Changes in treatment of intracranial aneurysms during the last decade in a large European neurovascular center.

OBJECTIVE: Treatment modality for ruptured and unruptured intracranial aneurysms has shifted during the last two decades from microsurgical treatment towards endovascular treatment. We present how this transition happened in a large European neurovascular center. METHODS: We conducted a retrospective observational study consecutive patients treated for an unruptured or ruptured intracranial aneurysm at Helsinki University Hospital during 2012-2022. We used Poisson regression analysis to report age-adjusted treatment trends by aneurysm location and rupture status. RESULTS: A total of 2491 patients with intracranial aneurysms were treated (44% ruptured, 56% unruptured): 1421 (57%) surgically and 1070 (43%) endovascularly. A general trend towards fewer treated aneurysms was noted. The proportion of patients treated surgically decreased from 90% in 2012 to 20% in 2022. The age-adjusted decrease of surgical versus endovascular treatment was 6.9%/year for all aneurysms, 6.8% for ruptured aneurysms, and 6.8% for unruptured aneurysms. The decrease of surgical treatment was most evident in unruptured vertebrobasilar aneurysms (10.8%/year), unruptured communicating artery aneurysms (10.1%/year), ruptured communicating artery aneurysms (10.0%/year), and ruptured internal carotid aneurysms (9.0%/year). There was no change in treatment modality for middle cerebral artery aneurysms, of which 85% were still surgically treated in 2022. A trend towards an increasing size for treated ruptured aneurysms was found (p = 0.033). CONCLUSION: A significant shift of the treatment modality from surgical to endovascular treatment occurred for all aneurysm locations except for middle cerebral artery aneurysms. Whether this shift has affected long-term safety and patient outcomes should be assessed in the future.

Trends in incidence and treatments of spontaneous subarachnoid hemorrhage- a 10 year hospital based study.

BACKGROUND: Improved endovascular methods make it possible to treat complex ruptured aneurysms, but surgery is still needed in certain cases. We evaluated the effects on the clinical results of the changes in aneurysm treatment. METHODS: The study cohort was 837 patients with spontaneous subarachnoid hemorrhage (SAH) and one or multiple aneurysms, admitted to Dept of Neurosurgery, Uppsala University Hospital from 2012 to 2021. Demography, location and treatment of aneurysms, neurologic condition at admission and discharge, mortality and last tier treatment of high intracranial pressure (ICP) was evaluated. Functional outcome was measured using the Extended Glasgow Outcome Scale (GOSE) Data concerning national incidences of stroke diseases was collected from open Swedish databases. RESULTS: Endovascular methods were used in 666 cases (79.6%). In 111 (13.3%) with stents. Surgery was performed in 115 cases (13.7%) and 56 patients (6.7%) had no aneurysm treatment. The indications for surgery were a hematoma (51 cases, 44.3%), endovascular treatment not considered safe (47 cases, 40.9%), or had been attempted without success (13 cases, 11.3%). Treatment with stent devices increased, and with surgery decreased over time. There was a trend in decrease in hemicraniectomias over time. Both the patient group admitted awake (n = 681) and unconscious (n = 156) improved significantly in consciousness between admission and discharge. Favorable outcome (GOSE 5-8) was seen in 69% for patients admitted in Hunt & Hess I-II and 25% for Hunt & Hess III-V. Mortality at one year was 10.9% and 42.7% for those admitted awake and unconscious, respectively.The number of cases decreased during the study period, which was in line with Swedish national data. CONCLUSIONS: The incidence of patients with SAH gradually decreased in our material, in line with national data. The treatment policy in our unit has been shifting to more use of endovascular methods. During the study period the use of hemicraniectomies decreased.

Metabolic alterations of peripheral blood immune cells and heterogeneity of neutrophil in intracranial aneurysms patients.

