Increased brain volume in the early phase of aneurysmal subarachnoid hemorrhage leads to delayed cerebral ischemia.

Objective: To investigate the correlation between the swelling rate of brain volume within the first 48 h after aneurysmal subarachnoid hemorrhage and the subsequent development of delayed cerebral ischemia. Methods: A retrospective analysis was conducted on patients with spontaneous aneurysmal subarachnoid hemorrhage admitted to the Neurosurgery Intensive Care Unit of the First Affiliated Hospital of Chongqing Medical University between January 2020 and January 2023. The clinical data, treatment outcomes, and imaging data were analyzed. Brain volume was evaluated using 3D-Slicer software at two time points post-hemorrhage: within the first 24 h and between 24 and 48 h. The swelling rate of brain volume was defined as the ratio of the absolute difference between two measurements to the smaller of values. Patients were categorized into two groups based on established diagnostic criteria of delayed cerebral ischemia. Univariate and multivariate logistic regression analyses were performed to identify factors influencing delayed cerebral ischemia. Results: A total of 140 patients were enrolled in this study. 46 patients experienced delayed cerebral ischemia after bleeding. The swelling rate of brain volume was larger in the DCI group (10.66 ± 8.45) compared to the non-DCI group (3.59 ± 2.62), which showed a statistically significant difference. Additionally, advanced age, smoking history, history of hypertension, loss of consciousness, poor Hunt-Hess grade, high mFisher score, brain volume within 24 h, and IVH were also statistically different between the two groups. Multivariate logistic regression analysis revealed that the swelling rate of brain volume was an independent risk factor for DCI with adjusting the advanced age, smoking history, history of hypertension, poor Hunt-Hess grade, high mFisher score, brain volume within 24 h, and IVH. Conclusion: Brain volume significantly increased in patients with aneurysmal subarachnoid hemorrhage during the early phase (within 48 h post-onset). The larger swelling rate of brain volume is an independent risk factor for the development of delayed cerebral ischemia, and it may hold significant predictive value for the incidence of delayed cerebral ischemia.

The Potential Therapeutic Effects of Tadalafil on the Endothelium in a Subarachnoid Hemorrhage Animal Model: Insights from Immunohistochemical Staining.

This study investigated the potential of phosphodiesterase type 5 (PDE-5) inhibitors, specifically tadalafil, in preventing the delayed cerebral ischemia (DCI) post-rupture of cerebral aneurysms. A total of 19 rabbits were used in this study, divided into different treatment groups, including nimodipine alone, tadalafil alone, and a combination of nimodipine and tadalafil. Both nimodipine and tadalafil showed some impact on reducing endothelial apoptosis in the basilar arteries, although the effects were not statistically significant. Notably, the nimodipine group exhibited significantly lower levels of Bax in the small arterioles compared to the SAH group. These findings suggest that while tadalafil may not directly prevent endothelial cell death like nimodipine, its neuroprotective properties hint at its potential utility in DCI treatment. Further research involving a broader range of apoptosis-related proteins is recommended to enhance our understanding in this area.

Value of Glycemic Indices for Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Retrospective Single-Center Study.

Delayed cerebral ischemia (DCI) is a severe complication following aneurysmal subarachnoid hemorrhage (aSAH), linked to poor functional outcomes and prolonged intensive care unit (ICU) stays. Timely DCI diagnosis is crucial but remains challenging. Dysregulated blood glucose, commonly observed after aSAH, may impair the constant glucose supply that is vital for brain function, potentially contributing to DCI. This study aimed to assess whether glucose indices could help identify at-risk patients and improve DCI detection. This retrospective, single-center observational study examined 151 aSAH patients between 2016 and 2019. Additionally, 70 of these (46.4%) developed DCI and 81 did not (no-DCI). To determine the value of glycemic indices for DCI, they were analyzed separately in patients in the period before (pre-DCI) and after DCI (post-DCI). The time-weighted average glucose (TWAG, p = 0.024), mean blood glucose (p = 0.033), and novel time-unified dysglycemic rate (TUDR140, calculated as the ratio of dysglycemic to total periods within a glucose target range of 70-140 mg/dL, p = 0.042), showed significantly higher values in the pre-DCI period of the DCI group than in the no-DCI group. In the time-series analysis, significant increases in TWAG and TUDR140 were observed at the DCI onset. In conclusion, DCI patients showed elevated blood glucose levels before and a further increase at the DCI onset. Prospective studies are needed to confirm these findings, as this retrospective, single-center study cannot completely exclude confounders and limitations. In the future blood glucose indices might become valuable parameters in multiparametric models to identify patients at risk and detect DCI onset earlier.

