Management Of Unruptured Intracranial Aneurysms Research Articles

European survey on follow-up strategies for unruptured intracranial aneurysms

IntroductionThe increasing detection rates of unruptured intracranial aneurysms (UIA) pose a challenge for both neurovascular centers, tasked with managing a growing pool of patients requiring regular monitoring with imaging, and the healthcare system that must bear the costs of such surveillance. While there is consensus on the need for follow-up of UIA, uncertainties persist regarding the optimal cessation of surveillance, especially when considering diverse patient risk factors and, notably, in cases of treated aneurysms with stable rest perfusion. Detailed guidelines on UIA follow-up are currently lacking, exacerbating these challenges. Research questionWe sought to investigate European strategies for follow-up of untreated, microsurgically and endovascularly treated UIA. Material and methodsAn online survey consisting of 15 questions about follow-up management of UIA was sent out to the cerebrovascular section of the European Association of Neurosurgical Societies (EANS). ResultsThe survey response rate was 27.3% (68/249). There was consenus upon the necessity for long-term follow-up of UIA (100% [n = 68]). The recommendation to perform follow-up was inversely correlated with patient age and more prevalent among endovascularly compared to microsurgically treated patients (92.6% [n = 63] vs. 70.6% [n = 48]). A majority recommended continued follow-up of treated aneurysms with stable rest perfusion, with lifelong surveillance in patients under 60 years and continuation for 5–10 years in patients aged 61–80, irrespective of whether they underwent microsurgical (38.3% [n = 23]; 33.3% [n = 20]) or endovascular (41.9% [n = 26]; 30.6% [n = 19]) treatment. Discussion and conclusionThis survey confirmed a European consensus on the necessity of long-term follow-up for untreated UIA. However, significant variations in follow-up strategies, especially for treated UIA and post-treatment rest perfusion, were noted. Despite limited evidence suggesting low risk from aneurysm remnants, respondents favored long-term follow-up, highlighting uncertainty in management. This underscores the need for collaborative research on aneurysm remnants and standardized follow-up protocols for UIA in Europe.

Optimal PHASES Scoring for Risk Stratification of Surgically Treated Unruptured Aneurysms

The PHASES (Population, Hypertension, Age, Size, Earlier subarachnoid hemorrhage, Site) score was developed to facilitate risk stratification for management of unruptured intracranial aneurysms (UIAs). This study aimed to identify the optimal PHASES score cutoff for predicting neurologic outcomes in patients with surgically treated aneurysms. All patients who underwent microneurosurgical treatment for UIA at a large quaternary center from January 1, 2014, to December 31, 2020, were retrospectively reviewed. Inclusion criteria included a modified Rankin Scale (mRS) score of ≤2 at admission. The primary outcome was 1-year mRS score, with a "poor" neurologic outcome defined as an mRS score >2. In total, 375 patients were included in the analysis. The mean (SD) PHASES score for the entire study population was 4.47 (2.67). Of 375 patients, 116 (31%) had a PHASES score ≥6, which was found to maximize prediction of poor neurologic outcome. Patients with PHASES scores ≥6 had significantly higher rates of poor neurologic outcome than patients with PHASES scores <6 at discharge (58 [50%] vs. 90 [35%], P= 0.005) and follow-up (20 [17%] vs. 18 [6.9%], P= 0.002). After adjusting for age, Charlson Comorbidity Index score, nonsaccular aneurysm, andaneurysm size, PHASES score ≥6 remained a significant predictor of poor neurologic outcome at follow-up (odds ratio, 2.75; 95% confidence interval, 1.42-5.36, P= 0.003). In this retrospective analysis, a PHASES score ≥6 was associated with significantly greater proportions of poor outcome, suggesting that awareness of this threshold in PHASES scoring could be useful in risk stratification and UIA management.

Safety and Efficacy of Endovascular Coils and Non–Flow-Diverting Stents for Management of Unruptured Intracranial Aneurysms: A Location-Specific Outcomes Analysis

IntroductionThe relationship between the anatomical location of an unruptured saccular aneurysm, the efficacy and the potential complications associated with coil and non-flow-diverting stents remains poorly documented. Therefore, the aim of this study is to evaluate the efficacy and safety of endovascular treatment based on the anatomical position of the unruptured intracranial aneurysm (UIA). MethodsA retrospective cohort study was conducted using an anonymized database of patients who underwent endovascular therapy for UIA between 2014 and 2021. Results138 patients with 147 UIA were included. The immediate Raymond Roy I-II occlusion was achieved in 99.2% of patients in all anatomical locations, with a 96.2% occlusion rate at the 12-month follow-up. Complications occurred more frequently in the anterior cerebral artery (35%) and the internal carotid artery in its ophthalmic segment (25%), however the difference was not statistically significant. ConclusionOur study shows that endovascular treatment with stents and coils is effective and safe for managing unruptured intracranial aneurysms in various anatomical locations. Thromboembolic complications were significantly higher in the anterior cerebral artery located aneurysms.

