Growth Of Unruptured Intracranial Aneurysms Research Articles

From conservative to interventional management in unruptured intracranial aneurysms.

Indication for treatment of unruptured intracranial aneurysms (UIAs) is based on several factors, such as patient age, previous medical history, and UIA location and size. For patients harboring UIAs initially managed noninvasively, the treatment strategy during follow-up (FU) can be changed to include surgical or endovascular intervention. This study aims to identify characteristic patterns and potential predictors of UIAs that require revision of the initial management strategy. The authors identified intracranial aneurysm (IA) cases newly diagnosed between 2006 and 2022 and initially assigned conservative management. These cases were retrospectively reviewed for 1) patient and UIA characteristics at the time of diagnosis (patient age, comorbidities, previous medical history, potential risk factors, as well as UIA angioarchitecture, location, and size), and 2) any changes in treatment strategy (reason for change, time until intervention, modality of intervention). Among 1041 IA cases diagnosed in the study period, 144 were initially assigned conservative management. In 10 (6.9%) of these 144 cases, the treatment indication was modified to microsurgical clipping (n = 6) or endovascular embolization (n = 4) after a median FU of 26 months (IQR 8.5-64.5 months). In these 10 cases, the indication for intervention was attributable to IA growth (n = 7), a change in IA configuration (n = 2), or both (n = 1). Exploratory analyses of the effects of UIA size on diagnosis in terms of the hazard for a change of decision suggested an effect starting from 3 mm. No conservatively managed UIAs (n = 144) ruptured during the study period (median FU 24.5 months, IQR 7.75-55.75 months). The likelihood of a shift to invasive UIA treatment is relatively low if a conservative therapeutic strategy was initially established. However, for cases with changes to the treatment strategy, the change is most often attributable to UIA growth over time. UIAs measuring < 3 mm at initial diagnosis are less likely to be later treated interventionally than those > 3 mm at diagnosis. Therefore, conservatively managed patients with UIAs should be closely monitored with regular radiographic FUs, particularly if the UIA measured > 3 mm at the time of diagnosis.

A Decision Tree Model to Help Treatment Decision-Making for Unruptured Intracranial Aneurysms: A Multi-center, Long-Term Follow-up Study in a Large Chinese Cohort.

Chinese population have a high prevalence of unruptured intracranial aneurysm (UIA). Clinical and imaging risk factors predicting UIA growth or rupture are poorly understood in the Chinese population due to the lack of large-scale longitudinal studies, and the treatment decision for UIA patients was challenging. Develop a decision tree (DT) model for UIA instability, and validate its performance in multi-center studies. Single-UIA patients from two prospective, longitudinal multicenter cohort studies were analyzed, and set as the development cohort and validation cohort. The primary endpoint was UIA instability (rupture, growth, or morphological change). A DT was established within the development cohort and validated within the validation cohort. The performance of clinicians in identifying unstable UIAs before and after the help of the DT was compared using the area under curve (AUC). The development cohort included 1270 patients with 1270 UIAs and a follow-up duration of 47.2 ± 15.5months. Aneurysm instability occurred in 187 (14.7%) patients. Multivariate Cox analysis revealed hypertension (hazard ratio [HR], 1.54; 95%CI, 1.14-2.09), aspect ratio (HR, 1.22; 95%CI, 1.17-1.28), size ratio (HR, 1.31; 95%CI, 1.23-1.41), bifurcation configuration (HR, 2.05; 95%CI, 1.52-2.78) and irregular shape (HR, 4.30; 95%CI, 3.19-5.80) as factors of instability. In the validation cohort (n = 106, 12 was unstable), the DT model incorporating these factors was highly predictive of UIA instability (AUC, 0.88 [95%CI, 0.79-0.97]), and superior to existing UIA risk scales such as PHASES and ELAPSS (AUC, 0.77 [95%CI, 0.67-0.86] and 0.76 [95%CI, 0.66-0.86], P < 0.001). Within all 1376 single-UIA patients, the use of the DT significantly improved the accuracy of junior neurosurgical clinicians to identify unstable UIAs (AUC from 0.63 to 0.82, P < 0.001). The DT incorporating hypertension, aspect ratio, size ratio, bifurcation configuration and irregular shape was able to predict UIA instability better than existing clinical scales in Chinese cohorts. CLINICAL TRIAL REGISTRATION: IARP-CP cohort were included (unique identifier: ChiCTR1900024547. Published July 15, 2019. Completed December 30, 2020), with 100-Project phase-I cohort (unique identifier: NCT04872842, Published May 5, 2021. Completed November 8, 2022) as the development cohort. The 100-Project phase-II cohort (unique identifier: NCT05608122. Published November 8, 2022) as the validation cohort.

