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Abstract To elucidate the pathogenesis of vein of Galen malformations (VOGMs), the most common and most severe of congenital brain arteriovenous malformations, we performed an integrated analysis of 310 VOGM proband-family exomes and 336,326 human cerebrovasculature single-cell transcriptomes. We found the Ras suppressor p120 RasGAP (RASA1) harbored a genome-wide significant burden of loss-of-function de novo variants (2042.5-fold, p = 4.79 x 10−7). Rare, damaging transmitted variants were enriched in Ephrin receptor-B4 (EPHB4) (17.5-fold, p = 1.22 x 10−5), which cooperates with p120 RasGAP to regulate vascular development. Additional probands had damaging variants in ACVRL1, NOTCH1, ITGB1, and PTPN11. ACVRL1 variants were also identified in a multi-generational VOGM pedigree. Integrative genomic analysis defined developing endothelial cells as a likely spatio-temporal locus of VOGM pathophysiology. Mice expressing a VOGM-specific EPHB4 kinase-domain missense variant (Phe867Leu) exhibited disrupted developmental angiogenesis and impaired hierarchical development of arterial-capillary-venous networks, but only in the presence of a “second-hit” allele. These results illuminate human arterio-venous development and VOGM pathobiology and have implications for patients and their families.

The management of unruptured brain arteriovenous malformations (ubAVMs) is a complex challenge to neurovascular practitioners. This meta-analysis aimed to identify the optimal management of ubAVMs comparing conservative management, embolization, radiosurgery, microsurgical resection, and multimodality. The search strategy was developed a priori according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the Ovid Medline, Embase, Web of Science, and Cochrane Library databases to identify relevant papers. Using R version 4.1.1., a frequentist network meta-analysis was conducted to compare different management modalities for the ubAVMs. Overall, the conservative group had the lowest risk of rupture (P-score=0.77), and the lowest rate of complications was found in the conservative group (P-score=1). Among different interventions, the multimodality group had the highest rupture risk (P-score=0.34), the lowest overall complications (P-score=0.75), the best functional improvement (P-score=0.65), and the lowest overall mortality (P-score=0.8). However, multimodality treatment showed a significantly higher risk of rupture (odds ratio [OR]=2.13; 95% confidence interval [95% CI]=1.18–3.86) and overall complication rate (OR=5.56; 95% CI=3.37–9.15) compared to conservative management; nevertheless, there were no significant differences in overall mortality or functional independence when considered independently. Conservative management is associated with the lowest rupture risk and complication rate overall. A multimodal approach is the best option when considering mortality rates and functional improvement in the context of existing morbidity/symptoms. Microsurgery, embolization, and radiosurgery alone are similar to the natural history in terms of functional improvement and mortality, but have higher complication rates.

Introduction Patients with baseline disability account for one‐third of stroke presentations. However, there remains controversy in treatment selection for endovascular thrombectomy (EVT). We compared long‐term outcomes and likelihood of transitioning to comfort care for large vessel occlusion (LVO) patients with severe pre‐stroke disability treated with EVT versus medical management at a single center from 2017‐2020. Methods Individuals who presented with LVO were identified retrospectively from a prospectively maintained database. Severe baseline disability was defined as modified Rankin Scale (mRS) 3‐5. Delta mRS was defined as the difference between baseline and 90‐day mRS. Logistic and ordinal regressions were performed to evaluate the relationships between EVT and outcomes. A mixed‐methods analysis was performed to assess rates and reasons for transitions to comfort care. Results A total of 175/1008 (17%) were identified with severe baseline disability. The median age was 82 (IQR 70‐89), and 59% were female. Thirty‐two (18%) with severe baseline disability were treated with EVT. EVT was independently associated with improved delta mRS (B=‐1.048; 95%CI=‐1.777,‐0.318; p=0.005) accounting for age and NIHSS. However, EVT did not reduce the odds of transitioning to comfort care (aOR=0.794; 95%CI=0.347,1.818; p=0.585) accounting for age and NIHSS. Seventy‐six (43%) with severe baseline disability were transitioned to comfort care. Of the 99 not transitioned to comfort care, 18 were treated with EVT, and EVT was independently associated with improved delta mRS (B=‐2.794; 95%CI=‐4.002,‐1.586; p

