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BACKGROUND: Cerebral vasospasm (CV) is a feared complication which occurs after 20-40% of subarachnoid haemorrhage (SAH). It is standard practice to admit patients with SAH to intensive care for an extended period of resource-intensive monitoring. We used machine learning to predict CV requiring verapamil (CVRV) in the largest and only multi-center study to date. METHODS: Patients with SAH admitted to UCLA from 2013 to 2022 and a validation cohort from VUMC from 2018 to 2023 were included. For each patient, 172 unique intensive care unit (ICU) variables were extracted through the primary endpoint, namely first verapamil administration or no verapamil. At each institution, a light gradient boosting machine (LightGBM) was trained using five-fold cross validation to predict the primary endpoint at various hospitalization timepoints. FINDINGS: A total of 1750 patients were included from UCLA, 125 receiving verapamil. LightGBM achieved an area under the ROC (AUC) of 0.88 > 1 week in advance and ruled out 8% of non-verapamil patients with zero false negatives. Our models predicted no CVRV vs CVRV within three days vs CVRV after three days with AUCs = 0.88, 0.83, and 0.88, respectively. From VUMC, 1654 patients were included, 75 receiving verapamil. VUMC predictions averaged within 0.01 AUC points of UCLA predictions. INTERPRETATION: We present an accurate and early predictor of CVRV using machine learning with multi-center validation. This represents a significant step towards optimized clinical management and resource allocation in patients with SAH. FUNDING: Robert E. Freundlich is supported by National Center for Advancing Translational Sciences federal grant UL1TR002243 and National Heart, Lung, and Blood Institute federal grant K23HL148640; these funders did not play any role in this study. The National Institutes of Health supports Vanderbilt University Medical Center which indirectly supported these research efforts. Neither this study nor any other authors personally received financial support for the research presented in this manuscript. No support from pharmaceutical companies was received.

Background and Purpose Methods Results Conclusions Prognostication in patients with spontaneous subarachnoid hemorrhage (SAH) can be challenging. The aim of this study was to assess whether cerebrospinal fluid (CSF) red blood cell (RBC) count and total protein (TP) concentration are associated with SAH prognosis.Patients with SAH treated at the neurological intensive care unit (ICU) in Innsbruck were included in this real‐world, observational study. Longitudinal CSF samples were collected as part of routine diagnostics. RBC count and CSF TP at the time of admission (RBCfirst, TPfirst), in Week 1 (RBCDays1–7, TPDays1–7), Week 2 (RBCDays8–14, TPDays8–14), and Week 3 or thereafter (RBCDay>14, TPDay>14), the highest detected value (RBChighest, TPhighest), as well as the RBC count adjusted for disease duration (RBCadjusted) were assessed. Primary outcomes were good functional outcome after 3 months, defined as modified Rankin scale score ≤2 and ICU survival.A total of 183 SAH patients with a female predominance (69%), a median (interquartile range [IQR]) age of 60 (50–70) years and median (IQR) Hunt and Hess score of 4 (3–5) were included. Multivariable analyses revealed that lower values of RBCfirst, RBCadjusted, RBChighest, TPfirst and TPhighest were associated with good functional outcome and hospital survival. Lower TP concentrations in Weeks 1, 2 and 3 were associated with good functional outcome, and in Weeks 1 and 2 with ICU survival. Early RBC measurements (Week 1) were associated with good functional outcome and ICU survival.Low CSF RBC counts and TP concentrations were associated with good functional outcome and ICU survival in a real‐world cohort of SAH patients requiring external ventricular drainage. [ABSTRACT FROM AUTHOR]

Reversible cerebral vasoconstriction syndrome (RCVS) is a rare but significant cause of intracranial arteriopathy and stroke in young adults. The syndrome encompasses a spectrum of disorders radiologically characterized by reversible narrowing and dilation of intracranial arteries, often triggered by vasoactive drugs or the postpartum period. The hallmark clinical feature of RCVS is thunderclap headache with or without other neurological signs. Though endothelial dysfunction and sympathetic hyperactivation are hypothesized to be key mechanisms, the exact pathogenesis of RCVS is still unclear. RCVS's diagnosis could be challenging, since vasospasm proceeds centripetally, initially involving distal small pial and cortical arteries, and angiographic studies, especially brain magnetic resonance angiography (MRA) and computed tomography angiography (CTA), may miss it in the early phase of the disease, while early signs such as vascular hyperintensities may be visible on T2/FLAIR sequences before vasospasm onset. Catheter angiography is the gold standard and it could be used to assess vasospasm reversibility post-intra-arterial vasodilator administration. Treatment is mainly symptomatic, and nimodipine is the most commonly administered therapy, given orally or intra-arterially in severe cases. Since many aspects of RCVS remain partially known, further research is needed to better understand the complex pathophysiology of this unique clinical condition and to optimize specific management strategies. [ABSTRACT FROM AUTHOR]

Background/Objectives: Intracranial aneurysms (IAs) may be connected to interactions between large and small intracranial vessels. We aimed to investigate the association between IAs and cerebral small-vessel disease (CSVD) and assess CSVD impact on IA patient management. Methods: This retrospective study analyzed clinical data and MRI features of CSVD in 192 subarachnoid hemorrhage (SAH) patients: 136 with incidental IA, 147 with severe CSVD without SAH/IA, and 50 controls without SAH, IA, or severe CSVD. MRI assessments followed the Standards for Reporting Vascular Changes on Neuroimaging (STRIVE), with a total burden of small-vessel disease (TBSVD) score calculated. Statistical analyses included forward selection and binary logistic regression. Results: TBSVD differed significantly across groups (p < 0.001), except between SAH and IA groups (p = 0.8). Controls had the lowest TBSVD (1.00; 1.22 ± 0.996), followed by SAH (2.00; 2.08 ± 1.013) and IA groups (2.00; 2.04 ± 1.141), with the highest in the CSVD group (1.00; 1.22 ± 0.996). White-matter hyperintensity (WMH) patterns varied with IA rupture status (p = 0.044); type A was prevalent in SAH patients and type D in the IA group. Incorporating MRI CSVD features and TBSVD into risk assessments did not enhance IA prediction or outcome models. Conclusions: IA patients exhibit a higher CSVD burden than controls, suggesting a link between small and large intracranial vessels. WMH patterns distinguish between ruptured and unruptured IA patients, offering potential markers for IA rupture risk assessment and signaling a paradigm shift in understanding IAs and CSVD. [ABSTRACT FROM AUTHOR]

Cerebral vasospasm (CVS) is an important contributor to delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage (aSAH), leading to high morbidity and long-term disability. While several microRNAs (miRNAs) have been implicated in vasospasm, the underlying mechanisms for CVS remain poorly understood. Our study aims to identify miRNAs that may contribute to the development of CVS. Whole-blood samples were obtained during or outside of vasospasm from aSAH patients whose maximal vasospasm was moderate or severe. MiRNAs were isolated from serial whole-blood samples, and miRNA sequencing was performed. Differentially expressed miRNAs were identified and the expression levels in patients' samples were verified using real-time qPCR. The biological functions of identified miRNA were evaluated in human brain endothelial cells (HBECs). MiRNA profiling revealed significant upregulation of miR-148b-3p in patients during CVS. We demonstrated that miR-148b-3p directly targeted and decreased the expression of ROCK1, affecting cell proliferation, migration, and invasion of HBECs through the ROCK-LIMK-Cofilin pathway. We propose that the upregulation of miRNA-148b-3p plays a role in the development of CVS by regulating actin cytoskeletal dynamics in HBECs, which is crucial for vascular function. Our study highlights miR-148b-3p as a potential diagnostic marker as well as therapeutic target for CVS following aSAH. [ABSTRACT FROM AUTHOR]