BACKGROUND: Intracranial aneurysms (IAs) represent a severe cerebrovascular disease that can potentially lead to subarachnoid haemorrhage. Previous studies have demonstrated the involvement of peripheral immune cells in the formation and progression of IAs. Nevertheless, the impact of metabolic alterations in peripheral immune cells and changes in neutrophil heterogeneity on the occurrence and progression of IAs remains uncertain. METHODS: Single-cell Cytometry by Time-of-Flight (CyTOF) technology was employed to profile the single-cell atlas of peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) in 72 patients with IAs. In a matched cohort, metabolic shifts in PBMC subsets of IA patients were investigated by contrasting the expression levels of key metabolic enzymes with their respective counterparts in the healthy control group. Simultaneously, compositional differences in peripheral blood PMNs subsets between the two groups were analysed to explore the impact of altered heterogeneity in neutrophils on the initiation and progression of IAs. Furthermore, integrating immune features based on CyTOF analysis and clinical characteristics, we constructed an aneurysm occurrence model and an aneurysm growth model using the random forest method in conjunction with LASSO regression. RESULTS: Different subsets exhibited distinct metabolic characteristics. Overall, PBMCs from patients elevated CD98 expression and increased proliferation. Conversely, CD36 was up-regulated in T cells, B cells and monocytes from the controls but down-regulated in NK and NKT cells. The comparison also revealed differences in the metabolism and function of specific subsets between the two groups. In terms of PMNs, the neutrophil landscape within patients group revealed a pronounced shift towards heightened complexity. Various neutrophil subsets from the IA group generally exhibited lower expression levels of anti-inflammatory functional molecules (IL-4 and IL-10). By integrating clinical and immune features, the constructed aneurysm occurrence model could precisely identify patients with IAs with high prediction accuracy (AUC = 0.987). Furthermore, the aneurysm growth model also exhibited superiority over ELAPSS scores in predicting aneurysm growth (lower prediction errors and out-of-bag errors). CONCLUSION: These findings enhanced our understanding of peripheral immune cell participation in aneurysm formation and growth from the perspectives of immune metabolism and neutrophil heterogeneity. Moreover, the predictive model based on CyTOF features holds the potential to aid in diagnosing and monitoring the progression of human IAs.

Trend of cerebral aneurysms over the past two centuries: need for early screening.

OBJECTIVE: Cerebral aneurysms (CAs) are linked to variations in the cerebral basal arterial network (CBAN). This study aimed to find the optimal age for screening to detect brain arterial variations and predict aneurysms before rupture. DESIGN: An observational, quantitative and retrospective research. SETTING: The study analysed 1127 cases of CAs published from 1761 to 1938. Additionally, CT angiography images of 173-patients at the Royal Adelaide Hospital (RAH), South Australia between 2011 and 2019 were examined for the presence and the location of aneurysms in CBAN. PARTICIPANTS: The data were collected from patients at RAH and 407 published sources, including males and females across the entire age range, up to 100 years old. OUTCOME MEASURES AND RESULTS: Data, CAs cases, from 1761 to 1938 included (526 males, 573 females and 28 unknown sexes). The age of these patients varied from 18 months to 89 years (mean age=42, SD=18). Approximately 11.5% of the CAs occurred in patients aged <20 years. Among the 1078 aneurysms whose location was reported, 76% were located in the internal carotid (IC), middle cerebral (MC) and anterior communicating artery complex (AcomAC) regions, while the remaining 24% were in the vertebrobasilar region. Among 173 patients from RAH aged between 18 and 100 years (male=83 and female=90, mean age=60, SD=16), 94% of the CAs were found in the IC, MC and AcomAC regions. The pattern of aneurysm occurrence, as indicated by values at the 25th, 50th and 75th percentiles, along with the minimum and maximum patient ages, has remained consistent from 1761 to 2019. CONCLUSION: The distribution pattern of CAs in relation to sex, age and locations in the CBAN, remained steady over the last 260 years resulting in risk of strokes early in life. Therefore, early screening for CBAN segment variations is advised for stroke prevention if possible.

Risk factors of unruptured intracranial aneurysms instability in the elderly.

BACKGROUND: Presently, a consistent strategy for determining the stability of unruptured intracranial aneurysms (UIAs) in elderly patients is lacking, primarily due to the unique characteristics of this demographic. Our objective was to assess the risk factors contributing to aneurysm instability (growth or rupture) within the elderly population. METHODS: In this study, we compiled data from follow-up patients with UIAs spanning from November 2016 to August 2021. We specifically focused on patients aged ≥ 60 years. Clinical histories were gathered, and morphological parameters of aneurysms were measured. The growth of aneurysms was determined using the computer-assisted semi-automated measurement (CASAM). Growth and rupture rates of UIAs were calculated, and both univariate and multivariate Cox regression analyses were conducted. Additionally, Kaplan-Meier survival curves were plotted. RESULTS: A total of 184 patients with 210 aneurysms were enrolled in the study. The follow-up period encompasses 506.6 aneurysm-years and 401.4 patient-years. Among all the aneurysms, 23 aneurysms exhibited growth, with an annual aneurysm growth rate of 11.0%, and 1 (4.5%) experienced rupture, resulting in an annual aneurysm rupture rate of 0.21%. Multivariate Cox analysis identified poorly controlled hypertension (P = 0.011) and high-risk aneurysms (including anterior cerebral artery (ACA), anterior communicating artery (AcoA), posterior communicating artery aneurysm (PcoA), posterior circulation (PC) > 4 mm or distal internal carotid artery (ICAd), middle cerebral artery (MCA), and PC > 7 mm) (P = 0.006) as independent risk factors for the development of unstable aneurysms. CONCLUSIONS: In the elderly, poorly controlled hypertension and high-risk aneurysms emerge as significant risk factors for aneurysm instability. This underscores the importance of rigorous surveillance or timely intervention in patients presenting with these risk factors.

