Development Of Vasospasm Research Articles

Electroencephalographic monitoring in detection and prediction of delayed cerebral ischemia due to non-traumatic subarachnoid hemorrhage

Intensive care of patients with acute non-traumatic subarachnoid hemorrhage primarily relies on diagnostics of delayed cerebral ischemia (DCI). The major difficulty in detecting DCI emerges upon suppression of wakefulness, when clinical assessment of growing neurological deficit becomes complicated. Widely used transcranial dopplerography allows solely to verify a vasospasm development not always leading to DCI exhibiting a multifactorial underlying mechanism. Electroencephalography (EEG) is the only broadly available instrumental tool ensuring a continuous monitoring of cerebral functional status including in subjects at intensive care unit. To date, non-specific EEG parameters pointing at development of acute cerebral injury were identified that provide varying diagnostic and predictive informative value in DCI. We reviewed publications aimed at assessing the data on visual and quantitative EEG parameters such as regional slowing, alpha rhythm spectral power and relative variability, alpha-to-delta power ratio, and detection of epileptiform activity. Having searched international and Russia-wide medical databases, we found only 7 publications quantitatively assessing diagnostic value of EEG monitoring, which showed that for DCI diagnosis its sensitivity ranged from 76% to 100%, and specificity – from 54% to 100%. We also present a clinical case with a 70-year-old female patient who underwent surgery for non-traumatic subarachnoid hemorrhage due to a ruptured aneurysm of the communicating segment of the right internal carotid artery. During the continuous videoEEG monitoring 2 days before clinical deterioration and appearance of ischemic changes in the right cerebral hemisphere on computed tomography scans, an ictal-interictal continuum pattern was noted to emerge. Future studies should be aimed at clarifying and validating the most informative DCI biomarkers including while recording EEG with intracranial electrodes that may contribute to development of automated algorithms for DCI detection.

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<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<0.05) higher mean IL-6 values in CSF on the 3rd day, while the differences on the 7th and 10th days (p<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.

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.

Molecular Basis of Cerebral Vasospasm: What Can We Learn from Transcriptome and Temporal Gene Expression Profiling in Intracranial Aneurysm?

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

Blood DNA Methylation Analysis Reveals a Distinctive Epigenetic Signature of Vasospasm in Aneurysmal Subarachnoid Hemorrhage.

Vasospasm is a potentially preventable cause of poor prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH). Epigenetics might provide insight on its molecular mechanisms. We aimed to analyze the association between differential DNA methylation (DNAm) and development of vasospasm. We conducted an epigenome-wide association study in 282 patients with aSAH admitted to our hospital. DNAm was assessed with the EPIC Illumina chip (> 850K CpG sites) in whole-blood samples collected at hospital admission. We identified differentially methylated positions (DMPs) at the CpG level using Cox regression models adjusted for potential confounders, and then we used the DMP results to find differentially methylated regions (DMRs) and enriched biological pathways. A total of 145 patients (51%) experienced vasospasm. In the DMP analysis, we identified 31 CpGs associated with vasospasm at p-value < 10-5. One of them (cg26189827) was significant at the genome-wide level (p-value < 10-8), being hypermethylated in patients with vasospasm and annotated to SUGCT gene, mainly expressed in arteries. Region analysis revealed 13 DMRs, some of them annotated to interesting genes such as POU5F1, HLA-DPA1, RUFY1, and CYP1A1. Functional enrichment analysis showed the involvement of biological processes related to immunity, inflammatory response, oxidative stress, endothelial nitric oxide, and apoptosis. Our findings show, for the first time, a distinctive epigenetic signature of vasospasm in aSAH, establishing novel links with essential biological pathways, including inflammation, immune responses, and oxidative stress. Although further validation is required, our results provide a foundation for future research into the complex pathophysiology of vasospasm.

Correlation of Inflammatory Parameters with the Development of Cerebral Vasospasm, Takotsubo Cardiomyopathy, and Functional Outcome after Spontaneous Subarachnoid Hemorrhage.