Comment on, "Differential DNA methylation associated with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: a systematic review".

The article "Differential DNA Methylation Associated with Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Systematic Review" by Tomasz Klepinowski et al. offers an in-depth analysis of the relationship between DNA methylation and delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). By systematically reviewing databases like PubMed, MEDLINE, Scopus, and Web of Science, the authors identify key genes, including ITPR3, HAMP, INSR, and CDHR5, as potential biomarkers for early DCI diagnosis. Their meticulous adherence to PRISMA guidelines and the STROBE statement for quality assessment enhances the study's credibility. However, the review could be improved by discussing methodological variability, statistical power, and the functional relevance of identified CpG sites. Additional sections on mechanistic pathways, integration with other omics data, clinical translation, and ethical considerations would further strengthen the review, providing a more comprehensive understanding of epigenetic factors in DCI and paving the way for future therapeutic interventions.

Risk factors for the development of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a common neurosurgical disorder with high morbidity and poor prognosis, and the associated delayed cerebral ischemia (DCI) is a key factor contributing to poor prognosis. Despite extensive research on the risk factors associated with DCI development, the evidence remains conflicting. Therefore, this meta-analysis of case-control studies aimed to investigate the risk factors for DCI occurrence during hospitalization in patients with aSAH. METHODS: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials for eligible studies published before November 20, 2023. Two independent reviewers extracted relevant data from the included studies using a pre-established data extraction form. The primary outcome was DCI occurrence during hospitalization in patients with aSAH. RESULTS: A total of 42 studies involving 21,726 patients with aSAH were included. The pooled meta-analysis showed that female sex; Hunt-Hess, modified Fisher, and World Federation of Neurosurgical Societies (WFNS) scale scores of 4-5, 3-4, and 4-5, respectively; vasospasm; combined intraventricular hemorrhage (IVH); pre-existing hypertension; hydrocephalus; intracranial infections (ICI); and high white blood cell (WBC) count on admission were independent risk factors for the development of postoperative DCIs in patients with aSAH. CONCLUSIONS: Patients with aSAH who have a Hunt-Hess scale score ≥4, a modified Fisher scale score ≥3, a WFNS scale score ≥4, IVH, pre-existing hypertension, cerebral vasospasm, a high WBC count on admission, ICI, and female sex are at high risk of DCI and hence should be carefully monitored in the intensive care unit.

Subarachnoid hemorrhage-associated brain injury and neurobehavioral deficits are reversed with synthetic adropin treatment through sustained Ser1179 phosphorylation of endothelial nitric oxide synthase.

