Flow diversion of ruptured intracranial aneurysms: a single-center study with a standardized antithrombotic treatment protocol.

BACKGROUND: The use of antithrombotic medication following acute flow diversion for a ruptured intracranial aneurysm (IA) is challenging with no current guidelines. We investigated the incidence of treatment-related complications and patient outcomes after flow diversion for a ruptured IA before and after the implementation of a standardized antithrombotic medication protocol. METHODS: We conducted a single-center retrospective study including consecutive patients treated for acutely ruptured IAs with flow diversion during 2015-2023. We divided the patients into two groups: those treated before the implementation of the protocol (pre-protocol) and those treated after the implementation of the protocol (post-protocol). The primary outcomes were hemorrhagic and ischemic complications. A secondary outcome was clinical outcome using the modified Ranking Scale (mRS). RESULTS: Totally 39 patients with 40 ruptured IAs were treated with flow diversion (69% pre-protocol, 31% post-protocol). The patient mean age was 55 years, 62% were female, 63% of aneurysms were in the posterior circulation, 92% of aneurysms were non-saccular, and 44% were in poor grade on admission. Treatment differences included the use of glycoprotein IIb/IIIa inhibitors (pre-group 48% vs. post-group 100%), and the use of early dual antiplatelets (pre-group 44% vs. 92% post-group). The incidence of ischemic complications was 37% and 42% and the incidence of hemorrhagic complications was 30% and 33% in the pre- and post-groups, respectively, with no between-group differences. There were three (11%) aneurysm re-ruptures in the pre-group and none in the post-group. There were no differences in mortality or mRS 0-2 between the groups at 6 months. CONCLUSION: We found no major differences in the incidence of ischemic or hemorrhagic complications after the implementation of a standardized antithrombotic protocol for acute flow diversion for ruptured IAs. There is an urgent need for more evidence-based guidelines to optimize antithrombotic treatment after flow diversion in the setting of subarachnoid hemorrhage.

Rapidly Growing and Ruptured Great Saphenous Vein Aneurysm in a Liver Transplant Patient.

Venous aneurysms are rare vascular malformations that can lead to significant clinical complications, including thrombosis, pulmonary embolism, rupture, and even fatal outcomes when not promptly and adequately managed. This case report presents a liver transplant patient under immunosuppressive therapy who developed a rapidly progressing great saphenous vein aneurysm, ultimately requiring urgent surgical intervention due to acute bleeding from the ruptured aneurysm. Immunosuppression emerges as a potential key factor in the formation and rapid growth of the aneurysm, with the pathophysiological mechanism potentially involving increased expression of specific matrix metalloproteinases. Further research is warranted to gain a better understanding of the role of immunosuppression in the development of venous aneurysms.

Fecal calprotectin is a novel biomarker to predict the clinical outcomes of patients with ruptured intracranial aneurysm.

BACKGROUND: Intracranial aneurysm (IA) is a common cerebrovascular disease and the leading cause of spontaneous subarachnoid hemorrhage. Recent evidence suggests that gut microbiota is involved in the pathophysiological process of IA through the gut-brain axis. However, the role of gut inflammation in the development of IA has yet to be clarified. Our study aimed to investigate whether fecal calprotectin (FC) level, a sensitive marker of gut inflammation, is correlated with the development of IA and the prognosis of patients with ruptured IA (RIA). METHODS: 182 patients were collected from January 2022 to January 2023, including 151 patients with IA and 31 healthy individuals. 151 IA patients included 109 patients with unruptured IA (UIA) and 42 patients with RIA. The FC level was measured by enzyme-linked immunosorbent assay. Other detailed information was obtained from an electronic medical record system. RESULTS: Compared with healthy controls, the FC levels in patients with IA were increased (P < 0.0001). Patients with RIA had significantly higher FC levels than UIA patients (P < 0.0001). Moreover, the FC level in RIA patients with unfavorable outcomes was higher than in RIA patients with favorable outcomes. Logistic regression analysis showed that the elevated FC level was an independent risk factor for a 3-month poor prognosis in patients with RIA (OR=1.005, 95% CI = 1.000 -1.009, P = 0.044). CONCLUSION: Fecal calprotectin level is significantly elevated in IA patients, especially those with RIA. FC is a novel biomarker of 3-month poor outcomes in RIA patients.

