Physician Approaches to Antithrombotic Therapies for Recently Symptomatic Carotid Stenosis.

BACKGROUND: Whereas the beneficial effect of antiplatelet therapy for recurrent stroke prevention has been well established, uncertainties remain regarding the optimal antithrombotic regimen for recently symptomatic carotid stenosis. We sought to explore the approaches of stroke physicians to antithrombotic management of patients with symptomatic carotid stenosis. METHODS: We employed a qualitative descriptive methodology to explore the decision-making approaches and opinions of physicians regarding antithrombotic regimens for symptomatic carotid stenosis. We conducted semi-structured interviews with a purposive sample of 22 stroke physicians (11 neurologists, 3 geriatricians, 5 interventional-neuroradiologists, and 3 neurosurgeons) from 16 centers on four continents to discuss symptomatic carotid stenosis management. We then conducted thematic analysis on the transcripts. RESULTS: Important themes revealed from our analysis included limitations of existing clinical trial evidence, competing surgeon versus neurologist/internist preferences, and the choice of antiplatelet therapy while awaiting revascularization. There was a greater concern for adverse events while using multiple antiplatelet agents (e.g., dual-antiplatelet therapy (DAPT)) in patients undergoing carotid endarterectomy compared to carotid artery stenting. Regional variations included more frequent use of single antiplatelet agents among European participants. Areas of uncertainty included antithrombotic management if already on an antiplatelet agent, implications of nonstenotic features of carotid disease, the role of newer antiplatelet agents or anticoagulants, platelet aggregation testing, and timing of DAPT. CONCLUSION: Our qualitative findings can help physicians critically examine the rationale underlying their own antithrombotic approaches to symptomatic carotid stenosis. Future clinical trials may wish to accommodate identified variations in practice patterns and areas of uncertainty to better inform clinical practice.

In vitro flow diversion effect of the ReSolv stent with the shelf technique in a bifurcation aneurysm model.

BACKGROUND: Flow-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. METHODS: A 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. RESULTS: The 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. CONCLUSIONS: The 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.

Neighbourhood deprivation, distance to nearest comprehensive stroke centre and access to endovascular thrombectomy for ischemic stroke: a population-based study.

BACKGROUND: Endovascular thrombectomy (EVT) has revolutionized ischemic stroke care. We aimed to assess whether neighbourhood socioeconomic status is predictive of access to EVT after receipt of alteplase for ischemic stroke among patients living in Alberta, Canada, and whether this relation is mediated by the distance a person lives to the nearest comprehensive stroke centre (CSC). METHODS: We performed a retrospective study including all people older than 18 years living in Alberta who were admitted to hospital with an ischemic stroke and who received intravenous alteplase treatment between Jan. 1, 2017, and Dec. 31, 2019. Data were obtained through administrative data sets. The primary outcome was treatment with EVT. We assigned neighbourhood deprivation quintile based on the Material and Social Deprivation Index. We used logistic regression modelling to assess for a relation between deprivation and treatment with EVT. We adjusted for age, sex, stroke severity and distance to the nearest CSC. We calculated the average causal mediation effect of distance to the nearest CSC on the relation between neighbourhood deprivation level and treatment with EVT. RESULTS: The study cohort consisted of 1335 patients, of whom 181 (13.6%) had missing data and were excluded from the main regression analysis. Endovascular thrombectomy was performed or attempted in 314 patients (23.5%). In the primary model, patients from the most deprived neighbourhoods were less likely than those from less deprived neighbourhoods to have received EVT (adjusted odds ratio 0.43, 95% confidence interval 0.24 to 0.77). Neighbourhood deprivation level was not significantly associated with EVT when distance to the nearest CSC was included as a covariate. Mediation analysis suggested that 48% of the total effect that neighbourhood deprivation level had on the odds of receiving EVT was attributable to the distance a person lived from the nearest CSC. INTERPRETATION: The results suggest that people from more deprived neighbourhoods in Alberta were less likely to be treated with EVT than those from less deprived neighbourhoods. Improving access to EVT for people living in remote locations may improve the equitable distribution of this treatment.

Immediate flow-diversion characteristics of a novel primarily bioresorbable flow-diverting stent.

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.

Intra-arterial injection of mesenchymal stem cells to accelerate neointima formation after endovascular stenting in a rabbit model.

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.

Fluoroscopy, CT, and MR imaging characteristics of a novel primarily bioresorbable flow-diverting stent for aneurysms.

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.

Equipoise in Management of Patients With Acute Symptomatic Carotid Stenosis (Hot Carotid).

