Cerebral Vasospasm Research Articles

Vasospasm in Pediatric Subarachnoid Hemorrhage.

Cerebral vasospasm (CV) is a common severe complication of subarachnoid hemorrhage (SAH), a severe type of intracranial bleeding that is uncommon in children. The purpose of this article is to review the current literature regarding this potentially devastating complication. CV may be asymptomatic and is less common in children compared to adults. Several molecular phenomena, including inflammatory ones, contribute to its pathophysiology. Better collateral circulation and higher cerebral blood flow are protective factors in children. When clinically apparent, CV may manifest as a change in the child's neurologic status or vital signs. CV can be diagnosed using brain vessel imaging, such as computed tomography angiography, magnetic resonance angiography, digital subtraction angiography, transcranial Doppler ultrasonography, and computed tomography perfusion. A reduction of < 50% in the artery's caliber confirms the diagnosis. Besides general supportive measures and causative treatment of SAH, CV management options include the administration of calcium channel blockers and neurointerventional approaches, such as intra-arterial vasodilators and balloon angioplasty. Long-term outcomes in children are usually favorable.

The Landscape of Randomized Clinical Trial Meta-analyses on Statins for Aneurysmal Subarachnoid Hemorrhage: A Scoping Review.

Aneurysmal subarachnoid hemorrhage (aSAH) is a type of non-traumatic SAH that can have detrimental effects on the central nervous system, resulting in severe disability or death. Early nimodipine is currently the only strongly recommended pharmacological treatment that has shown efficacy in improving neurological/functional outcomes in aSAH patients. Whether statin treatment is of benefit to aSAH patients is an issue that has generated considerable interest and debate. In the present scoping review, we mapped and analyzed the available literature on metaanalyses of randomized clinical trials (RCTs) examining the effect of statins on aSAH. Seventeen meta-analyses of RCTs, published between 2008 and 2023, were identified. Treatments in included meta-analyses were based on various regimens of simvastatin, pravastatin, pitavastatin or atorvastatin for up to 21 days. Eleven of the included reports indicated some beneficial effect of statin treatment, reducing rates of at least one of the following: cerebral vasospasm, delayed cerebral ischemia/delayed ischemic neurologic deficit, mortality or functional/ neurological outcome. In contrast, six meta-analyses, showed no such effects. The limitations reported by several meta-analyses, included low patient numbers or disproportionate representation of patients from certain RCTs, differences in drug treatment, patient diagnostic criteria and outcome evaluation between RCTs, as well as poor data quality or lack of RCTs data. Knowledge of the reported limitations may aid the design of future clinical trials and/or their meta-analyses.

Vasospasm management: a meta-synthesis of current modalities used by different medical societies

Background: Cerebral vasospasm is a life-threatening complication of an aneurysmal subarachnoid hemorrhage (aSAH), with approximately 6 to 10 cases per 100,000 patients yearly. Despite the publication of numerous guidelines from various medical societies, there is a lack of standardized consensus on what the optimal management strategies for this severe complication truly are. This meta-synthesis aims to synthesize these endorsed recommendations to ultimately identify standardized care guidelines and improve patient outcomes after aSAH. Methods: A comprehensive database search of existing guidelines published by major medical societies in the past 10 years was performed. Results: The analysis included 28 relevant documents from 7 major medical societies. Key findings included: 1) Unanimous endorsement for oral nimodipine administration for 21 days post-aSAH. 2) Varying recommendations for alternative calcium channel blockers and hemodynamic management methods. 3) Targeted hypermagnesemia and routine statin therapy were not universally recommended due to insufficient evidence. 4) Use of antifibrinolytics was considered on a case-by-case basis. 5) Endovascular interventions were recommended for refractory cases, specifically. Conclusion: This meta-synthesis reveals consistencies and divergences in vasospasm management recommendations across medical societies, highlighting the need for more robust clinical trials, regular guideline updates, and increased medical society collaboration. Keywords: Vasospasm, cerebral vasospasm, aSAH, management, guidelines, meta-synthesis

