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In this randomized trial involving patients who had moderate-to-severe acute ischemic stroke with proximal vessel occlusion and a small infarct core, endovascular treatment improved functional outcomes. Ischemic stroke is a devastating condition with a high burden of neurologic disability and death. As a systemic treatment, intravenous alteplase has been shown to be better than conservative care. 1 , 2 Among patients with a proximal vessel occlusion in the anterior circulation, 60 to 80% of patients die within 90 days after stroke onset or do not regain functional independence despite alteplase treatment. 3 , 4 The major reason for the limited efficacy of alteplase is the modest rate of early reperfusion among patients with a large-vessel occlusion. 5 , 6 Local treatment of large-vessel occlusion began with intraarterial delivery of thrombolytic drugs. 7 The . . .

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. 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. 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. 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.

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.

Les caractéristiques du thrombus sont associées aux collatérales et à l’architecture vasculaire dans l’accident vasculaire cérébral aigu. Contexte: Nous avons émis l’hypothèse que les caillots avec stase sont plus longs. Nous avons donc exploré la relation entre les caractéristiques du caillot, à l’imagerie par tomodensitométrie (CT) sans agent de contraste (CTSAC) et à l’imagerie par résonance magnétique (IRM), et la longueur du caillot et les vaisseaux collatéraux pie-mériens à l’angiographie CT initiale (CTA). Méthode: Cette étude prospective porte sur des patients ayant subi un accident vasculaire cérébral ischémique entre 2005 et 2009 qui ont consulté à l’Université Keinyung. Les patients dont le moment du début des symptômes d’AVC était connu, dont le CTA initial et l’IRM étaient au dossier et qui présentaient une occlusion de l’artère cérébrale moyenne M1 (ACM) ± de la carotide interne intracrânienne (CIIC), ont été inclus dans l’étude. La longueur du caillot et les collatérales pie-mériennes ont été mesurées sur le CTA initial. Résultats: Cent quatre patients, dont l’âge moyen était de 65,1 ans ± 12,28 ans et dont 56,7% étaient des hommes, ont été inclus dans l’étude. Ils présentaient une occlusion de la CIIC avec occlusion de l’ACM-M1 (n=50) ou une occlusion isolée de l’ACM-M1 (n=54). La longueur médiane du caillot était de 42,3 mm lorsqu’il y avait présence de signe d’hyperdensité au CTSAC et de 29,5 mm lorsqu’il n’y en avait pas (p=0,02). Les caillots ayant l’aspect d’un artéfact à l’aspect efflorescent (blooming artifact) à l’IRM gradient recall echo avaient une longueur médiane de 39,1 mm par rapport à 24,5 mm pour ceux qui ne présentaient pas cet aspect (p=0,005). Les patients qui avaient des collatérales médiocres au CTA initial avaient des caillots plus longs que ceux qui avaient des collatérales intermédiaires ou de bonnes collatérales (longueur médiane du caillot 49,4 mm par rapport à 34,9 mm et 20,5 respectivement, p < 0,001). Le modèle de régression logistique censuré a permis de constater que la longueur du caillot était un facteur de prédiction indépendant de la présence du signe d’hyperdensité (p=0,05) et de la présence d’un artéfact efflorescent (p=0,006). Conclusions: La longueur du caillot et l’état initial des collatérales sont des facteurs de prédiction indépendants de l’hyperdensité du caillot au CTSAC et d’un artéfact à l’aspect efflorescent au gradient recall echo. Les caillots plus longs sont plus susceptible d’être hyperdense et de présenter plus d’efflorescence, probablement parce que la formation locale de certaines parties de ces caillots est récente à cause de la stase du sang autour du caillot original. Cette stase pourrait être due à des collatérales médiocres et à une architecture vasculaire inefficace du réseau artériel cérébral.

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.