Prevalence of pre-eclampsia in 265 patients with an intracranial aneurysm, 393 female relatives versus a control cohort: A case-control study.

BACKGROUND AND OBJECTIVES: There is emerging evidence on the connection between pre-eclampsia and saccular intracranial aneurysms (sIAs). Our aim was to study the prevalence of pre-eclampsia in sIA patients, their female relatives, and matched controls, and to examine familial sIA disease and familial pre-eclampsia in sIA patients' families. METHODS: We included all female sIA patients in the Kuopio Intracranial Aneurysm Patient and Family Database from 1995 to 2018. First, we identified the sIA patients, their female relatives, and matched population controls with the first birth in 1987 or later and studied the prevalence of pre-eclampsia. Second, all female sIA patients and all female relatives were analyzed for familial sIA disease and familial pre-eclampsia. Using the Finnish nationwide health registries, we obtained data on drug purchases, hospital diagnoses, and causes of death. RESULTS: In total, 265 sIA patients, 57 daughters, 167 sisters, 169 nieces, and 546 matched controls had the first birth in 1987 or later. Among them, 29 (11%) sIA patients, 5 (9%) daughters, 10 (6%) sisters, 10 (6%) nieces, and 32 (6%) controls had pre-eclampsia. Of all the 1895 female sIA patients and 12,141 female relatives, 68 sIA patients and 375 relatives had pre-eclampsia, including 32 families with familial pre-eclampsia. CONCLUSIONS: Pre-eclampsia was significantly more common in the sIA patients than in their matched controls. Familial sIA disease and familial pre-eclampsia co-occurred in seven families. Further studies of the mechanisms by which pre-eclampsia could affect the walls of brain arteries and increase the rupture risk in sIA disease are indicated.

Thromboembolic Events With the Woven Endobridge Device: Incidence, Predictive Factors, and Management.

BACKGROUND AND OBJECTIVES: The Woven EndoBridge (WEB) device has been increasingly used to treat wide-neck aneurysms showing a safe and effective profile, but a relatively high number of thromboembolic events (TEEs) have been reported with such treatment. We aimed to evaluate the incidence and management of TEEs and possible predictive factors related to WEB embolization of ruptured and unruptured intracranial aneurysms. METHODS: A single-center database with consecutive aneurysms treated with a WEB device between July 2012 and May 2022 was reviewed for intraoperative and delayed TEEs. Univariate and multivariable analyses were used to determine factors associated with TEEs. RESULTS: A total of 266 independent aneurysms were treated with WEB devices in 245 patients (mean age 55.78 ± 11.64 years, 169 (63.5%) females, 80 (30%) ruptured). The overall rate of TEEs is 13% (35/266), including 8.7% intraoperative. Symptomatic TEEs with clinical sequelae at a 3-month follow-up are reported to be 2.6% (7/266) with no TEE-related mortality. Both the replacement of a WEB device during the procedure (adjusted odds ratio = 2.61, 95% CI 1.24-5.49; P = .01) and ruptured aneurysms (adjusted odds ratio = 2.74, 95% CI 1.31-5.7; P = .007) were independent predictors of TEEs. A case-by-case management of intraprocedural TEE is also presented; tirofiban was successfully used in most cases of this cohort. CONCLUSION: In this study, we demonstrated that ruptured aneurysms and WEB device replacement during the procedure were independent predictive factors for TEEs. As a result, making the correct choice of WEB is crucial for improving treatment outcomes. Moreover, with proper medical management of TEEs, minimal morbidity and no mortality could be achieved, which reinforces the safety of the technique.

Gender Differences in Procedural Clinical Complications and Outcomes of Intracranial Aneurysms: Analysis of the Stroke Thrombectomy and Aneurysm Registry.

