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BACKGROUND: Subarachnoid hemorrhages secondary to intracranial aneurysms (IAs) are events of high mortality. These neurological vascular diseases arise from local and systemic inflammation that culminates in vessel wall changes. They may also have a possible relationship with chronic viral infections, such as human herpesvirus (HHV), and especially Epstein-Barr virus (EBV), which causes several medical conditions. This is the first description of the presence of HHV deoxyribonucleic acid (DNA) in a patient with IA. OBSERVATIONS: A 61-year-old woman with a downgraded level of consciousness underwent radiological examinations that identified a 10-mm ruptured aneurysm in the anterior communicating artery. A microsurgery clip was performed to definitively treat the aneurysm and occurred without surgical complications. Molecular analysis of the material obtained revealed the presence of EBV DNA in the aneurysm wall. The patient died 21 days after admission due to clinical complications and brain swelling. LESSONS: This is the first description of the presence of herpesvirus DNA in a patient with IA, presented in 2.8% of our data. These findings highlight that viral infection may contribute to the pathophysiology and is an additional risk factor for IA formation, progression, and rupture by modulating vessel wall inflammation and structural changes in chronic infections.

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OBJECTIVE: Intracranial aneurysms (IAs) are more often diagnosed in women. Hormones and vessel geometry, which influences wall shear stress, may affect pathophysiological processes of the arterial wall. Here, the authors investigated sex-related differences in the remodeling of the aneurysm wall and in intraluminal thrombus resolution. METHODS: A well-characterized surgical side-wall aneurysm model was used in female, male, and ovariectomized rats. Decellularized grafts were used to model highly degenerated and decellularized IA walls and native grafts to model healthy IA walls. Aneurysm growth and thrombus composition were analyzed at 1, 7, 14, and 28 days. Sex-related differences in vessel wall remodeling were compared with human IA dome samples of men and pre- and postmenopausal women. RESULTS: At 28 days, more aneurysm growth was observed in ovariectomized rats than in males or non-ovariectomized female rats. The parent artery size was larger in male rats than in female or ovariectomized rats, as expected. Wall inflammation increased over time in all groups and was most severe in the decellularized female and ovariectomized groups at 28 days compared with the male group. Likewise, in these groups the most elastin fragmentation was seen at 28 days. In female rats, on days 1, 7, and 14, the intraluminal thrombus was mainly composed of red blood cells and fibrin. On days 14 and 28, macrophage and smooth muscle cell invasion inside the thrombus was shown, leading to the removal of red blood cells and deposition of collagen and elastin. On days 14 and 28, similar profiles of thrombus reorganization were observed in male and ovariectomized female rats. However, collagen content in thrombi and vessel wall macrophage content were higher in aneurysms of male rats at 28 days than in those of female rats. On day 28, thrombus coverage by endothelial cells was lower in ovariectomized than in female or male rats. Finally, analysis of human IA domes showed that endothelial cell coverage was lower in men and postmenopausal women than in younger women. CONCLUSIONS: Aneurysm growth and intraluminal thrombus resolution show sex-dependent differences. While certain processes (endothelial cell coverage and collagen deposition) point to a strong hormonal dependence, others (wall inflammation and aneurysm growth) seem to be influenced by both hormones and parent artery size.

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OBJECTIVE: In the last several decades, various factors have been studied for a better evaluation of the risk of rupture in incidentally discovered intracranial aneurysms (IAs). With advanced MRI, attempts were made to delineate the wall of IAs to identify weak areas prone to rupture. However, the field strength of the MRI investigations was insufficient for reasonable image resolution in many of these studies. Therefore, the aim of this study was to analyze findings of IAs in ultra-high field MRI at 7 Tesla (7 T). METHODS: Patients with incidentally found IAs of at least 5 mm in diameter were included in this study and underwent MRI investigations at 7 T. At this field strength a hyperintense intravascular signal can be observed on nonenhanced images with a brighter "rim effect" along the vessel wall. Properties of this rim effect were evaluated and compared with computational fluid dynamics (CFD) analyses. RESULTS: Overall, 23 aneurysms showed sufficient image quality for further evaluation. In 22 aneurysms focal irregularities were identified within this rim effect. Areas of such irregularities showed significantly higher values in wall shear stress and vorticity compared to areas with a clearly visible rim effect (p = 0.043 in both). CONCLUSIONS: A hyperintense rim effect along the vessel wall was observed in most cases. Focal irregularities within this rim effect showed higher values of the mean wall shear stress and vorticity when compared by CFD analyses. Therefore, these findings indicate alterations in blood flow in IAs within these areas.