OBJECTIVE: To explore differences in antithrombotic management of patients with acutely symptomatic carotid stenosis ("hot carotid") awaiting revascularization with endarterectomy or stenting (CEA/CAS). METHODS: We used a worldwide electronic survey with practice-related questions and clinical questions about 3 representative scenarios. Respondents chose their preferred antithrombotic regimen (1) in general, (2) if the patient was already on aspirin, or (3) had associated intraluminal thrombus (ILT) and identified clinical/imaging factors that increased or decreased their enthusiasm for additional antithrombotic agents. Responses among different groups were compared using multivariable logistic regression. RESULTS: We received 668 responses from 71 countries. The majority favored CT angiography (70.2%) to evaluate carotid stenosis, CEA (69.1%) over CAS, an aspirin-containing regimen (88.5%), and a clopidogrel-containing regimen (64.4%) if already on aspirin. Whereas diverse antithrombotic regimens were chosen, monotherapy was favored by 54.4%-70.6% of respondents across 3 scenarios. The preferred dual therapy was low-dose aspirin (75-100 mg) plus clopidogrel (22.2%) or high-dose aspirin (160-325 mg) plus clopidogrel if already on aspirin (12.2%). Respondents favoring CAS more often chose ≥2 agents (adjusted odds ratio [aOR] vs CEA: 2.00, 95% confidence interval 1.36-2.95, p = 0.001) or clopidogrel-containing regimens (aOR: 1.77, 1.16-2.70, p = 0.008). Regional differences included respondents from Europe less commonly choosing multiple agents if already on aspirin (aOR vs United States/Canada: 0.57, 0.35-0.93, p = 0.023), those from Asia more often favoring multiple agents (aOR: 1.95, 1.11-3.43, p = 0.020), vs those from the United States/Canada preferentially choosing heparin-containing regimens with ILT (aOR vs rest: 3.35, 2.23-5.03, p < 0.001). Factors increasing enthusiasm for ≥2 antithrombotics included multiple TIAs (57.2%), ILT (58.5%), and ulcerated plaque (57.4%); 56.3% identified MRI microbleeds as decreasing enthusiasm. CONCLUSIONS: Our results highlight the heterogeneous management and community equipoise surrounding optimal antithrombotic regimens for hot carotids.

Findings Predictive of Poor Outcome in Grade 5 Subarachnoid Hemorrhage: A Cohort Study.

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 <= 4, absence of >= 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.

A Novel Parameter to Predict Supraclinoid Aneurysm Persistence After Flow Diversion with the Pipeline Embolization Device.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 size >4 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; P < 0.001) and institution B (ratio, 1.36 vs. 1.11; P = 0.002). CONCLUSIONS: 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.

Current and future usefulness and potential of virtual simulation in improving outcomes and reducing complications in endovascular treatment of unruptured intracranial aneurysms.

BACKGROUND: Simulation training has been used in the aviation industry and surgical specialties for many years, but integration into neurointerventional practice is lagging behind. OBJECTIVE: To 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. METHODS: A 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. RESULTS: 233 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. CONCLUSION: Although 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.

Physician factors influencing endovascular treatment decisions in the management of unruptured intracranial aneurysms.

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.

Unfavorable Outcome After Good Grade Aneurysmal Subarachnoid Hemorrhage: Exploratory Analysis.

OBJECTIVE: Patients with good-grade aneurysmal subarachnoid hemorrhage (aSAH) are thought to recover well, yet some do not. This work sought to identify predictors of unfavorable functional outcome after good-grade aSAH. METHODS: We performed a post-hoc analysis of the CONSCIOUS-1 trial. Patients with World Federation of Neurosurgical Societies grades I or II aSAH were included. The primary outcome was unfavorable functional outcome (defined as a modified Rankin Scale score >2) at 12 weeks. Parametric and nonparametric testing were used as appropriate. Variables were classified as modifiable or nonmodifiable, depending on whether they were present at patient admission. Stepwise logistic regression models were created for modifiable and nonmodifiable predictors of outcome. Independent predictors in the respective multivariate analyses were combined into a final multivariate regression model. RESULTS: We included 301 patients, 67 of whom (22%) had an unfavorable outcome. Of the nonmodifiable predictors, higher admission systolic blood pressure (P = 0.002) and female sex (P = 0.011) were independently associated with unfavorable outcome. Potentially modifiable independent predictors of outcome were delayed cerebral ischemia (P = 0.039), higher maximum temperature (0.036), suffering a respiratory system complication (P = 0.004), and suffering an intracranial hemorrhagic complication (P = 0.022). All variables found to be independently predictive of poor outcome in their respective models retained statistical significance in the combined multivariate analysis. CONCLUSIONS: About 1 in 5 good-grade aSAH patients enrolled in CONSCIOUS-1 suffered an unfavorable functional outcome. Admission systolic blood pressure, female sex, hyperthermia, delayed cerebral ischemia, respiratory complications, and intracranial hemorrhagic complications may be predictive of outcome.

