The Role of Long Noncoding RNAs in Vascular Smooth Muscle Cell Phenotype and the Pathogenesis of Cardiovascular and Cerebrovascular Aneurysms.

ABSTRACT: Aneurysms are localized dilations of blood vessels, which can expand to 50% of the original diameter. They are more common in cardiovascular and cerebrovascular vessels. Rupture is one of the most dangerous complications. The pathophysiology of aneurysms is complex and diverse, often associated with progressive vessel wall dysfunction resulting from vascular smooth muscle cell death and abnormal extracellular matrix synthesis and degradation. Multiple studies have shown that long noncoding RNAs (lncRNAs) play a significant role in the progression of cardiovascular and cerebrovascular diseases. Therefore, it is necessary to find and summarize them. LncRNAs control gene expression and disease progression by regulating target mRNA or miRNA and are biomarkers for the diagnosis and prognosis of aneurysmal cardiovascular and cerebrovascular diseases. This review explores the role, mechanism, and clinical value of lncRNAs in aneurysms, providing new insights for a deeper understanding of the pathogenesis of cardiovascular and cerebrovascular aneurysms.

Stent-to-vessel diameter ratio is associated with in-stent stenosis after flow-diversion treatment of intracranial aneurysms.

BACKGROUND AND PURPOSE: Flow-diversion treatment for intracranial aneurysms has been associated with the development of in-stent stenosis (ISS) for unclear reasons. We assess whether the size of the stent relative to that of the vessel (the stent-to-vessel diameter ratio, or SVR) may be predictive of the development of ISS after treatment with flow diverters. METHODS: We retrospectively reviewed patients with unruptured intracranial aneurysms who underwent flow-diversion treatment using either the Pipeline or Tubridge embolization device from September 2018 to September 2022. The relationship between SVR and ISS was analyzed. Multiple logistic regression models were used to determine the significant predictors. RESULTS: A total of 458 patients with 481 aneurysms were included. In a mean angiographic follow-up of 10.73 ± 3.97 months, ISS was detected in 68 cases (14.1 %). After adjusting for candidate variables, a higher distal SVR (DSVR) was associated with an increased risk of ISS (adjusted odds ratio [aOR] = 3.420, 95 % confidence interval [CI] = 1.182 - 9.889, p = 0.023). We conducted a subgroup analysis of the two different flow diverters to assess the effects of their individual characteristics. Our results showed a significant association between the DSVR and the incidence of ISS in both the Pipeline (aOR = 4.033, 95 % CI = 1.156-14.072, p = 0.029) and Tubridge groups (aOR = 11.981, 95 % CI=1.005-142.774, p = 0.049). CONCLUSION: A higher DSVR was associated with an increased risk of ISS. This may help neurointerventionalists select an appropriate stent size when conducting flow-diversion treatment for intracranial aneurysms.

Effects of induced arterial hypertension for vasospasm on unruptured and unsecured cerebral aneurysms (growth and rupture). A retrospective case-control study.

OBJECTIVES: Unruptured cerebral aneurysms (UCAs) often coexist with the ruptured one but are typically left unsecured during the weeks following aneurysmal subarachnoid hemorrhage (aSAH). We compared the rate of UCAs rupture or volume growth (≥5 mm3) between patients exposed to induced arterial hypertension (iHTN) for vasospasm and those not exposed (control group). MATERIALS AND METHODS: From 2013 to 2021, we retrospectively included consecutive adult patients with aSAH who had ≥1 UCA. Custom software for digital subtraction angiography (DSA) image analysis characterized UCAs volume, going beyond merely considering UCAs long axis. RESULTS: We analyzed 118 patients (180 UCAs): 45 in the iHTN group (64 UCAs) and 73 in the control group (116 UCAs). Systolic blood pressure in the iHTN group was significantly higher than in the control group for several days after aSAH. During the 107 day-monitoring period [interquartile range(IQR):92;128], no UCA rupture occurred in either group. UCA volume analysis was performed in 44 patients (60 UCAs): none of the UCAs in the iHTN group and 3 out of 42 (7%) in the control group had a >5 mm3 volume growth (p=0.55). Other morphologic parameters did not exhibit any variations that might indicate an increased risk of rupture in the iHTN group compared to the control group. CONCLUSION: iHTN did not increase the risk of rupture or volume growth of UCAs within several weeks following aSAH. These reassuring results encourage not to refrain, because of the existence of UCAs, from iHTN as an option to prevent cerebral infarction during cerebral vasospasm.