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OBJECTIVE: The objective of this study was to determine patterns of care and outcomes in ruptured intracranial aneurysms (IAs) of the middle cerebral artery (MCA) in a contemporary national cohort. METHODS: The authors conducted a retrospective analysis of prospective data from a nationwide multicenter registry of all aneurysmal subarachnoid hemorrhage (aSAH) cases admitted to a tertiary care neurosurgical department in Switzerland in the years 2009-2015 (Swiss Study on Aneurysmal Subarachnoid Hemorrhage [Swiss SOS]). Patterns of care and outcomes at discharge and the 1-year follow-up in MCA aneurysm (MCAA) patients were analyzed and compared with those in a control group of patients with IAs in locations other than the MCA (non-MCAA patients). Independent predictors of a favorable outcome (modified Rankin Scale score ≤ 3) were identified, and their effect size was determined. RESULTS: Among 1866 consecutive aSAH patients, 413 (22.1%) harbored an MCAA. These MCAA patients presented with higher World Federation of Neurosurgical Societies grades (p = 0.007), showed a higher rate of concomitant intracerebral hemorrhage (ICH; 41.9% vs 16.7%, p < 0.001), and experienced delayed cerebral ischemia (DCI) more frequently (38.9% vs 29.4%, p = 0.001) than non-MCAA patients. After adjustment for confounders, patients with MCAA were as likely as non-MCAA patients to experience DCI (aOR 1.04, 95% CI 0.74-1.45, p = 0.830). Surgical treatment was the dominant treatment modality in MCAA patients and at a significantly higher rate than in non-MCAA patients (81.7% vs 36.7%, p < 0.001). An MCAA location was a strong independent predictor of surgical treatment (aOR 8.49, 95% CI 5.89-12.25, p < 0.001), despite statistical adjustment for variables traditionally associated with surgical treatment, such as (space-occupying) ICH (aOR 1.73, 95% CI 1.23-2.45, p = 0.002). Even though MCAA patients were less likely to die during the acute hospitalization (aOR 0.52, 0.30-0.91, p = 0.022), their rate of a favorable outcome was lower at discharge than that in non-MCAA patients (55.7% vs 63.7%, p = 0.003). At the 1-year follow-up, 68.5% and 69.6% of MCAA and non-MCAA patients, respectively, had a favorable outcome (p = 0.676). CONCLUSIONS: Microsurgical occlusion remains the predominant treatment choice for about 80% of ruptured MCAAs in a European industrialized country. Although patients with MCAAs presented with worse admission grades and greater rates of concomitant ICH, in-hospital mortality was lower and long-term disability was comparable to those in patients with non-MCAA.

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OBJECTIVE: Aspirin has emerged as a potential agent in the prevention of rupture of intracranial aneurysms (IAs). In this study, the authors' goal was to test if aspirin is protective against aneurysm growth in patients harboring multiple IAs ≤ 5 mm. METHODS: The authors performed a retrospective review of a prospectively maintained database covering the period July 2009 through January 2019. Patients' data were included if the following criteria were met: 1) the patient harbored multiple IAs; 2) designated primary aneurysms were treated by surgical/endovascular means; 3) the remaining aneurysms were observed for growth; and 4) a follow-up period of at least 5 years after the initial treatment was available. Demographics, earlier medical history, the rupture status of designated primary aneurysms, aneurysms' angiographic features, and treatment modalities were gathered. RESULTS: The authors identified 146 patients harboring a total of 375 IAs. At the initial encounter, 146 aneurysms were treated and the remaining 229 aneurysms (2-5 mm) were observed. During the follow-up period, 24 (10.48%) of 229 aneurysms grew. All aneurysms observed to grow later underwent treatment. None of the observed aneurysms ruptured. Multivariate analysis showed that aspirin was significantly associated with a decreased rate of growth (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.05-0.63). Variables associated with an increased rate of growth included hypertension (OR 14.38, 95% CI 3.83-53.94), drug abuse (OR 11.26, 95% CI 1.21-104.65), history of polycystic kidney disease (OR 9.48, 95% CI 1.51-59.35), and subarachnoid hemorrhage at presentation (OR 5.91, 95% CI 1.83-19.09). CONCLUSIONS: In patients with multiple IAs, aspirin significantly decreased the rate of aneurysm growth over time. Additional prospective interventional studies are needed to validate these findings.