A novel self-expanding primarily bioabsorbable braided flow-diverting stent for aneurysms: initial safety results.

INTRODUCTION: The 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. METHODS: Braided 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. RESULTS: Crush 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. CONCLUSION: The 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.

Intraluminal Thrombi in the Cervico-Cephalic Arteries.

Background and Purpose- Intraluminal thrombus (ILT) is an uncommon finding among patients with ischemic stroke. We report clinical-imaging manifestations, treatment offered, and outcome among patients with ischemic stroke/transient ischemic attack and ILT in their cervico-cephalic arteries. Methods- Sixty-one of 3750 consecutive patients with acute ischemic stroke/transient ischemic attack (within 24 hours of onset) and ILT on initial arch-to-vertex computed tomography angiography from April 2015 through September 2017 constituted the prospective study cohort. Functional outcome was assessed using the modified Rankin Scale score with functional independence at discharge defined as modified Rankin Scale score ≤2. Results- Prevalence of ILT on computed tomography angiography was 1.6% (95% CI, 1.2%-2.1%). Median age was 67 years (interquartile range, 56-73), and 40 subjects (65%) were male. The initial clinical presentation included transient ischemic attack in 12 (20%) and stroke in 49 patients (80%); most strokes (76%) were mild (National Institutes of Health Stroke Scale ≤5). The most common ILT location was cervical carotid or vertebral artery (n=48 [79%]) followed by intracranial (n=11 [18%]) and tandem lesions (n=2 [3%]). The most common initial treatment strategy was combination antithrombotics (heparin with single antiplatelet agent) among 57 patients (93%). Follow-up computed tomography angiography (n=59), after a median 6 days (interquartile range 4-10 days), revealed thrombus resolution in 44 patients (75% [completely in 27%]). Twenty four of 30 patients (80%) with >50% residual carotid stenosis underwent carotid revascularization (endarterectomy in 15 and stenting in 9 patients) without peri-procedural complications a median of 9 days after symptom onset. In-hospital stroke recurrence occurred in 4 patients (6.6%). Functional independence was achieved in 46 patients (75%) at discharge. Conclusions- Patients presenting with acute stroke/transient ischemic attack with ILT on baseline imaging have a favorable clinical course in hospital with low stroke recurrence, high rate of thrombus resolution, and good functional outcome when treated with combination antithrombotic therapy.

Practice Current: How do you manage patients with a "hot carotid"?

Patients presenting with acutely symptomatic carotid stenosis (a "hot carotid") are known to be at a high up-front risk of recurrent strokes. Uncertainties remain regarding the appropriate management of such patients in the acute period, particularly with respect to anti-thrombotic treatment as they await revascularisation with carotid endarterectomy (CEA) or angioplasty/stenting (CAS). Decision-making is further complicated when intraluminal thrombi are encountered on vessel imaging. Given these uncertainties, and the paucity of high-quality data in the literature, we sought expert opinion from around the globe on how to manage patients with a "hot carotid" as they await CEA/CAS, with a focus on anti-thrombotic treatment options. Similar questions were posed to the rest of our readership in an online survey, the results of which are also presented.

Rapid cardiac ventricular pacing to facilitate embolization of vein of Galen malformations: technical note.

In BriefBabies born with life-threatening brain blood-vessel malformations can be helped with new heart pacemaker technology to temporarily stop the flow of blood in their bodies during surgery, for inducing hypotension to aid in controlled embolization.

Imaging features and safety and efficacy of endovascular stroke treatment: a meta-analysis of individual patient-level data.