Clinical Development of the GluN2B-selective NMDA Receptor Inhibitor NP10679 for the Treatment of Neurologic Deficit after Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) may be associated with cerebral vasospasm, which can lead to delayed cerebral ischemia, infarction, and worsened functional outcomes. The delayed nature of cerebral ischemia secondary to SAH-related vasculopathy presents a window of opportunity for the evaluation of well-tolerated neuroprotective agents administered soon after ictus. Secondary ischemic injury in SAH is associated with increased extracellular glutamate, which can overactivate NMDA receptors (NMDARs), thereby triggering NMDAR-mediated cellular damage. In this study, we have evaluated the effect of the pH-sensitive GluN2B-selective NMDAR inhibitor, NP10679, on neurologic impairment after SAH. This compound demonstrates a selective increase in potency at the acidic extracellular pH levels that occur in the setting of ischemia. We found that NP10679 produced durable improvement of behavioral deficits in a well-characterized murine model of SAH, and these effects were greater than those produced by nimodipine alone, the current standard of care. In addition, we observed an unexpected reduction in SAH-induced luminal narrowing of the middle cerebral artery. Neither nimodipine nor NP10679 alter each other's pharmacokinetic profile, suggesting no obvious drug-drug interactions. Based on allometric scaling of both toxicological and efficacy data, the therapeutic margin in man should be at least 2. These results further demonstrate the utility of pH-dependent neuroprotective agents and GluN2B-selective NMDAR inhibitors as potential therapeutic strategies for the treatment of aSAH. Significance Statement This report describes the properties and utility of the GluN2B-selective pH-sensitive NMDA receptor inhibitor, NP10679, in a well-characterized rodent model of subarachnoid hemorrhage. We show that the administration of NP10679 improves long-term neurological function following subarachnoid hemorrhage, and that in rats there are no drug-drug interactions between NP10679 and nimodipine, the standard of care for this indication.

Early mobilization in patients with aneurysmal subarachnoid haemorrhage may im-prove functional status and reduce cerebral vasospasm rate: a systematic review with meta-analysis.

The primary aim of this study was to evaluate the safety and efficacy of early mobilization in patients with aneurysmal subarachnoid haemorrhage. Systematic review with meta-analysis of randomized controlled studies and observational studies. Patients with aneurysmal subarachnoid haemorrhage. PubMed, Embase, CINAHL, Web of Science, Pedro, and the Cochrane Library databases were searched. A systematic review and meta-analysis were performed. Screening and data extraction were performed by 2 independent reviewers. Sixteen studies involving 1,757 patients were included. Meta-analysis of the data estimated that early mobilization improved mRS score at discharge (mean difference -1.39, 95% CI -2.51 to -0.28, I2 = 86%) and at 3 months (mean difference -1.10, 95% CI -1.54 to -0.66, I2 = 7%). Early mobilization was associated with a reduction in cerebral vasospasm rate, both radiological (OR 0.66, 95% CI 0.45 to 0.96, I2 = 7%) and clinical (OR 0.44, 95% CI 0.27 to 0.72, I2 = 8%); 6% of mobilization sessions involved adverse events, mostly haemodynamic changes. This review found moderate-quality evidence supporting the safety and effectiveness of early mobilization in patients with SAH. Further randomized controlled trials are needed to identify the appropriate mobilization strategy and confirm these results.

Treatment of Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage Using the Compliant Manually Adjustable Mesh Comaneci.

Background and purpose: Cerebral vasospasm (CV) following aneurysmal subarachnoid hemorrhage (aSAH) may lead to morbidity and mortality. Endovascular mechanical angioplasty may be performed if symptomatic CV is refractory to noninvasive medical management. Compliant and noncompliant balloons and manually adjustable mesh may be used in this indication. We describe our initial experience with the Comaneci (Rapid Medical, Yokneam, Israel) in cerebral vasospasm treatment following aSAH. Methods: All patients included in the prospective observational SAVEBRAIN PWI (NCT05276934 on clinicaltrial.gov) study who underwent cerebral angioplasty using the Comaneci device for the treatment of medically refractory and symptomatic CV after aSAH were identified. Patient demographic information, procedural details, and outcomes were obtained from electronic medical records. Results: Between February 2022 and June 2023, seven consecutive patients underwent CV treatment with the Comaneci. Angioplasty of 37 arterial segments (supraclinoid internal carotid artery, A1, A2, and A3 segments of the anterior cerebral artery and M1 and M2 segments of the middle cerebral artery) was attempted, and 35/37 (95%) were performed. The vessel diameter improved significantly following angioplasty (+64%), while brain hypoperfusion decreased (-45% of the mean T Max). There was no long-term clinical complication, and 6% per-procedural complications occurred. Conclusions: The Comaneci is effective in the treatment of cerebral vasospasm following aSAH, bringing a new device in the armamentarium of the neurointerventionalist to perform intracranial angioplasty.