Background: Early severe cerebral edema and chronic hydrocephalus are the primary cause of poor prognosis in patients with subarachnoid hemorrhage (SAH). This study investigated the role of cerebrospinal fluid (CSF) inflammatory cytokines and coagulation factors in the development of severe cerebral edema and chronic hydrocephalus in patients with SAH. Methods: Patients with SAH enrolled in this study were categorized into mild and severe cerebral edema groups based on the Subarachnoid Hemorrhage Early Brain Edema Score at admission. During long-term follow-up, patients were further classified into hydrocephalus and non-hydrocephalus groups. CSF samples were collected within 48 h post-SAH, and levels of inflammatory cytokines and coagulation factors were measured. Univariate and multivariate logistic regression analyses were performed to identify independent factors associated with severe cerebral edema and chronic hydrocephalus. The correlation between inflammatory cytokines and coagulation factors was further investigated and validated in a mouse model of SAH. Results: Seventy-two patients were enrolled in the study. Factors from the extrinsic coagulation pathway and inflammatory cytokines were associated with both severe cerebral edema and chronic hydrocephalus. Coagulation products thrombin-antithrombin complexes (TAT) and fibrin, as well as inflammatory cytokines IL-1β, IL-2, IL-5, IL-7, and IL-4, were independently associated with severe cerebral edema. Additionally, Factor VII, fibrin, IL-2, IL-5, IL-12, TNF-α, and CCL-4 were independently associated with chronic hydrocephalus. A positive correlation between extrinsic coagulation factors and inflammatory cytokines was observed. In the SAH mouse model, tissue plasminogen activator was shown to alleviate neuroinflammation and cerebral edema, potentially by restoring glymphatic-meningeal lymphatic function. Conclusions: Elevated levels of inflammatory cytokines and extrinsic coagulation pathway factors in the CSF are associated with the development of early severe cerebral edema and chronic hydrocephalus following SAH. These factors are interrelated and may contribute to post-SAH glymphatic-meningeal lymphatic dysfunction. [ABSTRACT FROM AUTHOR]

Subarachnoid hemorrhage (SAH) can be associated with neurological deficits and has profound consequences for mortality and morbidity. Cerebral vasospasm (CVS) and delayed cerebral ischemia affect neurological outcomes in SAH patients, but their mechanisms are not fully understood, and effective treatments are limited. Here, we report that urotensin II receptor UT plays a pivotal role in both early events and delayed mechanisms following SAH in male mice. Few days post-SAH, UT expression is triggered by blood or hemoglobin in the leptomeningeal compartment. UT contributes to perimeningeal glia limitans astrocyte reactivity, microvascular alterations and neuroinflammation independent of CNS-associated macrophages (CAMs). Later, CAM-dependent vascular inflammation and subsequent CVS develop, leading to cognitive dysfunction. In an SAH model using humanized UTh+/h+ male mice, we show that post-SAH CVS and behavioral deficits, mediated by UT through Gq/PLC/Ca2+ signaling, are prevented by UT antagonists. These results highlight the potential of targeting UT pathways to reduce early meningeal response and delayed cerebral ischemia in SAH patients. "In subarachnoid hemorrhage (SAH), therapies are limited and clinical outcomes remain disappointing. The authors show a contribution of the urotensin II system in microvascular changes, vasospasm, neuroinflammation and cognitive deficits post-SAH, primarily through meningeal cells and border-associated macrophages [ABSTRACT FROM AUTHOR]

Aim: Most of the subarachnoid hemorrhage (SAH) patients experienced the symptom of severe headache caused by intracranial hypertension. Piezo1 is a mechanosensitive ion channel protein. This study aimed to investigate the effect of Piezo1 on neurons in response to intracranial hypertension. Methods: The SAH rat model was performed by the modified endovascular perforation method. Piezo1 inhibitor GsMTx4 was administered intraperitoneally after SAH induction. To investigate the underlying mechanism, the selective Piezo1 agonist Yoda1, Piezo1 shRNA, and MY‐875 were administered via intracerebroventricular injection before SAH induction. In vitro, we designed a pressurizing device to exclusively explore the effect of Piezo1 activation on primary neurons. Neurons were pretreated with Piezo1 inhibition followed by intracranial hypertension treatment, and then apoptosis‐related proteins were detected. Results: Piezo1 inhibition significantly attenuated neuronal apoptosis and improved the outcome of neurological deficits in rats after SAH. The Hippo pathway agonist MY‐875 reversed the anti‐apoptotic effects of Piezo1 knockdown. In vitro, intracranial hypertension mimicked by the pressurizing device induced Piezo1 expression, resulting in Hippo pathway activation and neuronal apoptosis. The Hippo pathway inhibitor Xmu‐mp‐1 attenuated Yoda1‐induced neuronal apoptosis. In addition, the combination of hypertension and oxyhemoglobin treatment exacerbated neuronal apoptosis. Conclusions: Intracranial hypertension induced Piezo1 expression, neuronal apoptosis, and the Hippo pathway activation; the Hippo signaling pathway is involved in Piezo1 activation‐induced neuronal apoptosis in respond to intracranial hypertension. Primary neurons treated with intracranial hypertension and oxyhemoglobin together can better characterize the circumstance of SAH in vivo, which is contributed to construct an ideal in vitro SAH model. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH), known as nontraumatic cerebrovascular rupture and hemorrhage, often occurs in the deep basal brain segment. It is known for its high morbidity and mortality rates. Subarachnoid hemorrhage (SAH) is a clinical syndrome caused by the rupture of blood vessels at the base or surface of the brain that allows blood to flow directly into the subarachnoid space. It progresses quickly and typically manifests at younger ages compared with ICH. ICH and SAH are both devastating events in the category of hemorrhagic strokes and are attracting increasing attention from researchers. Flavonoids, being important natural molecules, have remarkable anti-inflammatory and antioxidant effects. Flavonoids have extensive biological activities in inflammation and oxidative stress (OS), and have protective effects in vascular function associated with cerebrovascular diseases. They have an impact on the onset of ICH and SAH by targeting various pathways, including the suppression of inflammation and OS. Recently, the role of flavonoid compounds in ICH and SAH has also received increasing interest. Thus, to serve as a resource for the prevention and treatment of ICH and SAH, the present review provided an overview of the research on flavonoid compounds in the prevention of brain damage after these two conditions have occurred. [ABSTRACT FROM AUTHOR]

Clazosentan prevents vasospasms after aneurysmal subarachnoid hemorrhage (SAH). However, clinical data on patients with SAH with ruptured vertebral artery dissecting aneurysms (VADAs) are limited. We report the case of a 49-year-old male patient with mild-grade (WFNS grade 1) thick and diffuse (modified Fisher grade 3) SAH who underwent endovascular trapping of a ruptured VADA, resulting in a poor functional outcome with a modified Rankin Scale score of 4 due to severe symptomatic vasospasm refractory to clazosentan, requiring repeated rescue endovascular therapies and chronic communicating hydrocephalus. A retrospective analysis of the clot density in the basal and Sylvian cisterns, assessed by the Hounsfield unit (HU) values of serial CT scans, in this patient showed persistent higher values, distinct from another VADA case that showed a decline in HU values with a good clinical course. These results imply the limited effectiveness of clazosentan in cases of thick and diffuse SAH after a ruptured VADA, even in good-clinical-grade patients treated with less invasive modalities. The HU values may become a simple quantitative marker for predicting symptomatic vasospasms and chronic hydrocephalus. [ABSTRACT FROM AUTHOR]

Reversible cerebral vasoconstriction syndrome (RCVS) is a collective term used to describe pathological conditions with a similar clinical and radiological picture which is characterized by thunderclap headaches with a sudden onset and reversible segmental (multifocal) constriction of the cerebral arteries. The article is devoted to issues of terminology, genetic and clinical features of RSCV, and also discusses risk factors, differential diagnosis, complications and prognosis. Modern pathogenetic mechanisms and possible approaches to the treatment of this condition are presented.

Abstract Cerebral vasospasm (CVS) is an important contributor to delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage (aSAH), leading to high morbidity and long-term disability. While several microRNAs (miRNAs) have been implicated in vasospasm, the underlying mechanisms for CVS remain poorly understood. Our study aims to identify miRNAs that may contribute to the development of CVS. Whole-blood samples were obtained during or outside of vasospasm from aSAH patients whose maximal vasospasm was moderate or severe. MiRNAs were isolated from serial whole-blood samples, and miRNA sequencing was performed. Differentially expressed miRNAs were identified and the expression levels in patients’ samples were verified using real-time qPCR. The biological functions of identified miRNA were evaluated in human brain endothelial cells (HBECs). MiRNA profiling revealed significant upregulation of miR-148b-3p in patients during CVS. We demonstrated that miR-148b-3p directly targeted and decreased the expression of ROCK1, affecting cell proliferation, migration, and invasion of HBECs through the ROCK-LIMK-Cofilin pathway. We propose that the upregulation of miRNA-148b-3p plays a role in the development of CVS by regulating actin cytoskeletal dynamics in HBECs, which is crucial for vascular function. Our study highlights miR-148b-3p as a potential diagnostic marker as well as therapeutic target for CVS following aSAH.

