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Background Five to ten percent of the global population have unruptured intracranial aneurysms, and ruptured brain aneurysms cause approximately 500,000 deaths a year. Flow-diverting stent treatment is a less invasive intracranial aneurysm treatment that induces aneurysm thrombosis. The imaging characteristics of a novel primarily bioresorbable flow-diverting stent (BFDS) are assessed in comparison to the leading metal stent using fluoroscopy, CT, and MRI. Methods X-ray/fluoroscopic images of stents were taken using a human cadaveric skull model. CT and MRI were acquired using silicone flow models of residual aneurysms. Images were analyzed with Likert scales in anonymous surveys by neurointerventionalists. Quantitative measurements of radiographic density (CT) and artifact boundary size (CT & MRI) were also obtained. Results Visibility of the BFDS on X-ray was less than the metal stent but deemed adequate for deployment and intraprocedural assessment. The metal stent was more radiopaque than the BFDS on CT, but qualitative assessment was not significantly different for the two stents. MRI imaging was significantly better using the BFDS in terms of overall artifact and intraluminal assessment. Conclusions The BFDS has adequate visualization on X-ray/fluoroscopy and should be clinically acceptable for fluoroscopic deployment. On MRI, there is less quantitative artifact as well as overall improved qualitative assessment that will allow for more detailed non-invasive imaging follow-up of treated aneurysms, potentially reducing the need for digital subtraction catheter angiography.

OBJECTIVE Routine antiplatelet responsiveness testing for patients undergoing carotid artery stenting procedures is not performed at most endovascular centers and remains a topic of controversy within the neurointerventional community. The objective of this study was to determine if nonresponsiveness to acetylsalicylic acid or clopidogrel was associated with the development of symptomatic thromboembolic events in patients undergoing carotid stenting procedures. METHODS A prospective study was conducted at the Foothills Medical Centre in Calgary, Alberta, Canada, from August 2019 to July 2021. Patients undergoing carotid artery stenting procedures and who were receiving dual antiplatelet therapy were enrolled in the study. Responsiveness to the antiplatelet medications was determined through whole blood impedance aggregometry. The primary outcome was development of a symptomatic thromboembolic event within 90 days after the procedure. The treating physicians were blinded to the aggregometry results for the duration of the study. RESULTS One hundred two procedures were performed in 100 patients. Eight thromboembolic events (8%) occurred during the study. Age (p = 0.03) and nonresponsiveness to clopidogrel (p = 0.003) were associated with the development of thromboembolic events. The multivariable model showed that clopidogrel nonresponsiveness was independently associated with the development of a thromboembolic event (adjusted OR 6.14, 95% CI 1.25–30.11, p = 0.03). CONCLUSIONS This study demonstrated that patients who were identified as clopidogrel nonresponders, using whole blood impedance aggregometry, were at an increased risk of developing thromboembolic events. Larger studies are needed to assess the utility of routine platelet function testing prior to carotid artery stenting procedures.

OBJECTIVE Flow-diverting stents with a resorbable component have significant theoretical benefits over full metal stents, although currently there are none in clinical use. In this study, the authors sought to determine the immediate flow-diversion characteristics of a novel primarily bioresorbable flow-diverting stent. METHODS Bioresorbable stents were deployed into glass tube models to determine porosity and pore density. In vitro flow diversion behavior was evaluated using high frame rate angiography under pulsatile flow conditions in a patient-specific silicone aneurysm model treated with the resorbable stent as well as the Surpass Evolve stent. In vivo flow diversion was characterized by deployment into 20 rabbit saccular aneurysm models, and grading was based on the O’Kelly-Marotta scale and the 4F-flow diversion predictive score. RESULTS Porosities and pore densities of the bioresorbable stent were in the flow-diverting range for all target vessel diameters. Quantified results of immediate angiography after placement of the bioresorbable stent into a silicone aneurysm model demonstrated greater flow diversion compared to the Evolve stent. Bioresorbable stent placement in saccular aneurysm models resulted in an immediate O’Kelly-Marotta grade of A3 or better and a 4F-flow diversion predictive score of 4 or better in all cases. CONCLUSIONS The bioresorbable stent has immediate flow-diversion characteristics that are comparable to commercially available metal stents. Longer-term studies are underway to determine the ability of the resorbable fibers to act as a neointimal scaffold and result in long-term aneurysm occlusion.

Intramedullary spinal cord cavernous malformations (SCCMs) account for only 5% of overall cavernous malformations (CMs). The occurrence of recurrent or residual SCCMs has not been well discussed, nor have the technical nuances of resection.To assess the characteristics of residual SCCMs and surgical outcomes and describe the techniques to avoid leaving lesion remnants during primary resection.Demographic, radiologic, intraoperative findings and surgical outcomes data for a cohort of surgically managed intramedullary SCCMs were obtained from an institutional database and retrospectively analyzed. A systematic literature review was performed using PRISMA guidelines.Of 146 SCCM resections identified, 17 were for residual lesions (12%). Patients with residuals included 13 men and 4 women, with a mean age of 43 years (range 16-70). All patients with residual SCCMs had symptomatic presentations: sensory deficits, paraparesis, spasticity, and pain. Residuals occurred between 3 and 264 months after initial resection. Approaches for 136 cases included posterior midline myelotomy (28.7%, n = 39), pial surface entry (37.5%, n = 51), dorsal root entry zone (27.9%, n = 38), and lateral entry (5.9%, n = 8). Follow-up outcomes were similar for patients with primary and residual lesions, with the majority having no change in modified Rankin Scale score (63% [59/93] vs 75% [9/12], respectively, P = .98).SCCMs may cause significant symptoms. During primary resection, care should be taken to avoid leaving residual lesion remnants, which can lead to future hemorrhagic events and neurological morbidity. However, satisfactory results are achievable even with secondary or tertiary resections.

