Cerebral Vasospasm Research Articles

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.

Management of Psychiatric Diagnoses in Reversible Cerebral Vasoconstriction Syndrome: The Dangers of Worsening Pathology with Serotonergic Medications: A Case Report and Literature Review.

Reversible cerebral vasoconstriction syndrome (RCVS) represents a group of conditions that show reversible multifocal narrowing or constriction of the cerebral arteries that supply blood to the brain. The initial manifestation of RCVS often includes a "thunderclap" headache that is sudden, severe, and often disabling. Stimulants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and antipsychotics with serotonergic activity can alter the cerebral arterial tone, trigger vasoconstriction, and place patients at risk of a cerebrovascular accident. Thus, psychiatric medications are commonly discontinued on admission for RCVS, and psychiatry is often consulted for input on acute medication management and longitudinal treatment options. Currently, there is a dearth of literature on managing psychiatric medications in RCVS, resulting in variable practice patterns that place patients at risk of withdrawal, decompensation, and relapse. In this article, we provide a case example and aim to consolidate the limited data surrounding the management of psychiatric illness with comorbid RCVS in our discussion. There is a clear concern about worsening and even potentially lethal consequences due to serotonin or stimulant-induced vasospasm both during an acute episode and in long-term management of RCVS. We discuss the underlying pathophysiologic mechanisms proposed for serotonergic-, noradrenergic-, and dopaminergic-induced cerebral vasospasm and how this correlates with the clinical management of patients on psychiatric medications. These data will then be organized to create a risks versus benefits outline to equip psychiatrists to make decisions about when to stop and when to restart psychiatric medications in the setting of RCVS.

Effect of Levobupivacaine Hydrochloride-Loaded Nanospheres on Delayed Cerebral Vasospasm Following Subarachnoid Hemorrhage in Rabbits

This research was aimed to analyze the mechanism of action of levobupivacaine hydrochloride-loaded nanospheres on delayed cerebral vasospasm following subarachnoid hemorrhage (SAH). Levobupivacaine hydrochloride-loaded nanospheres (LevoBPV Hcl/PLGA) were prepared using the solvent evaporation methodology, with the raw material as a control. The blood drug concentrations were detected by HPLC after subcutaneous and subarachnoid administration in experimental rabbits. Forty New Zealand white rabbits were randomly assigned into Sham group, SAH group, LevoBPV Hcl group (10 mg/kg), and LevoBPV Hcl/PLGA group (10 mg/kg), with 10 rabbits in each group. The SAH model was induced using the double blood injection methodology combined with internal carotid artery ligation. Brain tissue samples were collected on day 7 for pathological characterization, determination of neuronal apoptosis, and measurement of basilar artery diameter and area. The levels of oxidative stress factors (superoxide (SOD), malondiadehyde (MDA), glutathione peroxidase (GSH-Px)) and vasoconstrictor factors (nitric oxide (NO), endothelin-1 (ET-1)) in the cerebrospinal fluid (CSF) were detected using assay kits. The results revealed that the drug loading capacity of LevoBPV Hcl/PLGA was 29.13%, encapsulation efficiency was 87.09%, and the average particle size was 81.43 μm. Under the same dosage, both subcutaneous and subarachnoid administration of LevoBPV Hcl/PLGA exhibited two concentration peaks in the blood drug concentration, with lower concentration values versus LevoBPV Hcl group, and a longer average residence time than LevoBPV Hcl group (P &lt; 0.05). Relative to Sham group, SAH group exhibited decreased diameter and area of the basilar artery, reduced neuronal density, increased neuronal apoptosis rate, decreased levels of SOD, GSH-Px, and NO in the CSF, and increased levels of MDA and ET-1 (P &lt; 0.05). Moreover, LevoBPV Hcl group and LevoBPV Hcl/PLGA group showed increased diameter and area of the basilar artery, higher neuronal density, reduced neuronal apoptosis rate, elevated levels of SOD, GSH-Px, and NO in the CSF, and decreased levels of MDA and ET-1 versus SAH group (P &lt; 0.05). The LevoBPV Hcl/PLGA group exhibited increased diameter and area of the basilar artery, higher neuronal density, reduced neuronal apoptosis rate, elevated levels of SOD, GSH-Px, and NO in the CSF, and decreased levels of MDA and ET-1 versus LevoBPV Hcl group (P &lt; 0.05). In short, LevoBPV HCl-loaded nanospheres can prolong the in vivo residence time of subcutaneous and subarachnoid administration, reduce the maximum blood drug concentration, and enhance drug safety. Furthermore, these nanospheres can inhibit neuronal apoptosis following SAH, regulate oxidative stress and vasoconstrictor factor expression, thereby suppressing the occurrence of delayed cerebral vasospasm and alleviating brain tissue damage.