BACKGROUND: Evidence regarding whether imaging can be used effectively to select patients for endovascular thrombectomy (EVT) is scarce. We aimed to investigate the association between baseline imaging features and safety and efficacy of EVT in acute ischaemic stroke caused by anterior large-vessel occlusion. METHODS: In this meta-analysis of individual patient-level data, the HERMES collaboration identified in PubMed seven randomised trials in endovascular stroke that compared EVT with standard medical therapy, published between Jan 1, 2010, and Oct 31, 2017. Only trials that required vessel imaging to identify patients with proximal anterior circulation ischaemic stroke and that used predominantly stent retrievers or second-generation neurothrombectomy devices in the EVT group were included. Risk of bias was assessed with the Cochrane handbook methodology. Central investigators, masked to clinical information other than stroke side, categorised baseline imaging features of ischaemic change with the Alberta Stroke Program Early CT Score (ASPECTS) or according to involvement of more than 33% of middle cerebral artery territory, and by thrombus volume, hyperdensity, and collateral status. The primary endpoint was neurological functional disability scored on the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included symptomatic intracranial haemorrhage, parenchymal haematoma type 2 within 5 days of randomisation, and mortality within 90 days. For the primary analysis, we used mixed-methods ordinal logistic regression adjusted for age, sex, National Institutes of Health Stroke Scale score at admission, intravenous alteplase, and time from onset to randomisation, and we used interaction terms to test whether imaging categorisation at baseline modifies the association between treatment and outcome. This meta-analysis was prospectively designed by the HERMES executive committee but has not been registered. FINDINGS: Among 1764 pooled patients, 871 were allocated to the EVT group and 893 to the control group. Risk of bias was low except in the THRACE study, which used unblinded assessment of outcomes 90 days after randomisation and MRI predominantly as the primary baseline imaging tool. The overall treatment effect favoured EVT (adjusted common odds ratio [cOR] for a shift towards better outcome on the mRS 2·00, 95% CI 1·69-2·38; p<0·0001). EVT achieved better outcomes at 90 days than standard medical therapy alone across a broad range of baseline imaging categories. Mortality at 90 days (14·7% vs 17·3%, p=0·15), symptomatic intracranial haemorrhage (3·8% vs 3·5%, p=0·90), and parenchymal haematoma type 2 (5·6% vs 4·8%, p=0·52) did not differ between the EVT and control groups. No treatment effect modification by baseline imaging features was noted for mortality at 90 days and parenchymal haematoma type 2. Among patients with ASPECTS 0-4, symptomatic intracranial haemorrhage was seen in ten (19%) of 52 patients in the EVT group versus three (5%) of 66 patients in the control group (adjusted cOR 3·94, 95% CI 0·94-16·49; pinteraction=0·025), and among patients with more than 33% involvement of middle cerebral artery territory, symptomatic intracranial haemorrhage was observed in 15 (14%) of 108 patients in the EVT group versus four (4%) of 113 patients in the control group (4·17, 1·30-13·44, pinteraction=0·012). INTERPRETATION: EVT achieves better outcomes at 90 days than standard medical therapy across a broad range of baseline imaging categories, including infarcts affecting more than 33% of middle cerebral artery territory or ASPECTS less than 6, although in these patients the risk of symptomatic intracranial haemorrhage was higher in the EVT group than the control group. This analysis provides preliminary evidence for potential use of EVT in patients with large infarcts at baseline. FUNDING: Medtronic.

A refined experimental model of fusiform aneurysms in a rabbit carotid artery.

OBJECTIVE: Reliable 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. METHODS: Twelve 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. RESULTS: All 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. CONCLUSIONS: The 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.

Surgical clipping or endovascular coiling for unruptured intracranial aneurysms: a pragmatic randomised trial.

BACKGROUND: Unruptured intracranial aneurysms (UIAs) are increasingly diagnosed and are commonly treated using endovascular treatment or microsurgical clipping. The safety and efficacy of treatments have not been compared in a randomised trial. How to treat patients with UIAs suitable for both options remains unknown. METHODS: We randomly allocated clipping or coiling to patients with one or more 3-25 mm UIAs judged treatable both ways. The primary outcome was treatment failure, defined as: initial failure of aneurysm treatment, intracranial haemorrhage or residual aneurysm on 1-year imaging. Secondary outcomes included neurological deficits following treatment, hospitalisation >5 days, overall morbidity and mortality and angiographic results at 1 year. RESULTS: The trial was designed to include 260 patients. An analysis was performed for slow accrual: 136 patients were enrolled from 2010 through 2016 and 134 patients were treated. The 1-year primary outcome, available for 104 patients, was reached in 5/48 (10.4% (4.5%-22.2%)) patients allocated surgical clipping, and 10/56 (17.9% (10.0%-29.8%)) patients allocated endovascular coiling (OR: 0.54 (0.13-1.90), p=0.40). Morbidity and mortality (modified Rankin Scale>2) at 1 year occurred in 2/48 (4.2% (1.2%-14.0%)) and 2/56 (3.6% (1.0%-12.1%)) patients allocated clipping and coiling, respectively. New neurological deficits (15/65 vs 6/69; OR: 3.12 (1.05-10.57), p=0.031), and hospitalisations beyond 5 days (30/65 vs 6/69; OR: 8.85 (3.22-28.59), p=0.0001) were more frequent after clipping. CONCLUSION: Surgical clipping or endovascular coiling of UIAs did not show differences in morbidity at 1 year. Trial continuation and additional randomised evidence will be necessary to establish the supposed superior efficacy of clipping.