Characteristics and Trends in Median Arcuate Ligament Syndrome (MALS) Associated Visceral Artery Aneurysms: A Systematic Descriptive Review of the Literature.

Introduction: Median Arcuate Ligament Syndrome (MALS) is associated with true aneurysms, mainly of both the pancreaticoduodenal artery (PDA) and gastroduodenal artery (GDA). Although rare, their potential for rupture and adverse clinical outcomes warrants analysis. Prior studies suggest high rupture rates even for smaller aneurysms under 2 cm in this setting. We performed a systematic literature review, synthesising the evidence on visceral artery aneurysms related to MAL syndrome, with a focus on descriptive analyses of aneurysm size, presentation, rupture rates, and management. Methods: Literature search was performed using (Medline, EMBASE, Emcare and CINAHL). Inclusion criteria included true aneurysms secondary to MALS with or without rupture. The cases with pseudoaneurysms, concomitant pathologies eg, pancreatitis, conservatively managed aneurysms and articles with non-granular pooled data were excluded. Cases were assessed according to demographics, clinical presentation, aneurysm diameter, aneurysm rupture and management technique. Results: 39 articles describing 72 patients were identified. Aneurysm diameter in symptomatic patients was not significantly different from asymptomatic patients {21.0 and 22.3 mm respectively, P = .84}. Ruptured aneurysms were overall smaller than non-ruptured at presentation {12.3 mm v 30.8 mm respectively, P = .02}. Patients presented with abdominal pain (75.6%), nausea/vomiting (15.6%), hypotension (33.9%), shock (20.0%) and haemodynamic collapse (8.9%). 56.9% of all cases were managed with an endovascular approach, 19.4% were managed with an open surgical approach, and 23.6% were managed hybrid. Conclusion: This review suggests visceral artery aneurysms associated with median arcuate ligament rupture at variable sizes. Despite inability to clearly correlate size and rupture risk, our data supports prompt intervention irrespective of size, given the adverse outcomes. Further research is critically needed to clarify size thresholds or other predictors to guide management.

Dietary Iron Restriction Protects against Aneurysm Rupture in a Mouse Model of Intracranial Aneurysm.

INTRODUCTION: Iron accumulation in vessel walls induces oxidative stress and inflammation, which can cause cerebrovascular damage, vascular wall degeneration, and intracranial aneurysmal formation, growth, and rupture. Subarachnoid hemorrhage from intracranial aneurysm rupture results in significant morbidity and mortality. This study used a mouse model of intracranial aneurysm to evaluate the effect of dietary iron restriction on aneurysm formation and rupture. METHODS: Intracranial aneurysms were induced using deoxycorticosterone acetate-salt-induced hypertension and a single injection of elastase into the cerebrospinal fluid of the basal cistern. Mice were fed an iron-restricted diet (n = 23) or a normal diet (n = 25). Aneurysm rupture was detected by neurological symptoms, while the presence of intracranial aneurysm with subarachnoid hemorrhage was confirmed by post-mortem examination. RESULTS: The aneurysmal rupture rate was significantly lower in iron-restricted diet mice (37%) compared with normal diet mice (76%; p < 0.05). Serum oxidative stress, iron accumulation, macrophage infiltration, and 8-hydroxy-2'-deoxyguanosine in the vascular wall were lower in iron-restricted diet mice (p < 0.01). The areas of iron positivity were similar to the areas of CD68 positivity and 8-hydroxy-2'-deoxyguanosine in both normal diet and iron-restricted diet mouse aneurysms. CONCLUSIONS: These findings suggest that iron is involved in intracranial aneurysm rupture via vascular inflammation and oxidative stress. Dietary iron restriction may have a promising role in preventing intracranial aneurysm rupture.