BACKGROUND AND OBJECTIVES: Some studies have shown that female patients had a poorer prognosis after endovascular treatment for ruptured intracranial aneurysm than male patients. However, data have been sparse regarding differences in the periprocedural and perioperative complication rate with ruptured and unruptured intracranial aneurysms. METHODS: This retrospective cohort study used data from the Stroke Thrombectomy and Aneurysm Registry, a database of 9 institutions in the United States, Europe, and Asia. The study presented intracranial aneurysms after microsurgical and/or endovascular treatment from January 1, 2013, to December 31, 2022. The primary outcome was incidence of periprocedural cerebral infarction. Secondary outcomes were periprocedural intracranial hemorrhage, periprocedural mortality, perioperative vasospasm, and functional outcome at 90 days after procedure. RESULTS: Among 3342 patients with aneurysm, 2447 were female and 857 were male, and the mean age of female and male patients was 59.6 and 57.1 years, respectively. Current smoker, family history of aneurysm, and ruptured aneurysm were observed in 23.5% vs 35.7 %, 10.8 % vs 5.7%, and 28.2% vs 40.5% of female and male patients, respectively. In female patients, internal carotid artery aneurysms were more commonly observed (31.1% vs 17.3%); however, anterior cerebral artery aneurysms were less commonly observed (18.5% vs 33.8%) compared with male patients. Periprocedural cerebral infarction rate was lower in female than male patients (2.4% vs 4.4%; P = .002). The adjusted odds ratio of primary outcome of female to male patients was 0.72 (95% CI, 0.46-1.12). Incidence of periprocedural intracranial hemorrhage and periprocedural mortality and perioperative symptomatic vasospasm and functional outcome was similar in both groups. In subgroup analysis, periprocedural cerebral infarction due to microsurgical treatment occurred frequently in male patients while incidence in endovascular treatment was similar in both groups (interaction P = .005). CONCLUSION: This large multicenter registry of patients undergoing intracranial aneurysm treatment found that female patients were not at increased risk of perioperative complications.

Role of temporary arterial occlusion in subarachnoid hemorrhage outcomes: a prospective cohort study.

PURPOSE: Temporary arterial occlusion (TAO) is a widespread practice in the surgical treatment of intracranial aneurysms. This study aimed to investigate TAO's role during ruptured aneurysm clipping as an independent prognostic factor on short- and long-term outcomes. METHODS: This prospective cohort included 180 patients with ruptured intracranial aneurysms and an indication of microsurgical treatment. Patients who died in the first 12 hours after admission were excluded. RESULTS: TAO was associated with intraoperative rupture (IOR) (odds ratio - OR = 10.54; 95% confidence interval - 95%CI 4.72-23.55; p < 0.001) and surgical complications (OR = 2.14; 95%CI 1.11-4.07; p = 0.01). The group with TAO and IOR had no significant difference in clinical (p = 0.06) and surgical (p = 0.94) complications compared to the group that had TAO, but no IOR. Among the 111 patients followed six months after treatment, IOR, number of occlusions, and total time of occlusion were not associated with Glasgow Outcome Scale (GOS) in the follow-up (respectively, p = 0.18, p = 0.30, and p = 0.73). Among patients who underwent TAO, IOR was also not associated with GOS in the follow-up (p = 0.29). CONCLUSIONS: TAO was associated with IOR and surgical complications, being the latter independent of IOR occurrence. In long-term analysis, neither TAO nor IOR were associated with poor clinical outcomes.

Natural history of intracavernous aneurysms: a consecutive single-center study of 250 patients with 276 aneurysms.

OBJECTIVE: The natural history of cavernous carotid aneurysms (CCAs) is not fully understood. For robust clinical decision-making, the behavior of CCAs needs to be fully understood. The objective of this paper was to calculate the mortality and morbidity rates of patients with diagnosed but untreated CCAs from a relatively large single-center cohort. METHODS: The authors identified 250 patients with 276 CCAs from August 1946 to August 2017 from an aneurysm database including 12,000 intracranial aneurysm patients. Patient and aneurysm characteristics were extracted for further analysis. RESULTS: The cumulative patient follow-up was 1560 years, with a mean of 6.3 years. For patients presenting with a cranial nerve deficit caused by a CCA, those with a ruptured CCA, and patients who received treatment for a CCA, the cumulative patient follow-up was 121 years, with a mean of 1.3 years. For patients with symptom-free or conservatively treated CCAs, the cumulative patient follow-up was 1093 years, with a mean of 7.2 years. Of the 276 aneurysms, 57 (21%) caused cranial nerve deficits and 18 (6.5%) other symptoms, while 201 (73%) remained symptom free. A total of 264 (96%) of the CCAs remained unruptured, and 2 were considered possibly ruptured. Ten (3.6%) ruptures of the CCAs were found. However, none of the ruptured aneurysms caused subarachnoid hemorrhage or death of the patient. Of the CCAs, 51 were multiple, and 131 patients had ≥ 1 intradural aneurysm. The CCAs were analyzed separately. CONCLUSIONS: The majority of the CCAs were asymptomatic during follow-up, and none caused the death of the patient. The incidence of symptoms increased with aneurysm size. Because CCAs have a benign natural course, treatment should be considered mainly if the CCA is symptomatic or grows during follow-up.

Analysis of independent risk factors for aneurysm rupture based on carotid tortuosity index and morphological parameters of single intracranial aneurysms in anterior circulation.