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

Investigation of the effect of carnitine on cerebral vasospasm in experimental subarachnoid hemorrhage model

The vasospasm, which develops after subarachnoid hemorrhage (SAH), is an unenlightened table in terms of etiology and results. It is usually associated with decreased perfusion, which is associated with decreased blood flow distal to the affected artery and can be demonstrated radiologically. Acetyl-L-carnitine (ALCAR) can be found in brain tissue and easily crosses the blood–brain barrier. Therefore, in this study, we aimed to investigate the therapeutic efficacy of ALCAR, which is an effective antioxidant amine, on vasospasm development after experimental SAH. In our study, 35 adults male Wistar RATs weighing between 235–250 g were used. These RATs were divided into five groups with n = 7. Group 1 Control group, Group 2 SAH + SF (carrier solution), Group 3 SAH + ALCAR 50 mg\\kg intraperitoneally, Group 4 SAH + ALCAR 100 mg\\kg intraperitoneally and Group 5 SAH. Subarachnoid hemorrhage was induced by giving autologous arterial blood to the cisterna magna of the animals in groups 2, 3, 4, and 5. At 0.-12.- 24.- 36.- 48.- 60. and 72. h, Group 2 was injected with SF, Group 3 with intraperitoneally ALCAR 50 mg\\kg, and Group 4 with intraperitoneally ALCAR 100 mg\\kg, respectively. Following perfusion and fixation, the animals were subjected to a wide craniectomy, and the brain, cerebellum, and brain stems were removed globally. Then, sections were taken from the basilar arteries of all animals and photographed at 40X magnification. Basilar artery lumen cross-sectional areas, basilar artery areas, and wall thicknesses were measured from these sections. The basilar artery lumen cross-sectional area was found to be significantly larger in the groups in which SAH was formed and ALCAR 50 mg\\kg and ALCAR 100 mg\\kg were given compared to the group with only SAH and SAH + SF (p = 0.0408). Basilar artery wall thickness increased in all groups except the control group (p < 0.05). In light of all these findings, it was concluded in our study that Carnitine was effective in the resolution of vasospasm in the experimental SAH model.

Increased plasma periostin concentration predicts angiographic vasospasm development in non-severe aneurysmal subarachnoid hemorrhage

It is unknown whether plasma concentrations of a matricellular protein periostin change in association with the development of angiographic vasospasm after aneurysmal subarachnoid hemorrhage (SAH). In 113 patients with aneurysmal SAH of World Federation of Neurological Surgeons grades 1–3 at admission, plasma periostin concentrations were serially measured at days 1–3, 4–6, 7–9 and 10–12 after SAH onset. Measured periostin levels and clinical variables were compared between patients with and without angiographic vasospasm. Periostin concentrations were significantly higher in patients with angiographic vasospasm at days 4–6 and 7–9. Receiver operating characteristic curve analyses indicated that cutoff plasma periostin values of 54.3 ng/ml at days 4–6 and 58.1 ng/ml at days 7–9 predicted or diagnosed angiographic vasospasm development with a specificity of 66.0 % and a sensitivity of 72.7 %, and a specificity of 75.0 % and a sensitivity of 55.0 %, respectively. Multivariate analyses also revealed that increased plasma periostin concentrations at days 7–9 was independently associated with angiographic vasospasm development. This study showed for the first time that plasma periostin levels were increased in patients with angiographic vasospasm. These findings suggest that plasma periostin can serve as a biomarker and may be a new therapeutic target for angiographic vasospasm after SAH.

Ultrastructural changes of vascular smooth muscle cells and resistance to vasospasm treatment in femoral arteries of an arteriosclerotic rat model.

The objective of this study was to establish an animal model of arteriosclerosis for assessing vasospasm and to investigate the relationship between arteriosclerosis and vasospasm. Twelve-week-old male Sprague-Dawley rats were fed a diet supplemented with adenine and vitamin D (adenine/vitD). Body weight, blood, and femoral artery histopathology were assessed at 2, 4, and 6weeks. Change in the femoral artery was examined by transmission electron microscope (TEM). Vasospasm was induced by administering epinephrine extravascularly into the femoral artery and released by the treatment with lidocaine as a vasodilator. During this period, the extravascular diameter and blood flow were measured. The rats in the adenine/vitD group developed renal dysfunction, uremia, hyperphosphatemia, and elevated serum alkaline phosphatase. Histological and TEM analyses of the femoral arteries in the treated rats revealed the degeneration of elastic fibers and extensive calcification of the tunica media and intima. Vascular smooth muscles were degenerated and osteoblasts were developed, resulting in calcified arteriosclerosis. Vasospasm in arteriosclerotic arteries was detected; however, vasodilation as well as an increase in the blood flow was not observed. This study revealed the development of vasospasm in the femoral arteries of the arteriosclerotic rats and, a conventional vasodilator did not release the vasospasm.