Introduction The mantra ‘time is brain’ cannot be overstated for patients suffering from acute ischemic stroke. This is especially true for those with large vessel occlusions (LVO) requiring transfer to an endovascular thrombectomy (EVT) capable center. We sought to evaluate the spoke hospital door in‐door out (DIDO) times for patients transferred to our hub center for EVT. Methods Individuals who first presented with LVO to a spoke hospital and were then transferred to the hub for EVT were retrospectively identified from a prospectively maintained database from January 2019 to November 2022. DIDO was defined as the time between spoke hospital door in arrival and door out exit. Baseline characteristics, treatments, and outcomes were compared, dichotomizing DIDO at 90 min based in the American Heart Association goal for DIDO ≤90 min for 50% of transfers. Multivariable regression analyses were performed for determinants of 90‐day ordinal modified Ranking Scale (mRS) and DIDO. Results We identified 194 patients transferred for EVT with available DIDO. The median age was 67 (IQR 57‐80), and 46% were female. The median NIHSS was 16 (10‐20), 50% were treated with intravenous thrombolysis at a spoke, and TICI 2B‐3 reperfusion was achieved in 87% at the hub. The median DIDO was 120 min (97‐149), with DIDO ≤90 min achieved in 18%. DIDO was a significant determinant of 90‐day ordinal mRS (B=0.007, 95%CI=0.001‐0.012, p=0.013), even when accounting for last known well‐to‐spoke door in, spoke door out‐to‐hub arrival, hub arrival‐to‐puncture, puncture‐to‐first pass, age, NIHSS, intravenous thrombolysis, TICI 2B‐3, and symptomatic intracranial hemorrhage. Importantly, determinants of DIDO included Black race or Hispanic ethnicity (B=0.918, 95%CI=0.010‐1.826, p=0.048), atrial fibrillation or heart failure (B=0.793, 95%CI=0.257‐1.329, p=0.004), and basilar LVO location (B=2.528, 95%CI=1.154‐3.901, p

Introduction Coma is an unresponsive state of disordered consciousness characterized by impaired arousal and awareness. The epidemiology and pathophysiology of coma in ischemic stroke has been underexplored. We sought to characterize the incidence and clinical features of coma as a presentation of large vessel occlusion (LVO) stroke. Methods Individuals who presented with LVO were retrospectively identified from July 2018 to December 2020. Coma was defined as an unresponsive state of impaired arousal and awareness, operationalized as a score of 3 on NIH Stroke Scale (NIHSS) item 1a. Results A total of 28/637 (4.4%) patients with LVO stroke were identified as presenting with coma. The median NIHSS was 32 (IQR 29‐34) for those with coma versus 11 (5‐18) for those without (p

Background For acute proximal intracranial artery occlusions, contact aspiration may be more effective than stent‐retriever for first‐line reperfusion therapy. Due to the lack of data regarding medium vessel occlusion thrombectomy, we evaluated outcomes according to first‐line technique in a large, multicenter registry. Methods Imaging, procedural, and clinical outcomes of patients with acute proximal medium vessel occlusions (M2, A1, or P1) or distal medium vessel occlusions (M3, A2, P2, or further) treated at 37 sites in 10 countries were analyzed according to first‐line endovascular technique (stent‐retriever versus aspiration). Multivariable logistic regression and propensity‐score matching were used to estimate the odds of the primary outcome, expanded Thrombolysis in Cerebral Infarction score of 2b–3 (“successful recanalization”), as well as secondary outcomes (first‐pass effect, expanded Thrombolysis in Cerebral Infarction 2c‐3, intracerebral hemorrhage, and 90‐day modified Rankin scale, 90‐day mortality) between treatment groups. Results Of the 440 included patients (44.5% stent‐retriever versus 55.5% aspiration), those treated with stent‐retriever had lower baseline Alberta Stroke Program Early Computed Tomography Scale scores (median 8 versus 9; P