Statistical evaluation of measured biomechanical properties of human brain aneurysm samples.

Background and purpose:

Human brain aneurysms may often prove fatal if not re­cognized in time and treated accordingly. The understanding of development and rupture of aneurysms can significantly be improved by the application of numerical modelling, which in turn, requires the knowledge of mechanical properties of vessel wall. This study aims to identify assumed differences with respect to age, sex, spatial orientation, and rupture by utilizing detailed statistical analysis of uniaxial tensile measurements of human brain aneurysm samples, performed by the authors in a previous project.

At surgery of 42 patients, aneu­rysm fundi were cut distally to the clip. In each case, depending on size, varying number of stripes (altogether 88) were prepared and uniaxial stress-strain measurements were performed. Quantities related to the capacity, energy absorption or stiffness were determined and statistically analysed.

The number of specimens in the aneurysm sample was sufficient to establish statistical differences with respect to sex and rupture (p<0.05). No significant differences were detected in orientation, though higher values of stresses and deformations were ob­tained in the circumferential direction com­pared to the meridional direction. 

Significant differences bet­ween sexes with respect to ultimate deformations were demonstrated according to expectation, and the hypothesis on equality of energy capacity could be supported. Similarity of curves with respect to specimen orientation was also observed and ruptured aneurysm sacs tended to be smaller in size. It seems that differences and trends described in this paper are realistic and need to be applied in numerical modelling.

Characterizing Tissue Remodeling and Mechanical Heterogeneity in Cerebral Aneurysms.

Accurately assessing the complex tissue mechanics of cerebral aneurysms (CAs) is critical for elucidating how CAs grow and whether that growth will lead to rupture. The factors that have been implicated in CA progression - blood flow dynamics, immune infiltration, and extracellular matrix remodeling - all occur heterogeneously throughout the CA. Thus, it stands to reason that the mechanical properties of CAs are also spatially heterogeneous. Here, we present a new method for characterizing the mechanical heterogeneity of human CAs using generalized anisotropic inverse mechanics, which uses biaxial stretching experiments and inverse analyses to determine the local Kelvin moduli and principal alignments within the tissue. Using this approach, we find that there is significant mechanical heterogeneity within a single acquired human CA. These results were confirmed using second harmonic generation imaging of the CA's fiber architecture and a correlation was observed. This approach provides a single-step method for determining the complex heterogeneous mechanics of CAs, which has important implications for future identification of metrics that can improve accuracy in prediction risk of rupture.

Roles of Phytoestrogen in the Pathophysiology of Intracranial Aneurysm.

Background and Purpose: The incidences of intracranial aneurysm and aneurysmal subarachnoid hemorrhage are high in postmenopausal women. Although population-based studies suggest that hormone replacement therapy is beneficial for postmenopausal women with intracranial aneurysms, estrogen replacement may no longer be recommended for the prevention of chronic diseases given its association with adverse outcomes, such as cancer and ischemic stroke. The isoflavone daidzein and its intestinal metabolite equol are bioactive phytoestrogens and potent agonists of estrogen receptors. Given their estrogenic properties, we investigated whether the isoflavones daidzein and equol are protective against the formation and rupture of intracranial aneurysms in a mouse model of the postmenopausal state. Methods: We induced intracranial aneurysms in ovariectomized adult female mice using a combination of induced systemic hypertension and a single injection of elastase into the cerebrospinal fluid. We fed the mice with an isoflavone-free diet with/without daidzein supplementation, or in a combination of intraperitoneal equol, or oral vancomycin treatment. We also used estrogen receptor beta knockout mice. Results: Both dietary daidzein and supplementation with its metabolite, equol, were protective against aneurysm formation in ovariectomized mice. The protective effects of daidzein and equol required estrogen receptor-ß. The disruption of the intestinal microbial conversion of daidzein to equol abolished daidzein's protective effect against aneurysm formation. Mice treated with equol had lower inflammatory cytokines in the cerebral arteries, suggesting that phytoestrogens modulate inflammatory processes important to intracranial aneurysm pathogenesis. Conclusions: Our study establishes that both dietary daidzein and its metabolite, equol, protect against aneurysm formation in ovariectomized female mice through the activation of estrogen receptor-ß and subsequent suppression of inflammation. Dietary daidzein's protective effect required the intestinal conversion to equol. Our results indicate the potential therapeutic value of dietary daidzein and its metabolite, equol, for the prevention of the formation of intracranial aneurysms and related subarachnoid hemorrhage.