Risk identification for the development of large-artery vasospasm after aneurysmatic subarachnoid hemorrhage – a multivariate, risk-, and location-adjusted prediction model

BackgroundVasospasm of the large cerebral arteries (CVS) after aneurysmatic subarachnoid hemorrhage (aSAH) reduces cerebral perfusion and causes delayed cerebral ischemia. Although endovascular spasmolysis shows convincing angiographic results, patients often do...

The effect of induced hypertension in aneurysmal subarachnoid hemorrhage: A narrative review.

Aneurysmal subarachnoid hemorrhage ‎(aSAH) ‎accounts for 2-5% of all strokes, and 10%-15% of ‎aSAH patients will not survive until hospital admission. Induced hypertension (IH) is an emerging therapeutic option being used for the treatment of vasospasm in ‎aSAH. For patients with cerebral vasospasm (CVS) consequent to SAH, IH is implemented to increase systolic blood pressure (SBP) in order to optimize cerebral blood flow (CBF) and prevent delayed cerebral ischemia (DCI). Prophylactic use of IH has been associated with the development of vasospasm and cerebral ischemia in SAH patients. Various trials have defined several different parameters to help clinicians decide when to initiate IH in a SAH patient. However, there is insufficient evidence to recommend therapeutic IH in aSAH due to the possible serious complications like myocardial ischemia, development of posterior reversible encephalopathy syndrome (PRES), pulmonary edema, and even rupture of another unsecured aneurysm. This narrative review showed the favorable impact of IH therapy on aSAH patients; however, it is crucial to conduct further clinical and molecular experiments to shed more light on the effects of IH in aSAH.

Circulating Extracellular Vesicles in Subarachnoid Hemorrhage Patients: Characterization and Cellular Effects.

Circulating extracellular vesicles (EVs) may play a pathophysiological role in the onset of complications of subarachnoid hemorrhage (SAH), potentially contributing to the development of vasospasm (VP). In this study, we aimed to characterize circulating EVs in SAH patients and examine their effects on endothelial and smooth muscle cells (SMCs). In a total of 18 SAH patients, 10 with VP (VP), 8 without VP (NVP), and 5 healthy controls (HC), clinical variables were recorded at different time points. EVs isolated from plasma samples were characterized and used to stimulate human vascular endothelial cells (HUVECs) and SMCs. We found that EVs from SAH patients expressed markers of T-lymphocytes and platelets and had a larger size and a higher concentration compared to those from HC. Moreover, EVs from VP patients reduced cell viability and mitochondrial membrane potential in HUVECs and increased oxidants and nitric oxide (NO) release. Furthermore, EVs from SAH patients increased intracellular calcium levels in SMCs. Altogether, our findings reveal an altered pattern of circulating EVs in SAH patients, suggesting their pathogenic role in promoting endothelial damage and enhancing smooth muscle reactivity. These results have significant implications for the use of EVs as potential diagnostic/prognostic markers and therapeutic tools in SAH management.

The Role of Computed Tomographic Angiography in Predicting the Development of Vasospasm Following Ruptured Intracranial Aneurysm Microsurgery.

Introduction Following subarachnoid hemorrhage, cerebral vasospasm is the primary cause of morbidity and death. The aim of this study is to predict the development of vasospasm by detecting changes in vessel diameter after surgery using computed tomography angiography. Methods We retrospectively evaluated the patients who underwent aneurysm clipping due to a bleeding aneurysm between 2019-2022. Age, gender, location, subarachnoid hemorrhage grades, development of perioperative rupture, and temporary clip use were examined. Preoperative and postoperative diameters of the internal carotid artery, A1-A2, and M1-M2 were measured. Radiological and clinical vasospasm development in the postoperative period was also documented. Results The aneurysm localizations of the 100 patients (mean age: 50.38±13.04 years) were anterior cerebral artery in 50 patients, internal carotid artery in 37 patients, and middle cerebral artery in 30 patients. In the postoperative follow-up, radiological vasospasm was apparent in 41 patients. The changes in arterial diameter reveal a statistically significant decrease in the internal carotid artery, M1-M2, and A1-A2 artery diameters on the operated side compared to the contralateral side (p<0.001). Based on the receiver operating characteristic (ROC) analysis, the most likely change in arterial diameter on the operated side to indicate the presence of vasospasm was calculated from the available data, where the decrease in total arterial diameter was 13.7%. Conclusion Vasospasm remains one of the significant causes of morbidity and mortality post subarachnoid hemorrhage. While there have been advances in imaging modalities, predicting which patients will develop vasospasm has remained elusive. Our research attempts to provide a quantifiable metric (13.7% decrease in vessel diameter) that can be an early predictor of this complication.