Introduction As more large vessel occlusion stroke patients are treated with endovascular thrombectomy (EVT), understanding the pathophysiology of reperfusion injury and the risks of hemorrhagic transformation (HT) are increasingly important. Pre‐EVT infarct topography may have implications for acute interventional treatments such as stenting, and post thrombectomy care such as antithrombotic choice. We sought to quantify region‐specific volumes of infarcted tissue on pre‐EVT MRI, understand their importance for HT, and identify associations with clinical and imaging characteristics. Methods Patients with pre‐EVT MRI were identified retrospectively from a prospectively maintained database. Each patient’s diffusion weighted sequence underwent manual infarct delineation and was registered to a standard space for overlay with cortical, subcortical, and white matter atlases. Structure‐specific lesion volumes were determined. HT was defined as PH1 or PH2 hemorrhage by ECASS criteria. Variables with p< 0.10 in univariate analyses were included in multivariable models. Logistic regression was performed for associations with hemorrhagic transformation and linear regressions for infarct volumes. Results 165 participants [median age 69 years (interquartile range, IQR 56–79), 56% women] were identified. Risk factors included hypertension (70%), diabetes (20%), atrial fibrillation (34%), and prior stroke/TIA (13%). 52% were treated with intravenous alteplase; 70% achieved TICI 2b‐3 reperfusion. HT occurred in 8%. Pre‐EVT infarct volumes [median (IQR)] were 22 cc (12‐43 cc) for total, 11 cc (6‐19 cc) for white matter, 5 cc (1‐19 cc) for cortex, and 3 cc (1‐6 cc) for basal ganglia. Pre‐EVT infarcts [median (IQR)] were made up of 48% (38‐60%) white matter, 23% (6‐47%) cortex, and 15% (4‐28%) basal ganglia. Paramagnetic sequences showed 3% had petechial hemorrhage and 40% had susceptibility vessel sign. Basal ganglia infarct volume was independently associated with HT (OR = 1.342, 95%CI = 1.002,1.797) in a model including white matter infarct volume, cortex infarct volume, smoking, and puncture‐recanalization time. Basal ganglia infarct volume was linked to susceptibility vessel sign (Beta = 0.233, p = 0.006) and NIHSS (Beta = 0.220, p = 0.012), when controlling for total infarct volume. Conclusions In this cohort, greater basal ganglia infarct volume was associated with a higher risk of hemorrhagic transformation, even when accounting for infarct volume in other regions. Susceptibility vessel sign was associated with basal ganglia infarct volume, which may be related to acute middle cerebral artery thrombus occlusion of perforators. These findings require further study in larger cohorts.

Introduction Direct carotid‐cavernous fistulas (dCCF) are acquired, abnormal high‐flow connections between the internal carotid artery and cavernous sinus. Interventions are often required due to the high risk of incipient morbidity and mortality if left untreated. Treatment approaches have rapidly evolved over time, and have included the use of detachable balloons, liquid embolic agents, and coil embolization through transarterial, transvenous, or combined approaches. Case series level data support an emerging role for the use of flow diversion (FD) as a stand‐alone or adjunctive treatment in dCCFs. We describe a case of FD use as an adjunctive treatment in a patient with a treatment‐resistant dCCF, and review the literature on FD use in dCCF. Methods We describe the clinical course, imaging findings, and outcomes of a 25‐year old patient who presented with a traumatic carotid‐cavernous fistula requiring multiple interventions. We also performed a literature review of Pubmed and Embase databases using combinations of MeSH and key terms to include all relevant full‐text publications of FD use in the treatment of dCCFs, up to and including February 2022. Results Our patient achieved angiographic cure and significant improvement in symptoms at 6‐month follow‐up. A total of 24 papers were identified and included, for a total number of 53 cases (23 male, 23 female, 7 unspecified). The median age of patients was 44 years (Interquartile range (IQR) 23–62). The etiology of the dCCF was traumatic (acute or as a delayed presentation) in 31 cases (58%), spontaneous in 10 cases (19%), and iatrogenic in 12 cases (23%). FD was the primary mode of treatment of the CCF in approximately half of cases (27, 51%), and was a stand‐alone treatment modality in one third of cases (18, 34%). The median number of FD devices used on initial treatment was 1 device, though retreatment was needed in 42% of cases.Angiographic resolution was achieved in 90% of cases at a median follow‐up duration of 6 months.One half of all patients had complete resolution of symptoms and a further third noted clinical improvement in at least some of their symptoms. In 10% of cases, symptoms persisted, or other complications developed that were attributed to concurrent injuries. Conclusions Treatment approaches for dCCFs have evolved over time as safer and more effective treatments become available. There is an emerging role for FD as a safe stand‐alone or adjunctive treatment option for dCCFs. Our case further supports its role in treatment‐resistant fistulas with high‐risk features. As treatment approaches continue to evolve, prospective randomized data is needed to better establish the role of flow divertors among the hierarchy of available treatment options for dCCFs.