Risk factors of unruptured intracranial aneurysms instability in the elderly.

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. 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 ≥ 60years. 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. 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) > 4mm or distal internal carotid artery (ICAd), middle cerebral artery (MCA), and PC > 7mm) (P = 0.006) as independent risk factors for the development of unstable aneurysms. 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.

Peri-Aneurysmal Contact as a Risk Factor for Aneurysmal Rupture in Unruptured Intracranial Aneurysms: An Overview

The occurrence and growth of unruptured intracranial aneurysms are believed to be influenced by intraluminal factors of blood flow dynamics and pathological factors of the aneurysm wall. In addition to these, the deformation and rupture of aneurysms require consideration of physical extra-luminal factors due to contact between the aneurysm and surrounding structures including brain parenchyma, cranial nerves, arteries, veins, cranial base bone and dura mater. The extra-luminal factors of aneurysms were evaluated based on the presence of peri-aneurysmal contact. Peri-aneurysmal contact, depending on the type, location, and size of aneurysms, influenced the growth pattern of the aneurysm. Recently, with the imaging of magnetic resonance cisternography, it had become possible to non-invasively assess the anatomical relationship between the outer wall of aneurysms and the surrounding structures. Fusion images overlaying 3D magnetic resonance cisternography with 3D computed tomography angiography or 3D magnetic resonance angiography detailed the anatomical relationship of peri-aneurysmal contact, position of contact sites, and depth. We depicted the anatomical construction of peri-aneurysmal contact and bleb in unruptured intracranial aneurysms using fusion images and studied the intraluminal blood flow dynamics using computational fluid dynamics. As a result, peri-aneurysmal contact was observed to be involved as an independent variable in the process of bleb formation. It was suggested that factors extra-luminal to the aneurysm, such as peri-aneurysmal contact, might have a greater impact on bleb formation than intraluminal factors like blood flow dynamics. Peri-aneurysmal contact emerged as a noteworthy extra-luminal factor, particularly associated with bleb formation, presenting a substantial risk of rupture in unruptured intracranial aneurysms. These findings underscore the importance of considering the presence and extent of peri-aneurysmal contact alongside intraluminal and wall-related factors in future evaluations. The implications of this overview extend to the development of risk assessment protocols, providing valuable insights for guiding early intervention strategies and ultimately contributing to improved patient outcomes.

Clinical, 3D Morphological, and Hemodynamic Risk Factors for Instability of Unruptured Intracranial Aneurysms.

Neurosurgeons can manage unruptured intracranial aneurysms (UIAs). However, the stability of UIAs under follow-up remains uncertain. This study aimed to examine the risk factors associated with the instability (rupture or growth) of UIAs during follow-up. We obtained information on patients with UIA who underwent ≥ 6months of the time of flight-magnetic resonance angiography (TOF-MRA) imaging follow-up in two centers. Computer-assisted semi-automated measurement (CASAM) techniques were used for recording morphological parameters and determining the growth of these aneurysms. We also recorded hemodynamic parameters at the beginning of the follow-up. The univariate and multivariate Cox regression analyses were performed to calculate hazard ratios with corresponding 95% confidence intervals for the clinical, morphological, and hemodynamic risk factors for aneurysm instability. A total of 304aneurysms from 263patients (80.4%) were included for analysis. The annual aneurysm growth rate was 4.7%. Significant predictive factors for aneurysm instability in the multivariate analysis were as follows: poorly controlled hypertension (hazard ratio (HR), 2.97 (95% CI, 1.27-6.98), P = 0.012); aneurysms located on posterior circulation (HR, 7.81 (95% CI, 2.28-26.73), P = 0.001), posterior communication artery (HR, 3.01 (95% CI, 1.07-8.46), P = 0.036), and cavernous carotid artery (HR, 3.78 (95% CI, 1.18-12.17), P = 0.026); and size ratio ≥ 0.87 (HR, 2.54 (95% CI, 1.14-5.68), P = 0.023). The management of UIAs should focus on the control of hypertension during the follow-up. Aneurysms on the posterior communicating artery, posterior circulation, and cavernous carotid arteries require intensive surveillance or timely treatment.