BackgroundLimited research exists regarding the impact of neuroimaging on endovascular thrombectomy (EVT) decisions for late-window cases of large vessel occlusion (LVO) stroke.ObjectiveT0 assess whether perfusion CT imaging: (1) alters the proportion of recommendations for EVT, and (2) enhances the reliability of EVT decision-making compared with non-contrast CT and CT angiography.MethodsWe conducted a survey using 30 patients drawn from an institutional database of 3144 acute stroke cases. These were presented to 29 Canadian physicians with and without perfusion imaging. We used non-overlapping 95% confidence intervals and difference in agreement classification as criteria to suggest a difference between the Gwet AC1 statistics (κG).ResultsThe percentage of EVT recommendations differed by 1.1% with or without perfusion imaging. Individual decisions changed in 21.4% of cases (11.3% against EVT and 10.1% in favor). Inter-rater agreement (κG) among the 29 raters was similar between non-perfusion and perfusion CT neuroimaging (κG=0.487; 95% CI 0.327 to 0.647 and κG=0.552; 95% CI 0.430 to 0.675). The 95% CIs overlapped with moderate agreement in both. Intra-rater agreement exhibited overlapping 95% CIs for all 28 raters. κG was either substantial or excellent (0.81–1) for 71.4% (20/28) of raters in both groups.ConclusionsDespite the minimal difference in overall EVT recommendations with either neuroimaging protocol one in five decisions changed with perfusion imaging. Regarding agreement we found that the use of automated CT perfusion images does not significantly impact the reliability of EVT decisions for patients with late-window LVO.

Endovascular embolization is the standard approach for management of carotid cavernous fistulas (CCFs) due to the ease of access and reduced level of risk associated with the procedure compared with open surgery. We present here a case of a CCF that eventually led to the development of brainstem venous congestion from perimedullary venous drainage. This fistula was not amenable to endovascular embolization due to lack of either ophthalmic vein or petrosal sinus drainage. Therefore, a craniotomy with direct puncture of the cavernous sinus was performed, followed by coil embolization to completely treat this fistula. This case demonstrates an uncommon progression of venous drainage to Cognard grade V, rare development of symptomatic brainstem venous congestion and a unique method to combine an open surgical approach with endovascular embolization to treat CCFs.

Background Stentrievers have resulted in faster recanalization times in patients with acute ischemic stroke. Nonetheless, when strokes occur during evenings and weekends, delays are introduced in achieving this goal. We assessed the feasibility of achieving fast and successful endovascular reperfusion in patients with stroke treated during evenings and weekends and whether this has an impact on the outcome. Methods A retrospective review was performed of a longitudinal database of patients with acute anterior ischemic stroke treated with endovascular therapy in a comprehensive stroke center between January 2011 and December 2012. The imaging to reperfusion time was defined as the time from completion of the unenhanced CT scan to the time of angiographic successful reperfusion (TICI 2b–3). This time interval was compared between patients treated during working hours (Monday to Friday 07:00–18:00 h) and those treated in the evening outside these hours and at weekends. The 24-h NIH Stroke Scale score and 90-day favorable outcome score (modified Rankin scale ≤2) were compared between the two groups. Results In a cohort of 110 patients, 56 (50.9%) were treated on evenings and weekends. The median imaging to reperfusion time in these patients was 111 min compared with 90 min during working hours (p=0.019). The proportion of patients with successful reperfusion (TICI 2b or 3) during the evenings and weekends was 82.1% compared with 76.7% during working hours (p=0.4). The proportion of patients with a 90-day favorable outcome was not significantly different in the two groups (64.3% in those treated during evenings and weekends vs 52.1% in working hours, p=0.2). Conclusions Some delays were encountered during evenings and weekend hours. Despite that, it was feasible to achieve a relatively short imaging to reperfusion times during these hours, in comparison to existing literature. A target universal time metric is needed to assess the timeliness of endovascular therapy in stroke centers.

Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke. For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1:1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0–2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0–1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018. Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0–2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96–1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups. Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo. Canadian Institutes for Health Research, Alberta Innovates, and NoNO.

A middle aged patient presented with acute ischemic stroke due to basilar artery occlusion. The patient clinically deteriorated despite intravenous thrombolysis and was referred for mechanical thrombectomy. The right vertebral artery was occluded and could not be accessed despite attempting various shaped catheters, even when a radial artery access was used. The left vertebral artery ended in the posterior inferior cerebellar artery. Eventually, ultrasound guided V3 segment vertebral artery direct puncture was successfully done and the procedure was completed. No access related complications were encountered. Direct cervical arterial puncture can be safely used by experienced operators as a last resort in acute stroke cases with difficult access.