Background: Subarachnoid hemorrhage (SAH) is a life-threatening vascular condition without satisfactory treatment options. The secreted peptide adropin is highly expressed in the human brain and has neuroprotective effects in brain injury models, including actions involving the cerebrovasculature. Here, we report an endothelial nitric oxide synthase (eNOS)-dependent effect of synthetic adropin treatment that reverses the deleterious effects of SAH. Methods: We tested the molecular, cellular, and physiological responses of cultured brain microvascular endothelial cells and two mouse models of SAH to treatment using synthetic adropin peptide or vehicle. Results: SAH decreases adropin expression in cultured brain microvascular endothelial cells and in murine brain tissue. In two validated mouse SAH models, synthetic adropin reduced cerebral edema, preserved tight junction protein expression, and abolished microthrombosis at 1 day post-SAH. Adropin treatment also prevented delayed cerebral vasospasm, decreased neuronal apoptosis, and reduced sensorimotor deficits at seven days post-SAH. Delaying initial treatment of adropin until 24 h post-SAH preserved the beneficial effect of adropin in preventing vasospasm and sensorimotor deficits. Mechanistically, adropin treatment increased eNOS phosphorylation (Ser1179) at 1 & 7 days post-SAH. Treating eNOS-/- mice with adropin failed to prevent vasospasm or behavioral deficits, indicating a requirement of eNOS signaling. Conclusions: Adropin is an effective treatment for SAH, reducing cerebrovascular injury in both the acute (1 day) and delayed (7 days) phases. These findings establish the potential of adropin or adropin mimetics to improve outcomes following subarachnoid hemorrhage.

Perfusion imaging for delayed cerebral ischemia detection in patients following ruptured aneurysmal subarachnoid hemorrhage: Interrater reliability assessment.

BACKGROUND: Delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) is associated with adverse neurological outcomes. Early and accurate diagnosis of DCI is crucial to prevent cerebral infarction. This study aimed to assess the diagnostic accuracy and interrater agreement of the visual assessment of neuroimaging perfusion maps to detect DCI in patients suspected of vasospasm after aSAH. METHODS: In this case-control study, cases were adult aSAH patients with DCI who underwent magnetic resonance perfusion or computed tomography perfusion (CTP) imaging in the 24 h prior to digital subtraction angiography for vasospasm diagnosis. Controls were patients with dizziness and no aSAH on CTP imaging. Three independent raters, blinded to patients' clinical information, other neuroimaging studies, and angiographic results, visually assessed anonymized perfusion color maps to classify patients as either having DCI or not. Tmax delay was classified by symmetry into no delay, unilateral, or bilateral. RESULTS: Perfusion imaging of 54 patients with aSAH and 119 control patients without aSAH was assessed. Sensitivities for DCI diagnosis ranged from 0.65 to 0.78, and specificities ranged from 0.70 to 0.87, with interrater agreement ranging from 0.60 (moderate) to 0.68 (substantial). CONCLUSION: Visual assessment of perfusion color maps demonstrated moderate to substantial accuracy in diagnosing DCI in aSAH patients.

Predictors of neurological outcomes in patients with poor Glasgow Coma Scale scores 1 week after aneurysmal subarachnoid hemorrhage.

BACKGROUND: This study assessed neurological outcomes and variables associated with favorable outcomes in aSAH patients with low functional status (Glasgow Coma Scale [GCS] score ≤8) on postbleed day 7 (PBD7). METHODS: A retrospective analysis was conducted of all patients in the Barrow Ruptured Aneurysm Trial (January 1, 2014-July 31, 2019) treated for a ruptured aneurysm and who had a GCS score ≤8 on PBD7. The primary outcome was a favorable neurological outcome (modified Rankin Scale score ≤2) at last follow-up. RESULTS: Of 312 patients, 63 had low GCS scores at PBD7. These patients had a significantly greater proportion of poor Hunt and Hess scale grades (≥4) (44/63 [70%] vs 49/249 [19.7%], P < 0.001) and poor Fisher grades (grade=4) (58/63 [92%] vs 174/249 [69.9%], P < 0.001) compared to patients who did not have low GCS scores on PBD7, but no differences were found in age, sex, anterior location, aneurysm size, or type of treatment. Of the 63 patients, 7 (11%) experienced a favorable neurological outcome. On univariate analysis, none of the physical examination reflexes predicted a favorable neurological outcome. The middle cerebral artery aneurysm territory was the only significant predictor of a favorable neurological outcome by multivariate analysis (odds ratio, 10.8; 95% confidence interval, 1.16-100], P = 0.04). CONCLUSIONS: This study yielded no significant physical examination findings that predict a favorable outcome in patients with GCS score ≤8 on PBD7. This finding may inform the decision of whether to prolong hospital management or arrange for end-of-life care.