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OBJECTIVE: Middle cerebral artery (MCA) aneurysms are a particular subset of intracranial aneurysms that can be excluded by clipping or coiling. A comparison of the results between these two methods is often limited by a selection bias in which wide-neck and large aneurysms are frequently treated with surgery. Here, the authors report the results of two centers using opposing policies in the management of MCA aneurysms: one center used a clip-first policy while the other used a coil-first policy, which limited the selection bias and ensured a good comparison of these two treatment modalities. METHODS: All patients treated for either ruptured or unruptured MCA aneurysms at one of two institutions between January 2012 and December 2015 were eligible for inclusion in this study. At one center a clip-first policy was applied, whereas the other applied a coil-first policy. The authors retrospectively reviewed the medical records of these patients and compared their clinical and radiological outcomes. RESULTS: A total of 187 aneurysms were treated during the inclusion period; 88 aneurysms were treated by coiling and 99 aneurysms by clipping. The baseline patient and radiological characteristics were similar between the two groups, but the clinical presentation of the ruptured aneurysm cohort differed slightly. In the ruptured cohort (n = 90), although patients in the coiling group had a higher rate of additional surgery, the complication rate, functional outcome, and risk of death were similar between the two treatment groups. In the unruptured cohort (n = 97), the complication rate, functional outcome, and risk of death were also similar between the two treatment groups, although the risk of discomfort related to the temporal muscle atrophy was higher in the surgical group. Overall, the rate of complete occlusion was higher in the clipping group (84.2%) than in the coiling group (31%), which led to a higher risk in the coiling group of aneurysm retreatment within the first 2 years (p = 0.04). CONCLUSIONS: Clipping and coiling for MCA aneurysm treatment provide the same clinical outcome for ruptured and unruptured aneurysms. However, clipping provides higher short- and long-term rates of complete exclusion, which in turn decreases the risk of aneurysm retreatment. Whether this lower occlusion rate can have a clinical impact in the long-term must be further evaluated.

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OBJECTIVE: Emerging evidence shows that frequent recurrence of intracranial aneurysms (IAs) after endovascular coiling is attributable to the lack of endothelialization across the aneurysm neck. Recently, much attention has been given to the role of microRNAs (miRs) in vascular disease, although their contributory role to IA is poorly understood. METHODS: Adult male Sprague-Dawley rats were subjected to microsurgery to create a coiled embolization aneurysm model, and were injected with miR-31a-5p agomir or a negative control agomir via the tail vein at a dose of 10 mg/kg per week for 4 weeks after IA induction. H & E staining, scanning electron microscopy, and flow cytometry were performed to evaluate the effects of miR-31a-5p agomir on endothelialization and the number of circulating endothelial progenitor cells (EPCs). The effects of miR-31a-5p on the viability and functioning of EPCs were also determined using Cell Counting Kit-8, wound-healing assay, and tube formation assays. RESULTS: The authors tested the ability of miR-31a-5p to promote EPC-induced endothelialization in a model of coiled embolization aneurysm. miR-31a-5p agomir improved endothelialization and elevated the number of circulating EPCs in the peripheral blood compared to a negative control agomir-treated group. In addition, the number of vWF- and KDR-positive cells in the aneurysm neck was increased in the miR-31a-5p agomir-treated group. Furthermore, upregulation of miR-31a-5p promoted EPC proliferation, migration, and tube formation and enhanced the expression of the proangiogenic factor vascular endothelial growth factor in vitro. Mechanistically, miR-31a-5p directly targeted the 3' untranslated region (3'UTR) of Axin1 messenger RNA and repressed its expression. Besides, miR-31a-5p exerted its effect on EPCs by regulating the Axin1-mediated Wnt/ß-catenin pathway. CONCLUSIONS: Collectively, these results indicate that miR-31a-5p is an important regulator of EPC mobilization and endothelialization and may have a positive effect on aneurysm repair.