Glypican-1 may be a plasma biomarker for predicting the rupture of small intracranial aneurysms.

Currently, there are no effective methods for predicting the rupture of asymptomatic small intracranial aneurysms (IA) (<7 mm). In this study the aim was to identify early warning biomarkers in peripheral plasma for predicting IA rupture. Four experimental groups were included: ruptured intracranial aneurysm (RIA), unruptured intracranial aneurysm (UIA), traumatic subarachnoid hemorrhage control (tSAHC), and healthy control (HC) groups. Plasma proteomics of these four groups were detected using iTRAQ combined LC-MS/MS. Differentially expressed proteins (DEPs) were identified in RIA, UIA, tSAHC compared with HC. Target proteins associated with aneurysm rupture were obtained by comparing the DEPs of the RIA and UIA groups after filtering out the DEPs of the tSAHC group. The plasma concentrations of target proteins were validated using enzyme-linked immunosorbent assay (ELISA). The iTRAQ analysis showed a significant increase in plasma GPC1 concentration in the RIA group compared to the UIA group, which was further validated among the IA patients. Logistic regression analysis identified GPC1 as an independent risk factor for predicting aneurysm rupture. The ROC curve indicated that the GPC1 plasma cut-off value for predicting aneurysms rupture was 4.99 ng/ml. GPC1 may be an early warning biomarker for predicting the rupture of small intracranial aneurysms. SIGNIFICANCE: The current management approach for asymptomatic small intracranial aneurysms (<7 mm) is limited to conservative observation and surgical intervention. However, the decision-making process regarding these options poses a dilemma due to weighing their respective advantages and disadvantages. Currently, there is a lack of effective diagnostic methods to predict the rupture of small aneurysms. Therefore, our aim is to identify early warning biomarkers in peripheral plasma that can serve as quantitative detection markers for predicting intracranial aneurysm rupture. In this study, four experimental populations were established: small ruptured intracranial aneurysm (sRIA) group, small unruptured intracranial aneurysm (sUIA) group, traumatic subarachnoid hemorrhage control (tSAHC) group, and healthy control (HC) group. The tSAH group was the control group of spontaneous subarachnoid hemorrhage caused by ruptured aneurysm. Compared with patients with UIA, aneurysm tissue and plasma GPC1 in patients with RIA is significantly higher, and GPC1 may be an early warning biomarker for predicting the rupture of intracranial small aneurysms.

Clinical and Morphological Factors for Ruptured Anterior Communicating Artery Aneurysms.

Introduction: The anterior communicating artery (ACoA) aneurysm, the most frequent cerebral aneurysm to rupture, carries a significant clinical burden, yet the factors influencing its rupture are limited in Indonesia. This study aims to determine the clinical and morphological features associated with ruptured ACoA compared to non-AcoA aneurysms among Indonesians. Patients and Methods: We retrospectively reviewed our center's aneurysm patient registry from January 2019 to December 2022, and compared the clinical and morphological features between ruptured ACoA aneurysms and ruptured aneurysms elsewhere with univariate and multivariate analyses. Results: Of the 292 patients with 325 ruptured aneurysms, 89 were from ACoA. The mean age of patients was 54.99 years, with female preponderance in the non-ACoA group (non-ACoA: 73.31%, ACoA: 46.07%). On univariate analysis, ages ≥60 [ages 60-69: OR = 0.311 (0.111-0.869), p=0.026; ages ≥70: OR = 0.215 (0.056-0.819), p=0.024], female gender [OR = 0.311 (0.182-0.533), p<0.001], and smoking [OR=2.069 (1.036-4.057), p=0.022] exhibited significant association with ruptured ACoA aneurysm. On multivariate analysis, only the female gender was independently associated with ruptured ACoA aneurysm (aOR 0.355 [0.436-1.961], p=0.001). Conclusion: In our study, ruptured ACoA aneurysm was inversely associated with advanced age, female gender, presence of daughter aneurysm, and directly associated with smoking. After multivariate adjustment, the female gender showed an independent association with ruptured ACoA aneurysm.