OBJECTIVE Flow diverters have revolutionized the endovascular treatment of intracranial aneurysms. Here, the authors present the first large-scale North American multicenter experience using the Flow Redirection Endoluminal Device (FRED) in the treatment of cerebral aneurysms. METHODS Consecutive cerebral aneurysms treated with FRED at 7 North American centers between June 2020 and November 2021 were included. Data collected included patient demographic characteristics, aneurysm characteristics, periprocedural and long-term complications, modified Rankin Scale (mRS) scores, and radiological follow-up. RESULTS In total, 133 aneurysms in 116 patients were treated with 123 FRED deployment procedures and included in this study. One hundred twenty-six aneurysms (94.7%) were unruptured, 117 (88.0%) saccular, and 123 (92.5%) located in anterior circulation. The mean (range) aneurysm maximal width and neck width sizes were 7.2 (1.5–42.5) mm and 4.1 (1.0–15.1) mm, respectively. Successful FRED deployment was achieved in 122 procedures (99.2%). Adjunctive coiling was used in 4 procedures (3.3%). Radiological follow-up was available for 101 aneurysms at a median duration of 7.0 months. At last follow-up, complete occlusion was observed in 55.4% of patients, residual neck in 8.9%, and filling aneurysm in 35.6%; among cases with radiological follow-up duration > 10 months, these values were 21/43 (48.8%), 3/43 (7.0%), and 19/43 (44.2%), respectively. On multivariate regression analysis, age (OR 0.93, p = 0.001) and aneurysm neck size (OR 0.83, p = 0.048) were negatively correlated with odds of complete occlusion at latest follow-up. The retreatment rate was 6/124 (4.8%). The overall complication rate was 31/116 (26.7%). Parent vessel occlusion, covered branch occlusion, and in-stent stenosis were detected in 9/99 (9.1%), 6/63 (9.5%), and 15/99 (15.2%) cases, respectively. The FRED-related, symptomatic, thromboembolic, and hemorrhagic complication rates were 22.4%, 12.9%, 6.9%, and 0.9% respectively. The morbidity rate was 10/116 patients (8.6%). There was 1 death due to massive periprocedural internal carotid artery stroke, and 3.6% of the patients had an mRS score > 2 at the last follow-up (vs 0.9% at baseline). CONCLUSIONS As the first large-scale North American multicenter FRED experience, this study confirmed the ease of successful FRED deployment but suggested lower efficacy and a higher rate of complications than reported by previous European and South American studies on FRED and other flow-diverting devices. The authors recommend judicious use of this device until future studies can better elucidate the long-term outcomes of FRED treatment.

Hyperglycemia has been associated with poor outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, there remains debate as to what optimal glucose targets should be in this patient population.To assess whether we could identify an optimal glucose target for patients with aSAH.We performed a post hoc analysis of the "clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage" trial data set. Patients had laboratory results drawn daily for the entirety of their intensive care unit stay. Maximum blood glucose levels were assessed for a relationship with unfavorable outcomes using multiple logistic regression analysis. Maximum blood glucose levels were dichotomized based on the Youden index, which identified a maximum level of9.2 mmol/L as the optimal cut point for prediction of unfavorable outcomes. Nearest neighbor matching was used to assess the relationship between maintaining glucose levels below the cut point and unfavorable functional outcomes (defined as a modified Rankin score of2 at 3 mo post-aSAH). The matching was performed after calculation of a propensity score based on identified predictors of outcome and glucose levels.Three hundred eighty-nine patients were included in the matched analysis. Propensity scores were balanced on both the covariates and outcomes of interest. There was a significant average treatment effect (-0.143: 95% confidence interval -0.267 to -0.019) for patients who maintained glucose levels9.2 mmol/L.Maintaining glucose levels below the identified cut point was associated with a decreased risk for unfavorable outcomes in this retrospective matched study.

Acute pro-myelocytic leukemia (APML) is associated with an elevated risk of bleeding and thrombosis due to disseminated intravascular coagulation that is frequently present prior to initiation of therapy. We report the case of a 13 year-old male with Trisomy 21 diagnosed with APML found to have an asymptomatic aortic valve thrombus who developed a thromboembolic arterial ischemic stroke. Endovascular thrombectomy (EVT) restored cerebral circulation and a fibrin thrombus containing APML cells was retrieved. The patient made a neurologic recovery, nearing his baseline within one week post-EVT. We highlight that thromboembolic stroke can be a rare complication in APML and present unique management challenges.

Creating aneurysm sizes in animal models that resemble human aneurysms is essential to study and test neuroendovascular devices. The commonly used rabbit surgical elastase model, however, produces saccular aneurysms that are smaller than those typically treated in humans. The goal of this study was to determine whether an increased vessel stump length and the addition of calcium chloride to the incubation solution has an effect on the resulting aneurysm size.Using a modified aneurysm creation method, 32 female New Zealand White rabbits underwent aneurysm creation procedures. Subjects were equally allocated into 4 different groups based on vessel stump length (2 cm controls vs. 3 cm) and incubation solution (elastase alone controls vs. a 1:1 mixture of elastase and calcium chloride). At 4 weeks, all animals underwent angiography to determine the resulting aneurysm size by a neurointerventionalist who was blinded to treatment group.An increase in stump length from 2 cm to 3 cm resulted in a significant increase in the height of aneurysm (P0.05). Compared with control animals, the combination of a 3-cm stump length and the addition of calcium chloride to the incubation solution resulted in a significant increase in aneurysm height, width, and volume (P0.05).Creating larger aneurysms is necessary for the rabbit model to be more clinically relevant. Our study demonstrated that the utilization of a 3-cm vessel stump as well as both calcium chloride and elastase in the incubation solution results in aneurysm sizes that more closely resemble the population of aneurysms treated in humans.

Epidural fat contains a population of mesenchymal progenitor cells (MPCs), and this study explores the behavior of these cells on the adjacent dura mater during growth and in response to injury in a p21 knockout mouse model. p21

BackgroundFlow-diverting stents are not currently indicated for the treatment of bifurcation aneurysms, and some case series have demonstrated low occlusion rates, possibly due to a lack in neck coverage. The ReSolv stent is a unique hybrid metal/polymer stent that can be deployed with the shelf technique in order to improve neck coverage.MethodsA Pipeline, unshelfed ReSolv, and shelfed ReSolv stent were deployed in the left-sided branch of an idealized bifurcation aneurysm model. After determining stent porosity, high-speed digital subtraction angiography runs were acquired under pulsatile flow conditions. Time–density curves were created using two region of interest (ROI) paradigms (total aneurysm and left/right), and four parameters were extracted to characterize flow diversion performance.ResultsThe shelfed ReSolv stent demonstrated better aneurysm outflow alterations compared to the Pipeline and unshelfed ReSolv stent when using the total aneurysm as the ROI. On the left side of the aneurysm, there was no significant difference between the shelfed ReSolv stent and the Pipeline. On the right side of the aneurysm, however, the shelfed ReSolv stent had a significantly better contrast washout profile than the unshelfed ReSolv stent and the Pipeline stent.ConclusionsThe ReSolv stent with the shelf technique demonstrates the potential to improve flow diversion outcomes for bifurcation aneurysms. Further in vivo testing will help to determine whether the additional neck coverage leads to better neointimal scaffolding and long-term aneurysm occlusion.