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OBJECTIVE: Subarachnoid hemorrhage (SAH) has a poor outcome despite modern advancements in medical care. The development of a novel therapeutic strategy to prevent rupture of intracranial aneurysms (IAs) or a novel diagnostic marker to predict rupture-prone lesions is thus mandatory. Therefore, in the present study, the authors established a rat model in which IAs spontaneously rupture and examined this model to clarify histopathological features associated with rupture of lesions. METHODS: Female Sprague Dawley rats were subjected to bilateral ovariectomy; the ligation of the left common carotid, the right external carotid, and the right pterygopalatine arteries; induced systemic hypertension; and the administration of a lysyl oxidase inhibitor. RESULTS: Aneurysmal SAH occurred in one-third of manipulated animals and the locations of ruptured IAs were exclusively at a posterior or anterior communicating artery (PCoA/ACoA). Histopathological examination using ruptured IAs, rupture-prone IAs induced at a PCoA or ACoA, and IAs induced at an anterior cerebral artery-olfactory artery bifurcation that never ruptured revealed the formation of vasa vasorum as an event associated with rupture of IAs. CONCLUSIONS: The authors propose the contribution of a structural change in an adventitia, i.e., vasa vasorum formation, to the rupture of IAs. Findings from this study provide important insights about the pathogenesis of IAs.

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The pathogenesis of intracranial aneurysms remains complex and multifactorial. While vascular, genetic, and epidemiological factors play a role, nascent aneurysm formation is believed to be induced by hemodynamic forces. Hemodynamic stresses and vascular insults lead to additional aneurysm and vessel remodeling. Advanced imaging techniques allow us to better define the roles of aneurysm and vessel morphology and hemodynamic parameters, such as wall shear stress, oscillatory shear index, and patterns of flow on aneurysm formation, growth, and rupture. While a complete understanding of the interplay between these hemodynamic variables remains elusive, the authors review the efforts that have been made over the past several decades in an attempt to elucidate the physical and biological interactions that govern aneurysm pathophysiology. Furthermore, the current clinical utility of hemodynamics in predicting aneurysm rupture is discussed.

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Computational blood flow modeling in intracranial aneurysms (IAs) has enormous potential for the assessment of highly resolved hemodynamics and derived wall stresses. This results in an improved knowledge in important research fields, such as rupture risk assessment and treatment optimization. However, due to the requirement of assumptions and simplifications, its applicability in a clinical context remains limited.This review article focuses on the main aspects along the interdisciplinary modeling chain and highlights the circumstance that computational fluid dynamics (CFD) simulations are embedded in a multiprocess workflow. These aspects include imaging-related steps, the setup of realistic hemodynamic simulations, and the analysis of multidimensional computational results. To condense the broad knowledge, specific recommendations are provided at the end of each subsection.Overall, various individual substudies exist in the literature that have evaluated relevant technical aspects. In this regard, the importance of precise vessel segmentations for the simulation outcome is emphasized. Furthermore, the accuracy of the computational model strongly depends on the specific research question. Additionally, standardization in the context of flow analysis is required to enable an objective comparison of research findings and to avoid confusion within the medical community. Finally, uncertainty quantification and validation studies should always accompany numerical investigations.In conclusion, this review aims for an improved awareness among physicians regarding potential sources of error in hemodynamic modeling for IAs. Although CFD is a powerful methodology, it cannot provide reliable information, if pre- and postsimulation steps are inaccurately carried out. From this, future studies can be critically evaluated and real benefits can be differentiated from results that have been acquired based on technically inaccurate procedures.

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OBJECTIVE: Incidental aneurysms pose a challenge for physicians, who need to weigh the rupture risk against the risks associated with treatment and its complications. A statistical model could potentially support such treatment decisions. A recently developed aneurysm rupture probability model performed well in the US data used for model training and in data from two European cohorts for external validation. Because Japanese and Finnish patients are known to have a higher aneurysm rupture risk, the authors' goals in the present study were to evaluate this model using data from Japanese and Finnish patients and to compare it with new models trained with Finnish and Japanese data. METHODS: Patient and image data on 2129 aneurysms in 1472 patients were used. Of these aneurysm cases, 1631 had been collected mainly from US hospitals, 249 from European (other than Finnish) hospitals, 147 from Japanese hospitals, and 102 from Finnish hospitals. Computational fluid dynamics simulations and shape analyses were conducted to quantitatively characterize each aneurysm's shape and hemodynamics. Next, the previously developed model's discrimination was evaluated using the Finnish and Japanese data in terms of the area under the receiver operating characteristic curve (AUC). Models with and without interaction terms between patient population and aneurysm characteristics were trained and evaluated including data from all four cohorts obtained by repeatedly randomly splitting the data into training and test data. RESULTS: The US model's AUC was reduced to 0.70 and 0.72, respectively, in the Finnish and Japanese data compared to 0.82 and 0.86 in the European and US data. When training the model with Japanese and Finnish data, the average AUC increased only slightly for the Finnish sample (to 0.76 ± 0.16) and Finnish and Japanese cases combined (from 0.74 to 0.75 ± 0.14) and decreased for the Japanese data (to 0.66 ± 0.33). In models including interaction terms, the AUC in the Finnish and Japanese data combined increased significantly to 0.83 ± 0.10. CONCLUSIONS: Developing an aneurysm rupture prediction model that applies to Japanese and Finnish aneurysms requires including data from these two cohorts for model training, as well as interaction terms between patient population and the other variables in the model. When including this information, the performance of such a model with Japanese and Finnish data is close to its performance with US or European data. These results suggest that population-specific differences determine how hemodynamics and shape associate with rupture risk in intracranial aneurysms.