Treatment factors to suppress delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage based on VASOGRADE: multicenter cohort study.

Delayed cerebral ischemia (DCI) is one of the most important outcome determinants for aneurysmal subarachnoid hemorrhage (aSAH). VASOGRADE, which combines World Federation of Neurological Surgeons grade and modified Fisher grade, is a useful scale for predicting DCI after aSAH. However, no studies have investigated whether VASOGRADE influences the treatment options. We retrospectively analyzed 781 aSAH patients who were prospectively enrolled in 9 primary stroke centers from 2013 to 2021. The total cohort consisted of 76 patients (9.7%) with VASOGRADE-Green, 390 patients (49.9%) with VASOGRADE-Yellow, and 315 patients (40.3%) with VASOGRADE-Red. Worse VASOGRADE had higher incidences of DCI, which occurred in 190 patients (24.3%). As only 5 patients (6.6%) with VASOGRADE-Green developed DCI, we searched for DCI-associated factors in patients with VASOGRADEs-Yellow and -Red. Multivariate analyses revealed independent treatment factors suppressing DCI as follows: no postoperative hemorrhagic complication, combined administration of fasudil hydrochloride and cilostazol, combination of clipping and cisternal drainage, and coiling for VASOGRADE-Yellow; and clipping, and administration of fasudil hydrochloride with or without cilostazol for VASOGRADE-Red. The findings suggest that treatment strategies should be determined based on VASOGRADE to prevent DCI after aSAH.

Volatile Sedation in Neurointensive Care Patients After Aneurysmal Subarachnoid Hemorrhage: Effects on Delayed Cerebral Ischemia, Cerebral Vasospasm, and Functional Outcome.

BACKGROUND: Volatile anesthetics have shown neuroprotective effects in preclinical studies, but clinical data on their use after aneurysmal subarachnoid hemorrhage (aSAH) are limited. This study aimed to analyze whether the use of volatile anesthetics for neurocritical care sedation affects the incidence of delayed cerebral ischemia (DCI), cerebral vasospasm (CVS), DCI-related infarction, or functional outcome. METHODS: Data were retrospectively collected for ventilated aSAH patients (2016-2022), who received sedation for at least 180 hours. For comparative analysis, patients were assigned to a control and a study group according to the sedation used (intravenous vs. volatile sedation). Logistic regression analysis was performed to identify independent predictors of DCI, CVS, DCI-related infarction, and functional outcome. RESULTS: Ninety-nine patients with a median age of 58 years (interquartile range: 52-65 years) were included. Forty-seven patients (47%) received intravenous sedation, while 52 patients (53%) received (additional) volatile sedation with isoflurane (n = 30, 58%) or sevoflurane (n = 22, 42%) for a median duration of 169 hours (range: 5-298 hours). There were no significant differences between the 2 groups regarding the occurrence of DCI, angiographic CVS, DCI-related infarction, or functional outcome. In a multivariable logistic regression analysis, the use of volatile anesthetics had no impact on the incidence of DCI-related infarction or the patients' functional outcome. CONCLUSIONS: Volatile sedation in aSAH patients is not associated with the incidence of DCI, CVS, DCI-related infarction, or functional outcome. Although we could not demonstrate neuroprotective effects of volatile anesthetics, our results suggest that volatile sedation after aSAH has no negative effect on the patient's outcome.