Abstract 176: Management of Unruptured Intracranial Aneurysms in SubArachnoid Hemorrhage

Introduction Subarachnoid hemorrhage (SAH) has an estimated prevalence of 7.9 per 100,000 person yearsi. It is primarily caused by the rupture of intracranial aneurysms, leading to severe consequences and a 60% 6‐month mortality rateii. The management of UIAs in SAH cases poses a unique dilemma due to the potential increased risk of rupture, especially when the exact source of SAH remains ambiguous in the presence of multiple UIAs. Although tools like the PHASES scoreiii and the Unruptured Intracranial Aneurysms Treatment Score (UIATS)iv help guide aneurysm management, they are not tailored specifically to the scenario of UIAs in SAH. Thus, there is a need to study and comprehend the management strategies and outcomes of these cases. We reviewed the management and outcomes of UIAs in SAH at our institution in the past 10 years. Methods A retrospective review of all patients presenting between July 2013 and July 2023 with SAH and one concomitant UIA at our institution were analyzed. Results A total of 79 patients with confirmed UIA on angiography met inclusion criteria. Of these, 20 patients (25.3%) with UIAs were intervened on, as opposed to 59 (74.7%) that were not. UIAs &gt;7 mm in diameter were found in 6 patients, and of these, 5 patients received intervention. 45.6% of the patients had a Hunt Hess Score of ≥3, and of these, 27.8% were intervened on. 72.2% of the patients had a Modified Fisher score &gt;2, and of these, only 22.8% of the UIAs were intervened on. 58.2% of patients had a PHASES score &gt;3, and of these, 34.7% were intervened on. Of the patients that were intervened on, 80% had a PHASES score &gt;3. There was no significant difference in the UIATS score between the two groups. 34.9% of patients were noted to have the UIA in the same vascular territory as the SAH and of these 36.3% were intervened on. Current use of blood thinning medication, personal history of SAH or UIA, hypertension history, age, nor gender significantly affected the rate of UIA intervention Conclusion The majority of the UIAs in SAH were not intervened on, and the PHASES score and the UIATS score did not correlate with the decision on intervention. Of the ones that were intervened on, most of them were in the same vascular territory as the SAH. The decision to intervene appears to be on a case‐by‐case basis.

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.

Differences between real-world and score-based decision-making in the microsurgical management of patients with unruptured intracranial aneurysms.

Management of unruptured intracranial aneurysms (UIAs) is complex, balancing the risk of rupture and risk of treatment. Therefore, prediction scores have been developed to support clinicians in the management of UIAs. We analyzed the discrepancies between interdisciplinary cerebrovascular board decision-making factors and the results of the prediction scores in our cohort of patients who received microsurgical treatment of UIAs. Clinical, radiological, and demographical data of 221 patients presenting with 276 microsurgically treated aneurysms were collected, from January 2013 to June 2020. UIATS, PHASES, and ELAPSS were calculated for each treated aneurysm, resulting in subgroups favoring treatment or conservative management for each score. Cerebrovascular board decision-factors were collected and analyzed. UIATS, PHASES, and ELAPSS recommended conservative management in 87 (31.5%) respectively in 110 (39.9%) and in 81 (29.3%) aneurysms. The cerebrovascular board decision-factors leading to treatment in these aneurysms (recommended to manage conservatively in the three scores) were: high life expectancy/young age (50.0%), angioanatomical factors (25.0%), multiplicity of aneurysms (16.7%). Analysis of cerebrovascular board decision-making factors in the "conservative management" subgroup of the UIATS showed that angioanatomical factors (P=0.001) led more frequently to surgery. PHASES and ELAPSS subgroups "conservative management" were more frequently treated due to clinical risk factors (P=0.002). Our analysis showed more aneurysms were treated based on "real-world" decision-making than recommended by the scores. This is because these scores are models trying to reproduce reality, which is yet not fully understood. Aneurysms, which were recommended to manage conservatively, were treated mainly because of angioanatomy, high life expectancy, clinical risk factors, and patient's treatment wish. The UIATS is suboptimal regarding assessment of angioanatomy, the PHASES regarding clinical risk factors, complexity, and high life expectancy, and the ELAPSS regarding clinical risk factors and multiplicity of aneurysms. These findings support the need to optimize prediction models of UIAs.