Endovascular thrombectomy (EVT) has revolutionized large vessel occlusion (LVO) stroke management, but often requires advanced imaging. The collateral pattern on CT angiograms may be an alternative because a symmetric collateral pattern correlates with a slowly growing, small ischemic core. We tested the hypothesis that such patients will have favorable outcomes after EVT. Consecutive patients (n = 74) with anterior LVOs who underwent EVT were retrospectively analyzed. Inclusion criteria were available CTA and 90-day modified Rankin Scale (mRS). CTA collateral patterns were symmetric in 36%, malignant in 24%, or other in 39%. Median NIHSS was 11 for symmetric, 18 for malignant, and 19 for other (p = 0.02). Ninety-day mRS ≤2, indicating independent living, was achieved in 67% of symmetric, 17% of malignant, and 38% of other patterns (p = 0.003). A symmetric collateral pattern was a significant determinant of 90-day mRS ≤2 (aOR = 6.62, 95%CI = 2.24,19.53; p = 0.001) in a multivariable model that included age, NIHSS, baseline mRS, thrombolysis, LVO location, and successful reperfusion. We conclude that a symmetric collateral pattern predicts favorable outcomes after EVT for LVO stroke. Because the pattern also marks slow ischemic core growth, patients with symmetric collaterals may be suitable for transfer for thrombectomy. A malignant collateral pattern is associated with poor clinical outcomes.

Background Intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) for large‐vessel occlusion (LVO) stroke is increasingly controversial. Recent trials suggest MT without IVT is reasonable for patients presenting directly to MT‐capable “hub” centers. However, bypassing IVT has not been evaluated for patients presenting to IVT‐capable “spoke” hospitals that require hub transfer for MT. A perceived lack of efficacy of IVT to result in LVO early recanalization (ER) is often cited to support bypassing IVT, but data for IVT in patients who require interhospital transfer are limited. Here, we examined LVO ER rates after spoke‐administered IVT in our hub‐and‐spoke stroke network. Methods Patients presenting to 25 spokes before hub transfer for MT consideration from 2018 to 2020 were retrospectively identified from a prospectively maintained database. Inclusion criteria were pretransfer computed tomography angiography–defined LVO, Alberta Stroke Program Early Computed Tomography Score ≥6, and posttransfer repeat vessel imaging. Results Of 167 patients, median age was 69, and 51% were women. Seventy‐six received spoke IVT, and 91 did not. Alteplase was the only IVT used in this study. Comorbidities and National Institutes of Health Stroke Scale were similar between groups. ER frequency was increased 7.2‐fold in patients who received spoke IVT (12/76 [15.8%] versus 2/91 [2.2%]; P

Background For patients with large vessel occlusion (LVO) stroke, time to treatment with endovascular thrombectomy is crucial to prevent infarction and improve outcomes. We sought to evaluate the hub arrival‐to‐puncture times and outcomes for transferred patients accepted directly to the angio‐suite (LVO to operating room, LVO2OR) versus those accepted through the emergency department in a hub‐and‐spoke telestroke network. Methods Consecutive patients transferred for endovascular thrombectomy with spoke computed tomography angiography–confirmed LVO, spoke Alberta Stroke Program Early Computed Tomography score >6, and last known well–to–hub arrival