Early Termination versus Standard Regimen Duration of Dual Antiplatelet Therapy in Intracranial Aneurysm Patients Treated With Pipeline Embolization Device Flex With Shield Technology: Preliminary Experience of 3 U.S. Centers.

BACKGROUND: Pipeline Flex Embolization Device with Shield Technology (PED-Shield) is a third-generation flow diverter with reduced thromboembolic potential. However, safety profile and dual antiplatelet therapy (DAPT) recommendations with PED-Shield is not well -established. We aim to assess the safety and complication profile with early termination of DAPT with use of PED-Shield. METHODS: Databases of 3 high-volume cerebrovascular centers were retrospectively reviewed. We identified patients with unruptured and ruptured intracranial aneurysms treated with PED-Shield. Patient demographics, aneurysm characteristics, complications, and angiographic outcomes were extracted. All patients who had early termination of DAPT, defined as <180 days, as well as standard duration were included. RESULTS: A total of 37 patients, totaling 37 aneurysms, had early termination of DAPT and 24 patients with 24 aneurysms received standard duration (>180 days) of DAPT. There was no difference in pre-procedural DAPT regimens between the groups (P = 0.503). Following DAPT termination, o1ne major thromboembolic complication was observed in the early termination group while no major or minor thromboembolic or hemorrhagic complication was noted in the standard duration group. Time of angiographic follow-up was not statistically different (P = 0.063) between the early termination (343 days, interquartile range [IQR] 114-371 days) and the standard duration (175 days, IQR 111-224.5 days) groups. There were no statistically significant differences in complete aneurysm occlusion (P = 0.857), residual neck (P = 0.582), and aneurysm remnant (P = 0.352) rates between the groups on angiography. CONCLUSIONS: Early termination of DAPT proves safe after PED-Shield treatment of intracranial aneurysms with comparable complete occlusion rates.

A shift from open to endovascular repair in the treatment of ruptured middle cerebral artery aneurysms: a single institution experience.

PURPOSE: Middle cerebral aneurysms were underrepresented in the two largest trials (BRAT and ISAT) for the treatment of ruptured intracranial aneurysms. Recent institutional series addressing the choice between endovascular or open repair for this subset of aneurysms are few and have not yielded a definitive conclusion. We compare clinical outcomes of patients presenting with acute subarachnoid hemorrhage from ruptured middle cerebral artery aneurysms undergoing either open or endovascular repair. METHODS: We conducted a retrospective review of 138 consecutive patients with ruptured middle cerebral artery aneurysms admitted into our institution from January 2008 to March 2019 to compare endovascular and open surgical outcomes. RESULTS: Of the ruptured middle cerebral artery aneurysms, 57 underwent endovascular repair while 81 were treated with open surgery. Over the study period, there was a notable shift in practice toward more frequent endovascular treatment of ruptured MCA aneurysms (31% in 2008 vs. 91% in 2018). At discharge (49.1% vs 29.6%; p = .002) and at 6 months (84.3% vs 58.6%; p = 0.003), patients who underwent endovascular repair had a higher proportion of patients with good clinical outcomes (mRS 0-2) compared to those undergoing open surgery. Long-term follow-up data (endovascular 54.9 ± 37.9 months vs clipping 18.6 ± 13.4 months) showed no difference in rebleeding (1.8% vs 3.7%, p = 0.642) and retreatment (5.3% vs 3.7%, p = 0.691) in both groups. CONCLUSION: Our series suggests equipoise in the treatment of ruptured middle cerebral artery aneurysms and demonstrates endovascular repair as a potentially feasible treatment strategy. Future randomized trials could clarify the roles of these treatment modalities.