Endovascular and Medical Management of Unruptured Intracranial Aneurysms.

Unruptured intracranial aneurysms are often discovered incidentally on noninvasive imaging. As use of noninvasive imaging has increased, our understanding of the presumed prevalence of intracranial aneurysms in adults has increased. Incidentally found aneurysms are often asymptomatic; however, they can rarely rupture and cause life-threatening illness. Elective treatment of intracranial aneurysms carries risks which need to be considered along with patient-specific factors (e.g., anatomy, medical comorbidities, personal preferences). In this article, we review the natural history, risk factors for cerebral aneurysm formation and rupture, evidence for medical management, and the safety profile and efficacy of available endovascular treatment options.

Management of Unruptured Intracranial Aneurysms and Brain Arteriovenous Malformations.

Managing a patient with an unruptured brain aneurysm or brain arteriovenous malformation (AVM) can lead to uncertainty about preventive treatment. While the bleeding risks are low, the morbidity or mortality associated with a hemorrhagic event is not insignificant. The objective of this article is to review the natural history of these vascular entities, the risk factors for hemorrhage, preventive treatment options, and the risks of treatment. Randomized trials to inform preventive treatment strategies for unruptured intracranial aneurysms and brain AVMs are ongoing. Higher angiographic obliteration rates of unruptured intracranial aneurysms have been reported with the flow-diversion technique compared with alternative standard techniques. One randomized trial for unruptured brain AVMs showed a higher rate of morbidity and mortality in patients who underwent interventional treatment compared with observation. The decision to treat a patient with a brain aneurysm should consider patient factors, the patient's life expectancy, aneurysm anatomical factors, and treatment risks. Patients with unruptured brain AVMs should be observed in light of recent clinical trial data or enrolled in an ongoing clinical trial.

A comparison of antiplatelet therapy during the peri- and post-operative periods following flow-diverting stent insertion for unruptured intracranial aneurysms: A systematic review.

Flow diverters (FDs) are neuroendovascular stents indicated for the management of unruptured intracranial aneurysms. Due to their composition, dual antiplatelet therapy (DAPT) is essential during the peri- and post-operative periods to prevent thromboembolic events. However, there is limited consensus within the scientific community regarding which antiplatelets to use and dosing following neuroendovascular treatment of aneurysms. A systematic search of four electronic databases was conducted during November 2020 that included studies published between January 2010 and November 2020. Eligibility for inclusion included primary research articles, published in the English language and use of flow-diverting intracranial stents. Studies were excluded if they utilised combined therapies (e.g. FD with stent-assisted coiling), animal studies, clinical trial protocols and study population of less than 10 subjects. Eighteen studies were identified for inclusion with a total of 1312 patients with 1355 unruptured intracranial aneurysms treated with FDs. Of these, 13 studies primarily investigated the use of clopidogrel with aspirin with low rates of haemorrhagic and thromboembolic complications. A forest plot of nine of these studies showed average efficacy of 88% at 95% confidence interval (CI) (SD + 5%) with 63% heterogeneity. The large proportion of studies investigating clopidogrel and aspirin antiplatelet therapy presents a challenge in comparing antiplatelet regimens. Although prasugrel and ticagrelor have been identified as suitable alternatives to clopidogrel, these were based on studies with small cohort sizes. Glycoprotein IIb/IIIa inhibitors may be efficacious as rescue therapy for intra-procedural thrombosis. Further research is required to determine which antiplatelet is most suitable.

Altered gut microbiomes are associated with the symptomatic status of unruptured intracranial aneurysms.

Gut microbiome has recently been recognized as an important environmental factor affecting the occurrence and development of unruptured intracranial aneurysms (UIA). This study aimed to investigate the relationship between gut microbiome and symptomatic UIA, which is a predictor of instability and a high propensity to rupture. A total of 132 patients including 86 asymptomatic UIA and 46 symptomatic UIA were recruited in the study. The composition of gut bacterial communities was determined by 16S ribosomal RNA gene sequencing. In addition, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict the functional composition of the gut microbiome. There is no difference in the fecal microbial alpha diversity between symptomatic and asymptomatic UIA, but gut microbiome composition changed significantly. At the order level, the relative abundance of Clostridiales was significantly enriched in the symptomatic compared with asymptomatic UIA (p = 0.043). In addition, similar alterations were observed at the family levels of Ruminococcaceae. The Linear discriminant analysis (LEfSe) revealed Fournierella, Ruthenibacterium, and Anaerotruncus as discriminative features in the symptomatic group. Notably, functional differences in gut microbiome of patients with symptomatic UIA included decreased propionate metabolism pathway and enrichment of peptidoglycan biosynthesis pathways. The present study comprehensively characterizes gut microbiome in a large cohort of different risk statuses of UIA patients and demonstrates the potential biological function of gut microbiome involved in the development of UIA. It may provide additional benefits in guiding UIA management and improving patient outcomes.