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Intracranial aneurysms (IAs) are a result of complex interactions between biochemical and mechanical forces and can lead to significant morbidity if they rupture and cause subarachnoid hemorrhage. This review explores the role of matrix metalloproteinases (MMPs) in the pathogenesis and progression of IAs. In addition to providing a review of the normal function of MMPs, it is intended to explore the interaction between inflammation and abnormal blood flow and the resultant pathological vascular remodeling processes seen in the development and rupture of IAs. Also reviewed is the potential for the use of MMPs as a diagnostic tool for assessment of aneurysm development and progression.

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OBJECTIVE: Unruptured intracranial aneurysms (UIAs) are relatively common lesions that may cause devastating intracranial hemorrhage, thus producing considerable suffering and anxiety in those affected by the disease or an increased likelihood of developing it. Advances in the knowledge of the pathobiology behind intracranial aneurysm (IA) formation, progression, and rupture have led to preclinical testing of drug therapies that would prevent IA formation or progression. In parallel, novel biologically based diagnostic tools to estimate rupture risk are approaching clinical use. Arterial wall remodeling, triggered by flow and intramural stresses and mediated by inflammation, is relevant to both. METHODS: This review discusses the basis of flow-driven vessel remodeling and translates that knowledge to the observations made on the mechanisms of IA initiation and progression on studies using animal models of induced IA formation, study of human IA tissue samples, and study of patient-derived computational fluid dynamics models. RESULTS: Blood flow conditions leading to high wall shear stress (WSS) activate proinflammatory signaling in endothelial cells that recruits macrophages to the site exposed to high WSS, especially through macrophage chemoattractant protein 1 (MCP1). This macrophage infiltration leads to protease expression, which disrupts the internal elastic lamina and collagen matrix, leading to focal outward bulging of the wall and IA initiation. For the IA to grow, collagen remodeling and smooth muscle cell (SMC) proliferation are essential, because the fact that collagen does not distend much prevents the passive dilation of a focal weakness to a sizable IA. Chronic macrophage infiltration of the IA wall promotes this SMC-mediated growth and is a potential target for drug therapy. Once the IA wall grows, it is subjected to changes in wall tension and flow conditions as a result of the change in geometry and has to remodel accordingly to avoid rupture. Flow affects this remodeling process. CONCLUSIONS: Flow triggers an inflammatory reaction that predisposes the arterial wall to IA initiation and growth and affects the associated remodeling of the UIA wall. This chronic inflammation is a putative target for drug therapy that would stabilize UIAs or prevent UIA formation. Moreover, once this coupling between IA wall remodeling and flow is understood, data from patient-specific flow models can be gathered as part of the diagnostic workup and utilized to improve risk assessment for UIA initiation, progression, and eventual rupture.

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OBJECTIVE: Although several studies have suggested that the incidence of intracranial aneurysms (IAs) is higher in smokers, the higher prevalence of subarachnoid hemorrhage (SAH) in smokers remains uncertain. It is unclear whether smoking additionally contributes to the formation of multiple aneurysms and the risk of rupture. The aim of this study was to determine whether smoking is associated with IA formation, multiplicity, or rupture. METHODS: Patients from the prospective multicenter @neurIST database (n = 1410; 985 females [69.9%]) were reviewed for the presence of SAH, multiple aneurysms, and smoking status. The prevalence of smokers in the population of patients diagnosed with at least one IA was compared with that of smokers in the general population. RESULTS: The proportion of smokers was higher in patients with IAs (56.2%) than in the reference population (51.4%; p < 0.001). A significant association of smoking with the presence of an IA was found throughout group comparisons (p = 0.01). The presence of multiple IAs was also significantly associated with smoking (p = 0.003). A trend was found between duration of smoking and the presence of multiple IAs (p = 0.057). However, the proportion of smokers among patients suffering SAH was similar to that of smokers among patients diagnosed with unruptured IAs (p = 0.48). CONCLUSIONS: Smoking is strongly associated with IA formation. Once an IA is present, however, smoking does not appear to increase the risk of rupture compared with IAs in the nonsmoking population. The trend toward an association between duration of smoking and the presence of multiple IAs stresses the need for counseling patients with IAs regarding lifestyle modification.

