.63, 7.56], p < 0.001). Subgroup analyses based on the mode of endovascular treatment further supported the benefits of IAVI in lowering in-hospital mortality (RR = 0.5, 95% CI [0.27, 0.91], p = 0.023).
UNASSIGNED: Endovascular therapy, particularly IAVI, holds promising potential in reducing in-hospital mortality for patients with CV following aSAH. However, it did not show significant improvement in long-term prognosis and functional recovery. Further research with larger sample sizes and randomized controlled trials is necessary to validate these findings and optimize the treatment strategy for cerebral vasospasm in aSAH patients.
UNASSIGNED: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42023451741.

Recent studies suggest that differential DNA methylation could play a role in the mechanism of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Considering the significance of this matter and a lack of effective prophylaxis against DCI, we aim to summarize the current state of knowledge regarding their associations with DNA methylation and identify the gaps for a future trial. PubMed MEDLINE, Scopus, and Web of Science were searched by two authors in three waves for relevant DNA methylation association studies in DCI after aSAH. PRISMA checklist was followed for a systematic structure. STROBE statement was used to assess the quality and risk of bias within studies. This research was funded by the National Science Centre, Poland (grant number 2021/41/N/NZ2/00844). Of 70 records, 7 peer-reviewed articles met the eligibility criteria. Five studies used a candidate gene approach, three were epigenome-wide association studies (EWAS), one utilized bioinformatics of the previous EWAS, with two studies using more than one approach. Methylation status of four cytosine-guanine dinucleotides (CpGs) related to four distinct genes (ITPR3, HAMP, INSR, CDHR5) have been found significantly or suggestively associated with DCI after aSAH. Analysis of epigenetic clocks yielded significant association of lower age acceleration with radiological CVS but not with DCI. Hub genes for hypermethylation (VHL, KIF3A, KIFAP3, RACGAP1, OPRM1) and hypomethylation (ALB, IL5) in DCI have been indicated through bioinformatics analysis. As none of the CpGs overlapped across the studies, meta-analysis was not applicable. The identified methylation sites might potentially serve as a biomarker for early diagnosis of DCI after aSAH in future. However, a lack of overlapping results prompts the need for large-scale multicenter studies. Challenges and prospects are discussed.

There is an ongoing lack of consensus among clinicians regarding on the optimal aneurysmal subarachnoid hemorrhage (aSAH) management approach between endovascular coiling and microsurgical clipping.
Comprehensive literature search for randomized controlled trials (RCTs) was conducted in Medline and Cochrane databases until January 1st, 2023 without language constraints. Effectivity outcomes included one-year mortality, one-year poor outcomes, and one-year complete aneurysmal occlusion, while safety outcomes comprised the incidence of vasospasms, rebleeding, post-operative complications, and cerebral ischemia.
Eight RCTs, involving 3585 aSAH patients, underwent comprehensive quantitative analysis. Among them, 1792 underwent endovascular coiling and 1773 patients had microsurgical clipping. Regarding effectivity, the rates of one-year mortality (OR: 0.79, 95% CI: 0.61-1.03, p = 0.08) exhibited no significant difference. However, endovascular coiling demonstrated an inferior one-year complete aneurysmal occlusion rate (OR: 0.33, 95% CI: 0.21-0.53, p < 0.00001), although with significantly lower rates of poor outcomes (OR: 0.68, 95% CI: 0.57-0.81, p < 0.00001) compared to the microsurgical clipping group. As for safety, endovascular coiling group exhibited lower rates of vasospasm (OR: 0.58, 95% CI: 0.36-0.92, p = 0.02), post-operative complications (OR: 0.40, 95% CI: 0.23-0.71, p = 0.02), and cerebral ischemia (OR: 0.36, 95% CI: 0.20-0.63, p = 0.0004). No significant effect on the incidence of rebleeding was observed (OR: 1.09, 95% CI: 0.73-1.63, p = 0.68).
Endovascular coiling proves superior and safer for aSAH patients, but consideration of resources, patient condition, and surgeon preferences is crucial for selecting the optimal approach.

The cautionary stance normally taken towards tranexamic acid (TXA) is rooted in concerns regarding its complication profile, namely its purported risk for venous thromboembolic events (VTEs). In the present review, we intend to bring increased attention to TXA as a remarkably valuable tool that does not appear to increase the risk for VTE when used as indicated in select patients.
We queried three databases to identify reporting use of TXA during nontraumatic cranial neurosurgery procedures (excluded traumatic brain injury). Data gathered included VTE complications, deep venous thrombosis, use of allogeneic blood transfusions, estimated blood loss, and operative duration.
Twenty-eight studies were deemed eligible for inclusion in the present meta-analysis, including nine studies on surgical resection of intracranial neoplasms, ten studies on aneurysmal subarachnoid hemorrhage, and nine studies on craniosynostosis. In brain tumor surgery, TXA appears to successfully reduce blood loss without predisposing patients to VTE or seizure (P < 0.01). However, it does not appear to reduce rates of vasospasm in aneurysmal subarachnoid hemorrhage (P = 0.27), and its administration is not associated with clinically meaningful differences in long term neurological outcomes. For pediatric patients undergoing craniosynostosis procedures, TXA similarly reduces blood loss (P < 0.01). Nonetheless, low dosing protocols should be used because they appear effective and the effects of high dose TXA in children have not been studied.
TXA is an effective hemostatic agent that can be administered to reduce blood loss and transfusion requirements for a wide range of neurosurgical applications in a broad spectrum of patient populations.

UNASSIGNED: The use of magnesium sulfate for treating aneurysmal subarachnoid hemorrhage (aSAH) has shown inconsistent results across studies. To assess the impact of magnesium sulfate on outcomes after aSAH, we conducted a systematic review and meta-analysis of relevant randomized controlled trials.
UNASSIGNED: PubMed, Embase, and the Cochrane Library were searched for relevant literature on magnesium sulfate for aSAH from database inception to March 20, 2023. The primary outcome was cerebral vasospasm (CV), and secondary outcomes included delayed cerebral ischemia (DCI), secondary cerebral infarction, rebleeding, neurological dysfunction, and mortality.
UNASSIGNED: Of the 558 identified studies, 16 comprising 3,503 patients were eligible and included in the analysis. Compared with control groups (saline or standard treatment), significant differences were reported in outcomes of CV [odds ratio (OR) = 0.61, p = 0.04, 95% confidence interval (CI) (0.37-0.99)], DCI [OR = 0.57, p = 0.01, 95% CI (0.37-0.88)], secondary cerebral infarction [OR = 0.49, p = 0.01, 95% CI (0.27-0.87)] and neurological dysfunction [OR = 0.55, p = 0.04, 95% CI (0.32-0.96)] after magnesium sulfate administration, with no significant differences detected in mortality [OR = 0.92, p = 0.47, 95% CI (0.73-1.15)] and rebleeding [OR = 0.68, p = 0.55, 95% CI (0.19-2.40)] between the two groups.
UNASSIGNED: The superiority of magnesium sulfate over standard treatments for CV, DCI, secondary cerebral infarction, and neurological dysfunction in patients with aSAH was demonstrated. Further randomized trials are warranted to validate these findings with increased sample sizes.