Smartphone pupillometry for detection of cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

OBJECTIVES: Vasospasm is a complication of aneurysmal subarachnoid hemorrhage (aSAH) that can change the trajectory of recovery and is associated with morbidity and mortality. Earlier detection of vasospasm could improve patient outcomes. Our objective is to evaluate the accuracy of smartphone-based quantitative pupillometry in the detection of radiographic vasospasm and delayed cerebral ischemia (DCI) after aSAH. MATERIALS AND METHODS: We prospectively collected pupillary light reflex (PLR) parameters from patients with aSAH admitted to a neurocritical care unit at a single hospital twice daily using quantitative smartphone pupillometry recordings. PLR parameters included: Maximum pupil diameter, minimum pupil diameter, percent change in pupil diameter, latency in beginning of pupil constriction to light, mean constriction velocity, maximum constriction velocity, and mean dilation velocity. Two-tailed t-tests for independent samples were performed to determine changes in average concurrent PLR parameter values between the following comparisons: (1) patients with and without radiographic vasospasm (defined by angiography with the need for endovascular intervention) and (2) patients with and without DCI. RESULTS: 49 subjects with aSAH underwent 323 total PLR recordings. For PLR recordings taken with (n=35) and without (n=241) radiographic vasospasm, significant differences were observed in MIN (35.0 ± 7.5 pixels with vasospasm versus 31.6 ± 6.2 pixels without; p=0.002). For PLR recordings taken with (n=43) and without (n=241) DCI, significant differences were observed in MAX (48.9 ± 14.3 pixels with DCI versus 42.5 ± 9.2 pixels without; p<0.001). CONCLUSIONS: Quantitative smartphone pupillometry has the potential to be used to detect radiographic vasospasm and DCI after aSAH.

Primary decompressive craniectomy in patients with large intracerebral hematomas due to aneurysmal subarachnoid hemorrhage.

BACKGROUND: Decompressive craniectomy (DC) can alleviate increased intracranial pressure in aneurysmal subarachnoid hemorrhage patients with concomitant space-occupying intracerebral hemorrhage, but also carries a high risk for complications. We studied outcomes and complications of DC at time of ruptured aneurysm repair. METHODS: Of 47 patients treated between 2010 and 2020, 30 underwent DC during aneurysm repair and hematoma evacuation and 17 did not. We calculated odds ratios (OR) for delayed cerebral ischemia (DCI), angiographic vasospasm, DCI-related infarction, and unfavorable functional outcome (extended Glasgow Outcome Scale 1-5) at three months. Complication rates after DC and cranioplasty in the aneurysmal subarachnoid hemorrhage patients were compared to those of all 107 patients undergoing DC for malignant cerebral infarction during the same period. RESULTS: In DC versus no DC patients, proportions were for clinical DCI 37% versus 53% (OR = 0.5;95%CI:0.2-1.8), angiographic vasospasm 37% versus 47% (OR = 0.7;95%CI:0.2-2.2), DCI-related infarctions 17% versus 47% (OR = 0.2;95%CI:0.1-0.7) and unfavorable outcome 80% versus 88% (OR = 0.5;95%CI:0.1-3.0). ORs were similar after adjustment for baseline predictors for outcome. Complications related to DC and cranioplasty occurred in 18 (51%) of subarachnoid hemorrhage patients and 41 (38%) of cerebral infarction patients (OR = 1.7;95%CI:0.8-3.7). CONCLUSIONS: In patients with aneurysmal subarachnoid hemorrhage and concomitant space-occupying intracerebral hemorrhage, early DC was not associated with improved functional outcomes, but with a reduced rate of DCI-related infarctions. This potential benefit has to be weighed against high complication rates of DC in subarachnoid hemorrhage patients.

Clinical Value of Serum Secretoneurin Levels in Prediction of Delayed Cerebral Ischemia and Prognostic Analysis of Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study.