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.

Image-derived Metrics Quantifying Hemodynamic Instability Predicted Growth of Unruptured Intracranial Aneurysms.

While image-derived predictors of intracranial aneurysm (IA) rupture have been well-explored, current understanding of IA growth is limited. Pulsatility index (PI) and wall shear stress pulsatility index (WSSPI) are important metrics measuring temporal hemodynamic instability. However, they have not been investigated in IA growth research. The present study seeks to verify reliable predictors of IA growth with comparative analyses of several important morphological and hemodynamic metrics between stable and growing cases among a group of unruptured IAs. Using 3D images, vascular models of 16 stable and 20 growing cases were constructed and verified using Geodesic techniques. With an overall mean follow-up period of 25 months, cases exhibiting a 10% or higher increase in diameter were considered growing. Patient-specific, pulsatile simulations were performed, and hemodynamic calculations were computed at 5 important regions of each aneurysm (inflow artery, aneurysm neck, body, dome, and outflow artery). Index values were compared between growing and stable IAs using ANCOVA controlling for aneurysm diameter. Stepwise multiple logistic regression and ROC analyses were conducted to investigate predictive models of IA growth. Compared to stable IAs, growing IAs exhibited significantly higher intrasaccular PI, intrasaccular WSSPI, intrasaccular spatial flow rate deviation, and intrasaccular spatial wall shear stress (WSS) deviation. Stepwise logistic regression analysis revealed a significant predictive model involving PI at aneurysm body, WSSPI at inflow artery, and WSSPI at aneurysm body. Our results showed that high degree of hemodynamic variations within IAs is linked to growth, even after controlling for morphological parameters. Further, evaluation of PI in conjunction with WSSPI yielded a highly accurate predictive model of IA growth. Upon validation in future cohorts, these metrics may aid in early identification of IA growth and current understanding of IA remodeling mechanism.

Spotlight on the August 30 Issue

![Graphic][1]</img>#### Notable in Neurology This Week This issue features an article that examines the association between sex, menopause, and white matter hyperintensities; another determines optimal surveillance strategies for unruptured intracranial aneurysm growth. A featured article examines the association of healthy lifestyles with risk of Alzheimer disease and related dementias in low-income Black and White Americans. ### Quantitative Muscle Analysis in FSHD Using Whole-Body Fat-Referenced MRI: Composite Scores for Longitudinal and Cross-sectional Analysis This prospective, observational, multicenter study in patients with facioscapulohumeral muscular dystrophy (FSHD) type 1 demonstrated … [1]: /embed/inline-graphic-1.gif

European Stroke Organisation (ESO) guidelines on management of unruptured intracranial aneurysms.

Unruptured intracranial aneurysms (UIA) occur in around 3% of the population. Important management questions concern if and how to perform preventive UIA occlusion; if, how and when to perform follow up imaging and non-interventional means to reduce the risk of rupture. Using the Standard Operational Procedure of ESO we prepared guidelines according to GRADE methodology. Since no completed randomised trials exist, we used interim analyses of trials, and meta-analyses of observational and case-control studies to provide recommendations to guide UIA management. All recommendations were based on very low evidence. We suggest preventive occlusion if the estimated 5-year rupture risk exceeds the risk of preventive treatment. In general, we cannot recommend endovascular over microsurgical treatment, but suggest flow diverting stents as option only when there are no other low-risk options for UIA repair. To detect UIA recurrence we suggest radiological follow up after occlusion. In patients who are initially observed, we suggest radiological monitoring to detect future UIA growth, smoking cessation, treatment of hypertension, but not treatment with statins or acetylsalicylic acid with the indication to reduce the risk of aneurysm rupture. Additionally, we formulated 15 expert-consensus statements. All experts suggest to assess UIA patients within a multidisciplinary setting (neurosurgery, neuroradiology and neurology) at centres consulting >100 UIA patients per year, to use a shared decision-making process based on the team recommendation and patient preferences, and to repair UIA only in centres performing the proposed treatment in >30 patients with (ruptured or unruptured) aneurysms per year per neurosurgeon or neurointerventionalist. These UIA guidelines provide contemporary recommendations and consensus statement on important aspects of UIA management until more robust data come available.

Surveillance of Unruptured Intracranial Aneurysms: Cost-Effectiveness Analysis for 3 Countries.