Trends in blood pressure: following subarachnoid haemorrhage and preceding cerebral vasospasm

Background Trends in Blood Pressure (BP) following Subarachnoid Haemorrhage (SAH) have been reported in literature since 1982. Recent studies suggest a correlation to the incidence of Cerebral Vasospasm. This renders BP a candidate for possible early detection of Vasospasm. However, conflicting results regarding the nature and numerical of this correlation exist. Objectives To determine trends in BP following SAH in terms of Systolic (SBP), Diastolic (DBP) and Mean Arterial Pressure (MAP) and collaborate current literature evidence of their association to Cerebral Vasospasm. Methods Two databases (EBSCO Medline and PubMed) systematically reviewed using specified search criteria. Thirteen studies were portrayed, of which ten were accessible. Thorough critical appraisal of each paper was then manually performed using the CASP Cohort study checklist. Results A consistent pattern of change is seen through time in majority of studies with differences in the definite values of the BP variables. Collation of results showed a gradual rise in SBP followed by a plateau of 154.08 (±10.79) mmHg on days 4-8 post-SAH. Variations exist with regards to the association with Cerebral Vasospasm: a third of the studies depicted a significant steeper rise in SBP in Vasospasm patients, another third conversely reported sudden drops in SBP, and one study concluded that MAP has no significant relation to Vasospasm. Conclusion A biphasic trend is expected following SAH with an initial gradual rise followed by a sustained hypertensive plateau. Considerable conflict exists in the nature of association between BP and Vasospasm. Further analysis of such beneficial predictive potential is recommended for advancement in Vasospasm and Neuro-Cardiogenic care.

Intrathecal Nicardipine as Treatment for Severe Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Retrospective Clinical Study

Intrathecal Nicardipine as Treatment for Severe Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Retrospective Clinical Study

Comment on: Artificial-Intelligent Prediction Model of Occurrence of Cerebral Vasospasms Based on Machine-Learning.

Comment on: Artificial-Intelligent Prediction Model of Occurrence of Cerebral Vasospasms Based on Machine-Learning.

The value of IL-6 in cerebrospinal fluid for determining the development of cerebral vasospasm after subarachnoid hemorrhage

An inflammatory response following aneurysmal SubArachnoid Hemorrhage (aSAH) plays a significant role in the development of cerebral vasospasm. This study analyzes the correlation between the level of InterLeukin-6 (IL-6) in CerebroSpinal Fluid (CSF) after aSAH and the occurrence of cerebral vasospasm. We analyzed clinical manifestations, laboratory data, and instrumental examination methods in 45 patients who were treated for intracranial aSAH within 21 days, studying the relationship between the development of cerebral angiospasm and the concentration of the inflammatory factor. We found the potential significance of IL-6 in predicting vasospasm, confirmed by cerebral angiography. As a control, we analyzed the CSF samples of 15 patients treated for unruptured cerebral aneurysms. According to the study results, vasospasm developed in 44% of patients, on average on the 6th day from the onset of the disease. Patients with aSAH demonstrated statistically significant (p&lt;0.05) higher mean IL-6 values in CSF on the 3rd, 7th, and 10th days compared to the control group. Patients with vasospasm showed statistically significant (p&lt;0.05) higher mean IL-6 values in CSF on the 3rd day, while the differences on the 7th and 10th days (p&lt;0.05) were not statistically significant. The threshold value for predicting the formation of cerebral vasospasm was determined to be 325 pg/ml on the 3rd day from the onset of the disease. We concluded that IL-6 in cerebrospinal fluid is a potential early marker for predicting vascular spasm after subarachnoid hemorrhage on the 3rd day of the disease, before the onset of clinical manifestations. We concluded that monitoring the value of IL-6 in the cerebrospinal fluid on the third day after aneurysm rupture is potentially significant for the early diagnosis of vasospasm. Keywords: intracranial aneurysm, vasospasm, stroke, cytokines.

MiRNA expression profiling reveals a potential role of microRNA-148b-3p in cerebral vasospasm in subarachnoid hemorrhage

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.

The urotensin II receptor triggers an early meningeal response and a delayed macrophage-dependent vasospasm after subarachnoid hemorrhage in male mice

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.

Quantitative analysis of HSV‑1 shedding as a predictor of cerebral vasospasm severity in patients with subarachnoid hemorrhage.