Octa-Arginine-Conjugated Liposomal Nimodipine Incorporated in a Temperature-Responsive Gel for Nasoencephalic Delivery.

Nimodipine is the primary clinical drug used to treat cerebral vasospasm following subarachnoid hemorrhage. Currently, tablets have low bioavailability when taken orally, and injections contain ethanol. Therefore, we investigated a new method of nimodipine administration, namely, nasoencephalic administration. Nasal administration of nimodipine was carried out by attaching the cell-penetrating peptide octa-arginine (R8) to liposomes of nimodipine and incorporating it into a temperature-sensitive in situ gel. The prepared liposomes and gels underwent separate evaluations for in vitro characterization. In vitro release exhibited a significant slow-release effect. In vitro toad maxillary cilia model, RPMI 2650 cytotoxicity, and in vivo SD rat pathological histotoxicity experiments showed that all the dosage from the groups had no significant toxicity to toad maxillary cilia, RPMI 2650 cells, and SD rat tissues and organs, and the cilia continued to oscillate up to 694 ± 10.15 min, with the survival rate of the cells being above 85%. A transwell nasal mucosa cell model and an isolated porcine nasal mucosa model were established, and the results showed that the osmolality of the R8-modified nimodipine liposomal gel to nasal mucosal cells and isolated porcine nasal mucosa was 30.41 ± 2.14 and 65.9 ± 7.34 μg/mL, respectively, which was significantly higher than that of the NM-Solution and PEGylated nimodipine liposome gel groups. Animal fluorescence imaging studies revealed that the R8-modified nimodipine liposomal gel displayed increased brain fluorescence intensity compared to the normal liposomal gel. Pharmacokinetic results showed that after transnasal administration, the AUC(0-∞) of the R8-modified nimodipine liposomal gel was 11.662 ± 1.97 μg·mL-1, which was significantly higher than that of the plain nimodipine liposomal gel (5.499 ± 2.89 μg·mL-1). Brain-targeting experiments showed that the brain-targeting efficiencies of the PEGylated nimodipine liposome gel and R8-modified PEGylated nimodipine liposome gels were 20.44 and 33.45, respectively, suggesting that R8/PEG/Lip-NM-TSG significantly increased the brain-targeting of the drug.

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

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. 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. 99 patients with a median age of 58 years (IQR 52-65 years) were included. 47 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 two 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. 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 patient's outcome.

Artificial-intelligent prediction model of occurrence of cerebral vasospasms based on machine-learning.

Background and Study Aims Symptomatic cerebral vasospasms are deleterious complication of the rupture of a cerebral aneurysm and potentially lethal. The existing scales used to classify the initial presentation of a subarachnoid haemorrhage (SAH), offer a blink of the outcome and the possibility of occurrence of symptomatic cerebral vasospasms. Altogether, they are neither sufficient to predict outcome or occurrence of events reliably nor do they offer a unite front. This study tests the common grading scales and factors, that otherwise effect the outcome, in an artificial-intelligent based algorithm in order to create a reliable prediction model for the occurrence of cerebral vasospasms. Material and Methods Applying the R environment an easy to operate command line was programmed to prognosticate the occurrence of vasospasms. Eighty-seven patients with aneurysmal SAH during a 24 months-period of time were included for study purposes. The Holdout and the Cross-Validation methods were used to evaluate the algorithm (65 patients validation set. 22 patients test set). The Support Vector Machines (ksvm) classification method provided a high accuracy. The medical data set included demographic data, the Hunt & Hess scale, Fisher grade, BNI scale, length of intervention for aneurysmal repair, etc. Results Our prediction model based on the AI algorithm demonstrated an accuracy of 61%-86% for the event of symptomatic vasospasms. For the subgroup analysis, patients of the surgical cohort 28,8% (n=13) developed symptomatic vasospasm, whereas admitted with Fisher scale grade 4 50% (n=7), with H&H 5 37,5% (n=5) and 28,5% (n=4) with BNI 5. Respectively, in the endovascular cohort vasospasms occurred in 31,8% (n=14) patients, with Fisher grade 4 69% (n=9), H&H 5 23% (n=3) and 7% (n=1) with BNI 5. Conclusion From our data, we may believe that the algorithm presented can help in identifying patients with SAH being at 'high' or 'low risk' for the development of symptomatic vasospasms. This risk balancing might further allow the treating physician to go for an early intervention trying to prevent permanent sequelae. Certainly, accuracy will improve with a higher caseload and more statistical coefficients.