PURPOSE: Our study focused on the risk factors associated with anterior circulation intracranial aneurysm (IA) rupture by examining the carotid artery (CA) tortuosity index (TI) and anterior circulation IA morphological parameters. METHOD: This study conducted a retrospective analysis of clinical and imaging data from 163 patients with anterior circulation IA diagnosed by head and neck computed tomography angiography (CTA). The patients were categorized into two groups: the ruptured group (57 cases) and the unruptured group (106 cases). CA was categorized based on its location into three segments: the extracranial segment of the internal carotid artery (EICA) TI, the angle of the internal carotid artery (ICA) and the common carotid artery (CCA) TI. Measure the morphological parameters of all IA: IA length neck (L), IA height (H), aneurysm diameter width (D), the ratio of L to the mean diameter of the IA-bearing artery (SR), the ratio of H to D (AR), the angle of flow inflow (FA) and IA angle (AA). The study conducted five types of analysis to determine the risk factors for anterior circulation IA rupture. The first was an univariate analysis of the risk factors. The second was an analysis of the correlation between CA TI and IA morphological parameters. The third used multivariate logistic stepwise regression analysis to analyse independent risk factors for IA rupture. The fourth was to plot ROC curves to build a predictive model for IA rupture and calculate diagnostic thresholds. Finally, a data set from another hospital (78 cases) was used as a validation set to validate the multivariate model. RESULT: Univariate analysis revealed that there were statistically significant differences (P < 0.05) in gender, EICA TI, location of IA and IA morphological parameters (FA, H, AR, L, SR), which acted as risk factors for anterior circulation IA rupture. The results of Spearman correlation analysis indicate that CCA TI is significantly correlated with SR, H and L (P < 0.05), while EICA TI is significantly correlated with FA and L (P < 0.05). The results of multivariate logistic analysis showed that FA (OR = 1.072, 95%CI = 1.04-1.10, P < 0.001), SR (OR = 4.949, 95%CI = 1.96-12.53, P = 0.001), EICA TI (OR = 1.037, 95%CI = 1.01-1.07, P = 0.003) were independent risk factors for IA rupture. The ROC curve plotting results suggest that the area under the curve (AUC) of FA is 0.860 with a diagnostic threshold of 110.1°; the AUC of SR is 0.786 with a diagnostic threshold of 1.67; the AUC of EICA TI is 0.723 with a diagnostic threshold of 28.845; the AUC of the three combined is 0.903 with a threshold of 0.480. The combined factor diagnostic model is validated according to the validation set, and the results show that the AUC (0.866) of the validation set is not much different from the AUC (0.903) of the multivariate model, and the multivariate model has a better diagnostic effect. CONCLUSION: In clinical practice, it is important to consider the evaluation of aneurysm rupture in combination with imaging, as FA, SR and ECIA TI are independent risk factors for IA rupture in the anterior circulation. Unlike the IA morphological parameters, EICA TI is an often overlooked extracranial parameter, but is equally important in its power to predict IA rupture. When the EICA TI exceeds 28.845, the IA has the possibility of rupture. Finally, multivariate diagnostic model are of interest when considering rupture of the anterior circulation IA.

Subdural Hygroma After Management of Ruptured Intracranial Aneurysms: Incidence, Associated Factors, Clinical Course, and Management Options.

OBJECTIVE: To evaluate the incidence, associated factors, clinical course, and management options of subdural hygroma in patients treated for aneurysmal subarachnoid hemorrhage (aSAH). METHODS: From January 2013 until June 2022, 336 consecutive patients with aSAH underwent treatment in our center. No one patient was excluded from the study cohort. Computed tomography (CT) examinations were performed at admission, immediately after surgery and on the first postoperative day, and subsequently in case of any neurologic deterioration or, at least, once per week until discharge from the hospital. Thereafter, CT examinations were at the discretion of specialists in the rehabilitation facility, referring physicians, or neurosurgeons at the outpatient clinic. RESULTS: The length of radiologic follow-up starting from CT at admission ranged from 1 to 3286 days (mean, 673 ± 895 days; median, 150 days). Subdural hygromas developed in 84 patients (25%). An average interval until this imaging finding from the initial CT examination was 25 ± 55 days (median, 8 days; range, 0-362 days). Evaluation in the multivariate model showed that patient age ≥72 years (P < 0.0001), cerebrospinal fluid (CSF) shunting (P < 0.0001), and microsurgical clipping of ruptured intracranial aneurysm (RIA; P < 0.0001) are independently associated with the development of subdural hygroma. In 54 of 84 cases (64%), subdural hygromas required observation only. Increase of the lesion size with (5 cases) or without (10 cases) appearance of midline shift was associated with patient age <72 years (P = 0.0398), decompressive craniotomy (P = 0.0192), and CSF shunting (P = 0.0009), whereas evaluation of these factors in the multivariate model confirmed independent association of only CSF shunting (P = 0.0003). Active management of subdural hygromas included adjustment of the shunt programmable valve opening pressure, cranioplasty, external subdural drainage, or their combination. Overall, during follow-up (mean, 531 ± 824 days; median, 119 days; range, 2-3285 days) after the start of observation or applied treatment, subdural hygromas showed either decrease (50 cases) or stabilization (34 cases) of their sizes, and no one lesion showed progression again. CONCLUSIONS: The clinical course of subdural hygromas in patients treated for aSAH is generally favorable, but occasionally these lesions show progressive enlargement with or without the appearance of midline shift, which requires active management.