Wall shear stress gradient is independently associated with middle cerebral artery aneurysm development: a case-control CFD patient-specific study based on 77 patients.

BACKGROUND: Previously published computational fluid dynamics (CFD) studies regarding intracranial aneurysm (IA) formation present conflicting results. Our study analysed the involvement of the combination of high wall shear stress (WSS) and a positive WSS gradient (WSSG) in IA formation. METHODS: We designed a case-control study with a selection of 38 patients with an unruptured middle cerebral artery (MCA) aneurysm and 39 non-aneurysmal controls to determine the involvement of WSS, oscillatory shear index (OSI), the WSSG and its absolute value (absWSSG) in aneurysm formation based on patient-specific CFD simulations using velocity profiles obtained from transcranial colour-coded sonography. RESULTS: Among the analysed parameters, only the WSSG had significantly higher values compared to the controls (11.05 vs - 14.76 [Pa/mm], P = 0.020). The WSS, absWSSG and OSI values were not significantly different between the analysed groups. Logistic regression analysis identified WSS and WSSG as significant co-predictors for MCA aneurysm formation, but only the WSSG turned out to be a significant independent prognosticator (OR: 1.009; 95% CI: 1.001-1.017; P = 0.025). Significantly more patients (23/38) in the case group had haemodynamic regions of high WSS combined with a positive WSSG near the bifurcation apex, while in the control group, high WSS was usually accompanied by a negative WSSG (14/39). From the analysis of the ROC curve for WSSG, the area under the curve (AUC) was 0.654, with the optimal cut-off value -0.37 Pa/mm. The largest AUC was recognised for combined WSS and WSSG (AUC = 0.671). Our data confirmed that aneurysms tend to form near the bifurcation apices in regions of high WSS values accompanied by positive WSSG. CONCLUSIONS: The development of IAs is determined by an independent effect of haemodynamic factors. High WSS impacts MCA aneurysm formation, while a positive WSSG mainly promotes this process.

Prediction of postoperative motor deficits using intraoperative motor-evoked potentials in middle cerebral artery aneurysm.

To explore the relationship between postoperative motor deficits and the duration of reduced motor-evoked potentials (MEPs) in patients with middle cerebral artery (MCA) aneurysm. This study included 285 cases of MCA aneurysm treated with clipping surgery with MEP monitoring. The effects of MEP changes on postoperative motor function were assessed, and the key time point for minimizing the incidence of postoperative motor dysfunction was found through receiver operating characteristic (ROC) curve analysis. Motor dysfunction was significantly associated with the occurrence of MEP changes, and patients with irreversible changes were more likely to suffer motor dysfunction than were those with reversible changes. The critical duration of MEP changes that minimized the risk of postoperative motor dysfunction was 8.5 min. This study revealed that MEP monitoring is an effective method for preventing ischemic brain injury during surgical treatment of MCA aneurysm and proposes a critical cutoff for the duration of MEP deterioration of 8.5 min for predicting postoperative motor dysfunction.

Effect of bifurcation in the hemodynamic changes and rupture risk of small intracranial aneurysm.