Introduction Mechanical thrombectomy (MT) using stent retrievers or a direct aspiration first-pass technique has proven to yield better results over intravenous thrombolysis in treating acute ischaemic stroke caused by large vessel occlusion (LVO). However, the treatment of intracranial atherosclerotic stenosis-related LVO remains unclear and has been a critical problem in daily clinical practice, as it can cause a relatively high failure rate for MT. Whether direct angioplasty and/or stenting is clinically feasible and shows advantage in reducing delay to revascularisation with better functional outcome compared with MT with rescue angioplasty and/or stenting remains unclear. This study seeks to provide direct and practical clinical evidence for clinicians.Methods and analysis The main databases of PubMed, the Cochrane library, Embase and Web of Science will be screened for related studies published after1 January 2015. Primary outcomes include successful recanalisation and 90-day favourable outcome. Secondary outcomes include puncture to revascularisation time, vascular complication (perforation, dissection and vasospasm), intracerebral haemorrhage, hospital-related complications and 90-day mortality. The Newcastle-Ottawa Scale will be adopted to assess risk bias of observational studies. The I2 statistic will be used to assess heterogeneity.Ethics and dissemination No primary data of patients are needed. Therefore, ethics approval is unnecessary. The results of this systematic review and meta-analysis will be published in a peer-reviewed journal.PROSPERO registration number CRD42021268061.

Background Access to endovascular thrombectomy (EVT) is relatively limited. Hub‐and‐spoke networks seek to transfer appropriate large‐vessel occlusion stroke candidates to EVT‐capable hubs. However, some patients are ineligible upon hub arrival, and factors that drive transfer inefficiencies are not well described. We sought to quantify EVT transfer efficiency and identify reasons for EVT ineligibility. Methods Consecutive EVT candidates presenting to 25 spokes from 2018 to 2020 with pretransfer computed tomography angiography‐defined large‐vessel occlusion and Alberta Stroke Program Early Computed Tomography Score of ≥6 were identified from a prospectively maintained database. Outcomes of interest included hub EVT, reasons for EVT ineligibility, and 90‐day modified Rankin scale score of ≤2. Results Among 258 patients, the median age was 70 years (interquartile range, 60–81 years); 50% were women. A total of 56% were ineligible for EVT after hub arrival. Cited reasons were large established infarct (49%), mild symptoms (33%), recanalization (6%), distal occlusion (5%), subocclusive lesion (3%), and goals of care (3%). Late window patients (last known well >6 hours) were more likely to be ineligible (67% versus 43%; P

Background and purposeIn the landmark trials studying endovascular thrombectomy (EVT), pre-stroke dependent (PSD) patients were generally excluded. This systematic review and meta-analysis aimed to compare the safety and efficacy of EVT between PSD and pre-stroke independent (PSI) patients.MethodsWe searched CENTRAL, Embase, and Ovid MEDLINE up to 11 November 2021 for studies assessing PSD and PSI patients, which were separately defined as pre-stroke mRS score >2 or >1, and ≤2 or ≤1 accordingly. Two authors extracted data and assessed the risk of bias. A meta-analysis was carried out using the random-effects model. Adjusted OR and 95% CI were used to estimate adjusted pool effects. The main outcomes included favorable outcomes, successful recanalization, symptomatic intracranial hemorrhage, and 90-day mortality.ResultsA total of 8,004 records met the initial search strategy, and ten studies were included in the final decision. Compared with PSImRS≤2, PSDmRS>2 had a lower favorable outcome (OR 0.51; 95% CI, 0.33–0.79) and higher 90-day mortality (OR 3.32; 95% CI, 2.77–3.98). No significant difference was found in successful recanalization and sICH. After adjustment, only 90-day mortality (aOR 1.99; 95% CI, 1.58–2.49) remained significantly higher in PSDmRS>2. Compared with PSImRS≤1, PSDmRS>1 had lower 90-day mortality (OR, 3.10; 95% CI, 1.84–5.24). No significant difference was found regarding the favorable outcome, successful recanalization, and sICH. After adjustment, no significant difference was found in a favorable outcome, but a higher rate of 90-day mortality (aOR, 2.13; 95% CI, 1.66–2.72) remained in PSDmRS>1.ConclusionsPSD does not innately influence the EVT outcomes regarding sICH and favorable outcomes but may increase the risk of 90-day mortality. Until further evidence is available, it is reasonable to suggest EVT for patients with PSD.