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OBJECTIVE: Incidence rates of de novo aneurysm formation and recurrence after clip ligation remain controversial. In this meta-analysis, the authors provide data on pooled annual incidence rates and the association of patient characteristics with time to formation of de novo aneurysms and time to recurrence after clipping. METHODS: A search of the literature up to June 15, 2016, on PubMed and a systematic review were performed. The association of age, aneurysm rupture status, aneurysm multiplicity, and anatomical location with time to recurrence or formation of de novo aneurysm was estimated using multivariable Cox proportional-hazards models. Kaplan-Meier estimates (event-free survival curves) are shown. Pooled annualized incidence rates of recurrent and de novo aneurysms were estimated using Poisson regression. Proportions of aneurysms and average follow-up times are displayed as bubble plots with LOESS smoothers weighted for study size. RESULTS: Of the 7606 articles screened, 92 were included in the study. Case reports on 101 patients with recurrent aneurysms and 132 patients with de novo aneurysms were analyzed. Long-term follow-up studies on de novo aneurysm formation included 13,723 patients with 101,378 patient-years of follow-up; studies on aneurysm recurrence included 5922 patients with 31,055 patient-years of follow-up. Mean time to recurrence was 12.9 ± 6.6 years (mean ± standard deviation), and mean time to de novo formation was 9.3 ± 6.1 years. No association with sex, aneurysm location, and initial rupture could be shown. De novo aneurysms occurred later in patients with multiplicity of aneurysms at diagnosis (HR 0.63, p = 0.03) and in patients with increasing age (HR per 10 yrs 0.88, p = 0.06). Pooled annualized incidence rates were 0.35% for de novo aneurysms and 0.13% for recurrent aneurysms. CONCLUSIONS: Despite low reported annual incidence rates, the cumulative risk of 9.6%-22% for aneurysm recurrence or de novo formation 20 years after clip ligation warrants lifelong follow-up. Screening at 5, 10, and 20 years would detect 30.8% (95% CI 23.3%-37.6%), 64.2% (95% CI 55.9%-70.9%), and 95.9% (95% CI 90.9%-97.9%) of de novo aneurysms. Screening for recurrent aneurysms at 10, 15, and 20 years would detect 36.6% (95% CI 26.5%-45.4%), 65.3% (95% CI 54.7%-73.5%), and 95.1% (95% CI 85.8%-96.6%) of lesions.

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OBJECTIVEBecause simple intracranial aneurysms (IAs) are increasingly treated endovascularly, neurovascular surgery has become focused on complex IAs that may require deconstructive aneurysm therapy with concomitant surgical bypass. The authors describe the decision-making process concerning cerebral revascularization and present outcomes that were achieved in a large case series of complex IAs managed with cerebral revascularization and parent artery occlusion.METHODSThe authors retrospectively reviewed the medical records, including neuroimaging studies, operative reports, and follow-up clinic notes, of all patients who were treated at the National Brain Aneurysm Center between July 1997 and June 2015 using cerebral revascularization as part of the management of an IA. They recorded the location, rupture status, and size of each IA, as well as neurological outcome using the modified Rankin Scale (mRS), aneurysm and bypass status at follow-up, and morbidity and mortality.RESULTSThe authors identified 126 patients who underwent revascularization surgery for 126 complex, atheromatous, calcified, or previously coiled aneurysms. Ninety-seven lesions (77.0%) were unruptured, and 99 (78.6%) were located in the anterior circulation. Aneurysm size was giant (≥ 25 mm) in 101 patients, large (10-24 mm) in 9, and small (≤ 9 mm) in 16 patients. Eighty-four low-flow bypasses were performed in 83 patients (65.9%). High-flow bypass was performed in 32 patients (25.4%). Eleven patients (8.7%) underwent in situ or intracranial-intracranial bypasses. Major morbidity (mRS score 4 or 5) occurred in 2 (2.4%) low-flow cases and 3 (9.1%) high-flow cases. Mortality occurred in 2 (2.4%) low-flow cases and 2 (6.1%) high-flow cases. At the 12-month follow-up, 83 (98.8%) low-flow and 30 (93.8%) high-flow bypasses were patent. Seventy-five patients (90.4%) undergoing low-flow and 28 (84.8%) high-flow bypasses had an mRS score ≤ 2. There were no statistically significant differences in patency rates or complications between low- and high-flow bypasses.CONCLUSIONSWhen treating challenging and complex IAs, incorporating revascularization strategies into the surgical repertoire may contribute to achieving favorable outcomes. In our series, low-flow bypass combined with isolated proximal or distal parent artery occlusion was associated with a low rate of ischemic complications while providing good long-term aneurysm control, potentially supporting its wider utilization in this setting. The authors suggest that consideration should be given to managing complex IAs at high-volume centers that offer a multidisciplinary team approach and the full spectrum of surgical and endovascular treatment options to optimize patient outcomes.