No consensus exists on adequate surveillance of conservatively managed unruptured intracranial aneurysms (UIAs). We aimed to determine optimal MRI surveillance strategies for the growth of UIAs using cost-effectiveness analysis. A secondary aim was to develop a clinical tool for personalizing UIA surveillance. We designed a microsimulation model from a health care perspective simulating 100,000 55-year-old women to estimate costs and quality-adjusted life years (QALYs) over a lifetime horizon in the United States, the United Kingdom, and the Netherlands, using literature-derived model parameters. Country-specific costs and willingness-to-pay thresholds ($100,000/QALY for the United States, £30,000/QALY for the United Kingdom, and €80,000/QALY for the Netherlands) were used. Lifetime costs and QALYs were annually discounted at 3% for the United States, 3.5% for the United Kingdom, or 4% (costs) and 1.5% (QALYs) for the Netherlands. Strategies were no follow-up surveillance, follow-up with MRI in the first and fifth year after UIA discovery, every 5 years, every 2 years, or annually, or immediate intervention (i.e., clipping or coiling). Using the microsimulation model, we developed a tool for personalizing UIA surveillance for men and women, with different ages and varying aneurysm characteristics. Uncertainty in the input parameters was modeled with probabilistic sensitivity analysis. Among 55-year-old women, 2,222 individuals in the United States, 1,910 in the United Kingdom, and 2,040 in the Netherlands needed to undergo an annual MRI scan to prevent 1 case of subarachnoid hemorrhage per year. No surveillance MRI was most cost-effective in the United States (in 47% of the simulations) and United Kingdom (in 54% of simulations), whereas annual MRI was most cost-effective in the Netherlands (in 53% of simulations). In the United States and United Kingdom, annual surveillance or surveillance in the first and fifth year after discovery was cost-effective in patients <60 years and at increased risk of aneurysm growth. The optimal, personalized, surveillance strategies were summarized in a look-up table for use in clinical practice. Generally, the US and UK physicians should refrain from assigning patients, particularly older patients and those with few risk factors for aneurysm growth or rupture, to frequent MRI surveillance. In the Netherlands, annual follow-up is generally most cost-effective.

Relationship between 3D Morphologic Change and 2D and 3D Growth of Unruptured Intracranial Aneurysms.

Untreated unruptured intracranial aneurysms are usually followed radiologically to detect aneurysm growth, which is associated with increased rupture risk. The ideal aneurysm size cutoff for defining growth remains unclear and also whether change in morphology should be part of the definition. We investigated the relationship between change in aneurysm size and 3D quantified morphologic changes during follow-up. We performed 3D morphology measurements of unruptured intracranial aneurysms on baseline and follow-up TOF-MRAs. Morphology measurements included surface area, compactness, elongation, flatness, sphericity, shape index, and curvedness. We investigated the relation between morphologic change between baseline and follow-up scans and unruptured intracranial aneurysm growth, with 2D and 3D growth defined as a continuous variable (correlation statistics) and a categoric variable (t test statistics). Categoric growth was defined as ≥1-mm increase in 2D length or width. We assessed unruptured intracranial aneurysms that changed in morphology and the proportion of growing and nongrowing unruptured intracranial aneurysms with statistically significant morphologic change. We included 113 patients with 127 unruptured intracranial aneurysms. Continuous growth of unruptured intracranial aneurysms was related to an increase in surface area and flatness and a decrease in the shape index and curvedness. In 15 growing unruptured intracranial aneurysms (12%), curvedness changed significantly compared with nongrowing unruptured intracranial aneurysms. Of the 112 nongrowing unruptured intracranial aneurysms, 10 (9%) changed significantly in morphology (flatness, shape index, and curvedness). Growing unruptured intracranial aneurysms show morphologic change. However, nearly 10% of nongrowing unruptured intracranial aneurysms change in morphology, suggesting that they could be unstable. Future studies should investigate the best growth definition including morphologic change and size to predict aneurysm rupture.