Background and Purpose: Vasospasm is a common iatrogenic event during mechanical thrombectomy (MT). In such circumstances, intra‐arterial nimodipine administration is occasionally considered. However, its use in the treatment of iatrogenic vasospasm during MT has been poorly studied. We investigated the impact of iatrogenic vasospasm treated with intra‐arterial nimodipine on outcomes after MT for large vessel occlusion stroke. Methods: We conducted a retrospective analysis of the multicenter observational registry Endovascular Treatment in Ischemic Stroke (ETIS). Consecutive patients treated with MT between January 2015 and December 2022 were included. Patients treated with medical treatment alone, without MT, were excluded. We also excluded patients who received another in situ vasodilator molecule during the procedure. Outcomes were compared according to the occurrence of cervical and/or intracranial arterial vasospasm requiring intraoperative use of in situ nimodipine based on operator's decision, using a propensity score approach. The primary outcome was a modified Rankin Scale (mRS) score of 0–2 at 90 days. Secondary outcomes included excellent outcome (mRS score 0–1), final recanalization, mortality, intracranial hemorrhage and procedural complications. Secondary analyses were performed according to the vasospasm location (intracranial or cervical). Results: Among 13,678 patients in the registry during the study period, 434 received intra‐arterial nimodipine for the treatment of MT‐related vasospasm. In the main analysis, comparable odds of favorable outcome were observed, whereas excellent outcome was significantly less frequent in the group with vasospasm requiring nimodipine (adjusted odds ratio [aOR] 0.78, 95% confidence interval [CI] 0.63–0.97). Perfect recanalization, defined as a final modified Thrombolysis In Cerebral Infarction score of 3 (aOR 0.63, 95% CI 0.42–0.93), was also rarer in the vasospasm group. Intracranial vasospasm treated with nimodipine was significantly associated with worse clinical outcome (aOR 0.64, 95% CI 0.45–0.92), in contrast to the cervical location (aOR 1.37, 95% CI 0.54–3.08). Conclusion: Arterial vasospasm occurring during the MT procedure and requiring intra‐arterial nimodipine administration was associated with worse outcomes, especially in case of intracranial vasospasm. Although this study cannot formally differentiate whether the negative consequences were due to the vasospasm itself, or nimodipine administration or both, there might be an important signal toward a substantial clinical impact of iatrogenic vasospasm during MT. [ABSTRACT FROM AUTHOR]

Abstract Cerebral vasospasm is determined as a temporary narrowing of cerebral arteries a few days after an aneurysmal subarachnoid hemorrhage. The onset of this vascular event usually evolves with new neurological deficits or progression of ischemic areas. The success of interventions to treat or revert this condition is not satisfying. In addition to cerebral vasospasm, early brain injury plays an important role as a contributor to subarachnoid hemorrhage’s mortality. In this sense, stellate ganglion block appears as an alternative to reduce sympathetic system’s activation, one of the main pathophysiological mechanisms involved in brain injury. Over the past few years, there is growing evidence that stellate ganglion block can contribute to decline patient morbidity from subarachnoid hemorrhage. Is it time to include this procedure as a standard treatment after aneurysm rupture?

Arcanobacterium haemolyticum, found as normal flora in healthy individuals, is an unusual culprit for pharyngitis and sinusitis in young adults, rarely leading to severe infections. Here, we present a singular case involving a 19-year-old immunocompetent male who experienced complications arising from A haemolyticum sinusitis, leading to orbital and intracranial sinogenic complications. The patient developed severe cerebral vasospasm with delayed cerebral ischemia, necessitating aggressive management encompassing daily catheter-directed intra-arterial infusions, surgical source control, and maximal medical therapy.This case explores the challenging diagnostic and management aspects associated with cerebral artery vasospasm secondary to bacterial meningoencephalitis. The abrupt neurological decline in such patients presents a dilemma in recognizing the occurrence of cerebral vasospasm versus the progression of meningoencephalitis. By utilizing computed tomography brain perfusion scans, we were able to identify delayed cerebral ischemia due to cerebral vasospasm, acknowledging that this modality was not used to identify classical territorial stroke infarcts. This decision was made based on the understanding of the potential for bacterial-induced cerebral vasospasm to involve both hemispheres.

Background Delayed cerebral ischemia (DCI) is the leading cause of adverse outcome in patients who survive the initial phase of subarachnoid hemorrhage (SAH). While guidelines recommend induced hypertension as a first-line treatment for DCI, there is no high-level evidence confirming outcome benefit.

Abstract Background Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening neurosurgical emergency with a high mortality rate. Delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) are delayed products of early brain injury (EBI), which may constitute the principal determinant of an unfavorable patient prognosis. Consequently, the mitigation of DCI and CVS assumes paramount significance in the pursuit of enhanced patient outcomes. However, except for oral nimodipine, there is no effective therapy available in the current guideline. Hence, the exigency arises to proffer novel treatment paradigms. The diversity of hydrogen therapeutic targets has been largely reported in basic research, unveiling its latent capacity to ameliorate EBI in aSAH patients. Methods Early Hydrogen–Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA), a single-center, prospective, open-labeled, randomized controlled clinical trial, endeavors to evaluate the efficacy and safety of hydrogen–oxygen gas mixture inhalation therapy in aSAH patients. A cohort of 206 patients will be randomized to either hydrogen–oxygen gas mixture inhalation group (8 h per day, 3 L/min, hydrogen concentration of 67%, oxygen concentration of 33%) or oxygen inhalation group (8 h per day, 3 L/min, oxygen concentration of 33%) within 72 h after aSAH and treated for 7 days in the ICU ward. The primary outcomes are the incidence of DCI and CVS during hospitalization. Discussion The HOMA aims to evaluate the effectiveness of hydrogen–oxygen gas mixture inhalation therapy in preventing DCI or CVS and improving outcomes in aSAH patients. Notably, this is the first large-scale trial of hydrogen therapy in aSAH patients. Given that the Chinese population represents a significant portion of the global population and the increasing incidence of stroke due to aging, optimizing patient care is vital. Given the current challenges in aSAH patient outcomes, initiating more prospective clinical trials is essential. Recent research has shown hydrogen’s therapeutic potential, aligning with EBI in aSAH, driving our exploration of hydrogen therapy’s mechanisms in post-aneurysm rupture damage. Ethics and dissemination The protocol for the HOMA study was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University (KY 2022–020-02). All results of the present study will be published in peer-reviewed journals and presented at relevant conferences. Trial registration ClinicalTrials.gov NCT05282836. Registered on March 16, 2022.

Background: Fasudil and ozagrel are drugs with the same indications for the treatment of cerebral vasospasm in Japan. However, there have been no definitive conclusions on the clinical efficacy of fasudil hydrochloride and ozagrel sodium monotherapy or their combination. Therefore, we aimed to investigate the effectiveness of the combined administration of fasudil hydrochloride and ozagrel sodium in Japanese patients with subarachnoid hemorrhage (SAH). Methods: This cross-sectional study used Diagnosis Procedure Combination data to assess patients who were hospitalized with SAH and received fasudil hydrochloride or ozagrel sodium between April 2016 and March 2020 (n = 17,346). The participants were divided into three groups based on the treatment received: fasudil hydrochloride monotherapy (F group, n = 10,484), ozagrel sodium monotherapy (O group, n = 465), and fasudil hydrochloride and ozagrel sodium combination therapy (FO group, n = 6,397). The primary outcome was in-hospital mortality. Multivariable adjusted logistic regression analysis (significance level, 5%) was used for data analyses. Results: The results of the multivariable analysis, adjusted for factors considered to impact prognosis, showed that the adjusted odds ratio (OR) with the F group as the reference for in-hospital mortality was 0.94 in the FO group (95% confidence interval [CI]: 0.81–1.08, p = 0.355), with no differences compared to the F group. Conclusion: Fasudil hydrochloride and ozagrel sodium had different mechanisms of action, suggesting a synergistic effect of combination therapy. However, a comparison of fasudil hydrochloride monotherapy and combination therapy of fasudil hydrochloride and ozagrel sodium showed no difference in the prognostic effect. Therefore, it was suggested that fasudil hydrochloride monotherapy may be sufficient. [ABSTRACT FROM AUTHOR]