Cerebral vasospasm (CV) is a critical determinant of outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). Despite advances in neurocritical care, modifiable risk factors for CV remain poorly understood, and identifying them could significantly enhance patient management and treatment strategies. The present study explored the potential link between the reactivation of herpes simplex virus type 1 (HSV-1), a common resident virus in cranial nerves, and CV severity. It was hypothesized that higher HSV-1 viral load in saliva may be associated with increased CV severity. Saliva samples were collected on days 4, 7, 10 and 14 post-aSAH, and HSV-1 DNA levels were measured using quantitative PCR. CV severity was assessed using the Lindegaard ratio (LR), with an LR >3 considered the diagnostic threshold for CV. A total of 36 patients were enrolled, and 139 saliva samples were collected. HSV-1 DNA was detected in 19.4% of samples (27/139), and 44% of patients (16/36) developed CV. HSV-1 seropositive patients made up 88.9% (32/36) of the cohort, with 50% exhibiting viral shedding during the study period. None of the HSV-1 seronegative patients (11.1%, 4/36) exhibited viral shedding or developed CV. Regression analysis showed a positive association between HSV-1 viral load and CV severity, with viral load explaining 27.8% of the variability (P=0.005). Age was also significant, with older patients experiencing less severe CV (P<0.001). Supervised machine learning identified viral load thresholds that aligned with standard LR values for moderate and severe CV. While the small sample size and observational design limit the generalizability of the results, these findings suggested that earlier detection and intervention for CV could be informed by assessing HSV-1 serostatus and monitoring viral activity through saliva samples or other non-invasive methods, highlighting the need for larger, controlled studies to validate these results.

Symptomatic cerebral vasospasm after posterior fossa surgery in pediatric patients: single-center study and systematic literature review.

The most common cause of cerebral vasospasm is subarachnoid hemorrhage, less frequently it occurs after trauma, infection, and tumor resection. Vasospasm in children is rare and has not been systematically investigated in posterior fossa surgery. The authors undertook a single-center retrospective study of all the pediatric patients who underwent surgery on the posterior fossa and presented with postoperative symptomatic vasospasm in the period from January 2018 to February 2024. Subsequently, a systematic literature review in accordance with the PRISMA guidelines was performed in the PubMed and Scopus databases to identify the published papers on symptomatic vasospasm after posterior fossa surgery in children. Of the 178 patients who underwent surgery on the posterior fossa, only one patient was diagnosed with symptomatic diffuse vasospasm on postoperative day 21. The systematic literature review provided further 9 children. The underlying pathology comprised 8 intra-axial lesions with 4 medulloblastomas, 1 schwannoma in the medulla oblongata, 1 pilocytic astrocytoma, 1 primitive neuroectodermal tumor, and 1 arteriovenous malformation. The extra-axial lesions were 1 hypoglossal schwannoma and 1 oculomotor nerve schwannoma. Iatrogenic symptomatic vasospasm after posterior fossa surgery in children is a rare complication with an outcome ranging from complete recovery to the death of the patient. It is important for all staff involved in the care of patients undergoing surgery on the posterior fossa to be aware of this rare postoperative complication. The small number of patients affected does not allow a substantiated conclusion to be drawn about predictive risk factors.

Results of assessing cerebral vasospasm following subarachnoid hemorrhage using transcranial doppler ultrasound