Growth of unruptured aneurysms: A meta-analysis of natural history and endovascular studies

The growth of unruptured intracranial aneurysms (UIAs) is a strong predictor of rupture. Clinical observations suggest that some UIAs might grow faster after endovascular treatment than untreated UIAs. There are no head-to-head comparisons of incidence rates of UIAs thus far. MethodsWe searched PubMed, Embase and Google Scholar for relevant articles from the inception of the databases to March 2020. We pooled and compared the incidence rates for the growth of aneurysms from natural history studies and endovascular treatment studies. Generalized linear models were used for confounder adjustment for the prespecified confounders age, size and location. ResultsTwenty-five studies (10 describing growth in natural history and 15 reporting growth after endovascular therapy) considering 6325 aneurysms were included in the meta-analysis. The median size of aneurysms was 3.7 mm in the natural history studies and 6.4 mm in endovascular treatment studies (p = 0.001). The pooled incidence rate (IR) of growth was significantly higher in endovascular treatment studies (IR 52 per 1000 person-years, with a 95% confidence interval (CI) 36–79) compared to natural history studies (IR 28 per 1000 person-years, 95% CI 17 – 46, p-value < 0.01) after adjustment for confounders. ConclusionOur results suggest that the incidence rate of cerebral aneurysm growth might be higher after endovascular therapy than the incidence rates reported in natural history studies. These results should be viewed in light of the risk of bias of the individual studies and the risk of ecological bias.

Reliability and Agreement of 2D and 3D Measurements on MRAs for Growth Assessment of Unruptured Intracranial Aneurysms

Reliable and reproducible measurement of unruptured intracranial aneurysm growth is important for unruptured intracranial aneurysm rupture risk assessment. This study aimed to compare the reliability and reproducibility of 2D and 3D growth measurements of unruptured intracranial aneurysms. 2D height, width, and neck and 3D volume measurements of unruptured intracranial aneurysms on baseline and follow-up TOF-MRAs were performed by two observers. The reliability of individual 2D and 3D measurements and of change (growth) between paired scans was assessed (intraclass correlation coefficient) and stratified for aneurysm location. The smallest detectable change on 2D and 3D was determined. Proportions of growing aneurysms were compared, and Bland-Altman plots were created. Seventy-two patients with 84 unruptured intracranial aneurysms were included. The interobserver reliability was good-to-excellent for individual measurements (intraclass correlation coefficient > 0.70), poor for 2D change (intraclass correlation coefficient < 0.5), and good for 3D change (intraclass correlation coefficient = 0.76). For both 2D and 3D, the reliability was location-dependent and worse for irregularly shaped aneurysms. The smallest detectable changes for 2D height, width, and neck and 3D volume measurements were 1.5 , 2.0, and 1.9 mm and 0.06 mL, respectively. The proportion of growing unruptured intracranial aneurysms decreased from 10% to 2%, depending on the definition of growth (1 mm or the smallest detectable changes for 2D and 3D). The interobserver reliability of the size measurements of individual 2D and 3D unruptured intracranial aneurysms was good-to-excellent but lower for 2D and 3D growth measurements. For growth assessment, 3D measurements are more reliable than 2D measurements. The smallest detectable change for 2D measurements was larger than 1 mm, the current clinical definition of unruptured intracranial aneurysm growth.

Knowledge framework and emerging trends in intracranial aneurysm magnetic resonance angiography: a scientometric analysis from 2004 to 2020.