The article discusses a case study of a patient who experienced subarachnoid hemorrhage (SAH) after undergoing super-selective cerebral angiography (SSCA). The patient had an anterior communicating artery (Acom) aneurysm, which was treated with a Woven Endo Bridge (WEB) device. However, after the procedure, the patient developed aphasia and showed signs of SAH on imaging. The article explores various possible causes for the SAH, including rupture of the embolized aneurysm, lenticulostriate aneurysm, vessel perforation, contrast-induced SAH, and iatrogenic SAH. The authors conclude that the most likely cause was iatrogenic SAH with parenchymal enhancement induced by contrast injection into the smaller M2 segment of the middle cerebral artery (MCA). [Extracted from the article]

Background: Reversible Cerebral Vasoconstriction Syndrome (RCVS) involves cerebral vasculature constriction and dilation. While the exact pathophysiology of RCVS is still not fully understood, there are multiple etiological factors suggested to be implicated in triggering RCVS. We report two RCVS cases potentially linked to teprotumumab. Case 1: A 59-year-old female with Graves' eye disease (GED) developed leg weakness and headache after initiating teprotumumab, and neuroimaging studies revealed multifocal cerebral vasospasm (CVS). Verapamil mitigated vasospasm and the patient overall improved. Case 2: A 71-year-old female with GED developed thunderclap headache two months after starting teprotumumab, with subarachnoid hemorrhage (SAH) and CVS revealed on neuroimaging studies. The patient improved on verapamil and was discharged without deficits. Conclusions: The temporal correlation between teprotumumab initiation and RCVS's symptom onset raises concern for the potential involvement of teprotumumab in triggering RCVS via disrupting cerebrovascular modulation. Further research is needed to investigate this proposed association. [ABSTRACT FROM AUTHOR]

Background: Subarachnoid hemorrhage (SAH) represents a severe stroke subtype. Our study aims to develop gender‐specific prognostic prediction models derived from distinct prognostic factors observed among different‐gender patients. Methods: Inclusion comprised SAH‐diagnosed patients from January 2014 to March 2016 in our institution. Collected data encompassed patients' demographics, admission severity, treatments, imaging findings, and complications. Three‐month post‐discharge prognoses were obtained via follow‐ups. Analyses assessed gender‐based differences in patient information. Key factors underwent subgroup analysis, followed by univariate and multivariate analyses to identify gender‐specific prognostic factors and establish/validate gender‐specific prognostic models. Results: A total of 929 patients, with a median age of 57 (16) years, were analyzed; 372 (40%) were male, and 557 (60%) were female. Differences in age, smoking history, hypertension, aneurysm presence, and treatment interventions existed between genders (p < 0.01), yet no disparity in prognosis was noted. Subgroup analysis explored hypertension history, aneurysm presence, and treatment impact, revealing gender‐specific variations in these factors' influence on the disease. Screening identified independent prognostic factors: age, SEBES score, admission GCS score, and complications for males; and age, admission GCS score, intraventricular hemorrhage, treatment interventions, symptomatic vasospasm, hydrocephalus, delayed cerebral ischemia, and seizures for females. Evaluation and validation of gender‐specific models yielded an AUC of 0.916 (95% CI: 0.878–0.954) for males and 0.914 (95% CI: 0.885–0.944) for females in the ROC curve. Gender‐specific prognostic models didn't significantly differ from the overall population‐based model (model 3) but exhibited robust discriminative ability and clinical utility. Conclusion: Variations in baseline and treatment‐related factors among genders contribute partly to gender‐based prognosis differences. Independent prognostic factors vary by gender. Gender‐specific prognostic models exhibit favorable prognostic performance. [ABSTRACT FROM AUTHOR]

Cerebral vasospasm is determined as a temporary narrowing of cerebral arteries a few days after an aneurysmal subarachnoid hemorrhage. The onset of this vascular event usually evolves with new neurological deficits or progression of ischemic areas. The success of interventions to treat or revert this condition is not satisfying. In addition to cerebral vasospasm, early brain injury plays an important role as a contributor to subarachnoid hemorrhage's mortality. In this sense, stellate ganglion block appears as an alternative to reduce sympathetic system's activation, one of the main pathophysiological mechanisms involved in brain injury. Over the past few years, there is growing evidence that stellate ganglion block can contribute to decline patient morbidity from subarachnoid hemorrhage. Is it time to include this procedure as a standard treatment after aneurysm rupture? [ABSTRACT FROM AUTHOR]

Reversible cerebral vasoconstriction syndrome (RCVS) is a clinical radiographic phenomenon characterized by thunderclap headaches and transient vasoconstriction of cerebral vessels, which typically resolve within 3 months of symptom onset. Although RCVS has been extensively studied in adults, research on this condition in pediatric populations is limited, likely due to its perceived rarity. This comprehensive review aims to bridge the knowledge gap by examining the clinical presentation, diagnostic methods, treatment strategies, and prognostic outcomes of pediatric RCVS cases, including two case reports contributed by the authors. This study demonstrates an inconclusive sex distribution of RCVS in children, attributed to the scarcity of comprehensive studies of this demographic. Additionally, we identified several predictors of adverse neurological outcomes in children with RCVS, including motor deficits, aphasia, hypertension, and renal disease. This study offers a thorough overview of RCVS in the pediatric population, providing valuable insights to inform future research in this area. [ABSTRACT FROM AUTHOR]

Background: Aneurysmal subarachnoid hemorrhage (aSAH) patients typically have poor prognoses. The anion gap (AG) has been proven to correlate with mortality in various critically ill patients. However, hypoalbuminemia can lead to underestimations of the true anion gap levels. This study was conducted to verify the prognostic value of single AG and albumin-corrected anion gap (ACAG) among aSAH patients. Methods: Significant factors in the univariate logistic regression analysis were included in the multivariate logistic regression analysis to explore the risk factors for mortality in aSAH patients and to confirm the independent relationship between ACAG and mortality. The restricted cubic spline (RCS) was used to visually show the relationship between ACAG level and mortality risk of aSAH patients. The predictive model for mortality was developed by incorporating significant factors into the multivariate logistic regression analysis. The prognostic value of ACAG and the developed model was evaluated by calculating the area under the receiver operating characteristics curve (AUC). Results: Among 710 aSAH patients, a 30-day mortality was observed in 20.3% of the cases. A positive relationship was demonstrated between the ACAG level and mortality in aSAH patients using the RCS curve. The multivariate logistic regression analysis helped discover that only six factors were finally and independently related to mortality of aSAH patients after adjusting for confounding effects, including the Hunt-Hess scale score (p = 0.006), surgical options (p < 0.001), white blood cell count (p < 0.001), serum chloride levels (p = 0.023), ACAG (p = 0.039), and delayed cerebral ischemia (p < 0.001). The AUC values for the AG, albumin, and ACAG in predicting mortality among aSAH patients were 0.606, 0.536, and 0.617, respectively. A logistic regression model, which includes the Hunt-Hess scale score, surgical options, white blood cell count, serum chloride levels, ACAG, and delayed cerebral ischemia, achieved an AUC of 0.911 for predicting mortality. Conclusion: The ACAG is an effective prognostic marker for aSAH patients. A prognostic model incorporating ACAG could help clinicians evaluate the risk of poor outcomes among aSAH patients, thereby facilitating the development of personalized therapeutic strategies. [ABSTRACT FROM AUTHOR]