Supraorbital eyebrow approach and pterional approach in surgical treatment of ruptured and unruptured aneurysms: a propensity score-matched analysis.

The aim of this study is to reveal efficacy and efficiency of the supraorbital eyebrow approach (SEA) in clipping ruptured and unruptured aneurysms where both SEA and pterional approach (PA) are considered feasible by comparing SEA and PA using propensity score matching. A total of 229 patients who underwent surgical clipping of an aneurysm from 2013 to 2022 and met inclusion criteria were recruited in the study. A study group of 67 patients treated via the SEA and a comparison group of 162 patients treated via the PA were formed. Then, the subgroups of 66 patients each, with balanced incoming factors, were analyzed using the propensity score technique. The safety and efficacy endpoints were compared. Successful clipping was achieved in all cases of both groups. There were no patients in the SEA group who required conversion to the standard craniotomy. There were no procedure-related deaths in this series. No patient experienced early or late rebleeding in either group. Mean blood loss volume in the SEA group was lower than in the PA group by approximately 77.5 ml (p < 0.001). There were favorable differences in the SEA group regarding postoperative neurological deficit (p = 0.016), postoperative epileptic seizure rate (p = 0.013), ischemic and hemorrhagic complications (p = 0.028 and 0.0009, respectively), and outcomes (p < 0.001). Patients' satisfaction with cosmetic results measured by the visual analog scale was rated highly in both groups (p = 0.081). For patients where SEA provides adequate exposure, it results in safety and cosmetic outcomes not inferior to the PA.

Fetal-type posterior cerebral artery and association of rupture in posterior communicating artery aneurysms: A systematic review and meta-analysis.

BACKGROUND: The morbidity and mortality of intracranial aneurysm rupture motivate the risk evaluation of the patient´s characteristics and aneurysm's morphology. Brain vessel variants lead to hemodynamic changes that could increase risk. This study aims to evaluate the fetal posterior cerebral artery (fPCA) as a risk factor for the formation, rupture, and recurrence of the posterior communicating artery (PComA) aneurysm. METHODS: A search strategy was performed in MEDLINE, Scopus, Web of Science, and EMBASE databases for studies that evaluated the risk of appearance, rupture, and recurrence of PComA aneurysms with the presence of fPCA. Newcastle-Ottawa Scale and AXIS were used for quality assessment. The primary and secondary outcomes were evaluated and interpreted with an odds ratio (OR) and their 95% confidence intervals (CI). RESULTS: A total of 577 articles were reviewed. Thirteen studies were included for the qualitative analysis, and ten studies for the meta-analysis. All cohort studies were classified as poor quality, and all cross-sectional studies with moderate risk. The unadjusted OR resulted in 1.57 (n = 6, 95% CI 1.13-2.19, p = <0.001, I2 =0%) between the presence of fPCA and PComA aneurysm rupture. CONCLUSION: There is a significant association of aneurysm formation and rupture of PComA aneurysms in the presence of fPCA. This may be triggered by the hemodynamic alterations caused by the variation, leading to changes in the vessel wall.

Efficacy and safety of flow diverter combined with coil embolization and evidence-based antithrombotic regimen in the treatment of ruptured aneurysms.