As magnetic resonance angiography (MRA) has been increasingly used in the follow-up of intracranial aneurysms (IAs) as a non-invasive technique, the knowledge framework and areas of research interest in intracranial aneurysms magnetic resonance angiography (IAMRA) change approximately every 10 years. However, few studies have quantitatively analyzed the published literature in this field. In the present study, we used scientometrics to survey the knowledge field, development trends, and research focus of IAMRA with the aim of providing a reference for further study. We collected articles on IAMRA published from 2004 (Jan 1, 2004) to 2020 (May 24, 2020). Web of Science Core Collection databases (WoSCCd) including the Science Citation Index Expanded were searched. An experienced staff member from the Department of Radiology at Southern Medical University, assisted in screening articles for relevant articles. We used ArcGIS (a mapping and location analytics platform) to perform geographic visualization. Excel 2016 was used to analyze the literature data, including number of publications, impact factor (IF), and publication year. CiteSpace V was used to conduct a series of literature feature clustering, including author co-citation analysis, reference co-citation analysis (RCA), and burst keywords analysis. A total of 1,272 articles on IAMRA published between 2004 and 2020 were included. Of 257 journals, American Journal of Neuroradiology (IF 2018: 3.256) published the most IAMRA articles (109 publications, 8.57%), followed by Journal of Neurosurgery (IF 2018: 4.131, 51 publications, 4.16%), and Neuroradiology (IF 2018: 2.504, 51 publications, 4.01%). Of 56 countries, the USA published the most, with 347 articles [27.28%, IF: 3.14 (average IF of all journals in the country)], followed by Japan (242 articles, 19.03%, IF: 2.38), Germany (135 articles, 10.61%, IF: 3.21), and China (101 articles, 7.94%, IF: 2.86). A total of 1387 institutions published articles, with the Mayo Clinic publishing the most (33 articles, 2.59%), followed by Shanghai Jiao Tong University (25 article, 1.97%), Seoul National University (23 articles, 1.81%), and University Medical Center Utrecht (19 articles, 1.49%). Of 399 authors, Rinkel ranked first with 19 articles, followed by Li MH (18 articles), Uchino A (15 articles), and Saito N (13 articles). Cluster RCA showed that the first cluster was "#0 growth", followed by "#1 Guglielmi detachable coils". Timeline views showed that the time span of "#0 growth" was the closest to today. The modularity value was 0.6971, and the mean silhouette value was 0.5477. According to the burst keyword analysis, "risk factors associated to rupture" was the topic with the strongest burst since 2017. Studies conducted in several countries suggested that age is inversely related to the risk of rupture, which implies the importance of MRA follow-up for patients of different age. From 2004 to 2020, the number of published IAMRA-related articles gradually increased. The USA and Western Europe lead in the field, with a concentration of cutting-edge talents and high-level scientific research institutions. A synthesis of the clustering results of RCA and burst keyword analysis indicated that unruptured IA growth, stent-assisted coil embolization, and risk factors associated to rupture were the current hotspots in IAMRA research.

Atorvastatin and growth, rupture of small unruptured intracranial aneurysm: results of a prospective cohort study

Background and aims:The role of statins in unruptured intracranial aneurysm (UIA) growth and rupture remains ambiguous. This study sought to determine whether atorvastatin is associated with aneurysm growth and rupture in patients harboring UIA <7 mm.Methods:This prospective, multicenter cohort study consecutively enrolled patients with concurrent UIA <7 mm and ischemic cerebrovascular disease from four hospitals between 2016 and 2019. Baseline and follow-up patient information was recorded. Because of the strong anti-inflammatory effect of aspirin, patients using aspirin were excluded. Patients taking atorvastatin 20 mg daily were atorvastatin users. The primary and exploratory endpoints were aneurysm rupture and growth, respectively.Results:Among the 1087 enrolled patients, 489 (45.0%) took atorvastatin, and 598 (55%) took no atorvastatin. After a mean follow-up duration of 33.0 ± 12.5 months, six (1.2%) and five (0.8%) aneurysms ruptured in atorvastatin and non-atorvastatin groups, respectively. In the adjusted multivariate Cox analysis, UIA sized 5 to <7 mm, current smoker, and uncontrolled hypertension were associated with aneurysm rupture, whereas atorvastatin [adjusted hazard ratio (HR) 1.495, 95% confidence interval (CI) 0.417–5.356, p = 0.537] was not. Of 159 patients who had follow-up imaging, 34 (21.4%) took atorvastatin and 125 (78.6%) took no atorvastatin. Aneurysm growth occurred in five (14.7%) and 21 (16.8%) patients in atorvastatin and non-atorvastatin groups (mean follow-up: 20.2 ± 12.9 months), respectively. In the adjusted multivariate Cox analysis, UIAs sized 5 to <7 mm and uncontrolled hypertension were associated with a high growth rate; atorvastatin (adjusted HR 0.151, 95% CI 0.031–0.729, p = 0.019) was associated with a reduced growth rate.Conclusions:We conclude atorvastatin use is associated with a reduced risk of UIA growth, whereas atorvastatin is not associated with UIA rupture.The trial registry name:The Clinic Benefit and Risk of Oral Aspirin for Unruptured Intracranial Aneurysm Combined With Cerebral IschemiaClinical Trial Registration-URL: http://www.clinicaltrials.gov Unique identifier:NCT02846259

Scoring of Growth of Unruptured Intracranial Aneurysms.