Prognostic factors affecting the ruptured intracranial aneurysms: A 9-year multicenter study in Fujian, China.

BACKGROUND: A multicenter retrospective study was conducted to explore the factors affecting short-term prognosis and long-term outcomes of intracranial aneurysms (IA) rupture. Further, the prognosis prediction model was constructed based on survival analysis, contributing to the development of prevention strategies for aneurysmal subarachnoid hemorrhage. METHODS: Data of 1280 patients with IA rupture were gathered between 2014 and 2022 in Fujian, China. Logistic regression was implemented to study the short-term prognostic factors of IA rupture. Survival analysis of 911 patients among them was performed to explore the long-term outcome status by Cox risk assessment. Nomogram prognosis models were constructed using R software. RESULTS: The findings displayed that blood type O (OR = 1.79; P = 0.019), high systolic pressure (OR = 1.01; P < 0.001), Glasgow Coma score (GCS) 9-12 (OR = 2.73; P = 0.022), GCS < 9 (OR = 3.222; P = 0.006), diabetes (OR = 2.044; P = 0.040), and high white blood cell count (OR = 1.059, P = 0.040) were core influencing factors for poor short-term prognosis. Survival analysis revealed that age > 60 years (HR = 2.87; P = 0.001), hypertension (HR = 1.95; P = 0.001), conservative (HR = 6.89; P < 0.001) and endovascular treatment (HR = 2.20; P = 0.001), multiple ruptured IAs (HR = 2.37; P = 0.01), Fisher 3 (HR = 1.68; P = 0.09), Fisher 4 (HR = 2.75; P = 0.001), and Hunt-Hess 3 (HR = 0.55; P = 0.05) were the major risk factors for terrible long-term outcomes. CONCLUSIONS: People over 60 years with characteristics of type O blood, high systolic pressure, diabetes, high white blood cell count, and onset GCS < 12 will have more complications and a worse short-term prognosis. Those aged > 60 years with hypertension, conservative and endovascular treatment, multiple ruptured IAs, Fisher ≥ 3 and Hunt-Hess 3 have a greater risk of poor long-term prognosis.

Risk of de novo aneurysm formation in patients previously diagnosed with a ruptured or unruptured aneurysm: 18-year follow-up.

BACKGROUND: Data on de novo aneurysm formation after treatment for intracranial aneurysms remains scarce. We studied the incidence of de novo aneurysm formation in patients who had undergone aneurysm treatment more than 18 years prior to follow-up. As it is a disease affecting a younger patient population more specific guidelines are needed when planning a follow-up regime. METHODS: The rate of de novo aneurysm formation was assessed with Magnetic Resonance Angiography (MRA) follow-up >18 years after endovascular or microsurgical treatment for an intracranial aneurysm. Variables associated with de novo aneurysm formation were studied using logistic regression. Missing data were imputed using chained random forests. A data-driven model for the prediction of de novo aneurysm was created to calculate the relative variable importance of ten clinical features. RESULTS: De novo aneurysms were identified in 11/81 (13.6 %) patients, of whom 1 was male, over a median follow-up of 20 years. Sex was the most important variable associated with de novo aneurysm formation. Regarding the development of de novo aneurysm, men displayed an odds ratio (OR) of 0.16 (0.01-0.97), compared with women. OR for mRS score 2 or more was 0.20 (95 % CI 0.01-1.34), and OR for smokers was 3.70 (0.54-31.18). Six out of 11 patients (54.5 %) needed treatment; 1 underwent endovascular treatment (EVT) and 5 underwent microsurgical treatment (MST). The overall annual de novo aneurysm formation rate was 0.92 %. CONCLUSIONS: This study highlights the need for a longer follow-up imaging monitoring of patients that have previously undergone treatment for an intracranial aneurysm. These data are useful to take into consideration when planning a follow-up strategy.

Immunoliposomes for detection of rupture-prone intracranial aneurysms.