Prediction and analysis of periprocedural complications associated with endovascular treatment for unruptured intracranial aneurysms using machine learning.

BackgroundThe management of unruptured intracranial aneurysm (UIA) remains controversial. Recently, machine learning has been widely applied in the field of medicine. This study developed predictive models using machine learning to investigate periprocedural complications associated with endovascular procedures for UIA.MethodsWe enrolled patients with solitary UIA who underwent endovascular procedures. Periprocedural complications were defined as neurological adverse events resulting from endovascular procedures. We incorporated three machine learning algorithms into our prediction models: artificial neural networks (ANN), random forest (RF), and logistic regression (LR). The Shapley Additive Explanations (SHAP) approach and feature importance analysis were used to identify and prioritize significant features associated with periprocedural complications.ResultsIn total, 443 patients were included. Forty-eight (10.83%) procedure-related complications occurred. In the testing set, the ANN model produced the largest value (0.761) for area under the curve (AUC). The RF model also achieved an acceptable AUC value of 0.735, while the AUC value of the LR model was 0.668. SHAP and feature importance analysis identified distal aneurysm, aneurysm size and treatment modality as most significant features for the prediction of periprocedural complications following endovascular treatment for UIA.ConclusionPeriprocedural complications after endovascular treatment for UIA are not negligible. Prediction of periprocedural complications via machine learning is feasible and effective. Machine learning can serve as a promising tool in the decision-making process for UIA treatment.

Paraclinoid unruptured giant aneurysm with therapeutic success

The global prevalence of intracranial aneurysms (IA) ranges from 5–10%, with a demographic variation. Large and giant aneurysms typically involve cavernous and paraclinoid segments of the internal carotid artery (ICA), and represent 5% of IA. Typically, these lesions involve segments of the ICA, especially the cavernous and paraclinoid segments. The remaining cases affect the vertebrobasilar region, middle cerebral artery (MCA), and anterior cerebral artery (ACA). From the morphological point of view, they are divided into saccular and fusiform. In cases of rupture, the subarachnoid hemorrhage (SAH) is the most common presentation followed by intracerebral hemorrhage (ICH), or both. Other manifestations can occur as occlusion of perforating vessels, embolic events, seizures, and mass effects. The management of unruptured intracranial aneurysms (UIA) is controversial, and the aim of treatment is to exclude the lesions and preserve neurological function. Endovascular techniques for the treatment of paraclinoid aneurysms, in particular, ICA reconstruction using flow-diverting stents, have become a valid option. However, surgery or endovascular treatment has a number of limitations and the choice of treatment is individual in each case. This type of lesion has an extremely poor natural history, and treatment is a challenge regardless of the technique used. The report described a clinical case of a 55-year-old female, with a personal history of hypertension, hyperthyroidism, and depressive syndrome. The patient started complaints of moderate-intensity right frontal headache, progressively worsening with two months of evolution. She also reported blurred vision and diplopia. Brain computed tomography (CT) documented a partially calcified sellar and parasellar lesion. Subsequently, magnetic resonance imaging (MRI)/MRI angiographies were performed and showed a saccular aneurysm of the right ICA, cavernous segment. The patient underwent a diagnostic and therapeutic angiography with stent placement. Clinical and imaging improvements were documented by angiography and MRI angiography with progressive reduction of the aneurysm during the period of follow-up.

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.