Gβγ subunit signalling underlies neuropeptide Y-stimulated vasoconstriction in rat mesenteric and coronary arteries.

Raised serum concentrations of the sympathetic co-transmitter neuropeptide Y (NPY) are linked to cardiovascular diseases. However, the signalling mechanism for vascular smooth muscle (VSM) constriction to NPY is poorly understood. Therefore, the present study investigated the mechanisms of NPY-induced vasoconstriction in rat small mesenteric (RMA) and coronary (RCA) arteries. Third-order mesenteric or intra-septal arteries from male Wistar rats were assessed in wire myographs for isometric tension, VSM membrane potential and VSM intracellular Ca2+ events. NPY stimulated concentration-dependent vasoconstriction in both RMA and RCA, which was augmented by blocking NO synthase or endothelial denudation in RMA. NPY-mediated vasoconstriction was blocked by the selective Y1 receptor antagonist BIBO 3304 and Y1 receptor protein expression was detected in both the VSM and endothelial cells in RMA and RCA. The selective Gβγ subunit inhibitor gallein and the PLC inhibitor U-73122 attenuated NPY-induced vasoconstriction. Signalling via the Gβγ-PLC pathway stimulated VSM Ca2+ waves and whole-field synchronised Ca2+ flashes in RMA and increased the frequency of Ca2+ flashes in myogenically active RCA. Furthermore, in RMA, the Gβγ pathway linked NPY to VSM depolarization and generation of action potential-like spikes associated with intense vasoconstriction. This depolarization activated L-type voltage-gated Ca2+ channels, as nifedipine abolished NPY-mediated vasoconstriction. These data suggest that the Gβγ subunit, which dissociates upon Y1 receptor activation, initiates VSM membrane depolarization and Ca2+ mobilisation to cause vasoconstriction. This model may help explain the development of microvascular vasospasm during raised sympathetic nerve activity.

MicroRNA-130b May Induce Cerebral Vasospasm after Subarachnoid Hemorrhage via Modulating Kruppel-like Factor 4.

Recently, the diverse functions of microRNAs (miRNAs) in brain diseases have been demonstrated. We intended to uncover the functional role of microRNA-130b (miR-130b) in cerebral vasospasm (CVS) following subarachnoid hemorrhage (SAH). SAH was induced by injecting the autologous blood into the cisterna magna of Sprague Dawley rats. The cerebral vascular smooth muscle cells (cVSMCs) were extracted for invitro experimentation. In vitro and invivo assays were implemented with transfection of miR-130b mimic/inhibitor, sh-Kruppel-like factor 4 (KLF4), oe-KLF4 plasmids or p38/MAPK signaling pathway agonist (anisomycin), respectively, to elaborate the role of miR-130b in CVS following SAH. Elevated miR-130b and reduced KLF4 were found in SAH patients and rat models of SAH. KLF4 was the target gene of miR-130b. miR-130b promoted the proliferation and migration of cVSMCs through the Inhibition of KLF4. Besides, KLF4 inhibited the proliferation and migration of cVSMCs through blockage of the p38/MAPK pathway. Furthermore, invivo assay confirmed the inhibitory effect of decreased miR-130b in CVS following SAH. In conclusion, miR-130b may activate the p38/MAPK signaling pathway through targeted inhibition of KLF4, thereby contributing to some extent to the development of cerebral vasospasm after SAH.