BACKGROUND: It is estimated that significant (3.2%) of population carries intracranial aneurysm (IA). An increasing number of imaging studies have caused that the chance of finding an incidental aneurysm is becoming more common. Since IA rupture causes subarachnoidal hemorrhage (SAH) and have significant mortality and morbidity prophylactic treatment should be considered when IA is detected. The benefit and risk of treatment of IA is based on epidemiological estimate which takes account patient and aneurysm characteristics. However we know that aneurysm rupture is biological process where inflammation of aneurysm wall is actively leading to degeneration of aneurysm wall and finally weakens it until it bursts. Until now, there have not been imaging method to detect inflammatory process of aneurysm wall METHODS: We created targeting immunoliposome for use in the imaging of aneurysm. Immunoliposome comprises antibodies against at least one vascular inflammatory marker associated with aneurysm inflammation and a label and/or a contrast agent. RESULTS: Histological analysis of IAs where immunoliposome comprises antibodies against vascular inflammation with a label shows promising results for selectively detecting aneurysms inflammation. In magnetic resonance imaging (MRI) we were able to detect immunoliposomes carrying gadolinium. CONCLUSION: Our work opens a new avenue for using contrast labeled immunoliposomes for detecting rupture-prone aneurysms. Immunoliposomes can cary gadolinium and selectively bind to inflammatory section of aneurysm that can be detected with MRI. Further research is needed to develop immunoliposomes to be used with MRI in humans to target treatment to those patients who benefit from it the most.

Unruptured untreated intracranial aneurysms: a retrospective analysis of outcomes of 445 aneurysms managed conservatively.

BACKGROUND: Factors predicting the growth or rupture of unruptured intracranial aneurysms (UIAs) remain under debate. Increased availability of neuro-imaging has led to increasing incidental findings, therefore understanding the natural history is vital to make appropriate management and follow-up decisions. We analysed a large dataset of UIAs to better identify patients at increased risk, therefore requiring enhanced monitoring and/or prophylactic intervention. METHODS: Electronic patient records were reviewed from consecutive patients regarding the following data: baseline demographics; past medical and smoking history; indication for imaging detecting the UIA(s); size, location and morphology of UIA(s), duration of imaging follow-up, detection of growth and rupture. Logistic regression was used to identify risk factors for UIA growth or rupture. Subgroup analysis was performed for 'small' aneurysms (<7mm). RESULTS: 445 UIAs in 274 patients were analysed. Total imaging follow-up was 2268 aneurysm-years (median 3.8 years/UIA). 27 UIAs grew (1.2% annually), and 15 ruptured (0.46%). 70.1% of UIAs were detected incidentally. Mean aneurysm diameter was 4.1mm.Logistic regression identified age < 50, autosomal dominant polycystic kidney disease (ADPKD), hypertension and diameter > 7mm as significant risk factors for growth/rupture. Additionally, previous smoking compared to current smoking was a protective factor against growth or rupture, but no significant difference was seen when comparing current- with non-smokers. Small aneurysm subgroup analysis identified diameter > 5mm, age < 50, ADPKD, and ongoing smoking as risk factors. No significant difference was observed in risk between those with and without previous SAH. CONCLUSIONS: This study underlines the need for imaging surveillance of even small UIAs. Smoking is a modifiable risk factor for growth/rupture of pre-existing aneurysms, while ADPKD is a particularly strong risk factor.

Integrative analysis of multi-omics data to identify three immune-related genes in the formation and progression of intracranial aneurysms.

OBJECTIVE AND DESIGN: The prevalence of intracranial aneurysms (IAs) has increased globally. We performed bioinformatics analysis to identify key biomarkers associated with IA formation. METHODS AND RESULTS: We conducted a comprehensive analysis combined with multi-omics data and methods to identify immune-related genes (IRGs) and immunocytes involved in IAs. Functional enrichment analyses showed enhanced immune responses and suppressed organizations of extracellular matrix (ECM) during aneurysm progression. xCell analyses showed that the abundance of B cells, macrophages, mast cells, and monocytes significantly increased from levels in control to unruptured aneurysms and to ruptured aneurysms. Of 21 IRGs identified by overlapping, a three-gene (CXCR4, S100B, and OSM) model was constructed through LASSO logistic regression. The diagnostic ability of the three biomarkers in discriminating aneurysms from the control samples demonstrated a favorable diagnostic value. Among the three genes, OSM and CXCR4 were up-regulated and hypomethylated in IAs, while S100B was down-regulated and hypermethylated. The expression of the three IRGs was further validated by qRT-PCR and immunohistochemistry and mouse IA model using scRNA-seq analysis. CONCLUSION: The present study demonstrated heightened immune response and suppressed ECM organization in aneurysm formation and rupture. The three-gene immune-related signature (CCR4, S100B, and OSM) model may facilitate IA diagnosis and prevention.

Risk of Aneurysm Rupture (ROAR) study: protocol for a long-term, longitudinal, UK multicentre study of unruptured intracranial aneurysms.