SUMMARY Objective: Review the results of assessing cerebral vasospasm after subarachnoid hemorrhage using transcranial doppler ultrasound. Subjects and methods: A retrospective, cross-sectional descriptive study was performed on 39 patients with subarachnoid hemorrhage treated at the Neurology Center, Bach Mai Hospital from January 2020 to September 2023. Results: The mean age of the study group was 55.12 ± 14.33. The age group distribution with the highest incidence is 41-50 years old with a rate of 35.9%. The male/female ratio is 20/19. The most common symptoms were headache (97.4%), nausea and vomiting (92.3%), The least common symptoms were convulsions and hemiplegia in 5.1% of subjects. The most common clinical severity assessed by the Hunt and Hess scale is level 2 (59%), followed by level 3 (23.1%), level 4 (10.2%), and level 1 (5.1%). Evaluation of Fisher scale found that the most common fisher level is level 4 with a rate of 33.6%, followed by level 3 (28.2%), level 1 (25.6%), the least common is grade 2 with 2.6%. The results of the second transcranial Doppler ultrasound performed on the sixth to eighth day of the disease is the time with the highest rate of vasospasm, showing the most vasospasm cerebral artery is the middle cerebral artery: right middle cerebral artery. 35.9%, left middle cerebral artery 12.8%. Next is anterior cerebral artery spasm: right anterior cerebral artery 23.1%, left anterior cerebral artery 2.6%. Right posterior cerebral artery 10.3%, left posterior cerebral artery 5.1%. Compared to the gold standard for diagnosing vasospasm, which is 128-slices MSCT, transcranial Doppler ultrasound has a sensitivity of 0.91, a specificity of 0.88, a positive predictive value of 0.91, and a negative predictive value of 0.88. The appropriateness of transcranial Doppler ultrasound and 128-slices computed tomography scan in diagnosing cerebral vasospasm after subarachnoid hemorrhage is very high, Kappa coefficient = 0.791, statistically significant with p &lt; 0.05. Conclusion: Clinical symptoms of the disease are very diverse and non-specific, the most common symptom being headache is 97.4%. The most common Hunt and Hess scale to assess clinical severity is 2, however the most common Fisher scale is 4. Middle cerebral artery thrombosis has the highest rate of spasm, followed by the anterior cerebral artery. Compared to the gold standard for diagnosing vasospasm, which is 128-slices MSCT, transcranial Doppler ultrasound has a sensitivity of 0.91, a specificity of 0.88, a positive predictive value of 0.91, and a negative predictive value of 0.88

Bacterial Meningitis Following Aneurysmal Subarachnoid Hemorrhage and Its Association with Cerebral Vasospasm.

Aneurysmal subarachnoid hemorrhage (aSAH) is a critical condition with high in-hospital mortality rates. Delayed cerebral ischemia (DCI), a secondary complication associated with aSAH, can also contribute to morbidity and mortality. Although draining the hematoma from the subarachnoid space has been considered effective in preventing DCI, the placement of a drainage system could increase the risk of bacterial meningitis and ventriculitis. This study aimed to examine the association between meningitis following aSAH and the occurrence of DCI, focusing on the role of cerebral vasospasm. Patients who underwent endovascular coiling or surgical clipping for aSAH from April 2001 to March 2022 were included in this study, while those who did not undergo postoperative drainage were excluded. The patient's clinical characteristics, treatment modalities, and outcomes were then analyzed, after which logistic regression was used to assess the odds ratios (OR) for DCI. A total of 810 patients with aSAH were included in this study. Meningitis following aSAH was identified as an independent factor associated with DCI (odds ratio 5.0 [95% confidence intervals (CI) 2.3-11]). Other significant factors were female sex (odds ratio 1.5 [95% CI 0.89-2.5]) and surgical clipping (odds ratio 2.1 [95% CI 1.3-3.4]). This study demonstrated a significant association between meningitis following aSAH and the development of DCI, suggesting that the inflammatory environment associated with meningitis may contribute to cerebral vasospasm. Early recognition and treatment of meningitis in patients with aSAH could reduce the risk of DCI and improve patient outcomes.

Systemic C-Reactive Protein Predicts Cerebral Vasospasm and Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: A Retrospective Observational Study

Aneurysmal subarachnoid hemorrhage (aSAH) is often complicated by cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI), which significantly impact patient outcomes. The study aimed to investigate the predictive value of systemic serum biomarker levels for CVS and DCI following aSAH. We retrospectively analyzed data for 450 aSAH patients admitted to University Hospital Düsseldorf between January 2011 and October 2021. Serum biomarkers were measured on admission. The occurrence of CVS and DCI was assessed based on clinical and radiological criteria. Multivariate logistic regression analysis was performed to determine the independent association of serum biomarkers with CVS and DCI. We compared the predictive values of various models using the area under the receiver operating characteristic curve. Of the 450 patients, 126 (28.0%) developed CVS, 123 (27.3%) developed DCI, and 62 (13.8%) developed co-occurring CVS and DCI. Patients with CVS, DCI, or both had significantly higher admission C-reactive protein (CRP) levels than those without these complications (P<0.001). Elevated CRP levels were independently associated with an increased risk of CVS, DCI, and co-occurring CVS and DCI (P<0.05). CRP demonstrated a higher predictive value for CVS (area under the curve [AUC]: 0.811) and co-occurring CVS and DCI (AUC: 0.802) compared to DCI alone (AUC: 0.690). Our findings suggest that admission systemic CRP levels can serve as a more valuable predictor for developing CVS than DCI following aSAH. Incorporating CRP into clinical assessments may aid in risk stratification and early intervention strategies for patients at high risk of these complications.