Immunological Profile of Vasospasm after Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) carries high mortality and disability rates, which are substantially driven by complications. Early brain injury and vasospasm can happen after SAH and are crucial events to prevent and treat to improve prognosis. In recent decades, immunological mechanisms have been implicated in SAH complications, with both innate and adaptive immunity involved in mechanisms of damage after SAH. The purpose of this review is to summarize the immunological profile of vasospasm, highlighting the potential implementation of biomarkers for its prediction and management. Overall, the kinetics of central nervous system (CNS) immune invasion and soluble factors' production critically differs between patients developing vasospasm compared to those not experiencing this complication. In particular, in people developing vasospasm, a neutrophil increase develops in the first minutes to days and pairs with a mild depletion of CD45+ lymphocytes. Cytokine production is boosted early on after SAH, and a steep increase in interleukin-6, metalloproteinase-9 and vascular endothelial growth factor (VEGF) anticipates the development of vasospasm after SAH. We also highlight the role of microglia and the potential influence of genetic polymorphism in the development of vasospasm and SAH-related complications.

A Machine Learning Tool to Predict Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage (P13-7.003)

<h3>Objective:</h3> To utilize a machine learning and deep learning approach to derive a clinically applicable tool to predict the development of vasospasm in aneurysmal subarachnoid hemorrhage (aSAH) patients. <h3>Background:</h3> Cerebral vasospasm, is a common undesired and feared consequence of aSAH occurring in up to 70% of patients. Cerebral vasospasm may present anywhere from 24 hours to 7–10 days post SAH and is difficult to predict. Several radiological and clinical features have been proposed as potential predictors of cerebral vasospasm in previous models including, however, these predictors have not successfully been standardized and weighted through an artificial intelligence algorithm. While risk factors for vasospasm is known, there is also no validated single tool in practice that accounts for the broad diversity in indicators that may be predictive of cerebral vasospasm. <h3>Design/Methods:</h3> We retrospectively analyzed aneurysmal SAH patients who were admitted to the Carle Foundation Hospital in the Critical Care Unit from January 2016 to December 2021. Total of 52 patients met study criteria, out of which 23 (44%) patients were identified to have vasospasm through diagnostic imaging modalities. Clinical, radiological, and laboratory data were collected and analyzed through various feature selection and artificial intelligence models. Models were validated using 10-fold Cross-Validation. <h3>Results:</h3> We included Transcranial Doppler data from 14 days post aSAH, as well as Fisher Score, Hunt Hess Score, diameter of aneurysm, lymphocyte/monocyte/WBC counts, motor component from Glasgow Coma Scale, and home medication for anticoagulants in our model. Models including Logistic Model Trees, Logistic Regression, AdaBoost, LogitBoost, Hoeffding Tree, and Multilayer Perceptron (MP) were trained, with MP performing with the highest ROC AUC of 0.829, with a TP Rate of 73%, FP Rate of 28.5%, Precision of 73%, and F-Measure of 73%. <h3>Conclusions:</h3> A framework for predicting cerebral vasospasm after aSAH through deep learning is created with ROC AUC of 0.829. <b>Disclosure:</b> Mr. Patel has nothing to disclose. Mr. Pandya has nothing to disclose. Ms. Mann has nothing to disclose.

Glutamine Deficiency Promotes Immune and Endothelial Cell Dysfunction in COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has caused the death of almost 7 million people worldwide. While vaccinations and new antiviral drugs have greatly reduced the number of COVID-19 cases, there remains a need for additional therapeutic strategies to combat this deadly disease. Accumulating clinical data have discovered a deficiency of circulating glutamine in patients with COVID-19 that associates with disease severity. Glutamine is a semi-essential amino acid that is metabolized to a plethora of metabolites that serve as central modulators of immune and endothelial cell function. A majority of glutamine is metabolized to glutamate and ammonia by the mitochondrial enzyme glutaminase (GLS). Notably, GLS activity is upregulated in COVID-19, favoring the catabolism of glutamine. This disturbance in glutamine metabolism may provoke immune and endothelial cell dysfunction that contributes to the development of severe infection, inflammation, oxidative stress, vasospasm, and coagulopathy, which leads to vascular occlusion, multi-organ failure, and death. Strategies that restore the plasma concentration of glutamine, its metabolites, and/or its downstream effectors, in conjunction with antiviral drugs, represent a promising therapeutic approach that may restore immune and endothelial cell function and prevent the development of occlusive vascular disease in patients stricken with COVID-19.