Recruitment in a Pragmatic Randomized Trial on the Management of Unruptured Intracranial Aneurysms

The Comprehensive Aneurysm Management (CAM) study is a pragmatic trial designed to manage unruptured intracranial aneurysm (UIA) patients within a care research framework. CAM is an all-inclusive study. Management options are allocated according to an algorithm combining pre-randomization and clinical judgment. Eligible patients are offered 1:1 randomized allocation of intervention versus conservative management and 1:1 randomization allocation of surgical versus endovascular treatment. Ineligible patients are registered. The primary outcome is survival without dependency (modified Rankin Scale score <3) at 10 years. All UIA patients at 1 center are reported. Between February 2020 and July 2021, 403 UIA patients were recruited: 179 (44%) in one of the randomized controlled trials (RCTs) and 224 (56%) in one of the registries. Conservative management was recommended for 205 of 403 patients (51%); of 198 (49%) patients considered for curative treatment, 159 (80%) were randomly allocated conservative (n= 81) or curative treatment (n= 78). These patients were younger and had larger aneurysms than those in the observation registry (P= 0.004). In 39 of 198 patients (20%), conservative management was not considered reasonable (17 patients were recommended endovascular, 2 surgery, and 20 the RCT comparing endovascular with surgical treatment). In total, 70 patients were recruited in the RCT comparing surgery and endovascular treatment. After informed discussion at time of consent, 141 of 159 patients (89%) agreed with the randomly allocated management plan, while 11% crossed over to the alternative management option. CAM was successfully integrated into routine practice. Meaningful conclusions can be obtained if multiple centers actively participate in the trial.

Outpatient Day-Care Management of Unruptured Intracranial Aneurysm: A Retrospective Cohort Study.

ObjectiveThis study aimed to assess the outcomes of outpatient day-care management of unruptured intracranial aneurysm (UIA), and to present the risks associated with different management strategies by comparing the outcomes and adverse events between outpatient day-care management and management with longer admission periods.Materials and MethodsThis retrospective cohort study used prospectively registered data and was approved by a local institutional review board. We enrolled 956 UIAs from 811 consecutive patients (mean age ± standard deviation, 57 ± 10.7 years; male:female = 247:564) from 2017 to 2020. We compared the outcomes after embolization among the different admission-length groups (1, 2, and ≥ 3 days). The outcomes included pre- and post-modified Rankin Scale (mRS) scores and rates of adverse events, cure, recurrence, and reprocedure. Events were defined as any cerebrovascular problems, including minor and major stroke, death, or hemorrhage.ResultsThe mean admission period was 2 days, and 175 patients (191 aneurysms), 551 patients (664 aneurysms), and 85 patients (101 aneurysms) were discharged on the day of the procedure, day 2, and day 3 or later, respectively. During the mean 17-month follow-up period (range 6–53 months; 2757 patient years), no change in post-mRS was observed compared to pre-mRS in 99.6% of patients. Cure was achieved in 95.6% patients; minimal recurrence that did not require re-procedure occurred in 3.5% patients, and re-procedure was required in 2.3% (22 of 956) patients due to progressive enlargement of the recurrent sac during follow up (mean 17 months, range, 6–53 months). There were eight adverse events (0.8%), including five cerebrovascular (two major stroke, two minor strokes and one transient ischemic stroke), and three non-cerebrovascular events. Statistical comparison between groups with different admission lengths (1, 2, and ≥ 3 days) revealed no difference in the outcomes.ConclusionThis study revealed no difference in outcomes and adverse events according to the admission period, and suggested that UIA could be managed by outpatient day-care embolization.

Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa.

Background and Purpose: The management of unruptured intracranial aneurysms remains controversial. The decisions to treat are heavily informed by estimated risk of bleeding. However, these estimates are imprecise, and better methods for stratifying the risk or tailoring treatment strategy are badly needed. Here, we demonstrate an initial proof-of-principle concept for endovascular biopsy to identify the key molecular pathways and gene expression changes associated with aneurysm formation. We couple this technique with single cell RNA sequencing (scRNAseq) to develop a roadmap of the pathogenic changes of a dolichoectatic vertebrobasilar aneurysm in a patient with polyarteritis nodosa.Methods: Endovascular biopsy and fluorescence activated cell sorting was used to isolate the viable endothelial cells (ECs) using the established techniques. A single cell RNA sequencing (scRNAseq) was then performed on 24 aneurysmal ECs and 23 patient-matched non-aneurysmal ECs. An integrated panel of bioinformatic tools was applied to determine the differential gene expression, enriched signaling pathways, and cell subpopulations hypothesized to drive disease pathogenesis.Results: We identify a subset of 7 (29%) aneurysm-specific ECs with a distinct gene expression signature not found in the patient-matched control ECs. A gene set enrichment analysis identified these ECs to have increased the expression of genes regulating the leukocyte-endothelial cell adhesion, major histocompatibility complex (MHC) class I, T cell receptor recycling, tumor necrosis factor alpha (TNFα) response, and interferon gamma signaling. A histopathologic analysis of a different intracranial aneurysm that was later resected yielded a diagnosis of polyarteritis nodosa and positive staining for TNFα.Conclusions: We demonstrate feasibility of applying scRNAseq to the endovascular biopsy samples and identify a subpopulation of ECs associated with cerebral aneurysm in polyarteritis nodosa. Endovascular biopsy may be a safe method for deriving insight into the disease pathogenesis and tailoring the personalized treatment approaches to intracranial aneurysms.