INTRODUCTION: Unruptured intracranial aneurysms (UIA) are common in the adult population, but only a relatively small proportion will rupture. It is therefore essential to have accurate estimates of rupture risk to target treatment towards those who stand to benefit and avoid exposing patients to the risks of unnecessary treatment. The best available UIA natural history data are the PHASES study. However, this has never been validated and given the known heterogeneity in the populations, methods and biases of the constituent studies, there is a need to do so. There are also many potential predictors not considered in PHASES that require evaluation, and the estimated rupture risk is largely based on short-term follow-up (mostly 1 year). The aims of this study are to: (1) test the accuracy of PHASES in a UK population, (2) evaluate additional predictors of rupture and (3) assess long-term UIA rupture rates. METHODS AND ANALYSIS: The Risk of Aneurysm Rupture study is a longitudinal multicentre study that will identify patients with known UIA seen in neurosurgery units. Patients will have baseline demographics and aneurysm characteristics collected by their neurosurgery unit and then a single aggregated national cohort will be linked to databases of hospital admissions and deaths to identify all patients who may have subsequently suffered a subarachnoid haemorrhage. All matched admissions and deaths will be checked against medical records to confirm the diagnosis of aneurysmal subarachnoid haemorrhage. The target sample size is 20 000 patients. The primary outcome will be aneurysm rupture resulting in hospital admission or death. Cox regression models will be built to test each of the study's aims. ETHICS AND DISSEMINATION: Ethical approval has been given by South Central Hampshire A Research Ethics Committee (21SC0064) and Confidentiality Advisory Group support (21CAG0033) provided under Section 251 of the NHS Act 2006. The results will be disseminated in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN17658526.

An Analysis of the Incidence and Cost of Intracranial Aneurysm and Subarachnoid Haemorrhage Treatment between 2013 and 2021.

The incidence of unruptured intracranial aneurysms (UIAs) amounts to 3.2% among adults. The annual risk of aneurysm rupture is 2-10% and it results in subarachnoid haemorrhage (SAH). The aim of this study is to assess changes in the incidence of unruptured intracranial aneurysms and subarachnoid haemorrhages in Poland between 2013 and 2021 and the cost associated with their in-hospital treatment in the acute phase. The analysis was based on the National Health Fund database. Patients diagnosed with UIA and SAH and hospitalised between 2013 and 2021 were chosen. The statistical analysis was performed with an assumed significance level of α = 0.05. The ratio between the prevalence of SAH and UIA diagnoses was 4:6. The proportion of women in relation to men was higher in both diagnoses. The highest proportions of patients with diagnoses SAH and UIA were found in highly urbanised provinces. The value of medical services in 2021 compared to 2013 increased by 81.8%. The highest values in this period were recorded in Mazowieckie province, and the lowest were recorded in Opolskie province. The overall number of patients hospitalised with diagnosis of UIA or SAH did not decrease, but the risk of aneurysm rupture probably decreased, which resulted in lower incidence of SAH in subsequent years of observation. The recorded changes in the dynamics of the value of medical services per patient or per hospitalisation largely coincided. However, it is difficult to speculate on expected value levels as not all provinces showed linear changes in the value of services provided.

Risks for Oculomotor Nerve Palsy and Time to Recovery After Surgical Clipping of Posterior Communicating Artery Aneurysms: A Multicenter Retrospective Cohort Study.

BACKGROUND: Aneurysms of the posterior communicating segment of carotid artery (PcomA) have a high risk of rupture; when these nonruptured aneurysms are associated with oculomotor nerve palsy (ONP), the risk of rupture increases compared with asymptomatic nonruptured PcomA. OBJECTIVE: To retrospectively analyze the risk factors involved in ONP secondary to PcomA aneurysm and to study the factors involved in the recovery time of ONP once it is established. METHODS: This was a retrospective study of patients from 10 neurosurgery centers from October 2008 to December 2020. We analyzed age at diagnosis, presence of compressive neuropathy of the oculomotor nerve, presence of aneurysm rupture, largest aneurysm diameter, aneurysm projection, smoking, hypertension, diabetes, time between diagnosis and surgical treatment, as well as the outcome. RESULTS: Approximately 1 in 5 patients (119/511 23.3%) with a PcomA presented with ONP. We found that patients with aneurysms measuring greater than or equal to 7.5 mm were 1.6 times more likely to have ONP than those with aneurysms smaller than 7.5 mm. In our study, the prevalence of smoking in the PcomA + ONP group was 57.76%, and we also found that smokers were 2.51 times more likely to develop ONP. A total of 80.7% showed some degree of improvement, and 45.4% showed complete improvement with a median recovery time of 90 days. CONCLUSION: This study showed that 80.7% of patients with PcomA aneurysms undergoing surgical treatment with aneurysm clipping showed some degree of improvement of the ONP, with a median time to recovery between 90 and 120 days.