The role of bifurcations is prominent in the intracranial aneurysm (IA) evaluation, and there are many contradictions and complexities in the rupture risk of small IA. Therefore, in the present study, the effect of bifurcation on the manner of hemodynamic changes and the rupture risk of the small middle cerebral artery (MCA) aneurysm is investigated. 3D anatomical models of the MCAs of 21 healthy subjects, 19 patients/IA/bifurcation, and 19 patients/IA were generated, and the models were analyzed by the computational fluid dynamic (CFD) analysis. The presence of bifurcation in the pathway of the blood flow in the parent artery of healthy subjects has reduced the maximum velocity, flow rate, and wall shear stress (WSS) by 25.8%, 38.6%, and 11.1%, respectively. The bifurcation decreased the maximum velocity and flow rate in the neck and sac of the aneurysm by 1.65~2.1 times, respectively. It increased the maximum WSS, and phase lag between the WSS graph of healthy subjects and patients by 12.8%~13.9% and 10.2%~40.4%, respectively. The effect of bifurcation on the Womersley number change in the aneurysm was insignificant, and the blood flow was in the laminar flow condition in all samples. The results also showed bifurcation increased the phase lag between the flow rate and pressure gradient graphs up to approximately 1.5 times. The rupture prediction index for patients/IA/bifurcation and patients/IA was 62.1%(CV = 4.1) and 51.8%(CV = 4.4), respectively. Thus, in equal conditions, the presence of bifurcation increased the probability of the rupture of the aneurysm by 19.9%.

Flow diversion of fusiform intracranial aneurysms.

Fusiform aneurysms are less common than saccular aneurysms, but have higher associated mortality and rebleeding rates. Recently, flow diversion has emerged as a possible treatment option. The purpose of this study was to determine the safety and efficacy of the Pipeline Embolization Device (PED) for the treatment of ruptured and unruptured fusiform aneurysms. This was a retrospective analysis of patients with fusiform intracranial aneurysms treated with a PED at a quaternary care center between January 2012 and September 2019. Occlusion rates, neurologic morbidity/mortality, and other clinical variables were analyzed. Twenty-nine patients with 30 fusiform aneurysms were treated with a PED. Sixteen aneurysms (53%) were located in the anterior circulation and 14 aneurysms (47%) were in the posterior circulation. The mean maximal diameter of the aneurysms was 10.1 ± 5.6 mm (range 2.3-25 mm). Angiographic and clinical follow-up were available for 28 aneurysms (93%). The median follow-up was 17.4 months (IQR 4.8 to 28 months) and occlusion rates were graded according to the O'Kelly-Marotta (OKM) scale. Of patients with DSA follow-up, 15 aneurysms (60%) were completely occluded (OKM D) and 19 aneurysms (76%) had a favorable occlusion result (OKM C1-3 and D). The overall complication rate was 26.7% with a neurological morbidity rate of 6.7% and neurological mortality rate of 3.4%. Flow diversion can be an effective treatment for both ruptured and unruptured fusiform aneurysms. Nevertheless, complete occlusion rates are lower than for saccular aneurysms. Therefore, flow diversion should be considered only if other more direct treatment options, such as clipping or stent/coiling are not applicable. Flow diversion should be used cautiously in patients presenting with rupture.

Diagnostic impact of monitoring transcranial motor-evoked potentials to prevent ischemic complications during endovascular treatment for intracranial aneurysms.

The present study aimed to determine the incidence of intraprocedural motor-evoked potential (MEP) changes and to correlate them with intraprocedural ischemic complications and postprocedural neurological deficits in patients after endovascular intracranial aneurysm treatment. This study analyzed data from 164 consecutive patients who underwent endovascular coil embolization to treat intracranial aneurysms under transcranial MEP monitoring. We analyzed associations between significant changes in MEP defined as > 50% decrease in amplitude, and intraprocedural complications as well as postoperative neurological deficits. Factors associated with postprocedural neurological deficits were also assessed. The treated aneurysms were predominantly located in the anterior circulation (71%). Fourteen (9%) were located at perforators or branches that supplied the pyramidal tract. Intraprocedural complications developed in eight (5%) patients, and four of eight (50%) patients occurred postprocedural neurological deficits. Significant intraprocedural MEP changes occurred during seven of eight endovascular procedures associated with intraprocedural complications and salvage procedures were performed immediately. Among these changes, four transient MEP changes, recovered within 10 min, were not associated with postprocedural neurological deficits, whereas three permanent MEP changes were associated with postprocedural neurological deficits and mRS ≥ 1 at discharge. Aneurysms located at perforators/branches supplying the pyramidal tract, and permanent intraprocedural MEP changes were associated with postprocedural neurological deficits. We conclude that intraprocedural transcranial MEP monitoring can reliably identify ischemic changes and can initiate prompt salvage procedures during endovascular aneurysm treatment.