Background: Secretoneurin is a neuropeptide with several neuroprotective properties. Here, we discuss the importance of serum secretoneurin in assessing severity and predicting delayed cerebral ischemia (DCI) and functional outcomes following aneurysmal subarachnoid hemorrhage (aSAH). Methods: A prospective cohort study of 167 patients with aSAH and 100 controls was performed to determine serum secretoneurin levels. Severity was reflected by the Hunt-Hess and modified Fisher scores. Prognostic parameters included DCI and poor 6-month prognosis (extended Glasgow outcome scale scores of 1-4). Univariate analysis followed by multivariate analysis was performed to determine the correlation between severity and prognosis. Results: Compared to controls, patients exhibited a marked elevation in serum secretoneurin levels. Serum secretoneurin levels, which were independently correlated with Hunt-Hess scores and modified Fisher scores, independently predicted DCI and bad 6-month prognosis. Serum secretoneurin levels, which were linearly related to the risk of DCI and poor prognosis under a restricted cubic spline, effectively distinguished the risks under the receiver operating characteristic (ROC) curve. Subgroup analysis for prognosis or DCI prediction revealed no substantial interactions between serum secretoneurin levels and other variables, such as age, sex, hypertension, diabetes, alcohol consumption, and cigarette consumption. In addition, the prognosis model, in which serum secretoneurin, Hunt-Hess scale, and modified Fisher scale were merged, was graphically represented by a nomogram and performed well under the calibration, decision, and ROC curves. Conclusion: Serum secretoneurin levels significantly increased after aSAH, which was intimately correlated with disease severity and independently associated with DCI and worse outcomes, indicating that serum secretoneurin may be a potential prognostic biomarker of aSAH.

Prevention of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage-Summary of Existing Clinical Evidence.

The 2023 International Subarachnoid Hemorrhage Conference identified a need to provide an up-to-date review on prevention methods for delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage and highlight areas for future research. A PubMed search was conducted for key factors contributing to development of delayed cerebral ischemia: anesthetics, antithrombotics, cerebrospinal fluid (CSF) diversion, hemodynamic, endovascular, and medical management. It was found that there is still a need for prospective studies analyzing the best methods for anesthetics and antithrombotics, though inhaled anesthetics and antiplatelets were found to have some advantages. Lumbar drains should increasingly be considered the first line of CSF diversion when applicable. Finally, maintaining euvolemia before and during vasospasm is recommended as there is no evidence supporting prophylactic spasmolysis or angioplasty. There is accumulating observational evidence, however, that intra-arterial spasmolysis with refractory DCI might be beneficial in patients not responding to induced hypertension. Nimodipine remains the medical therapy with the most support for prevention.

Oxygen-Based Autoregulation Indices Associated with Clinical Outcomes and Spreading Depolarization in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Impairment in cerebral autoregulation has been proposed as a potentially targetable factor in patients with aneurysmal subarachnoid hemorrhage (aSAH); however, there are different continuous measures that can be used to calculate the state of autoregulation. In addition, it has previously been proposed that there may be an association of impaired autoregulation with the occurrence of spreading depolarization (SD) events. METHODS: Study participants with invasive multimodal monitoring and aSAH were enrolled in an observational study. Autoregulation indices were prospectively calculated from this database as a 10 s moving correlation coefficient between various cerebral blood flow (CBF) surrogates and mean arterial pressure (MAP). In study participants with subdural electrocorticography (ECoG) monitoring, SD was also scored. Associations between clinical outcomes using the modified Rankin scale and occurrence of either isolated or clustered SD were assessed. RESULTS: A total of 320 study participants were included, 47 of whom also had ECoG SD monitoring. As expected, baseline severity factors, such as modified Fisher scale score and World Federation of Neurosurgical Societies scale grade, were strongly associated with the clinical outcome. SD probability was related to blood pressure in a triphasic pattern, with a linear increase in probability below MAP of ~ 100 mm Hg. Multiple autoregulation indices were available for review based on moving correlations between mean arterial pressure (MAP) and various surrogates of cerebral blood flow (CBF). We calculated the pressure reactivity (PRx) using two different sources for intracranial pressure (ICP). We calculated the oxygen reactivity (ORx) using the partial pressure of brain tissue oxygen (PbtO2) from the Licox probe. We calculated the cerebral blood flow reactivity (CBFRx) using perfusion measurements from the Bowman perfusion probe. Finally, we calculated the cerebral oxygen saturation reactivity (OSRx) using regional cerebral oxygen saturation measured by near-infrared spectroscopy from the INVOS sensors. Only worse ORx and OSRx were associated with worse clinical outcomes. Both ORx and OSRx also were found to increase in the hour prior to SD for both sporadic and clustered SD. CONCLUSIONS: Impairment in autoregulation in aSAH is associated with worse clinical outcomes and occurrence of SD when using ORx and OSRx. Impaired autoregulation precedes SD occurrence. Targeting the optimal MAP or cerebral perfusion pressure in patients with aSAH should use ORx and/or OSRx as the input function rather than intracranial pressure.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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.