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OBJECTIVEFlow diverters (FDs) are designed to occlude intracranial aneurysms (IAs) while preserving flow to essential arteries. Incomplete occlusion exposes patients to risks of thromboembolic complications and rupture. A priori assessment of FD treatment outcome could enable treatment optimization leading to better outcomes. To that end, the authors applied image-based computational analysis to clinically FD-treated aneurysms to extract information regarding morphology, pre- and post-treatment hemodynamics, and FD-device characteristics and then used these parameters to train machine learning algorithms to predict 6-month clinical outcomes after FD treatment.METHODSData were retrospectively collected for 84 FD-treated sidewall aneurysms in 80 patients. Based on 6-month angiographic outcomes, IAs were classified as occluded (n = 63) or residual (incomplete occlusion, n = 21). For each case, the authors modeled FD deployment using a fast virtual stenting algorithm and hemodynamics using image-based computational fluid dynamics. Sixteen morphological, hemodynamic, and FD-based parameters were calculated for each aneurysm. Aneurysms were randomly assigned to a training or testing cohort in approximately a 3:1 ratio. The Student t-test and Mann-Whitney U-test were performed on data from the training cohort to identify significant parameters distinguishing the occluded from residual groups. Predictive models were trained using 4 types of supervised machine learning algorithms: logistic regression (LR), support vector machine (SVM; linear and Gaussian kernels), K-nearest neighbor, and neural network (NN). In the testing cohort, the authors compared outcome prediction by each model trained using all parameters versus only the significant parameters.RESULTSThe training cohort (n = 64) consisted of 48 occluded and 16 residual aneurysms and the testing cohort (n = 20) consisted of 15 occluded and 5 residual aneurysms. Significance tests yielded 2 morphological (ostium ratio and neck ratio) and 3 hemodynamic (pre-treatment inflow rate, post-treatment inflow rate, and post-treatment aneurysm averaged velocity) discriminants between the occluded (good-outcome) and the residual (bad-outcome) group. In both training and testing, all the models trained using all 16 parameters performed better than all the models trained using only the 5 significant parameters. Among the all-parameter models, NN (AUC = 0.967) performed the best during training, followed by LR and linear SVM (AUC = 0.941 and 0.914, respectively). During testing, NN and Gaussian-SVM models had the highest accuracy (90%) in predicting occlusion outcome.CONCLUSIONSNN and Gaussian-SVM models incorporating all 16 morphological, hemodynamic, and FD-related parameters predicted 6-month occlusion outcome of FD treatment with 90% accuracy. More robust models using the computational workflow and machine learning could be trained on larger patient databases toward clinical use in patient-specific treatment planning and optimization.

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The use of simulators has been described in a variety of fields as a training tool to gain technical skills through repeating and rehearsing procedures in a safe environment. In cerebrovascular surgery, simulation of skull base approaches has been used for decades. The use of simulation in neurointervention to acquire and enhance skills before treating a patient is a newer concept, but its utilization has been limited due to the lack of good models and deficient haptics. The advent of 3D printing technology and the development of new training models has changed this landscape. The prevalence of aneurysms in the pediatric population is much lower than in adults, and concepts and tools sometimes have to be adapted from one population to another. Neuroendovascular rehearsal is a valid strategy for the treatment of complex aneurysms, especially for the pediatric population. The authors present the case of an 8-year-old boy with a fusiform intracranial aneurysm and documented progressive growth, who was successfully treated after the authors rehearsed the placement of a flow diverter using a patient-specific 3D-printed replicator system model.