Introduction: Clazosentan, a selective endothelin receptor subtype A antagonist, reduces vasospasm-related morbidity and all-cause mortality following aneurysmal subarachnoid hemorrhage (SAH) in the Japanese population, as demonstrated by a recent randomized phase 3 trial. However, evidence to suggest clazosentan should be prioritized over the current standard of care to prevent cerebral vasospasm is still lacking. Therefore, we investigated the efficacy and safety of clazosentan in comparison with conventional postoperative management in real-world clinical practice. Methods: We conducted a single-center, retrospective, observational cohort study using prospectively collected data from consecutive patients with aneurysmal SAH. After clazosentan was approved for use in Japan, the conventional postoperative management protocol, composed of intravenous fasudil chloride and oral cilostazol (control group, April 2021 to March 2022), was changed to the clazosentan protocol (clazosentan group, April 2022 to March 2023). The primary endpoint was the incidence of vasospasm-related symptomatic infarction. The secondary endpoints were favorable functional outcomes (modified Rankin scale score < 3) at discharge, angiographic vasospasm, and the need for rescue therapy for delayed cerebral ischemia. Results: The analysis included 100 and 81 patients in the control and clazosentan groups, respectively. The incidence of vasospasm-related symptomatic infarction was significantly lower in the clazosentan group than in the control group (6.2% vs. 16%, p = 0.032). Multiple logistic analyses demonstrated that the use of clazosentan was independently associated with fewer incidence of vasospasm-related symptomatic infarct (23.8% vs. 47.5%, odds ratio 0.34 [0.12-0.97], p = 0.032). Clazosentan was significantly associated with favorable outcomes at discharge (79% vs. 66%, p = 0.037). Moreover, both the incidence of angiographic vasospasm (25.9% vs. 44%, p = 0.013) and the need for rescue therapy (16.1% vs. 34%, p = 0.006) was lower in the clazosentan group. The occurrence of pulmonary edema was significantly higher with clazosentan use (19.8% vs. 5%, p = 0.002), which did not result in morbidity. Conclusion: A postoperative management protocol centering on clazosentan was associated with the reduced vasospasm-related symptomatic infarction and improved clinical outcomes compared to the conventional management protocol in Japanese clinical practice. Clazosentan might be a promising treatment option for counteracting cerebral vasospasm after aneurysmal SAH. [ABSTRACT FROM AUTHOR]

Delayed cerebral ischemia (DCI) could lead to poor clinical outcome(s). The aim of the present study was to establish and validate a predictive model for DCI after aneurysmal subarachnoid hemorrhage (aSAH) based on clinical data. Data from a series of 217 consecutive patients with aSAH were reviewed and analyzed. Related risk factors within 72  h after aSAH were analyzed depending on whether DCI recurred. Least absolute shrinkage and selection operator (LASSO) analysis was performed to reduce data dimensions and screen for optimal predictors. Multivariable logistic regression was used to establish a predictive model and construct a nomogram. Receiver operating characteristic (ROC) and calibration curves were generated to assess the discriminative ability and goodness of fit of the model. Decision curve analysis was applied to evaluated the clinical applicability of the predictive model. LASSO regression identified 4 independent predictors, including Subarachnoid Hemorrhage Early Brain Edema Score (i.e., “SEBES”), World Federation of Neurosurgical Societies scale score (i.e., “WFNS”), modified Fisher Scale score, and intraventricular hemorrhage (IVH), which were incorporated into logistic regression to develop a nomogram. After verification, the area under the ROC curve for the model was 0.860. The calibration curve indicated that the predictive probability of the new model was in good agreement with the actual probability, and decision curve analysis demonstrated the clinical applicability of the model within a specified range. The prediction model could precisely calculate the probability of DCI after aSAH, and may contribute to better clinical decision-making and personalized treatment to achieve better outcomes. [ABSTRACT FROM AUTHOR]

Cerebral ischemic complications after pituitary surgery are not frequently reported. Multiple mechanisms have been proposed, including vasospasm, and delayed cerebral ischemia resulting from postoperative subarachnoid bleeding. Given the unknown etiology of vasospasm following these situations, little is known about its prevention. Through a case report and bibliographic review, the authors warn about the importance of recognizing key signs postoperatively that could indicate increased risk for cerebral vasospasm and must be recognized in a timely manner, with appropriate treatment strategies implemented once these symptoms present. [ABSTRACT FROM AUTHOR]

Background Delayed cerebral ischemia (DCI) is the leading cause of adverse outcome in patients who survive the initial phase of subarachnoid hemorrhage (SAH). While guidelines recommend induced hypertension as a first-line treatment for DCI, there is no high-level evidence confirming outcome benefit. Methods Patients admitted with nontraumatic SAH over 3 years period were identified. Demographics, clinical/radiological presentation, aneurysm repair method, and Glasgow outcome score (GOS) 3 months postdischarge were recorded. A subgroup of patients who suffered clinically significant vasospasm were identified, and their hypertensive therapy and outcomes were examined. Results A total of 532 patients were admitted with SAH; 68 developed vasospasm. The vasospasm subgroup was divided based on vasopressor treatment—norepinephrine alone (n = 27) versus norepinephrine plus vasopressin (n = 35). No correlation was found between percentage of days that mean arterial pressure (MAP) targets were met and GOS outcome. Patients treated with both agents had worse GOS outcomes at than those treated with norepinephrine alone. Conclusion In our study, 12.8% of patients SAH developed vasospasm. Twenty-seven patients were treated with norepinephrine alone and 35 were treated with norepinephrine plus vasopressin to achieve augmented MAP targets. There was no correlation between percentage of days that MAP targets were met and improved patient outcome. The 68 patients stayed a total of 783 days in ICU, with a mean length of stay of 11.5 days. Patients who required dual therapy to achieve MAP targets had significantly worse neurological outcomes. [ABSTRACT FROM AUTHOR]

Study design: Retrospective. Background: In the 1980s, aneurysmal subarachnoid clot lysis with urokinase or alteplase (rtPA) was proven to effectively reduce vasospasm and neurological ischemic deficits, improving survival and clinical outcomes. This therapeutic option has been less commonly used since the introduction of endovascular treatment, but renewed interest has sparked in recent years. Aims: To investigate if single bolus cisternal urokinase subarachnoid clot lysis reduces vasospasm, neurological ischemic deficits, mortality, and permanent CSF diversion rates and improves outcomes. Additionally, we want to unveil which subgroup of patients benefit most. Material and methods: Study period January 2007–December 2019. 415 patients with saccular aneurysms and >1-year follow-up analyzed. Six groups created according to the treatment applied: no treatment (42), only external ventricular drain (16), endovascular treatment (155), clipping (53), clipping + 100,000UI urokinase (116), and incidental brain aneurysm (33). Results: The rates and severity of vasospasm, permanent CSF diversion, and mortality in Fisher grades ≥3 subarachnoid hemorrhages were higher with endovascular treatment than with surgical clipping with simultaneous cisternal urokinase administration. The best GOSE results on discharge and 6- and 12-month follow-ups happened in this latter group. The differences were more significant the higher the Fisher grade. We neither saw intraventricular, subarachnoid, subdural, or epidural hemorrhages nor systemic fibrinolysis or infections that could be related to the urokinase administration. Conclusions: Single bolus cisternal 100,000UI urokinase administration during emergency aneurysm clipping reduces vasospasm, mortality, and the need for permanent CSF diversion. It is not associated with a significant increase in intracranial hemorrhages or systemic fibrinolysis.

CT perfusion (CTP) images can be easily and rapidly obtained on all modern CT scanners and have become part of the routine imaging protocol of patients with aneurysmal subarachnoid haemorrhage (aSAH). There is a growing body of evidence supporting the use of CTP imaging in these patients, however, there are significant differences in the software packages and methods of analysing CTP. In. addition, no quantitative threshold values for tissue at risk (TAR) have been validated in this patients’ population. Here we discuss the contribution of the technique in the identification of patients at risk of aSAH-related delayed cerebral ischemia (DCI) and in the assessment of the response to endovascular rescue therapy (ERT). We also address the limitations and pitfalls of automated CTP postprocessing that are specific to aSAH patients as compared to acute ischemic stroke (AIS).