Background: Most patients with World Federation of Neurological Surgeons (WFNS) grade 5 subarachnoid hemorrhage (SAH) have poor outcomes. Accurate assessment of prognosis is important for treatment decisions and conversations with families regarding goals of care. Unjustified pessimism may lead to “self-fulfilling prophecy,” where withdrawal of life-sustaining measures (WLSM) is invariably followed by death. Methods: We performed a cohort study involving consecutive patients with WFNS grade 5 SAH to identify variables with >= 90% and >= 95% positive predictive value (PPV) for poor outcome (1-year modified Rankin Score >= 4), as well as findings predictive of WLSM. Results: Of 140 patients, 38 (27%) had favorable outcomes. Predictors with >= 95% PPV for poor outcome included unconfounded 72-hour Glasgow Coma Scale motor score = 1 pupillary light reflex (PLR) at 24 hours, and intraventricular hemorrhage (IVH) score of >= 20 (volume >= 54.6 ml). Intracerebral hemorrhage (ICH) volume >= 53 ml had PPV of 92%. Variables associated with WLSM decisions included a poor motor score (p < 0.0001) and radiographic evidence of infarction (p = 0.02). Conclusions: We identified several early predictors with high PPV for poor outcome. Of these, lack of improvement in motor score during the initial 72 hours had the greatest potential for confounding from “self-fulfilling prophecy.” Absence of PLR at 24 hours, IVH score >= 20, and ICH volume >= 53 ml predicted poor outcome without a statistically significant effect on WLSM decisions. More research is needed to validate prognostic variables in grade 5 SAH, especially among patients who do not undergo WLSM.

Aneurysm recurrence after Pipeline Embolization Device (PED) placement can be caused by oversizing of the stent as well as poor wall apposition, both of which can lead to elongation. The objective of this study was to assess whether a novel parameter for measuring device elongation based on two-dimensional imaging could be predictive for persistent aneurysm filling after treatment with the PED.A retrospective cohort analysis was initially completed on 41 aneurysms from institution A, examining demographic, aneurysmal, and device measurements. Device measurements, including the ratio of the measured length to the nominal length (ML/NL) of the PED, were taken by reviewers blinded to the primary end point, which was aneurysm occlusion status on 6 month catheter angiogram. Findings were then externally validated against 30 aneurysms (supraclinoid only) from institution B.Data from institution A showed 61% complete aneurysm occlusion at 6 months, and were lower for aneurysms in the supraclinoid region. For supraclinoid aneurysms alone, combined data from both institutions showed higher rates of nonocclusion with aneurysm neck size4 mm (P = 0.008) and a trend toward significance in aneurysms with a branch vessel (P = 0.051). The mean ML/NL ratio was significantly larger in the nonoccluded group compared with the occluded group at both institution A (ratio, 1.37 versus 1.10; P0.001) and institution B (ratio, 1.36 vs. 1.11; P = 0.002).Our data suggest that a novel parameter based on two-dimensional angiography may serve as a rapid technique to measure device elongation and predict occlusion of supraclinoid aneurysms after PED placement.

Background Therapeutic hypothermia (TH) offers cerebral protection following ischemic stroke and may improve outcomes in conjunction with decompressive hemicraniectomy (DHC). We aimed to assess the effectiveness of TH in patients with malignant ischemic stroke and DHC. Methods We performed a meta-analysis in patients with malignant ischemic stroke undergoing DHC comparing TH versus normothermia in studies published up to August 2019. Included studies had ≥10 adults with acute ischemic stroke. Primary outcome was functional independence, and secondary outcomes included complications. Effect size was pooled and described by relative risk (RR) ratios and 95% confidence intervals (CIs). Results Five studies (n = 269 patients; n = 130 TH, n = 139 controls) were included, 4 of which were prospective (n = 2 randomized controlled trials). Median achieved body temperature of TH was 33.6°C (range 33°C−35°C). Median modified Rankin Scale at the study completion was similar between TH and controls (RR 1.08, 95% CI 0.56–2.07, P = 0.8). Three studies reported individual patient modified Rankin Scale outcomes demonstrated a shift toward worse outcomes with TH (unadjusted common odds ratio 1.74; 95% CI 1.05–2.88, P = 0.01). Overall complications were similar between groups (RR 1.20, 95% CI 0.70–2.05, random effects P = 0.5). A suggestion of higher mortality was seen in TH (RR 1.50, 95% CI 0.97–2.32, P = 0.07). Conclusions Clinical and functional outcomes were not overall different between patients undergoing systemic TH and controls following DHC despite the shift toward worse outcomes with TH observed in some studies.

Orbital AVFs, abnormal vascular connections between orbital arteries and veins, are extremely rare. Often traumatic, few reports of spontaneous orbital fistulas have been reported so far. Treatment is warranted for deteriorating visual symptoms, but obliteration of the fistula can be challenging. We present such a case that symptomatically mirrored a carotid cavernous fistula. A novel approach was used by traversing a thrombosed superior ophthalmic vein to embolize the lesion. In addition, a complete literature review is presented.

Intracranial flow-diverting (FD) stents have revolutionized the treatment of intracranial aneurysms in recent years, but complications resulting from failed endothelialization can still occur. Approaches to promote endothelialization are understudied, but hold promise in mitigating both short- and long-term complications associated with FD stent insertion. The aim of this review is to highlight the various features of and modifications that have been made to FD stents in order to expedite endothelialization. More specifically, we focus on how endothelialization can be influenced by the stent design, wall apposition, surface modifications, and the inclusion of biological agents.