Involvement of Microglia in the Pathophysiology of Intracranial Aneurysms and Vascular Malformations-A Short Overview.

Aneurysms and vascular malformations of the brain represent an important source of intracranial hemorrhage and subsequent mortality and morbidity. We are only beginning to discern the involvement of microglia, the resident immune cell of the central nervous system, in these pathologies and their outcomes. Recent evidence suggests that activated proinflammatory microglia are implicated in the expansion of brain injury following subarachnoid hemorrhage (SAH) in both the acute and chronic phases, being also a main actor in vasospasm, considerably the most severe complication of SAH. On the other hand, anti-inflammatory microglia may be involved in the resolution of cerebral injury and hemorrhage. These immune cells have also been observed in high numbers in brain arteriovenous malformations (bAVM) and cerebral cavernomas (CCM), although their roles in these lesions are currently incompletely ascertained. The following review aims to shed a light on the most significant findings related to microglia and their roles in intracranial aneurysms and vascular malformations, as well as possibly establish the course for future research.

Inflow Hemodynamics of Intracranial Aneurysms: A Comparison of Computational Fluid Dynamics and 4D Flow Magnetic Resonance Imaging.

PURPOSE: Although the inflow hemodynamics of cerebral aneurysms are key factors in their rupture and recurrence after endovascular treatments, the most available method for inflow hemodynamics evaluation remains unestablished. We compared the efficacy of inflow hemodynamics evaluation using computational fluid dynamics (CFD) analysis and that using four-dimensional (4D) flow magnetic resonance imaging (MRI). METHODS: In 23 unruptured cerebral aneurysms, the inflow hemodynamics was evaluated using both CFD and 4D flow MRI. The evaluated parameters included visually classified inflow jet patterns, the inflow rate ratio (the ratio of the inflow rate at the aneurysmal orifice to the flow rate in the proximal parent artery), and the velocity ratio (the ratio of the inflow velocity to the velocity in the proximal parent artery). The Shapiro-Wilk test was used to assess the normality of variable data, and logarithmic transformation was performed for variables with non-normal distributions. Data analysis was performed using Pearson correlation analyses and the chi-square test. RESULTS: There was a significant correlation between inflow jet patterns evaluated by CFD and 4D flow MRI (p = 0.008). Moreover, there was a strong correlation between the inflow rate ratios evaluated by CFD and 4D flow MRI (r = 0.801; p <0.001). Furthermore, there was a moderate correlation between the velocity ratios measured by CFD and 4D flow MRI (r = 0.559; p = 0.008). CONCLUSION: Inflow hemodynamics evaluated by CFD analysis and 4D flow MRI showed good correlations in inflow jet pattern, inflow rate ratio, and velocity ratio.

Incidence of Neo-Intimal Hyperplasia in Anterior Circulation Aneurysms Following Pipeline Flow Diversion.

INTRODUCTION: Flow diversion of the distal anterior circulation cerebral vasculature may be used for management of wide necked aneurysms not amenable to other endovascular approaches. Follow-up angiography sometimes demonstrates neo-intimal hyperplasia within or adjacent to the stent, however there is limited evidence in the literature examining the incidence in MCA and ACA aneurysms. We present our experience with flow diversion of the distal vasculature and evaluate the incidence of neo-intimal hyperplasia. MATERIALS AND METHODS: Retrospective review of patients who underwent Pipeline embolization device (PED) treatment for ruptured and unruptured anterior circulation aneurysms. RESULTS: A total of 251 anterior circulation aneurysms were treated by pipeline flow diversion, of which 175 were ICA aneurysms, 14 were ACA aneurysms and 18 were MCA aneurysms. 6-month follow-up angiography was available in 207 patients. The incidence of neo-intimal hyperplasia was 15.9%, 21.4%, and 61.1% in ICA, ACA, and MCA aneurysms, respectively. MCA-territory aneurysms developed neo-intimal hyperplasia at a significantly higher rate than aneurysms in other vessel territories. Rates of aneurysmal occlusion did not significantly differ from those patients who did not exhibit intimal hyperplasia on follow-up angiography. CONCLUSION: In our experience, flow diversion of distal wide-necked MCA and ACA aneurysms is a safe and effective treatment strategy. The presence of neo-intimal hyperplasia at 6-month angiography is typically clinically asymptomatic. Given the statistically higher rate of neo-intimal hyperplasia in MCA aneurysms at 6-month angiography, we propose delaying initial follow-up angiography to 12-months and maintaining dual antiplatelet therapy during that time.