Wall enhancement as an emerging marker of intracranial aneurysm stability: Roadmap toward a potential target for clinical trials.

The management of unruptured intracranial aneurysms (UIA) is challenging. The current risk evaluation based on traditional risk factors including size, location, irregular shape etc. has limited sensitivity and specificity. For example, more than half of ruptured intracranial aneurysms are smaller than the treatment threshold of 7mm. Therefore, finding more accurate biomarkers for UIA stability is urgently needed to improve patient management.

Current decision support tools fail to agree or predict therapeutic decisions in a single cohort of unruptured intracranial aneurysms

BackgroundThere is limited evidence to direct the management of unruptured intracranial aneurysms. Models extrapolated from existing data have been proposed to guide treatment recommendations. The aim of this study is to assess whether a consensus-based treatment score (UIATS) or rupture rate estimation model (PHASES) can be used to benchmark UK multi-disciplinary team (MDT) practice.MethodsProspective data was collected on a consecutive series of all patients with unruptured intracranial aneurysms (UIAs) presenting to a major UK neurovascular centre between 2012 and 2015. The agreement between the UIATS and PHASES scores, and their sensitivity and specificity in predicting the real-world MDT outcome were calculated and compared.ResultsA total of 366 patients (456 aneurysms) were included in the analysis. The agreement between UIATS and MDT recommendation was low (weighted kappa 0.26 [95% CI 0.19, 0.32]); sensitivity and specificity were also low at 36% and 52% respectively. Groups that the MDT allocated to treatment, equipoise or no treatment had significantly different PHASES scores (p = 0.004). There was no significant difference between the two scores when predicting patients for whom MDT outcome was to recommend aneurysm treatment, but the UIATS score was superior in predicting patients who received an MDT recommendation of ‘treatment-equipoise’, or ‘not-for-treatment’ (AUC of 0.73 compared to 0.59 for PHASES).ConclusionsThe models studied failed to agree with the consensus view of multi-disciplinary team in a major neurovascular centre. We conclude that decision support tools such as the UIATS and PHASES scores should not be blindly introduced in respective institutions without prior internal validation, as they may not represent the local reality.

Management of Unruptured Intracranial Aneurysms.

Unruptured intracranial aneurysms (UIAs) are common and are being detected with increasing frequency given the improved quality and higher frequency of cross-sectional imaging. The long-term natural history of UIAs remains poorly understood. To date, there is relative lack of clear guidelines for selection of patients with UIAs for treatment. Surveillance imaging for untreated UIAs is frequently performed, but frequency, duration, and modality of surveillance imaging need clearer guidelines. The authors review the current evidence on prevalence, natural history, role of treatment, and surveillance and screening imaging and highlight the areas for further research.

Unruptured aneurysms: Why observational studies fall short no matter how “Big” the Data

BackgroundThe best management of unruptured intracranial aneurysms (UIAs) remains unknown, despite multiple observational studies. A randomized trial (RCT) is in order. Yet, a National Institute Neurological Disorders and Stroke workshop has once again proposed to use prospective observational studies (POS) of large databases to address such problems. MethodsWe review the historical misconceptions that have been associated with observations of UIAs and their treatments. We critically examine some recent methods that have been proposed to address shortcomings of observational studies. We finally review the ethical principles underlying the use of trial methods in the care of patients. ResultsReplacing RCTs with POS submits patients to management options that have never been proven beneficial, while making them involuntary research subjects of studies that are inevitably biased. A science of practice cannot be an outsider's examination of the behavior of clinicians incapable of questioning their practice. The thesis we propose is that a science of practice must not only eventually determine what best practice will be; It must engage agents involved in medical practice to transparently reveal the uncertainty that calls for management options to be offered under the guidance of declared and controlled care research, to optimize patient outcomes in spite of the uncertainty. ConclusionTo use POS rather than RCTs in medical practice is to renege on scientific and ethical principles that characterize modern medicine. Instead, we must learn to integrate care research into our practice to provide optimal medical care in real time.