Objective: Clazosentan (CLA) reduces cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). However, adverse events including pulmonary edema were reported. We examined whether the strict management of fluid balance reduces the adverse events and improves patient outcomes. Methods: Patients with aSAH between 2020 and 2023 were included. They were divided into pre-CLA (before CLA approval) and post-CLA (after approval) groups. The patients in the post-CLA group were further divided into the post-CLA1 (before the change in fluid management) and post-CLA2 (after the change) groups. To achieve fluid balance of 0–500 ml/day according to the modified protocol, the infusion volume was restricted. Results: The daily fluid balance increased from the pre-CLA to the post-CLA1 periods (p = 0.01). The protocol changes decreased the pulmonary edema (post-CLA1 vs. post-CLA2, 44 vs. 22 %, p = 0.09) and discontinuation of CLA (44 vs. 9 %, p

An aneurysmal subarachnoid hemorrhage (aSAH) is a devastating event associated with a high mortality and morbidity rate. Though numerous medications are used to prevent cerebral vasospasm and vasospasm-related cerebral infarction after aSAH, no effective pharmacological treatment has been established. Clazosentan, a highly selective endothelin receptor type A antagonist, was approved for use in Japan in April 2022 based on results of two pivotal randomized, placebo-controlled phase 3 studies (JapicCTI-163369, JapicCTI-163368). These studies indicated that clazosentan significantly reduced the incidence of vasospasm-related morbidity and all-cause mortality after aneurysm coiling and clipping. Clazosentan is thus expected to become a “game changer” for improving the neurological prognosis after aSAH. However, other reports indicate that even when clazosentan or nimodipine are administered for prophylaxis against delayed neurological decline, patients treated with increased colloid administration or hypertonic saline (3% sodium chloride) load exhibit poor functional outcome and higher mortality, suggesting that extra fluid and sodium derived from prophylactic colloid administration contribute to negative outcomes after aSAH. Pharmacological treatments such as clazosentan in addition to perioperative management involving delivery of less water and sodium might be crucial for achieving better outcomes than conventional therapy. Based on a literature review, we present here the future perspectives regarding clazosentan and the necessity for modifying management of the water-electrolyte balance by focusing on endothelin-1 and blood–brain barrier disruption.

Objective: Our aim was to develop a nomogram that integrates clinical and radiological data obtained from computed tomography (CT) scans, enabling the prediction of chronic hydrocephalus in patients with aneurysmal subarachnoid hemorrhage (aSAH). Method: A total of 318 patients diagnosed with subarachnoid hemorrhage (SAH) and admitted to the Department of Neurosurgery at the Affiliated People's Hospital of Jiangsu University between January 2020 and December 2022 were enrolled in our study. We collected clinical characteristics from the hospital's medical record system. To identify risk factors associated with chronic hydrocephalus, we conducted both univariate and LASSO regression models on these clinical characteristics and radiological features, accompanied with penalty parameter adjustments conducted through tenfold cross-validation. All features were then incorporated into multivariate logistic regression analyses. Based on these findings, we developed a clinical-radiological nomogram. To evaluate its discrimination performance, we conducted Receiver Operating Characteristic (ROC) curve analysis and calculated the Area Under the Curve (AUC). Additionally, we employed calibration curves, and utilized Brier scores as an indicator of concordance. Additionally, Decision Curve Analysis (DCA) was performed to determine the clinical utility of our models by estimating net benefits at various threshold probabilities for both training and testing groups. Results: The study included 181 patients, with a determined chronic hydrocephalus prevalence of 17.7%. Univariate logistic regression analysis identified 11 potential risk factors, while LASSO regression identified 7 significant risk factors associated with chronic hydrocephalus. Multivariate logistic regression analysis revealed three independent predictors for chronic hydrocephalus following aSAH: Periventricular white matter changes, External lumbar drainage, and Modified Fisher Grade. A nomogram incorporating these factors accurately predicted the risk of chronic hydrocephalus in both the training and testing cohorts. The AUC values were calculated as 0.810 and 0.811 for each cohort respectively, indicating good discriminative ability of the nomogram model. Calibration curves along with Hosmer-Lemeshow tests demonstrated excellent agreement between predicted probabilities and observed outcomes in both cohorts. Furthermore, Brier scores (0.127 for the training and 0.09 for testing groups) further validated the predictive performance of our nomogram model. The DCA confirmed that this nomogram provides superior net benefit across various risk thresholds when predicting chronic hydrocephalus. The decision curve demonstrated that when an individual's threshold probability ranged from 5 to 62%, this model is more effective in predicting the occurrence of chronic hydrocephalus after aSAH. Conclusion: A clinical-radiological nomogram was developed to combine clinical characteristics and radiological features from CT scans, aiming to enhance the accuracy of predicting chronic hydrocephalus in patients with aSAH. This innovative nomogram shows promising potential in assisting clinicians to create personalized and optimal treatment plans by providing precise predictions of chronic hydrocephalus among aSAH patients. [ABSTRACT FROM AUTHOR]

Background: Early prediction of delayed cerebral ischemia (DCI) is critical to improving the prognosis of aneurysmal subarachnoid hemorrhage (aSAH). Machine learning (ML) algorithms can learn from intricate information unbiasedly and facilitate the early identification of clinical outcomes. This study aimed to construct and compare the ability of different ML models to predict DCI after aSAH. Then, we identified and analyzed the essential risk of DCI occurrence by preoperative clinical scores and postoperative laboratory test results. Methods: This was a multicenter, retrospective cohort study. A total of 1039 post-operation patients with aSAH were finally included from three hospitals in China. The training group contained 919 patients, and the test group comprised 120 patients. We used five popular machine-learning algorithms to construct the models. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, precision, and f1 score were used to evaluate and compare the five models. Finally, we performed a Shapley Additive exPlanations analysis for the model with the best performance and significance analysis for each feature. Results: A total of 239 patients with aSAH (23.003%) developed DCI after the operation. Our results showed that in the test cohort, Random Forest (RF) had an AUC of 0.79, which was better than other models. The five most important features for predicting DCI in the RF model were the admitted modified Rankin Scale, D-Dimer, intracranial parenchymal hematoma, neutrophil/lymphocyte ratio, and Fisher score. Interestingly, clamping or embolization for the aneurysm treatment was the fourth button-down risk factor in the ML model. Conclusions: In this multicenter study, we compared five ML methods, among which RF performed the best in DCI prediction. In addition, the essential risks were identified to help clinicians monitor the patients at high risk for DCI more precisely and facilitate timely intervention. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

Objective: Sex differences in outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) remain controversial. Therefore, the aim of this study was to investigate the sex differences in the prognosis of patients with aSAH. Methods: This study retrospectively analyzed the clinical data of aSAH patients admitted to the Department of Neurosurgery of General Hospital of Northern Theater Command, from April 2020 to January 2022. The modified Rankin Scale (mRS) was used to evaluate outcomes at 3-month post-discharge. Baseline characteristics, in-hospital complications and outcomes were compared after 1:1 propensity score matching (PSM). Results: A total of 665 patients were included and the majority (63.8%) were female. Female patients were significantly older than male patients (59.3 ± 10.9 years vs. 55.1 ± 10.9 years, P < 0.001). After PSM, 141 male and 141 female patients were compared. Comparing postoperative complications and mRS scores, the incidence of delayed cerebral ischemia (DCI) and hydrocephalus and mRS ≥ 2 at 3-month were significantly higher in female patients than in male patients. After adjustment, the analysis of risk factors for unfavorable prognosis at 3-month showed that age, sex, smoking, high Hunt Hess grade, high mFisher score, DCI, and hydrocephalus were independent risk factors. Conclusion: Female patients with aSAH have a worse prognosis than male patients, and this difference may be because females are more vulnerable to DCI and hydrocephalus. [ABSTRACT FROM AUTHOR]

Background: This study evaluates the effectiveness of Therapeutic Hypothermia (TH) in treating poor-grade aneurysmal subarachnoid hemorrhage (SAH), focusing on functional outcomes, mortality, and complications such as vasospasm, delayed cerebral ischemia (DCI), and hydrocephalus. Methods: Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a comprehensive literature search was conducted across multiple databases, including Medline, Embase, and Cochrane Central, up to November 2023. Nine studies involving 368 patients were selected based on eligibility criteria focusing on TH in poor-grade SAH patients. Data extraction, bias assessment, and evidence certainty were systematically performed. Results: The primary analysis of unfavorable outcomes in 271 participants showed no significant difference between the TH and standard care groups (risk ratio [RR], 0.87). However, a significant reduction in vasospasm was observed in the TH group (RR, 0.63) among 174 participants. No significant differences were found in DCI, hydrocephalus, and mortality rates in the respective participant groups. Conclusions: TH did not significantly improve primary unfavorable outcomes in poor-grade SAH patients. However, the reduction in vasospasm rates indicates potential specific benefits. The absence of significant findings in other secondary outcomes and mortality highlights the need for further research to better understand TH's role in treating this patient population. [ABSTRACT FROM AUTHOR]