The purpose was to obtain a reliable scoring for growth of unruptured intracranial aneurysms (UIAs) in a long-term follow-up study from variables known at baseline and to compare it with the ELAPSS (Earlier subarachnoid hemorrhage, Location of the aneurysm, Age > 60 years, Population, Size of the aneurysm, and Shape of the aneurysm) score obtained from an individual-based meta-analysis. The series consists of 87 patients with 111 UIAs and 1669 person-years of follow-up between aneurysm size measurements (median follow-up time per patient 21.7, range 1.2 to 51.0 years). These were initially diagnosed between 1956 and 1978, when UIAs were not treated in our country. ELAPSS scores at baseline did not differ between those with and those without aneurysm growth. The area under the curve (AUC) for the receiver operating curve (ROC) of the ELAPSS score for predicting long-term growth was fail (0.474, 95% CI 0.345–0.603), and the optimal cut-off point was obtained at ≥7 vs. <7 points for sensitivity (0.829) and specificity (0.217). In the present series UIA growth was best predicted by female sex (4 points), smoking at baseline (3 points), and age <40 years (2 points). The AUC for the ROC of the new scoring was fair (0.662, 95% CI 0.546–0.779), which was significantly better than that of ELAPSS score (p < 0.05). The optimal cut-off point was obtained at ≥4 vs. <4 points for sensitivity (0.971) and specificity (0.304). A new simple scoring consisting of only female sex, cigarette smoking and age <40 years predicted growth of an intracranial aneurysm in long-term follow-up, significantly better than the ELAPSS score.

Aspirin and Growth of Small Unruptured Intracranial Aneurysm: Results of a Prospective Cohort Study.

The role of aspirin in unruptured intracranial aneurysm (UIA) growth remains largely unknown. We aim to identify whether aspirin is associated with a lower rate of UIA growth in patients with UIA <7 mm. This prospective cohort study consecutively enrolled patients with UIAs <7 mm with ischemic cerebrovascular disease between January 2016 and December 2019. Baseline and follow-up patient information, including the use of aspirin and blood pressure level, were recorded. Patients were considered aspirin users if they took aspirin, including standard- and low-dose aspirin, ≥3× per week. The primary end point was aneurysm growth in any direction or an indisputable change in aneurysm shape. Among the 315 enrolled patients, 272 patients (86.3%) underwent imaging examinations during follow-up (mean follow-up time, 19.6±12.7 months). A total of 113 patients were continuously treated with aspirin. UIA growth occurred in 31 (11.4%) patients. In the multivariate Cox analysis, specific aneurysm locations (anterior communicating artery, posterior communicating artery, or middle cerebral artery; hazard ratio, 2.89 [95% CI, 1.22-6.88]; P=0.016) and a UIA size of 5 to <7 mm (hazard ratio, 7.61 [95% CI, 3.02-19.22]; P<0.001) were associated with a high risk of UIA growth, whereas aspirin and well-controlled blood pressure were associated with a low risk of UIA growth (hazard ratio, 0.29 [95% CI, 0.11-0.77]; P=0.013 and hazard ratio, 0.25 [95% CI, 0.10-0.66]; P=0.005, respectively). The cumulative annual growth rates were as high as 40.0 and 53.3 per 100 person-years in the high-risk patients (>1 risk factor) with and without aspirin, respectively. Aspirin therapy and well-controlled blood pressure are associated with a low risk of UIA growth; the incidence of UIA growth in high-risk patients in the first year is high, warranting intensive surveillance in this patient group. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02846259.

Increased Wall Enhancement During Follow-Up as a Predictor of Subsequent Aneurysmal Growth.

Background and Purpose- Absence of arterial wall enhancement (AWE) of unruptured intracranial aneurysms (UIA) has shown promise at predicting which aneurysms will not rupture. We here tested the hypothesis that increased enhancement during follow-up (increased intensity, extension, or thickness or appearance of de novo enhancement), assessed using vessel wall magnetic resonance imaging, was associated with higher rates of subsequent growth. Methods- Patients with UIA were included between 2012 and 2018. Two readers independently rated AWE modification on 3T vessel wall magnetic resonance imaging, and morphological changes on time-of-flight magnetic resonance angiography during follow-up. Results- A total of 129 patients harboring 145 UIA (mean size 4.1 mm) met study criteria, of which 12 (8.3%) displayed morphological growth at 2 years. Of them, 8 demonstrated increased AWE during follow-up before or concurrently to morphological growth, and 4 had preexisting AWE that remained stable before growth. In the remaining 133 (nongrowing) UIAs, no AWE modifications were found. In multivariable analysis, increased AWE, not size, was associated with UIA growth (relative risk, 26.1 [95% CI, 7.4-91.7], P<0.001). Sensitivity, specificity, positive predictive value, and negative predictive value for UIA growth of increased AWE during follow-up were, respectively, of 67%, 100%, 96%, and 100%. Conclusions- Increased AWE during follow-up of conservatively managed UIAs predicts aneurysm growth over a 2-year period. This may impact UIA management towards closer monitoring or preventive treatment. Replication in a different setting is warranted.