Use of dual intraventricular vasodilators for refractory cerebral vasospasm in a pediatric patient with traumatic subarachnoid hemorrhage: A case report.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Subarachnoid hemorrhage (SAH) is a rare but life-threatening clinical event for pediatric patients. Cerebral vasospasm is a common complication of SAH that often leads to poor outcomes. This case report describes the use of dual intraventricular (IVT) vasodilators in a pediatric patient. An 11-year-old male presented with traumatic diffuse SAH and cranial vasospasm. Despite treatment with IVT nicardipine, intravenous (IV) milrinone by continuous infusion, enteral nimodipine, and intraarterial verapamil and milrinone given during digital subtraction angiography, transcranial Doppler (TCD) mean velocities continued to rise. IVT milrinone was then added to IVT nicardipine and IV milrinone. The combination of IVT nicardipine, IV milrinone, and rescue therapy with IVT milrinone was continued for a total of 7 days. TCD mean velocities decreased into the mild to moderate range within 2 days of the patient receiving this combined regimen and remained globally low thereafter. This case illustrates the potential benefit of using dual IVT vasodilators to improve outcomes for pediatric patients with refractory cerebral vasospasm.

Localized Nicardipine Release Implants for Prevention of Vasospasm After Aneurysmal Subarachnoid Hemorrhage

Cerebral vasospasm largely contributes to a devastating outcome after aneurysmal subarachnoid hemorrhage (aSAH), with limited therapeutic options. To investigate the safety and efficacy of localized nicardipine release implants positioned around the basal cerebral vasculature at risk for developing proximal vasospasm after aSAH. This single-masked randomized clinical trial with a 52-week follow-up was performed between April 5, 2020, and January 23, 2023, at 6 academic neurovascular centers in Germany and Austria. Consecutive patients with World Federation of Neurological Surgeons grade 3 or 4 aSAH due to a ruptured anterior circulation aneurysm requiring microsurgical aneurysm repair participated. During aneurysm repair, patients were randomized 1:1 to intraoperatively receive 10 implants at 4 mg of nicardipine each plus standard of care (implant group) or aneurysm repair alone plus standard of care (control group). The primary end point was the incidence of moderate to severe cerebral angiographic vasospasm (aVS) between days 7 and 9 after aneurysm rupture as determined by digital subtraction angiography. Of 41 patients, 20 were randomized to the control group (mean [SD] age, 54.9 [9.1] years; 17 female [85%]) and 21 to the implant group (mean [SD] age, 53.6 [11.9] years; 14 female [67%]). A total of 39 patients were included in the primary efficacy analysis. In the control group, 11 of 19 patients (58%) developed moderate or severe aVS compared with 4 of 20 patients (20%) in the implant group (P = .02). This outcome was paralleled by a lower clinical need for vasospasm rescue therapy in the implant group (2 of 20 patients [10%]) compared with the control group (11 of 19 patients [58%]; P = .002). Between days 13 and 15 after aneurysm rupture, new cerebral infarcts were noted in 6 of 19 patients (32%) in the control group and in 2 of 20 patients (10%) in the implant group (P = .13). At 52 weeks, favorable outcomes were noted in 12 of 18 patients (67%) in the control group and 16 of 19 patients (84%) in the implant group (P = .27). The adverse event rate did not differ between groups. These findings show that placing nicardipine release implants during microsurgical aneurysm repair can provide safe and effective prevention of moderate to severe aVS after aSAH. A phase 3 clinical trial to investigate the effect of nicardipine implants on clinical outcome may be warranted. ClinicalTrials.gov Identifier: NCT04269408.

Sustained efficacy of angioplasty for cerebral vasospasm after aneurysmal subarachnoid hemorrhage: Risk features and device comparison