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 < 0.001. The rebleeding rate was 7.6% in the study group and 8.7% in the control group. On univariate analysis size >1 cm, multiplicity, multilobularity, vasospasm, and CSF drainage were significant risk factors for rebleeding (P < 0.001). On multivariate analysis aneurysm size >1 cm, CSF overdrainage >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. [ABSTRACT FROM AUTHOR]

Cerebral vasospasm (CV) is a significant complication following aneurysmal subarachnoid hemorrhage (aSAH), and lacks a comprehensive molecular understanding. Given the temporal trajectory of intracranial aneurysm (IA) formation, its rupture, and development of CV, altered gene expression might be a molecular substrate that runs through these clinical events, influencing both disease inception and progression. Utilizing RNA-Seq, we analyzed tissue samples from ruptured IAs with and without vasospasm to identify the dysregulated genes. In addition, temporal gene expression analysis was conducted. We identified seven dysregulated genes in patients with ruptured IA with vasospasm when compared with those without vasospasm. We found 192 common genes when the samples of each clinical subset of patients with IA, that is, unruptured aneurysm, ruptured aneurysm without vasospasm, and ruptured aneurysm with vasospasm, were compared with control samples. Among these common genes, TNFSF13B, PLAUR, OSM, and LAMB3 displayed temporal expression (progressive increase) with the pathological progression of disease that is formation of aneurysm, its rupture, and consequently the development of vasospasm. We validated the temporal gene expression pattern of OSM at both the transcript and protein levels and OSM emerges as a crucial gene implicated in the pathological progression of disease. In addition, RSAD2 and ATP1A2 appear to be pivotal genes for CV development. To the best of our knowledge, this is the first study to compare the transcriptome of aneurysmal tissue samples of aSAH patients with and without CV. The findings collectively provide new insights on the molecular basis of IA and CV and new leads for translational research. [ABSTRACT FROM AUTHOR]

Background: Endovascular treatment of the wide-necked aneurysm is still challenging. Temporary stent-assisted coiling (TSAC) was introduced to manage the ruptured wide-necked aneurysms to avoid the long-term use of dual antiplatelets as well as improving aneurysm filling with coils. Case presentation: Here, we reported a case of the coil entrapment into the stent device during TSAC for the treatment of a wide-necked large ruptured aneurysm. Patient presented with loss of consciousness following diffuse subarachnoid hemorrhage due to a wide-necked large aneurysm located in the left ICA bifurcation. During treatment of aneurysm with TSAC technique, the stent could not retrieve and re-sheath because of coil entrapment in the stent struts. Consequently, the stent was released by cutting the pushing wire at the puncture site. Conclusion: Entrapment of coils in the stent struts is a very rare technical complication of TSAC method. It is essential to be aware of this side effect and how to avoid. [ABSTRACT FROM AUTHOR]

This document is an editorial from the Journal of Clinical Medicine that introduces a special issue dedicated to addressing the challenges in the management of cerebral aneurysms (CA). The special issue includes ten publications covering various topics related to the diagnosis and treatment of CA. The editorial highlights the importance of early recognition of complications after subarachnoid hemorrhage (SAH) and the need for individualized treatment approaches. It also emphasizes the significance of precise patient selection for preventive interventions and efforts to improve treatment outcomes. The document provides a list of the contributions included in the special issue. [Extracted from the article]

Knowledge about biological rhythms of diseases may not only help in understanding the pathophysiology of diseases but can also help health service policy makers and emergency department directors to allocate resources efficiently. Aneurysmal subarachnoid haemorrhage (SAH) has high rates of morbidity and mortality. The incidence of SAH has been attributed to patient-related factors such as characteristics of aneurysms, smoking, and hypertension. There are studies showing that the incidence of aneurysmal SAH appears to behave in periodic fashions over long time periods. However, there are inconsistencies in the literature regarding the impact of chronobiological factors such as circadian, seasonal, and lunar cycle factors on the occurrence of SAH. In this study, we focused on the analysis of a temporal pattern of SAH (infradian rhythms) with a novel approach using circular statistical methods. We aimed to see whether there is a circular pattern for the occurrence of SAH at all and if so, whether it can be related to known temporal patterns based on available literature. Our study did not support the notion that aneurysmal subarachnoid haemorrhages occur on any specific day in a cycle with specific lengths up to 365 days including specific weekdays, full moon, equinoxes, and solstices. Hence, we found no relationship between SAH incidence and timing. Study in larger populations using similar circular statistical methods is suggested. [ABSTRACT FROM AUTHOR]

Subarachnoid hemorrhage (SAH) remains a major cause of cerebrovascular morbidity, eliciting severe headaches and vasospasms that have been shown to inversely correlate with vasodilator calcitonin gene-related peptide (CGRP) levels. Although dura mater trigeminal afferents are an important source of intracranial CGRP, little is known about the effects of SAH on these neurons in preclinical models. The present study evaluated changes in CGRP levels and expression in trigeminal primary afferents innervating the dura mater 72 h after experimentally induced SAH in adult rats. SAH, eliciting marked damage revealed by neurological examination, significantly reduced the density of CGRP-immunoreactive nerve fibers both in the dura mater and the trigeminal caudal nucleus in the medulla but did not affect the total dural nerve fiber density. SAH attenuated ex vivo dural CGRP release by ~40% and in the trigeminal ganglion, reduced both CGRP mRNA levels and the number of highly CGRP-immunoreactive cell bodies. In summary, we provide novel complementary evidence that SAH negatively affects the integrity of the CGRP-expressing rat trigeminal neurons. Reduced CGRP levels suggest likely impaired meningeal neurovascular functions contributing to SAH complications. Further studies are to be performed to reveal the importance of impaired CGRP synthesis and its consequences in central sensory processing. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the efficacy of using a newly formulated magnesium-rich artificial cerebrospinal fluid (MACSF) as an alternative to normal saline (NS) for intraoperative irrigation during aneurysm clipping in improving the prognosis of patients with Aneurysmal subarachnoid hemorrhage (aSAH). Methods: Patients with aSAH who underwent intraoperative irrigation with MACSF or NS during the clipping in the First Affiliated Hospital of Xi 'an Jiaotong University from March 2019 to March 2022 were selected as MACSF group and NS group, respectively. The primary prognostic indicators were the incidence of favorable outcomes (mRS 0-2). The secondary outcome measures included cerebral vasospasm (CVS), mortality, total hospital stay, and intensive care unit (ICU) stay. Safety was evaluated based on the occurrence rates of hypermagnesemia, meningitis, and hydrocephalus. Results: Overall, 34 and 37 patients were enrolled in the MACSF and NS groups, respectively. At 90 days after aSAH onset, the proportion of favorable prognosis in the MACSF group was significantly higher than that in the NS group (p = 0.035). The incidence of CVS within 14 days after surgery was significantly lower in the MACSF group than that in the NS group (p = 0.026). The mortality rate in the MACSF group was significantly lower than in the NS group (p = 0.048). The median lengths of hospital stay (p = 0.008) and ICU stay (p = 0.018) were significantly shorter in the MACSF group than in the NS group. No significant differences were observed in safety measures. Conclusion: Using MACSF as an irrigation fluid for aneurysm clipping can significantly improve the 90-day prognosis of patients with aSAH, which may be related to the reduced incidence of CVS. [ABSTRACT FROM AUTHOR]