Management of Unruptured Cerebral Aneurysms and Arteriovenous Malformations.

Unruptured intracranial aneurysms and brain arteriovenous malformations (AVMs) may be detected as incidental findings on cranial imaging. This article provides a practical approach to the management of unruptured intracranial aneurysms and unruptured brain AVMs and reviews the risk of rupture, risk factors for rupture, preventive treatment options with their associated risks, and the approach of treatment versus observation for both types of vascular malformations. For unruptured intracranial aneurysms, scoring systems on the risk of rupture can help with choosing preventive treatment or observation with follow-up imaging. Although the literature provides detailed information on the complication risks of preventive treatment of unruptured intracranial aneurysms, individualized predictions of these procedural complication risks are not yet available. With observation with imaging, growth of unruptured intracranial aneurysms can be monitored, and prediction scores for growth can help determine the optimal timing of monitoring. The past years have revealed more about the risk of complications of the different treatment modalities for brain AVMs. A randomized clinical trial and prospective follow-up data have shown that preventive interventional therapy in patients with brain AVMs is associated with a higher rate of neurologic morbidity and mortality compared with observation. The risk of hemorrhage from both unruptured intracranial aneurysms and brain AVMs varies depending on the number of risk factors associated with hemorrhage. For both types of vascular malformations, different preventive treatment options are available, and all carry risks of complications. For unruptured intracranial aneurysms, the consideration of preventive treatment versus observation is complex, and several factors should be included in the decision making. Overall, it is recommended that patients with unruptured asymptomatic brain AVMs should be observed.

Decreased contrast enhancement on high-resolution vessel wall imaging of unruptured intracranial aneurysms in patients taking aspirin.

Inflammation plays an integral role in the formation, growth, and progression to rupture of unruptured intracranial aneurysms (UIAs). Animal and human studies have suggested that, due to its antiinflammatory effect, aspirin (ASA) may decrease the risks of growth and rupture of UIAs. High-resolution vessel wall imaging (HR-VWI) has emerged as a noninvasive method to assess vessel wall inflammation and UIA instability. To the authors' knowledge, to date no studies have found a significant correlation between patient use of ASA and contrast enhancement of UIAs on HR-VWI. The University of Iowa HR-VWI Project database was analyzed. This database is a compilation of data on patients with UIAs who prospectively underwent HR-VWI on a 3T Siemens MRI scanner. The presence of aneurysmal wall enhancement was objectively defined using the aneurysm-to-pituitary stalk contrast ratio (CRstalk). This ratio was calculated by measuring the maximal signal intensity in the aneurysmal wall and the pituitary stalk on postcontrast T1-weighted images. Data on aneurysm size, morphology, and location and patient demographics and comorbidities were collected. Use of ASA was defined as daily intake of ≥ 81 mg during the previous 6 months or longer. Univariate and multivariate logistic regression analyses were performed to determine factors independently associated with increased contrast enhancement of UIAs on HR-VWI. In total, 74 patients harboring 96 UIAs were included in the study. The mean patient age was 64.7 ± 12.4 years, and 60 patients (81%) were women. Multivariate analysis showed that age (OR 1.12, 95% CI 1.05-1.19), aneurysm size ≥ 7 mm (OR 21.3, 95% CI 4.88-92.8), and location in the anterior communicating, posterior communicating, and basilar arteries (OR 10.7, 95% CI 2.45-46.5) were significantly associated with increased wall enhancement on HR-VWI. On the other hand, use of ASA was significantly associated with decreased aneurysmal wall enhancement on HR-VWI (OR 0.22, 95% CI 0.06-0.83, p = 0.026). The study results establish a correlation between use of ASA daily for ≥ 6 months and significant decreases in wall enhancement of UIAs on HR-VWI. The findings also demonstrate that detection of wall enhancement using HR-MRI may be a valuable noninvasive method for assessing aneurysmal wall inflammation and UIA instability.