BackgroundCerebral vasospasm is a leading source of delayed morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). Angioplasty may improve vasospasm, while optimal target and device selection remains controversial. This study aimed to identify features and devices associated with sustained efficacy. MethodsWe identified consecutive patients who underwent angioplasty for aSAH vasospasm. The primary outcome was a composite of adequate angioplasty (residual narrowing < 50 %) without complications. Secondary outcomes included rates of refractory/recurrent vasospasm and sustained improvement at follow-up. Associated features were identified through multivariable analysis. Outcomes were compared between balloon and Comaneci/stentriever in a propensity-score-matched cohort. ResultsA total of 149 vasospastic segments underwent angioplasty: 61.7 % in the proximal anterior circulation (ICA, M1, A1), 20.1 % in distal segments (A2 and M2) and 18.1 % in the posterior circulation. Adequate angioplasty was achieved without complication in 83.2 % of vessels, with a sustainable effect in 84.3 % at follow-up. Refractory/recurrent vasospasm was observed in 17.4 %, yielding a 10.1 % retreatment rate. Notably, only 35.3 % of vessels undergoing inadequate angioplasty demonstrated improvement at follow-up. Angioplasty targeting distal MCA (adjusted OR, 0.10) or BA-V4 (aOR, 0.10), and inadequate angioplasty (aOR, 0.03) were unfavorable predictors for sustained improvement. Efficacy outcomes were similar between balloon and Comaneci/stentriever in a matched subgroup analysis. ConclusionAngioplasty, when achieving residual narrowing < 50 %, demonstrated sustained improvement for vasospasm. Novel devices may exhibit comparable efficacy to balloon angioplasty for selected segments.

Fasudil hydrochloride and ozagrel sodium combination therapy for patients with aneurysmal subarachnoid hemorrhage: a cross-sectional study using a nationwide inpatient database

BackgroundFasudil 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).MethodsThis 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.ResultsThe 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.ConclusionFasudil 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.

Hyperbaric Oxygen Mediated PI3K/Akt/mTOR Pathway in Inhibiting Delayed Cerebral Vasospasm after Subarachnoid Hemorrhage.

Delayed cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) is a serious complication. This article aimed to explore the mechanism of hyperbaric oxygenation (HBO) inhibiting delayed CVS after SAH. The 60 SD rats were grouped: normal control group (NC), sham operation group (Sham), SAH Model (Model), and HBO treatment group. The SAH model was established by injecting blood twice into the cisterna magna (CM), and the neurological function of the rats were evaluated by modified Garcia scale. The plasma of the rats was collected at 1, 3, 6, and 9 days after HBO treatment. Plasma levels of PI3K/Akt/mTOR pathway-related proteins were detected by Western blot (WB). TUNEL method was used to observe the apoptosis rate of basilar artery (BA) endothelial cells (ECs). Hematoxylin-eosin staining (HE) staining was used to observe the inner diameter and the thickness of vessel wall of rat cerebral arteries. The relationship between mTOR and middle cerebral artery spasm was analyzed. As against the Model, the neurological function was visibly increased, the expressions of Bcl-2, PI3K, mTOR, and p-Akt/Akt protein in plasma were visibly increased, the expression of Bax protein was visibly decreased, and the degree of CVS was visibly reduced in the HBO group (all P < 0.05). The level of mTOR is negatively correlated with the degree of CVS after SAH, and HBO can inhibit the occurrence of delayed CVS.

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

BackgroundDecompressive 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.MethodsOf 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.ResultsIn 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).ConclusionsIn 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.

Smartphone pupillometry for detection of cerebral vasospasm after aneurysmal subarachnoid hemorrhage

ObjectivesVasospasm 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 MethodsWe 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. Results49 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). ConclusionsQuantitative smartphone pupillometry has the potential to be used to detect radiographic vasospasm and DCI after aSAH.

Critical care innovations: navigating pain relief in intensive care: the role of regional anesthesia.

The purpose of this article is to provide an update of regional anesthesia and its applications in the critical care patient population. Regional anesthesia including blocks of the abdomen and thorax, head and neck, as well as upper and lower extremities can be used to alleviate pain and assist in managing life-threatening conditions such as cerebral vasospasm and ventricular storm in the ICU population. There have been many advances in these techniques including ultrasound-guidance with innovative approaches that allow for more superficial procedures that are safer for critically ill patients. Regional anesthesia can decrease hospital length of stay (LOS), prevent ICU admission, shorten ICU LOS, and increase ventilator free days and may have mortality benefits. Pain management in the ICU is an important and sometimes challenging aspect of patient care. Regional anesthetic techniques have more indications and are safe, versatile tools that should be incorporated into care of critically ill patients.