The Predictive Value of PKC and ET-1 Levels in Cerebrospinal Fluid for Vasospasm and Prognosis in Patients with Aneurysmal Subarachnoid Hemorrhage.

To analyze the predictive value of protein kinase C (PKC) and endothelin-1 (ET-1) in cerebrospinal fluid for vasospasm and prognosis in patients with aneurysmal subarachnoid hemorrhage (ASH). One hundred and forty-eight ASH patients hospitalized in our hospital during February 2019 to February 2022 were optioned as observation subjects. These subjects were graded into good prognosis group (mRS score 0-2, n = 102) and poor prognosis group (mRS score 3-6, n = 46) according to the Rankin Revised Scale Score (mRS) after 6 months of follow-up. Cerebrospinal fluid was collected from patients to detect the content of ET-1 and PKC. The prognostic factors were analyzed using multifactorial logistic regression. The predictive value was assessed using receiver operating characteristic (ROC) curve. The patients with poor prognosis had a higher age level and a higher proportion of ≥2 aneurysms, aneurysm diameter ≥6 mm, cerebral vasospasm, and Hunt-Hess grade ≥III than those with good prognosis (P < 0.05). The patients with poor prognosis had higher content of PKC and ET-1 than those with good prognosis (P < 0.05). Age, aneurysm diameter ≥6 mm, cerebral vasospasm, Hunt-Hess classification ≥grade III, PKC and ET-1 were all risk factors related to the prognosis of ASH (P < 0.05). The area under the curve (AUC) of PKC and ET-1 for diagnosing poor prognosis of ASH was 0.803 and 0.720, respectively. The AUC of the combined detection was 0.873 (P < 0.05). Patients with cerebrovascular spasm had higher content of PKC and ET-1 than those without (P < 0.05). The AUC of PKC and ET-1 for diagnosing cerebral vasospasm in ASH was 0.891 and 0.816, respectively, which was 0.932 for combined detection (P < 0.05). The combination of PKC and ET-1 in cerebrospinal fluid had certain value in predicting the poor prognosis of patients with ASH.

Statistical Optimization and Characterization of Nimodipine Transferosomes

Background: Nimodipine is a vasodilator that is used for the prevention of cerebral vasospasm after subarachnoid hemorrhage. The oral and intravenous administration of the drug is associated with undesirable side effects. So, transdermal delivery using lipid-based nanovesicles, also known as transferosomes, can be thought of as an alternative. Objective: To optimize the formulation of transferosomes using the statistical design of experiments, with the aim of obtaining the most suitable transferosomes for the transdermal delivery of nimodipine. Methods: In the Box-Behenken statistical design, the independent variables were the quantities of nimodipine, phospholipon 90%, and sodium deoxycholate, while the dependent variables were the vesicle size, entrapment efficiency for nimodipine and its flux through the rat's skin. The optimized formulation was characterized through transmission electron microscopy and the deformability index. Results: The optimized formulation of transferosomes suggested by the software consisted of 30 mg nimodipine, 150 mg phospholipon 90% and 15 mg sodium deoxycholate. The resulted values were 248 nm for vesicles size, 81% for entrapment, and 476 μg/cm2/h. Under transmission electron microscopy, transferosomes appeared as vesicles, with a 0.98 deformability index for the optimized formula. Conclusions: Nimodipine can be formulated as transferosomes and efficiently applied for transdermal delivery.

Endovascular Treatment of Delayed Cerebral Vasospasms

Delayed cerebral vasospasm is a major complication following subarachnoid hemorrhage and a primary cause of delayed cerebral ischemia. While various preventive treatments exist, some patients still develop severe vasospasm, highlighting the need for better rescue therapies. This article explores endovascular treatment as a rescue option for vasospasm, focusing on the clinical characteristics and roles of intra-arterial vasodilator injection therapy and percutaneous transluminal angioplasty(PTA). Despite a lack of strong evidence from large clinical trials, advancements in endovascular technology have positioned both intra-arterial vasodilator injection therapy and PTA as promising and safe rescue options for severe vasospasm. Careful selection of the appropriate approach is crucial for achieving optimal clinical outcomes, considering the unique characteristics, advantages, and limitations of each method. Further clinical trials are necessary to definitively confirm this hypothesis.