OBJECTIVE Delayed neointima formation over a neurovascular stent is associated with thrombotic complications that can lead to stroke. The purpose of this study was to evaluate whether an intra-arterial injection of mesenchymal stem cells (MSCs) after stent placement leads to improved neointima and reduced thrombus formation over the device. METHODS Solitaire stents were placed into the aortas of rabbits that were divided into MSC and control groups. The MSC group received an intra-arterial injection of MSCs through the same microcatheter used for stent deployment. Optical coherence tomography (OCT) was used to evaluate and compare neointima and thrombus formation in a blinded fashion. Explanted specimens were also imaged with scanning electron microscopy (SEM) and evaluated by observers blinded to group allocation using an endothelialization scoring system. RESULTS The 3-day MSC group was similar to the 7-day controls in terms of stent strut coverage ratio and maximum neointimal thickness, but these values were significantly higher than the 3-day control group based on a hierarchical mixed-effects linear regression analysis. SEM revealed a significantly higher endothelialization score for the MSC group compared with controls at the same time point. There was no difference in thrombus formation between any of the groups. CONCLUSIONS The intra-arterial injection of MSCs after endovascular stenting accelerated early neointima formation but had no effect on thrombus formation in this study. Larger studies are required to verify these findings and determine the durability and mechanism of this effect.

Physiologically relevant intracranial aneurysm (IA) models are crucially required to facilitate testing treatment options for IA. Herein, we report the development of a new in vitro tissue-engineered platform, which recapitulates the microenvironment, structure, and cellular complexity of native human IA. A new modified liquid-assisted injection molding technique was developed to fabricate a three-dimensional hollow IA model with clinically relevant IA dimensions within a mechanically tuned Gelatin Methacryloyl (GelMA) hydrogel. An endothelium lining was created inside the IA model by culturing human umbilical vein endothelial cells over pre-cultured human brain vascular smooth muscle cells. These cellularized IA models were subjected to medium perfusion at flow rates between 6.3 and 15.75 mL/min for inducing biomimetic vessel wall shear stress (10–25 dyn/cm2) to the cells for ten days. Both cell types maintained their secretome profiles and showed more than 96% viability, demonstrating the biocompatibility of the hydrogel during perfusion cell culture at such flow rates. Based on the characterized viscoelastic properties of the GelMA hydrogel and with the aid of a fluid-structure interaction model, the capability of the IA model in predicting the response of the IA to different fluid flow profiles was mathematically shown. With physiologically relevant behavior, our developed in vitro human IA model could allow researchers to better understand the pathophysiology and treatment of IA. Statement of significance A three-dimensional intracranial aneurysm (IA) tissue model recapitulating the microenvironment, structure, and cellular complexity of native human IA was developed. • An endothelium lining was created inside the IA model over pre-cultured human brain vascular smooth muscle cells over at least 10-day successful culture. • The cells maintained their secretome profiles, demonstrating the biocompatibility of hydrogel during a long-term perfusion cell culture. • The IA model showed its capability in predicting the response of IA to different fluid flow profiles. • The cells in the vessel region behaved differently from cells in the aneurysm region due to alteration in hemodynamic shear stress. • The IA model could allow researchers to better understand the pathophysiology and treatment options of IA.

Epidural fat is commonly discarded during spine surgery to increase the operational field. However, mesenchymal progenitor cells (MPCs) have now been identified in human epidural fat and within the murine dura mater. This led us to believe that epidural fat may regulate homeostasis and regeneration in the vertebral microenvironment. Using two MPC lineage tracing reporter mice (Prx1 and Hic1), not only have we found that epidural fat MPCs become incorporated in the dura mater over the course of normal skeletal maturation, but have also identified these cells as an endogenous source of repair and regeneration post-dural injury. Moreover, our results reveal a partial overlap between Prx1+ and Hic1+ populations, indicating a potential hierarchical relationship between the two MPC populations. This study effectively challenges the notion of epidural fat as an expendable tissue and mandates further research into its biological function and relevance.

Background Spinal catheter angiography is commonly performed in the evaluation and treatment of spinal vascular lesions. The typical approach to spinal angiography consists of access through the femoral artery with the use of suitably shaped catheters for selective catheterization of the spinal segmental vasculature. The purpose of our study was to evaluate the safety and feasibility of distal transradial access through the “anatomical snuffbox” for targeted spinal angiography, for the investigation and treatment of selected spinal lesions Methods A retrospective review of patients who underwent transradial spinal angiography and embolization was performed from August 2019 to January 2022. A total of eight patients were identified, who underwent targeted spinal angiography through distal transradial access. Outcome measures were documented in a tabular manner. Results Radial access was successful in all patients. Seven patients had vascular tumors of the spinal column and underwent tumor embolization followed by segmental artery occlusion prior to surgery. One patient had a spinal dural AV fistula that could not be embolized due to feeding vessel tortuosity and eventually went on to have a laminectomy. Mean fluoroscopy time was 31.4 min. There were no access site hemorrhagic complications. One patient experienced transient mild hand numbness during the period of hemostasis with the vascular compression device that resolved completely within 24 h. Conclusions Distal transradial access is a feasible and safe option for targeted spinal angiography and treatment in selected patients.

Ischemic diseases such as myocardial infarction, ischemic stroke, and critical limb ischemia are immense public health challenges. Current pharmacotherapy and surgical approaches are insufficient to completely heal ischemic diseases and are associated with a considerable risk of adverse effects. Alternatively, human mesenchymal stem cells (hMSCs) have been shown to exhibit immunomodulation, angiogenesis, and paracrine secretion of bioactive factors that can attenuate inflammation and promote tissue regeneration, making them a promising cell source for ischemic disease therapy. This review summarizes the pathogenesis of ischemic diseases, discusses the potential therapeutic effects and mechanisms of hMSCs for these diseases, and provides an overview of challenges of using hMSCs clinically for treating ischemic diseases.