110 Macrophage Cross Talk following Subarachnoid Hemorrhage: Contribution of Peripheral Immune Activation in the Development of Cerebral Vasospasm

INTRODUCTION: Microglia respond to the initial insult of aneurysm rupture, but become overwhelmed by ferritin toxicity. These microglia release inflammatory cytokines that cause vasospasm to facilitate peripheral macrophage diapedesis. This process is dependent on the p-STAT3 pathway. METHODS: The autologous SAH pre-clinical model was utilized and compared to blood and CSF from human patients. Mouse blood was injected along the skull base to c57/bl6 and CCR2/Cx3CR1 mice. Microglia depletion was done with pexidartinib. Ferritin within microglia, TLR4, and NFKb were measured via immunohistochemistry. Vasospasm was measured via India Ink gelatin assay. The Modified Garcia Scale and right turn test was utilized. Clarity assay was utilized to determine association between macrophages and brain microglia. Cerebral doppler was used to measure spreading cortical depressions. p-STAT3 was measured via western blot. For all experiments, saline sham, subarachnoid hemorrhage, and subarachnoid hemorrhage with p-STAT3 inhibitor were utilized. RESULTS: Microglia recruitment occured within parenchyma along the skull base adjacent to subarachnoid blood. Ferritin toxicity was noted by day 5 (r-0.95, p &lt; 0.05) and persisted to day 9 (r-0.98, p &lt; 0.01). A shift in microglia occured following SAH with Cox-2 and INOS predominance (k1 0.76, k2 1.21). Blockade of p-STAT3 resulted in decreased vasospasm (p&lt;0.01), improved modified Garcia scores (p &lt; 0.05), and improved right turn test (p &lt; 0.05) following SAH. Peripheral macrophage diapedesis occured in regions of microglia activation. P-STAT3 blockade improved cerebral blood flow and prevented spreading cortical depressions (p &lt; 0.01). NFKb and TLR4 activation was markedly reduced by p-Stat3 inhibition (p &lt; 0.05). Results correlated closely to human aneurysmal blood and CSF data. CONCLUSIONS: Microglia ferritin toxicity contributes to vasospasm to facilitate peripheral macrophage diapedesis. Targeting the p-STAT3 pathway leads to reduced vasospasm and improved behavioral outcomes.

Abstract Number ‐ 246: Quantification of Hemorrhage Volume for Prediction of Complications of Aneurysmal Subarachnoid Hemorrhage

Introduction Aneurysmal subarachnoid hemorrhage (aSAH) can lead to life‐threatening complications such as vasospasm and hydrocephalus. The incidence of these events is influenced by the volume of intracranial hemorrhage. The Fisher score is a subjective adjudication of SAH volume. We developed an objective semi‐automated method to quantify the volume of intracranial hemorrhage. Moreover, we evaluated the association of aSAH volume with vasospasm and hydrocephalus. Methods A custom semi‐automated image segmentation algorithm quantifying aSAH volume was implemented in MATLAB. The volume of hemorrhage was retrospectively measured from non‐contrast brain CT scans with Fisher grade ≥ 2. The algorithm utilized region‐growing and 3D k‐means clustering. Performance was validated against the average of two sets of hemorrhage volumes manually measured. These measurements were obtained from two independent raters who selected regions of interest spanning areas of hemorrhage. The association between blood volume and clinical outcome (hydrocephalus or vasospasm) was evaluated using ROC analysis. Results Fifty‐seven patients were included in this study and 10 patients were used for validation of our method. The ICC between raters for manual measurements of hemorrhage in the validation group was 0.988 (CI: (0.911, 0.997), p &lt; 0.001). Validation of semi‐automated versus manual methods resulted in an ICC of 0.961 (CI: (0.756, 0.991), p &lt; 0.001). Bland‐Altman analysis revealed that the algorithm slightly underestimated blood volume (mean difference = ‐4.11 mL). Hemorrhage volume discriminated for the development of vasospasm (AUC = 0.781) and hydrocephalus (AUC = 0.776). Conclusions Volume of hemorrhage is a key factor that influences the incidence of complications in aSAH. We developed and validated a semi‐automated algorithm for quantifying the volume of aSAH. Vasospasm and hydrocephalus were associated with greater amounts of intracranial blood. Objective measurements of aSAH volume can aid in adjudicating risk of complications among patients with aSAH.