Background: The present work aimed to determine whether a relationship exists between inflammatory parameters and the development of vasospasm (VS) and Takotsubo cardiomyopathy (TTC), as well as clinical outcome, in patients suffering from spontaneous subarachnoid hemorrhage (SAH). Methods: In this study, the authors processed the prospectively collected laboratory and clinical data of spontaneous SAH patients admitted to the neurointensive care unit between March 2015 and October 2023. The highest values of neutrophils (NEUpeak), monocytes (MONOpeak), neutrophil-to-lymphocyte ratio (NLRpeak), and CRP (CRPpeak) during the initial 7 days were correlated with the occurrence of VS and TTC, and with the outcome measures at day 30 after onset. Results: Data were collected from 175 SAH patients. Based on ROC analysis, for the development of VS, MONOpeak was the most accurate indicator (AUC: 0.619, optimal cut-off: 1.45 G/L). TTC with severe left ventricular dysfunction (ejection fraction < 40%) was indicated most sensitively by NEUpeak (ROC: 0.763, optimal cut-off: 12.34 G/L). Both for GOS and Barthel Index at day 30, CRPpeak was the best predictor for the outcome (GOS: ROC: 0.846, optimal cut-off: 78.33 mg/L and Barthel Index: ROC: 0.819, optimal cut-off: 78.33 mg/L). Conclusions: Laboratory parameters referring to inflammation during the initial 7 days after SAH correlate with the development of VS and TTC, and thus may predict functional outcome. [ABSTRACT FROM AUTHOR]

Introduction: The major mechanism of morbidity of delayed cerebral ischemia after subarachnoid hemorrhage (SAH) is considered to be severe vasospasm. Quantitative MRA (QMRA) provides direct measurements of vessel-specific volumetric blood flow and may permit a clinically relevant assessment of the risk of ischemia secondary to cerebral vasospasm. Purpose: To evaluate the utility of QMRA as an alternative imaging technique for the assessment of cerebral vasospasm after SAH. Methods: QMRA volumetric flow rates of the anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) were compared with vessel diameters on catheter-based angiography. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of QMRA for detecting cerebral vasospasm was determined by receiver-operating characteristic curves. Spearman correlation coefficients were calculated for QMRA flow versus angiographic vessel diameter. Results: Sixty-six vessels (10 patients) were evaluated with QMRA and catheter-based angiography. The median percent QMRA flow of all vessels with angiographic vasospasm (55.0%, IQR 34.3–71.6%) was significantly lower than the median percent QMRA flow of vessels without vasospasm (91.4%, IQR 81.4–100.4%) (p < 0.001). Angiographic vasospasm reduced QMRA-assessed flow by 23 ± 5 (p = 0.018), 95 ± 12 (p = 0.042), and 16 ± 4 mL/min (p = 0.153) in the ACA, MCA, and PCA, respectively, compared to vessels without angiographic vasospasm. The sensitivity, specificity, PPV, and NPV of QMRA for the discrimination of cerebral vasospasm was 84%, 72%, 84%, and 72%, respectively, for angiographic vasospasm >25% and 91%, 60%, 87%, and 69%, respectively, for angiographic vasospasm >50%. The Spearman correlation indicated a significant association between QMRA flows and vessel diameters (rs = 0.71, p < 0.001). Conclusion: Reduction in QMRA flow correlates with angiographic vessel narrowing and may be useful as a non-invasive imaging modality for the detection of cerebral vasospasm after SAH. [ABSTRACT FROM AUTHOR]

Introduction: No evidence has established a direct causal relationship between early microcirculation disturbance after aneurysmal subarachnoid hemorrhage (aSAH) and neurological function prognosis, which is the key pathophysiological mechanism of early brain injury (EBI) in patients with aSAH. Methods: A total of 252 patients with aSAH were enrolled in the Neurosurgical Intensive Care Unit of Southwest Hospital between January 2020 and December 2022 and divided into the no neurological deterioration, early neurological deterioration, and delayed neurological deterioration groups. Indicators of microcirculation disorders in EBI included regional cerebral oxygen saturation (rSO2) measured by near-infrared spectroscopy (NIRS), brain oxygen monitoring, and other clinical parameters for evaluating neurological function and determining the prognosis of patients with aSAH. Results: Our data suggest that the rSO2 is generally lower in patients who develop neurological deterioration than in those who do not and that there is at least one time point in the population of patients who develop neurological deterioration where left and right cerebral hemisphere differences can be significantly monitored by NIRS. An unordered multiple-classification logistic regression model was constructed, and the results revealed that multiple factors were effective predictors of early neurological deterioration: reoperation, history of brain surgery, World Federation of Neurosurgical Societies (WFNS) grade 4–5, Fisher grade 3–4, SAFIRE grade 3–5, abnormal serum sodium and potassium levels, and reduced rSO2 during the perioperative period. However, for delayed neurological deterioration in patients with aSAH, only a history of brain surgery and perioperative RBC count were predictive indicators. Conclusions: The rSO2 concentration in patients with neurological deterioration is generally lower than that in patients without neurological deterioration, and at least one time point in the population with neurological deterioration can be significantly monitored via NIRS. However, further studies are needed to determine the role of microcirculation and other predictive factors in the neurocritical management of EBI after aSAH, as these factors can reduce the incidence of adverse outcomes and mortality during hospitalization. [ABSTRACT FROM AUTHOR]

Introduction: The case fatality rate among patients with aneurysmal subarachnoid hemorrhage (aSAH) has decreased progressively, with numerous patients subjected to contemporary paradigms that minimize the use of agonizing therapeutic processes. The concept of the "Textbook Outcome" (TO), a composite outcome that highlights numerous favorable outcomes, was developed in the context of gastrointestinal tumor surgeries and expeditiously extended across diverse surgical spheres. The aim of this study was to explore the factors hindering the achievement of optimal prognoses in postinterventional aSAH patients, employ textbook outcomes, and establish predictive models. Methods: We conducted a retrospective review of data from 1270 aSAH patients who received endovascular treatment between 2012 and 2018. We delineated an exemplary TO within the aSAH domain, characterized by favorable clinical results, minimal complications, and the absence of retreatments. This TO-oriented approach is explained within the manuscript. Results: The findings revealed that preoperative intraventricular hemorrhage (IVH), preoperative Hunt and Hess grade (H&H) ≥ 3, World Federation of Neurosurgical Societies (WFNS) grade ≥ 3, the presence of blebs on the aneurysm, aneurysms situated at branching sites, and non-stent-assisted endovascular intervention were the strongest risk factors for not achieving textbook outcomes (non-"Textbook Outcome" [N-TO]). Decision curve analysis and calibration analyses revealed strong concordance between the predictions of the N-TO nomogram model and the actual observations. Conclusions: Treatment Outcomes hold significant practical value in clinical studies of aSAH patients receiving endovascular treatment. The likelihood of N-TOs was predicted by IVH, H&H grade ≥ 3, WFNS grade ≥ 2, presence o f bleb on the aneurysm, and aneurysms located at branching sites. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to explore whether preoperative hemoglobin levels could serve as a prospective biomarker for early brain injury in patients with aneurysmal subarachnoid hemorrhage (aSAH). This investigation seeks to discern its association with postoperative complications and unfavorable clinical outcomes. Methods: We conducted a comprehensive analysis of data derived from the LongTeam registry, including patients with aSAH diagnosed between January 2015 and September 2021. These patients were stratified into three distinct groups based on their hemoglobin levels: anemic, standard, and elevated HGB. We employed logistic models featuring spline transformations to assess the relationship between HGB levels and in‐hospital complications. Furthermore, a multivariate Cox proportional hazard model was employed to estimate the impact of elevated hemoglobin levels on the hazard function, which was elucidated through Kaplan–Meier curves. Results: Our study comprised a total of 988 patients, among whom 115 (11.6%) presented preoperative anemia, and 63 (6.4%) exhibited elevated preoperative HGB levels. Following adjustments for potential confounding factors, no significant disparity in risk was evident between anemic patients and those with standard HGB levels. However, individuals with elevated HGB levels displayed a heightened incidence and an increased risk of developing deep vein thrombosis (DVT, odds ratio [OR] = 2.39, 95% confidence interval [CI] = 1.16–4.91, p = 0.018; hazard ratio [HR] = 2.05, 95% CI 1.08–3.92, p = 0.015). Aberrant HGB concentrations did not demonstrate an association with other clinical outcomes. Conclusion: Our findings emphasize that abnormal HGB levels show no association with adverse outcomes at the 90 days mark after accounting for clinical confounding factors in patients with aSAH. Simultaneously, the study illuminates the potential of HGB as an early indicator for identifying patients at a heightened risk of developing DVT. [ABSTRACT FROM AUTHOR]