Background Unruptured intracranial aneurysms (UIA) are increasingly being treated by endovascular coiling as opposed to open surgical clipping. Unfortunately, endovascular coiling imparts an approximate 25% recanalization rate, leading to additional procedures and increased rupture risk. While a new health technology innovation (HTI) that reduces this recanalization rate would benefit patients, few advancements have been made. We aim to determine whether cost-effectiveness has been a barrier to HTI. Methods A probabilistic Markov model was constructed from the healthcare payer perspective to compare standard endovascular treatment of UIA to standard treatment plus the addition of a HTI adjunct. Costs were measured in 2018 USD and health outcomes were measured in quality-adjusted life-years (QALY). In the base case, the HTI was a theoretical mesenchymal stem cell therapy which reduced the aneurysm recanalization rate by 50% and cost $10,000 per procedure. All other model inputs were derived from the published scientific literature. Results Based on the model results, we found that for a given HTI price (y) and relative risk reduction of aneurysm recanalization (x), the HTI was always cost-effective if the following equation was satisfied: y ≤ 20268 ∙ x, using a willingness-to-pay threshold of $50,000 per QALY. The uncertainty surrounding whether an aneurysm would recanalize was a significant driver within the model. When the uncertainty around the risk of aneurysm recanalization was eliminated, the 10-year projected additional benefit to the United States healthcare system was calculated to be $113,336,994. Conclusion Cost-effectiveness does not appear to be a barrier to innovation in reducing the recanalization rate of UIA treated by endovascular coil embolization. Our model can now be utilized by academia and industry to accentuate economically feasible HTI and by healthcare payers to calculate their maximum willingness-to-pay for a new technology. Our results also indicate that predicting a patient’s baseline risk of aneurysm recanalization is a critical area of future research.

PURPOSE Deciding about whether an unruptured intracranial aneurysm (UIA) should be treated or not is challenging because robust data on rupture risks, endovascular treatment complication rates, and treatment success rates are limited. We aimed to investigate how neurointerventionalists conceptually approach endovascular treatment decision-making in UIAs. METHODS In a web-based international multidisciplinary case-based survey among neurointerventionalists, participants provided their demographics and UIA treatment-volumes, estimated 5-year rupture rates, endovascular treatment complication and success rates and gave their endovascular treatment decision for 15 pre-specified UIA case-scenarios. Differences in estimated 5-year rupture rates, endovascular treatment complication and success rates based on physician and hospital characteristics were evaluated with the Kruskal-Wallis test. Multivariable logistic regression analysis was used to derive adjusted effect size estimates for predictors of endovascular treatment decision. RESULTS Two hundred-thirty-three neurointerventionalists from 38 countries participated in the survey (median age 47 years [IQR: 41-55], 25/233 [10.7%] females). The ranges of estimates for 5-year rupture risks, endovascular treatment complication rates, and particularly endovascular treatment success rates were wide, especially for UIAs in the posterior circulation. Estimated 5-year rupture risks, endovascular treatment complication and success rates differed significantly based on personal and institutional endovascular UIA treatment volume, and all three estimates were significantly associated with physicians' endovascular treatment decision. CONCLUSION Although several predictors of endovascular treatment decision were identified, there seems to be a high degree of uncertainty when estimating rupture risks, treatment complications, and treatment success for endovascular UIA treatment. More data on the clinical course of UIAs with and without endovascular treatment is needed.

Purpose: To describe a standardized orbital resection technique and outcomes for spheno-orbital meningiomas with soft-tissue invasion of the orbit. Methods: A retrospective case review of patients with spheno-orbital meningioma that underwent resection utilizing the Alberta Standardized Orbital Technique (ASOT) between 2008 and 2017 was performed. Results: Twenty patients met the inclusion criteria. Fifteen females and five males, with an average age of 53.4 years (SD ± 13.1 years). Mean follow-up was 57.3 months (SD ± 29.5 months). Eight cases (40%) had attempted resection prior to referral. Based on pre-operative plan, patients were divided into two groups based on goal of resection. Of those with planned complete resection (Group I), 11/13 patients (84.6%) underwent complete excision, with no cases of orbital recurrence. Incomplete resection in two cases occurred because of unexpected involvement of critical intra-cranial structures. Thus, in total 9/20 patients (Group II and 2 from Group I) underwent subtotal resection. Of these incomplete resections, five cases of orbital recurrence were observed; four patients required adjuvant external beam radiotherapy (EBRT) and one patient underwent further debulking surgery. Orbital control was achieved in three of these recurrent cases. Complications reported were persistent postoperative diplopia (three cases/15%) and wound infection (one case/5%). Overall, stable orbital disease was obtained in 18 patients (90%). Conclusion: The ASOT demonstrated to be effective, achieving the pre-operative plan of complete resection in 11/13 cases (84.6%) with no recurrence in those with clear orbital margins.

Introduction Implantation of cerebral stents are used in several disease conditions. Although stenting procedures offer many benefits, metal stents can elicit acute/subacute thrombosis and increase the chance of stroke. The risk of in-stent thrombus formation significantly decreases after formation of an endothelial cell layer over the stent, which typically takes several weeks to occur. One potential way to reduce the formation of thrombus is through biologic modifications that hasten endothelialization. In past studies, vascular endothelial growth factor (VEGF) has been shown to facilitate the recruitment and proliferation of cells that leads to endothelialization. Methods In this study, VEGF was coated onto Solitaire stents using polylactic-co-glycolic acid (PLGA). Coated stents were deployed into the infrarenal abdominal aorta of New Zealand White rabbits for 72 hours (n=5) (72h VEGF group) and compared to uncoated stents at 72 hours (n=3) (72h Control group) and seven days (n=3) (7d Control group). Optical coherence tomography (OCT) was performed through the stented portion of the vessel, and representative images taken every five millimetres were used for analysis. Images were analyzed for neointimal area (stent area – lumen area), neointimal ratio ([stent area – lumen area]/stent area), minimal and maximal neointima thickness, stent-strut neointima coverage ratio (number of struts covered by a neointimal layer over the total number of struts), as well as thrombus area formation. The analysis was performed by a cardiologist with clinical expertise in OCT imaging, who was also blinded to group allocation. Results Post-deployment digital subtraction angiography demonstrated that VEGF-coated stents were deployed similar to uncoated stents, and without any obvious acute thrombus formation. Using two-tailed unpaired t-tests, the 72h VEGF group showed significantly higher (p Conclusion VEGF-coated stents are a promising biomodification to reduce secondary complications that may occur in the initial days following the procedure. Disclosures K. Panchendrabose: None. B. Har: 3; C; Abbot. A. Mitha: 1; C; Stryker Neurovascular. 2; C; Microvention Inc., Cerus Endovascular, Stryker Corporation. 4; C; Fluid Biotech Inc.