OBJECTIVE: The use of a flow diverter (FD) in the treatment of ruptured aneurysms is limited due to the increased risk of perioperative ischemia and hemorrhagic complications. Adjunctive coil embolization and an evidence-based antithrombotic regimen may improve therapeutic safety, although evidence from relevant clinical research is limited. The authors' aim was to further assess the perioperative safety and long-term efficacy of this strategy. METHODS: Data on patients with FD insertion and coil embolization were collected retrospectively at two centers. The perioperative antithrombotic regimen consists of intraoperative tirofiban and continues for 24 hours postoperatively, with the initiation of an orally administered dual-antiplatelet regimen 4 hours prior to tirofiban cessation, rather than purposeful preoperative antiplatelet therapy. Perioperative cerebral ischemia and hemorrhagic complications and long-term aneurysm occlusion rates were recorded to evaluate the safety and efficacy of the procedure, respectively. RESULTS: In total, 67 cases were screened and 41 cases were ultimately included in this study. A total of 2 cases (4.9%) of perioperative cerebral hemorrhagic events occurred, 1 of which (2.4%) was attributable to rerupture of the aneurysm. Cerebral ischemic events were reported in 3 patients, including 1 with cortical thromboembolism and 2 with perforator occlusion of the basilar artery. A median 8-month follow-up was attained in 25 patients (61.0%), with a 92% complete or near-complete occlusion rate. CONCLUSIONS: FD insertion combined with coil embolization is a potentially safe and effective therapeutic strategy for ruptured aneurysms when accompanied with perioperative evidence-based antithrombotic therapy.

[Unruptured Intracranial Aneurysm:Indications and Outcomes].

Since most unruptured intracranial aneurysms(UIA)are asymptomatic, it is important to determine treatment indications. The purpose of UIA treatment is to prevent rupture and relieve the patient's mental burden. Therefore, building a good relationship between doctors and patients is a major premise for one of the indications for surgical treatments. In addition, long-term follow-up of patients is necessary because endovascular treatment has the possibility of recurrence and retreatment. Since endovascular treatment is "possible" and "suitable" is different, it is necessary to determine the treatment policy from a radical point of view.

Ruptured Pancreaticoduodenal Artery Aneurysm in a Patient With Celiac Artery Dissection: A Case Report.

Unlike other visceral artery aneurysms, pancreaticoduodenal artery aneurysms (PDAAs) should be treated regardless of their size. There are no reports on PDAA associated with celiac artery (CA) dissection. We, here, report the case of a patient with a ruptured PDAA with concomitant CA dissection. A 44-year-old Korean man presented to the emergency room of another hospital 29 days ago due to a sudden onset of abdominal pain. Contrast-enhanced abdominal computed tomography (CT) revealed a large right retroperitoneal hematoma and CA dissection. Subsequently, aortography revealed no specific bleeding focus. He underwent conservative treatment for 16 days, including a transfusion, and then was referred to us. His abdominal CT angiography revealed a diminishing retroperitoneal hematoma, a 7 mm × 8 mm PDAA at the anterior inferior pancreaticoduodenal artery aneurysm (PDA), and CA dissection. Selective celiac angiography revealed sluggish and diminished blood flow to the true lumen of the CA, and the hepatic, gastroduodenal, and splenic arteries were supplied by collaterals arising from the superior mesenteric artery (SMA). We performed elective coil embolization of the anterior PDA using the right femoral approach.We believe that postprocedural surveillance is required after CA dissection because of the potential risk of recurrent PDAA. Additionally, we suggest that hidden PDAA rupture should be considered for spontaneous retroperitoneal bleeding.

A nomogram to predict the risk of bleeding after discharge from stent-assisted ruptured aneurysm embolization in a Chinese population.

The occurrence of bleeding events after stent-assisted embolization of a ruptured artery requiring continuous double antiplatelet therapy may seriously affect the prognosis of this group of patients. A nomogram can provide a personalized, more accurate risk estimate based on predictors. We, therefore, developed a nomogram to predict the probability of bleeding events in patients with stent-assisted ruptured aneurysm embolization. We performed a single-center retrospective analysis of data collected from patients undergoing stent-assisted ruptured aneurysm embolization between January 2018 and December 2021. Forward stepwise logistic regression was performed to identify independent predictors of adverse events of bleeding after stent-assisted embolization and to establish nomograms. Discrimination and calibration of this model were performed using the area under the ROC curve (AUC-ROC) and the calibration plot. The model is internally validated by using resampling (1000 replicates). A total of 131 patients were identified, and a total of 118 patients met the study criteria. The predictors included in the nomogram were body mass index (BMI), AAi, and MA-ADP. The model showed good resolving power with a ROC area of 0.893 (95% CI: 0.834 ~ 0.952) for this model with good calibration. The nomogram can be used to individualize, visualize, and accurately predict the risk probability of bleeding events after stent-assisted embolization of ruptured aneurysms.