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OBJECTIVE: During the last decade, improvements in real-time, high-resolution imaging of surgically exposed cerebral vasculature have been realized with the successful introduction of intraoperative indocyanine green video angiography (ICGVA) and technical advances in intraoperative digital subtraction angiography (DSA). With the availability of 3D intraoperative DSA (3D-iDSA) in hybrid operating rooms, the present study offers a contemporary comparison for rates of accuracy and discordance. METHODS: In this retrospective study of prospectively collected data, 140 consecutive patients underwent microsurgical treatment of intracranial aneurysms (IAs) in a hybrid operating room. Variables analyzed included patient demographics, aneurysm-specific characteristics, intraoperative ICGVA and 3D-iDSA findings, and the need for intraoperative clip readjustment. The authors defined the discordance rate of the two modalities as a false-negative finding that necessitated clip repositioning after 3D-iDSA. RESULTS: In 120 patients, ICGVA and 3D-iDSA were used to evaluate 134 IA obliterations. Of 215 clips used, 29 (14%) were repositioned intraoperatively, improving the surgical result in all 29 patients (24%). Repositioning was prompted by visual inspection and microvascular Doppler ultrasonography in 8 (28%), ICGVA in 13 (45%), and 3D-iDSA in 7 (24%) patients. Clip repositioning was needed in 7 patients (6%) based on 3D-iDSA, yielding an ICGVA accuracy rate of 94%. Five (71%) of the ICGVA-3D-iDSA discordances that prompted clip repositioning occurred at the anterior communicating artery complex. CONCLUSIONS: A combination of vascular monitoring techniques most often achieved correct intraoperative interpretation of complete IA occlusion and parent artery integrity. Compared with 3D-iDSA imaging, ICGVA demonstrated high accuracy. Despite the relatively low discordance rate, iDSA was confirmed to be the gold standard. Improved imaging quality, including 3D-iDSA, supports its routine use in IA surgery, obviating the need for postoperative DSA.

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OBJECTIVE Obstructive sleep apnea (OSA) is associated with the progression of abdominal and thoracic aortic aneurysms. However, the role of OSA in the overall outcome of intracranial aneurysms (IAs) has not yet been established. Authors of this report investigated the role of OSA in the overall outcome of IAs. METHODS Radiological and clinical data on patients (from 2010 through 2015) with confirmed IA were retrospectively reviewed. Significant differences between the OSA and non-OSA groups were determined using a chi-square test. Logistic regression analysis was performed to identify the predictors of an unfavorable IA outcome. RESULTS Among the 283 patients with confirmed IAs, 45 patients (16%) were positively screened for OSA, a proportion that was significantly higher than the prevalence of OSA in nonaneurysmal neurosurgical patients (4%, p = 0.008). The percentage of patients with hypertension (p = 0.018), a body mass index ≥ 30 kg/m2 (p < 0.0001), hyperlipidemia (p = 0.034), diabetes mellitus (p = 0.005), chronic heart disease (CHD; p = 0.024), or prior stroke (p = 0.03) was significantly higher in the OSA group than in the non-OSA group. Similarly, the percentage of wide-necked aneurysms (p = 0.00001) and patients with a poor Hunt and Hess Grade IV-V (p = 0.01) was significantly higher in the OSA group than in the non-OSA group. In addition, the percentage of ruptured aneurysms (p = 0.03) and vasospasms (p = 0.03) was significantly higher in the OSA group. The percentage of patients with poor modified Rankin Scale (mRS) scores (3-6) was significantly higher in the OSA group (p = 0.03). A separate cohort of patients with ruptured IAs showed similar results. In both univariate (p = 0.01) and multivariate (p = 0.04) regression analyses, OSA was identified as an individual predictor of an unfavorable outcome. In addition, hypertension and prior stroke were revealed as predictors of a poor IA outcome. CONCLUSIONS Complications of IA such as rupture and vasospasm are often the consequence of uncontrolled OSA. Overall outcome (mRS) of IAs is also affected by the co-occurrence of OSA. Therefore, the coexistence of OSA with IA affects the outcome of IAs. Obstructive sleep apnea is a risk factor for a poor outcome in IA patients.

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