A prospective pilot study of gut microbiome in cerebral vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

A recent systematic review indicated that gut–microbiota–brain axis contributes to growth and rupture of intracranial aneurysms. However, gaps were detected in the role of intestinal microbiome in cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH). This is the first pilot study aiming to test study feasibility and identify differences in gut microbiota between subjects with and without CVS following aSAH. A prospective nested case–control pilot study with 1:1 matching was conducted recruiting subjects with aSAH: cases with CVS; and controls without CVS based on the clinical picture and structured bedside transcranial Doppler (TCD). Fecal samples for microbiota analyses by means of 16S rRNA gene amplicon sequencing were collected within the first 96 h after ictus. Operational taxonomic unit tables were constructed, diversity metrics calculated, phylogenetic trees built, and differential abundance analysis (DAA) performed. At baseline, the groups did not differ significantly in basic demographic and aneurysm-related characteristics (p > 0.05). Alpha-diversity (richness and Shannon Index) was significantly reduced in cases of middle cerebral artery (MCA) vasospasm (p < 0.05). In DAA, relative abundance of genus Acidaminococcus was associated with MCA vasospasm (p = 0.00013). Two butyrate-producing genera, Intestinimonas and Butyricimonas, as well as [Clostridium] innocuum group had the strongest negative correlation with the mean blood flow velocity in anterior cerebral arteries (p < 0.01; rho = − 0.63; − 0.57, and − 0.57, respectively). In total, 16 gut microbial genera were identified to correlate with TCD parameters, and two intestinal genera correlated with outcome upon discharge. In this pilot study, we prove study feasibility and present the first preliminary evidence of gut microbiome signature associating with CVS as a significant cause of stroke in subjects with aSAH.

Risk Factors for Cerebral Vasospasm After Subarachnoid Hemorrhage: A Systematic Review of Observational Studies.

Cerebral vasospasm (CV) following subarachnoid hemorrhage (SAH) remains one of the leading causes of high mortality and poor outcomes. Understanding the risk factors associated with CV is pivotal to improving patients' outcomes.We conducted an extensive search for analytical observational studies that analyzed the correlation between various variables and the likelihood of CV development among adult patients with SAH (age ≥ 18years). Five scholar databases were used, namely, PubMed, EBSCO, Web of Science, Science Direct, and Google Scholar. Relevant studies published between January 1st, 2016, and August 9th, 2023, were included. The Newcastle-Ottawa Scale was adopted to assess the risk of bias among included observational studies. A total of 33 studies met the inclusion criteria. Of the 24,958 patients with SAH who were identified, 6,761 patients had a subsequent CV (27.1%). Several statistically significant risk factors were reported across the literature. Younger age, female sex, smoking, alcohol intake, modified Fisher grade 3-4, higher Hunt and Hess grading, and the presence of multiple comorbidities (diabetes, hypertension, congestive heart failure, and history of stroke) were among the well-established risk factors for CV. Additionally, leukocytosis was consistently reported to be a significant predictor in multiple studies, providing compelling evidence for its association with CV. Even though single studies reported an association between CV and certain variables, further research is necessary to investigate the implications of these findings. These include arterial tortuosity, hypokalemia, potassium to glucose gradient, hypoalbuminemia, anemia, von Willebrand factor and vascular endothelial growth factor, use of desflurane, and hemodynamic stability. Overall, this systemic review provides a comprehensive summary of the current data that evaluates the potential risk factors for the development of CV after SAH. However, because of data heterogeneity, certain factors require further validation in their correlation with CV development. Larger-scale observational and clinical trials are mandatory to extensively investigate the significant predictors of CV to lay the scientific foundation for improving outcomes in susceptible patients with SAH.

Strategies and outcomes of endovascular treatment of posterior inferior cerebellar artery aneurysms: a single center experience.

To explore safe and reliable strategies and outcomes of endovascular procedures in the treatment of posterior inferior cerebellar artery (PICA) aneurysms. Retrospectively reviewed and analyzed the cases of PICA aneurysms that undergone endovascular therapy from July 2017 through January 2022 in our neurosurgical center, as well as outcomes of long-term follow-up. Total 24 cases were enrolled. Majority of the PICA aneurysms (87.5%, 21/24) presented initially with subarachnoid hemorrhage (SAH) and only 3 cases were not ruptured when they were clinically diagnosed as PICA aneurysms. The patients were endovascularly given either aneurysm occlusion with selective coils (12 cases), embolization of aneurysms and parent arteries (7 cases: 3 cases with coils and 4 cases with Onyx liquid embolic agent), or stent-assisted coiling of the aneurysms (5 cases). One patient, who had comorbidity of intracranial hemorrhage and severe cerebral vasospasm, declined further post-surgery therapy, and discharged from the hospital with anticipation of poor outcome. The rest 23 patients were followed up for 3-24 months with a recurrence rate of 17.4% (4/23). Endovascular procedure of embolizing PICA aneurysms with selective coils or stent-assisted coils is feasible, safe, and reliable. Simplified embolization of the aneurysms or occlusion of the parent artery is recommended as the first choice for the ruptured and bleeding PICA aneurysms.