Traumatic Distal Anterior Cerebral Artery Aneurysms - Pathomechanism and Revascularisation Strategies.

Traumatic intracranial aneurysms (TICA) of the distal anterior cerebral artery (dACA) are exceptionally rare and display therapeutic challenges due to their angioanatomical characteristics. The objective of this work was to discuss the mechanisms of TICA formation of the dACA and to elucidate the best treatment and revascularization strategies in these patients based on two illustrative cases. Case 1: 20-year-old patient with a traumatic, partially thrombosed 14 × 10 mm aneurysm of the right pericallosal artery (rPericA), distal to the origin of the right callosomarginal artery (rCMA). Complete trapping of the right dissection A3 aneurysm and flow replacement extra-to-intracranial (EC-IC) bypass (STA - radial artery - A4) was performed. Case 2: 16-year-old patient with a traumatic polylobulated, partially thrombosed 16 × 10 mm aneurysm of the rPericA. Microsurgical excision of the A3- segment harboring the aneurysm and flow replacement intra-to-intracranial (IC-IC) bypass via reimplantation of the right remaining PericA on the contralateral PericA (end-to-side anastomosis) was performed (in situ bypass). TICA of the dACA are exceptionally rare. Mechanical vessel wall injury and aneurysm formation of the dACA in blunt head trauma is very likely due to the proximity of the dACA with the rigid free edge of the falx. Given their nature as dissecting (complex) aneurysm, trapping and revascularization is a very important strategy. The interhemispheric cistern offers multiple revascularization options with its numerous donor vessels. The IC-IC bypass is often the simplest revascularization construct.

Acute Stenting and Concomitant Tirofiban Administration for the Endovascular Treatment of Acute Ischemic Stroke Related to Intracranial Artery Dissections: A Single Center Experience and Systematic Review of the Literature.

BACKGROUND: Intracranial artery dissection is an uncommon cause of acute ischemic stroke. Although acute stenting of the dissected arterial segment is a therapeutic option, the associated antiplatelet regimen remains a matter of debate. OBJECTIVES: To evaluate the efficacy and safety of acute intracranial stenting together with concomitant intravenous administration of tirofiban and to perform a systematic review of the literature. MATERIALS AND METHODS: A single-center, retrospective study of the clinical and radiological records of all patients treated at our center by intracranial stenting in the setting of acute ischemic stroke between January 2010 and December 2020. A systematic review of the literature was conducted according to the PRISMA-P guidelines for relevant publications from January 1976 to December 2020 on intracranial artery dissection treated by stent. RESULTS: Seven patients with intracranial artery dissections underwent acute stenting with concomitant tirofiban during the study period. Mid-term follow-up showed parent artery patency in 6/7 cases (85.7%). The modified Rankin Score was ≤ 0-2 at 3 months in 5/7 cases (71.4%). The literature review identified 22 patients with intracranial artery dissection treated with acute stenting in association with different antithrombotic therapies. Complete revascularization was obtained in 86.3% of cases with a modified Rankin Score of ≤ 0-2 in 68% of patients at 3-month follow-up. CONCLUSIONS: Acute intracranial stenting together with intravenous tirofiban administration could be a therapeutic option in patients with intracranial artery dissection and a small ischemic core.

Flow Diversion in Acute Sub Arachnoid Haemorrhage: A Single Centre Five Year Experience.