Background Anti-platelet therapy is an important part of the treatment regimen in patients who are receiving a cerebrovascular stent, in order to reduce the incidence of thromboembolic complications. However, there is a known variation in patient response to anti-platelet medications. Theoretically, patients with decreased responsiveness may be at increased risk of ischemic complications while those with increased responsiveness may be at a heightened risk of bleeding. The objective of this investigation was to determine if patients with an increased response to clopidogrel were at an increased risk of developing post-procedural hematomas. Methods A prospective Research Ethics Board (REB) approved study was performed on consecutive patients undergoing endovascular placement of a cerebrovascular stent at the Foothills Medical Centre in Calgary, Alberta from 2019–2020. Inclusion criteria were patients over 18 years of age, and on dual anti-platelet therapy consisting of aspirin and clopidogrel for at least 3 days prior to the procedure. Platelet function testing was performed on blood samples taken before insertion of the stent using whole blood impedance aggregometry to determine the responsiveness to aspirin and clopidogrel. As per the REB protocol, treating neurointerventionalists were blinded to the aggregometry results. The primary study endpoint was the development of hemorrhagic complications during or after the procedure. Parametric and receiver operator curve analysis was used to assess for predictors of our primary outcome. Results To determine the cut-offs for ASA and clopidogrel responsiveness, whole blood aggregometry was first performed on 25 control patients who were not on anti-platelet agents. Subsequently, 50 consecutive patients undergoing cerebrovascular stenting procedures fit our inclusion criteria. 7 (14.0%) of these patients developed a hematoma either intracranially (n=1) or at the puncture site (n=6). Age, gender, smoking status, access site, or stent location were not associated with hemorrhagic complications. Based on our controls, ASA hyper-responders could not be identified using whole blood aggregometry due to the normal response being 0–1 ohms. With these cut-offs, however, 49 (98%) of our patients were responsive to aspirin. Using whole blood aggregometry on patients receiving a cerebrovascular stent, the optimal electrical impedance value was identified as 2 ohms developed a hematoma. This association was found to be statistically significant (p=0.016). Conclusion Dual anti-platelet therapy is an important part of the treatment regimen in any patient who receives a cerebrovascular stent, but there are variations in patient response to these medications. Our study suggests that patients who have an increased response to clopidogrel may be at a higher risk of developing hemorrhagic complications. Disclosures S. Muram: None. K. Panchendrabose: None. M. Eagles: None. M. Suheel: None. A. Mitha: None.

Deciding about whether an unruptured intracranial aneurysm (UIA) should be treated or not is challenging because robust data on rupture risks, endovascular treatment complication rates, and treatment success rates are limited. We aimed to investigate how neurointerventionalists conceptually approach endovascular treatment decision-making in UIAs.In a web-based international multidisciplinary case-based survey among neurointerventionalists, participants provided their demographics and UIA treatment-volumes, estimated 5-year rupture rates, endovascular treatment complication and success rates and gave their endovascular treatment decision for 15 pre-specified UIA case-scenarios. Differences in estimated 5-year rupture rates, endovascular treatment complication and success rates based on physician and hospital characteristics were evaluated with the Kruskal-Wallis test. Multivariable logistic regression analysis was used to derive adjusted effect size estimates for predictors of endovascular treatment decision.Two hundred-thirty-three neurointerventionalists from 38 countries participated in the survey (median age 47 years [IQR: 41-55], 25/233 [10.7%] females). The ranges of estimates for 5-year rupture risks, endovascular treatment complication rates, and particularly endovascular treatment success rates were wide, especially for UIAs in the posterior circulation. Estimated 5-year rupture risks, endovascular treatment complication and success rates differed significantly based on personal and institutional endovascular UIA treatment volume, and all three estimates were significantly associated with physicians' endovascular treatment decision.Although several predictors of endovascular treatment decision were identified, there seems to be a high degree of uncertainty when estimating rupture risks, treatment complications, and treatment success for endovascular UIA treatment. More data on the clinical course of UIAs with and without endovascular treatment is needed.

BackgroundSimulation training has been used in the aviation industry and surgical specialties for many years, but integration into neurointerventional practice is lagging behind.ObjectiveTo investigate how neurointerventionalists perceive the usefulness and limitations of simulation tools for the treatment of unruptured intracranial aneurysms (UIAs), and to identify simulation applications that were perceived to be most valuable for endovascular UIA treatment.MethodsA web-based international multidisciplinary survey was conducted among neurointerventionalists. Participants were asked for their perceptions on the usefulness of current simulation tools and the potential impact of future simulation tools in endovascular UIA treatment. They identified simulation applications that could add most value to endovascular UIA treatment and help to specifically reduce endovascular UIA treatment complications.Results233 neurointerventionalists from 38 countries completed the survey, most of whom (157/233 (67.4%)) had access to a simulator as a trainee, but only 15.3% used it frequently. Most participants (117/233 (50.2%)) considered currently available simulation tools relatively useful for endovascular UIA treatment, with greater value for trainees than for staff. Simulation of new devices (147/233 (63.1%)) and virtual practice runs in individual patient anatomy (119/233 (51.1%)) were considered most valuable for reducing endovascular UIA treatment complications.ConclusionAlthough neurointerventionalists perceived currently available simulation tools relatively useful, they did not use them regularly during their training. A priori testing of new devices and practice runs in individual patient anatomy in a virtual environment were thought to have the greatest potential for reducing endovascular UIA treatment complications.

Background and purposeWe previously reported a single-centre study demonstrating that smoking confers a six-fold increased risk for having an unruptured intracranial aneurysm (UIA) in women aged between 30 and 60 years and this risk was higher if the patient had chronic hypertension. There are no data with greater generalisability evaluating this association. We aimed to validate our previous findings in women from a multicentre study.MethodsA multicentre case-control study on women aged between 30 and 60 years, that had magnetic resonance angiography (MRA) during the period 2016–2018. Cases were those with an incidental UIA, and these were matched to controls based on age and ethnicity. A multivariable conditional logistic regression was conducted to evaluate smoking status and hypertension differences between cases and controls.ResultsFrom 545 eligible patients, 113 aneurysm patients were matched to 113 controls. The most common reason for imaging was due to chronic headaches in 62.5% of cases and 44.3% of controls. A positive smoking history was encountered in 57.5% of cases and in 37.2% of controls. A multivariable analysis demonstrated a significant association between positive smoking history (OR 3.7, 95%CI 1.61 to 8.50), hypertension (OR 3.16, 95% CI 1.17 to 8.52) and both factors combined with a diagnosis of an incidental UIA (OR 6.9, 95% CI 2.49 to 19.24).ConclusionsWomen aged between 30 and 60 years with a positive smoking history have a four-fold increased risk for having an UIA, and a seven-fold increased risk if they have underlying chronic hypertension. These findings indicate that women aged between 30 and 60 years with a positive smoking history might benefit from a screening recommendation.