Beyond nimodipine: advanced neuroprotection strategies for aneurysmal subarachnoid hemorrhage vasospasm and delayed cerebral ischemia.

The clinical management of aneurysmal subarachnoid hemorrhage (SAH)-associated vasospasm remains a challenge in neurosurgical practice, with its prevention and treatment having a major impact on neurological outcome. While considered a mainstay, nimodipine is burdened by some non-negligible limitations that make it still a suboptimal candidate of pharmacotherapy for SAH. This narrative review aims to provide an update on the pharmacodynamics, pharmacokinetics, overall evidence, and strength of recommendation of nimodipine alternative drugs for aneurysmal SAH-associated vasospasm and delayed cerebral ischemia. A PRISMA literature search was performed in the PubMed/Medline, Web of Science, ClinicalTrials.gov, and PubChem databases using a combination of the MeSH terms "medical therapy," "management," "cerebral vasospasm," "subarachnoid hemorrhage," and "delayed cerebral ischemia." Collected articles were reviewed for typology and relevance prior to final inclusion. A total of 346 articles were initially collected. The identification, screening, eligibility, and inclusion process resulted in the selection of 59 studies. Nicardipine and cilostazol, which have longer half-lives than nimodipine, had robust evidence of efficacy and safety. Eicosapentaenoic acid, dapsone and clazosentan showed a good balance between effectiveness and favorable pharmacokinetics. Combinations between different drug classes have been studied to a very limited extent. Nicardipine, cilostazol, Rho-kinase inhibitors, and clazosentan proved their better pharmacokinetic profiles compared with nimodipine without prejudice with effective and safe neuroprotective role. However, the number of trials conducted is significantly lower than for nimodipine. Aneurysmal SAH-associated vasospasm remains an area of ongoing preclinical and clinical research where the search for new drugs or associations is critical.

Transcranial Doppler in the Detection of Cerebral Vasospasm After Subarachnoid Hemorrhage.

Background Transcranial Doppler (TCD) is a simple, noninvasive, nonionizing, portable technique but not widely practiced to detect cerebral vasospasm after subarachnoid hemorrhage (SAH). Objective The aim of this study was to assess the performance of TCD in the detection of cerebral vasospasm in patients with SAH considering CT angiography (CTA) as a gold standard. Methods and material This cross-sectional study included 50 patients with acute SAH admitted to the National Institute of Neurosciences & Hospital (NINS & H), Dhaka, Bangladesh, from February to June 2021. The neurological status, severity of SAH, and initial CT findings were recorded. All patients were screened for cerebral vasospasm with TCD on the 4th, 7th, 10th, and 14th days after the event. Screening of cerebral vasospasm by CTA was done on the 14th day of the event or earlier if TCD suggested vasospasm. Results The mean age of the participants was 51.4 ±13.4 years (mean ± SD), and females were predominant (N=29, 58%). CTA detected cerebral vasospasm in 18 (36%) participants, but TCD could detect it in only 13 (26%) cases. Among the participants who had no vasospasm by CTA, all but one were also found to have no vasospasm by TCD. The agreement between TCD and CTA in detecting cerebral vasospasm was significant (p<0.001, κ=0.726). TCD shows good specificity (96.9%) and positive predictive value (92.8%), but sensitivity (72.2%) and negative predictive value (81.6%) were comparatively lower. Overall, the diagnostic accuracy of TCD in detecting cerebral vasospasm was 88%. Conclusions Although compared to CTA, TCD is a highly specific but less sensitive tool in detecting vasospasm, TCD remains a reliable screening tool for detecting vasospasm following SAH.