Plasma metabolic signatures for intracranial aneurysm and its rupture identified by pseudotargeted metabolomics.

BACKGROUND AND AIMS: The vital metabolic signatures for IA risk stratification and its potential biological underpinnings remain elusive. Our study aimed to develop an early diagnosis model and rupture classification model by analyzing plasma metabolic profiles of IA patients. MATERIALS AND METHODS: Plasma samples from a cohort of 105 participants, including 75 IA patients in unruptured and ruptured status (UIA, RIA) and 30 control participants were collected for comprehensive metabolic evaluation using ultra-high-performance liquid chromatography-mass spectrometry-based pseudotargeted metabolomics method. Furthermore, an integrated machine learning strategy based on LASSO, random forest and logistic regression were used for feature selection and model construction. RESULTS: The metabolic profiling disturbed significantly in UIA and RIA patients. Notably, adenosine content was significantly downregulated in UIA, and various glycine-conjugated secondary bile acids were decreased in RIA patients. Enriched KEGG pathways included glutathione metabolism and bile acid metabolism. Two sets of biomarker panels were defined to discriminate IA and its rupture with the area under receiver operating characteristic curve of 0.843 and 0.929 on the validation sets, respectively. CONCLUSIONS: The present study could contribute to a better understanding of IA etiopathogenesis and facilitate discovery of new therapeutic targets. The metabolite panels may serve as potential non-invasive diagnostic and risk stratification tool for IA.

Profiling of Circulating Gene Expression Reveals Molecular Signatures Associated with Intracranial Aneurysm Rupture Risk.

BACKGROUND: Following detection, rupture risk assessment for intracranial aneurysms (IAs) is critical. Towards molecular prognostics, we hypothesized that circulating blood RNA expression profiles are associated with IA risk. METHODS: We performed RNA sequencing on 68 blood samples from IA patients. Here, patients were categorized as either high or low risk by assessment of aneurysm size (≥ 5 mm = high risk) and Population, Hypertension, Age, Size, Earlier subarachnoid hemorrhage, Site (PHASES) score (≥ 1 = high risk). Modified F-statistics and Benjamini-Hochberg false discovery rate correction was performed on transcripts per million-normalized gene counts. Protein-coding genes expressed in ≥ 50% of samples with a q value < 0.05 and an absolute fold-change ≥ 2 were considered significantly differentially expressed. Bioinformatics in Ingenuity Pathway Analysis was performed to understand the biology of risk-associated expression profiles. Association was assessed between gene expression and risk via Pearson correlation analysis. Linear discriminant analysis models using significant genes were created and validated for classification of high-risk cases. RESULTS: We analyzed transcriptomes of 68 IA patients. In these cases, 31 IAs were large (≥ 5 mm), while 26 IAs had a high PHASES score. Based on size, 36 genes associated with high-risk IAs, and two were correlated with the size measurement. Alternatively, based on PHASES score, 76 genes associated with high-risk cases, and nine of them showed significant correlation to the score. Similar ontological terms were associated with both gene profiles, which reflected inflammatory signaling and vascular remodeling. Prediction models based on size and PHASES stratification were able to correctly predict IA risk status, with > 80% testing accuracy for both. CONCLUSIONS: Here, we identified genes associated with IA risk, as quantified by common clinical metrics. Preliminary classification models demonstrated feasibility of assessing IA risk using whole blood expression.