IntroductionThe advent of metal flow-diverting stents has provided neurointerventionalists with an option for treating aneurysms without requiring manipulations within the aneurysm sac. The large amount of metal in these stents, however, can lead to early and late thrombotic complications, and thus requires long-term antiplatelet agents. Bioabsorbable stents have been postulated to mitigate the risk of these complications. Here we present early data on the first self-expandable primarily bioabsorbable stent for aneurysms.MethodsBraided stents were developed using poly-L-lactic acid fibers with material surface area similar to metal flow diverters. Crush resistance force, hemolysis, and thrombogenicity were determined and compared with existing commercial devices. Stents were deployed in infra-renal rabbit aortas to determine angiographic side branch patency and to study neointima formation for a 1-month follow-up period.ResultsCrush resistance force was determined to be on the order of existing commercial devices. Hemolytic behavior was similar to existing metal devices, and thrombogenicity was lower than metal flow-diverting stents. A smooth neointimal layer was found over the absorbable stent surface and all covered side branches were patent at follow-up.ConclusionThe design of self-expanding primarily bioabsorbable flow-diverting stents is possible, and preliminary safety data is consistent with a favorable profile in terms of mechanical behavior, hemocompatibility, side branch patency, and histological effects. Additional in vitro and long-term in vivo studies are in progress and will help determine aneurysm occlusion rates and absorption characteristics of the stent.

IntroductionDural venous sinus stenosis (DVSS) may lead to increased intracranial pressure, sometimes requiring a stent if a high pressure gradient exists. Many neuroendovascular physicians use microcatheters to measure gradients, yet there are no studies comparing the accuracies and precisions of modern day microcatheters. We examined pressure recordings from five commonly used microcatheters in an experimental DVSS model.MethodsUsing a programmable pump, dynamic flow was established in a closed circuit mimicking the venous sinus waveform. Microcatheters with 150 cm effective lengths were connected proximally to pressure transducers. Mean recording pressures were compared with a high fidelity microcatheter (HFM) in several configurations including no stenosis, proximal to a focal stenosis, and distal to a focal stenosis in opposing orientations.ResultsAll microcatheters recorded lower pressures than the HFM. Three of the five microcatheters successfully met intracranial pressure monitoring device standards in all conditions, while one did not meet standards in any configuration. The performance of the final microcatheter was variable, with inaccuracies occurring in unrestricted flow. All microcatheters demonstrated relatively high precision, but with variable accuracies. The larger diameter microcatheters displayed the least damping and therefore the greatest accuracies. Of the three smaller microcatheters, dimensions did not predict performance, suggesting that microcatheter construction may also play a role in pressure accuracy.ConclusionThe use of microcatheters to record dural venous sinus pressures must be done with an understanding of the inherent limitations and inaccuracies, especially if clinical decisions are made from the results.

We propose a magnetic resonance (MR) imaging protocol for the characterization of carotid web morphology, composition, and vessel wall dynamics. The purpose of this case series was to determine the feasibility of imaging carotid webs with MR imaging. Five patients diagnosed with carotid web on CT angiography were recruited to undergo a 30-min MR imaging session. MR angiography (MRA) images of the carotid artery bifurcation were acquired. Multi-contrast fast spin echo (FSE) images were acquired axially about the level of the carotid web. Two types of cardiac phase resolved sequences (cineFSE and cine phase contrast) were acquired to visualize the elasticity of the vessel wall affected by the web. Carotid webs were identified on MRA in 5/5 (100%) patients. Multi-contrast FSE revealed vessel wall thickening and cineFSE demonstrated regional changes in distensibility surrounding the webs in these patients. Our MR imaging protocol enables an in-depth evaluation of patients with carotid webs: morphology (by MRA), composition (by multi-contrast FSE), and wall dynamics (by cineFSE).

To explore phase contrast (PC) magnetic resonance imaging of aneurysms and arteriovenous malformations (AVM). PC imaging obtains a vector field of the velocity and can yield additional hemodynamic information, including: volume flow rate (VFR) and intravascular pressure. We expect to find lower VFR distal to aneurysms and higher VFR in vessels of the AVM.Five cerebral aneurysm and three AVM patients were imaged with PC techniques and compared to VFR of a healthy cohort. VFR was calculated in vessel segments in each patient and compared statistically to the healthy cohort by computing the z-score. Intravascular pressure was calculated in the aneurysms and in the nidus of each AVM.We found that patients with aneurysm had z-0.48 in vessels distal to the aneurysm (reduced flow), while AVM patients had z6 in some vessels supplying and draining the nidus (increased flow). Pressures in aneurysms were highly variable between subjects and location, while in the nidus of the AVM patients; pressure trended higher in larger AVMs.The study findings confirm the expectation of lower distal flow in aneurysm and higher arterial and venous flow in AVM patients.

Mesenchymal stem cells (MSCs) are present in fat tissues throughout the body, yet little is known regarding their biological role within epidural fat. We hypothesize that debridement of epidural fat and/or subsequent loss of MSCs within this tissue, disrupts homeostasis in the vertebral environment resulting in increased inflammation, fibrosis, and decreased neovascularization leading to poorer functional outcomes post-injury/operatively. Clinically, epidural fat is commonly considered a space-filling tissue with limited functionality and therefore typically discarded during surgery. However, the presence of MSCs within epidural fat suggests that itis more biologically active than historically believed and may contribute to the regulation of homeostasis and regeneration in the dural environment. While the current literature supports our hypothesis, it will require additional experimentation to determine if epidural fat is an endogenous driver of repair and regeneration and if so, this tissue should be minimally perturbed from its original location in the spinal canal. Also see the video abstract here https://youtu.be/MIol_IWK1os.