OBJECTIVES: The role of flow-diversion in acute sub-arachnoid haemorrhage (SAH) is controversial. Many of the published data warns of high rates of procedure-related complications and aneurysmal rebleed. This study evaluates the safety, efficacy, clinical and angiographic outcomes of acute flow-diversion at our institute. METHODS: The institutional database from June 2015 to June 2020 was retrospectively reviewed for aneurysmal SAH (aSAH) treated with flow diversion. Clinical presentation, procedural details, complications, anti-platelet usage, rebleeding and aneurysm occlusion rates and outcomes were recorded. RESULTS: 22 (59% females; median age 56 years) consecutive patients were identified. None of them were on regular antiplatelets/anticoagulation in the 15-days preceding the treatment. The mean aneurysm diameter was 5.4 mm and the median delay to flow-diversion was 2 days. Almost 73% (16/22) of patients had adjunctive coiling in the same session. There was no aneurysmal rebleed at a median follow up of 8.5 months and 86.3% (19/22 patients) had good clinical outcomes (3-month MRS 0-2). Adverse events related to the flow diversion procedure were seen in 3 patients; none of them had a medium to long-term clinical consequence. Three patients died from complications of SAH, unrelated to the procedure. Vascular imaging follow-up was available for 20 patients and the complete aneurysm occlusion rate was 95%. CONCLUSION: Flow-diversion could be a reasonably safe and effective technique for treating ruptured aneurysms in appropriately selected patients when conventional options of surgical clipping and coiling are considered challenging.

Enigma of what is Known about Intracranial Aneurysm Occlusion with Endovascular Devices.

Aneurysmal subarachnoid Hemorrhage is a major cause of neurological morbidity and mortality. Over the years vascular neurosurgery has witnessed technological advances aimed to reduce the morbidity and mortality. Several endovascular devices have been used in clinical practice to achieve this goal in the management of ruptured and unruptured cerebral aneurysms. Recurrence due to recanalization is encountered in all of these endovascular devices as well as illustrated by Barrow Ruptured Aneurysm Trial. Histological and molecular characterization of the aneurysms treated with endovascular devices is an area of active animal and human research studies. Yet, the pathobiology illustrating the mechanisms of aneurysmal occlusion and healing lacks evidence. The enigma of aneurysmal healing following treatment with endovascular devices needs to be de-mystified to understand the biological interaction of endovascular device and aneurysm and thereby guide the future development of endovascular devices aimed at better aneurysm occlusion. We performed a comprehensive and detailed literature review to bring all the known facts of the pathobiology of intracranial aneurysm healing, the knowledge of which is of paramount importance to neurosurgeons, an interventional neuroradiologist, molecular biologist, geneticists, and experts in animal studies. This review serves as a benchmark of what is known and platform for future studies basic science research related to intracranial aneurysms.

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.

Collagen Turnover in Relation to Risk Factors and Hemodynamics in Human Intracranial Aneurysms.

Background and Purpose- Determinants for molecular and structural instability, that is, impending growth or rupture, of intracranial aneurysms (IAs) remain uncertain. To elucidate this, we endeavored to estimate the actual turnover rates of the main molecular constituent in human IA (collagen) on the basis of radiocarbon (14C) birth dating in relation to IA hemodynamics. Methods- Collagen turnover rates in excised human IA samples were calculated using mathematical modeling of 14C birth dating data of collagen in relation to risk factors and histological markers for collagen maturity/turnover in selected IA. Hemodynamics were simulated using image-based computational fluid dynamics. Correlation, logistic regression, and receiver operating characteristic analyses were performed. Results- Collagen turnover rates were estimated in 46 IA (43 patients); computational fluid dynamics could be performed in 20 IA (20 patients). The mean collagen turnover rate (γ) constituted 126% (±1% error) per year. For patients with arterial hypertension, γ was greater than 2600% annually, whereas γ was distinctly lower with 32% (±1% error) per year for patients without risk factors, such as smoking and hypertension. There was a distinct association between histological presence of rather immature collagen in human IA and the presence of modifiable risk factors. Spatial-temporal averaged wall shear stress predicted rapid collagen turnover (odds ratio, 1.6 [95% CI, 1.0-2.7]). Receiver operating characteristic analysis demonstrated a good test accuracy (area under the curve, 0.798 [95% CI, 0.598-0.998]) for average wall shear stress with a threshold ≥4.9 Pa for rapid collagen turnover. Conclusions- Our data indicate that turnover rates and stability of collagen in human IA are strongly associated with the presence of modifiable risk factors and aneurysmal hemodynamics. These findings underline the importance of strict risk factor modification in patients with unruptured IA. Future should include more detailed risk factor data to establish a more causal understanding of hemodynamics and the rupture risk of individual IA.