ObjectiveThe only pharmacologic prophylaxis for cerebral vasospasm after subarachnoid hemorrhage is oral nimodipine. A novel way to mitigate this risk may be to design a drug eluting stent that elutes verapamil over the time period typically associated with vasospasm. In this study, we explore different methods of coating nitinol stents with a bioabsorbable polymer and determine the release profile of various verapamil coated stents for the potential treatment of vasospasm.MethodsNitinol stents were coated with different concentrations of poly(lactic acid-co-glycolic acid) (PLGA) in chloroform solution and using three coating techniques: dip coating, spin coating, and electrospinning. Morphology of the coatings were studied with scanning electron microscopy. 12 verapamil eluting stents were then prepared using different verapamil concentrations and coatings with different numbers of layers. Drug release behaviors were studied using UV spectroscopy for 21 days.ResultsElectrospinning at 20% w/v resulted in a smooth uniform coating without significant surface irregularities, and may be the most effective technique to coat stents. Stents with a single layer of PLGA/verapamil coating showed a two phase release profile (initial burst release followed by a slow rate of release) whereas stents with a bilayer coating showed a lower level of initial release followed by a slower sustained release phase.ConclusionsDevelopment of verapamil eluting stents that elute drug over the time course typical of cerebral vasospasm, and for either immediate or prophylactic treatment, is technically feasible. Further in vitro and in vivo studies are required to determine whether this can improve the outcome of patients after subarachnoid hemorrhage.

ObjectiveTo assess the feasibility and efficacy of clinically translatable adjuvant mesenchymal stem/stromal cells (MSCs) therapy in improving the healing of coiled aneurysms in a rabbit elastase aneurysm model.MethodsBone marrow-derived MSC populations were isolated from three rabbit donors in a serum-free environment and independently characterized to confirm their identity. Elastase-induced carotid aneurysms were created in nine New Zealand white rabbits. Each animal received one of the following treatments based on previous randomization: (1) coiling alone (control group); (2) coiling with an intra-aneurysmal injection of saline (vehicle group); and (3) coiling with an intra-aneurysmal injection of 5 million allogeneic MSCs (treatment group). The animals were followed for 4 weeks post-treatment, at the end of which blinded analyses of angiograms and histology were performed.ResultsHistological results in the treatment group showed improvements over the control and vehicle groups, although the improvement over the vehicle group was not significant. Intra-aneurysmal cell therapy with 5 million allogeneic MSCs did not result in any major adverse events. Angiographic results did not show any significant difference among groups.ConclusionsThis proof-of-concept study shows that adjuvant MSC therapy for intracranial aneurysms is feasible and may enhance histological improvement of coiled aneurysms at 4 weeks post-treatment.

Introduction/purpose The rabbit elastase model has become a standard in vivo representation of human intracranial aneurysms, mimicking their histology and offering a means for laboratory testing of current and novel endovascular devices. Variations of the aneurysm creation procedure in rabbits exist, such as endovascular versus surgical exposure of the right common carotid artery (RCCA), where the aneurysm is induced. One particular variation, the modified elastase technique, results in aneurysms that are generally smaller than treated human aneurysms, making the model less relevant. The purpose of this study was to determine whether larger sizes could be created by combining calcium chloride (CaCl2) with elastase in the solution used to induce aneurysms with this technique. Methods/materials Animals were assigned to one of two groups, including elastase only (control, n=7) or a combination of CaCl2 and elastase (experimental, n=9). After administration of anesthetic, the RCCA was exposed, a temporary clip was placed at the brachiocephalic bifurcation, and a silk suture was used to ligate the vessel distally. An angiocatheter was placed in the occluded portion of the vessel and, depending on group assignment, either elastase only or CaCl2/elastase was injected into the occluded segment. After 20 min of incubation, the catheter was withdrawn and a silk suture was tied just proximal to the catheter entry site (3 cm distal to the bifurcation) to permanently occlude blood flow. The clip was then removed, and blood was re-perfused into the stump of the RCCA. After 4 weeks, angiographic results were obtained from each rabbit. Statistical analysis was performed using Student’s t-test. Results Mean angiographic aneurysm heights and widths were 5.16 mm±0.96 mm (SEM) and 2.48 mm±0.50 mm, respectively, in the control group and 7.82 mm±0.58 mm and 4.19 mm±0.25 mm, in the experimental group (p-value=0.03, 0.005). Calculated mean volumes were 24.98 mm3±10.93 mm3 and 75.93 mm3±12.22 mm3 in the control and experimental groups, respectively (p-value=0.009). Conclusion In the modified elastase technique of aneurysm creation in a rabbit model, the combination of CaCl2 and elastase results in increased aneurysm size and volume, versus elastase alone. When comparing our technique to the most commonly employed variations of the rabbit model in the literature, our modification yields aneurysms that are larger and within the size range of treated human aneurysms. Disclosures B. Belanger: None. M. Avery: None. A. Mitha: None.

OBJECTIVEReliable animal models are an important aspect of translational research, especially for relatively uncommon clinical entities such as fusiform aneurysms. While several animal models exist, very few are tailored to cerebral fusiform aneurysms, which have unique attributes compared to abdominal fusiform aneurysms. The authors aimed to build from previous models to create a cerebral fusiform aneurysm model that is simple to use and reliable.METHODSTwelve female New Zealand White rabbits were assigned to 3 groups: group E, elastase only; group C, CaCl2 only; group EC, elastase + CaCl2. All rabbits underwent surgical exposure of the right common carotid artery (CCA) and 20 minutes of peri-carotid incubation with their respective chemicals. Angiography was performed 6 weeks later for arterial dilation measurements, with 50% increase in diameter being defined as fusiform aneurysm formation. The arterial segments, along with the contralateral CCAs, were harvested and assessed histologically for wall component measurements and elastin semiquantification. A separate rabbit underwent aneurysm creation per the group EC protocol and was treated with an endovascular flow-diversion device.RESULTSAll of the group EC rabbits developed fusiform aneurysms (mean dilation of 88%), while none of the group E or group C rabbits developed aneurysms (p = 0.001). Histological analysis revealed increased internal elastic lamina fragmentation in the group EC aneurysms, which also had less tunica intima hyperplasia. All aneurysms exhibited thinning of the tunica media and reduction in elastin content. The use of an endovascular flow-diverting stent was successful, with complete parent vessel remodeling, as expected, 4 weeks after deployment.CONCLUSIONSThe peri-arterial application of combined elastase and CaCl2 to the CCA appears sufficient to reliably produce fusiform aneurysms after 6 weeks. Exposure to elastase or CaCl2 individually appears insufficient, despite the observed histological changes to the arterial wall. The proposed fusiform aneurysm model is able to accommodate endovascular devices, simulating the tortuous pathway experienced in using such devices in human cerebral aneurysms and thus is a satisfactory model to use in translational research.