Dural arteriovenous fistulas (DAVFs) are rare intracranial vascular malformations that present with a variety of clinical signs and symptoms. Among these, intracranial hemorrhage is a severe complication. A 72-year-old male presented with headache and pulsatile tinnitus. Cerebral angiography revealed a Borden II/Cognard IIa+b DAVF. He underwent stage 1 transarterial embolization of the occipital artery which reduced shunting by 30%. Several attempts were made to access the fistula during stage 2 transvenous embolization, but it was not possible to access the left transverse sinus fistula site since there was no communication across the torcula from the right transverse sinus and the left inferior sigmoid–jugular bulb was occluded. Therefore, a single burr hole was drilled and direct access to the DAVF was achieved with a micropuncture needle under neuronavigational guidance. The left transverse–sigmoid sinus junction was then embolized with coils. After the procedure, angiography revealed that the DAVF was cured with no residual shunting. This case demonstrates how minimally invasive surgery provides an alternative method to access a DVAF when conventional transarterial and/or transvenous embolization treatment options are not possible. Each DAVF case has unique anatomy and physiology, and creative multi-disciplinary strategies can often yield the best results.

Background: Juvenile Paget's disease (JPD, OMIM #239,000) is a rare heritable disorder of the skeleton usually caused by bi-allelic loss-of-function mutation(s) of the tumor necrosis factor receptor superfamily member, 11B gene (TNFRSF11B), resulting in deficiency of the encoded protein osteoprotegerin (OPG). Deficiency of this signaling molecule leads to osteoclast activation and accelerated bone turnover. Vascular complications of JPD include intracranial carotid artery and brachial artery aneurysms. Iliac artery aneurysms have not been described in these patients. Case presentation: We report an 18-year-old man with JPD and bilateral common iliac artery aneurysms discovered incidentally during endovascular treatment of an intracranial internal carotid artery aneurysm (iICA). CT imaging showed a fusiform right common iliac artery aneurysm measuring 2.1 cm, and a fusiform left common iliac artery aneurysm measuring 1.8 cm. To our knowledge, our case is the first report of JPD associated with iliac artery aneurysms. Conclusions: Our experience supports an emerging association between OPG deficiency and arterial aneurysms. JPD from OPG deficiency requires surveillance for aortic and peripheral vasculopathies.

ObjectiveThis study was conducted to determine the safety and efficacy of the Esperance® Distal Access Catheter (0.071”), a novel large bore aspiration catheter in treating acute ischemic stroke (AIS) with large vessel occlusion (LVO).MethodsA prospective multicenter clinical trial involving 15 stroke centers was performed. Baseline characteristics, procedural data, and angiographic and clinical outcomes of all acute stroke procedures (from May 2020 to March 2021) using the novel large bore aspiration catheter were analyzed.ResultsDuring the study period, 160 consecutive patients were recruited. The mean age and median baseline NIHSS were 65.4 years and 16, respectively. Successful reperfusion was achieved in 147 (91.9%) cases [at least modified Thrombolysis in Cerebral Infarction (mTICI) 2b] with aspiration alone, with complete reperfusion (mTICI 3) in 94 (58.8%) cases. Successful/complete first pass reperfusion was achieved in 104 (64.60%) cases, including mTICI 2b in 34 (21.1%) cases and mTICI 3 in 70 (43.5%) cases. The time from groin puncture to successful reperfusion was 44 (33, 62) min. There were 16 (9.9%) cases requiring rescue therapy using stent-retriever. Procedure-related complications included 2 (1.3%) cases of arterial perforation, 2 (1.3%) cases of arterial dissection, 12 (7.5%) cases of distal embolization, and 1(0.6%) case of puncture site infection. The rate of symptomatic intracranial hemorrhage (sICH) was 3.8% and mortality rate was 13.8%. A total of 99 (62.3%) cases had a favorable outcome (mRS 0–2) at 90 days.ConclusionsIn current practice, the first-line aspiration approach with the Esperance® Distal Access Catheter is safe and efficacious. This device may achieve high reperfusion rates with lower instances of rescue stent retriever therapy.

Background The purpose of this study is to evaluate the impact multiple overlapping flow‐diverting stents have on aneurysm occlusion rates and iatrogenic complications relative to single flow‐diverting stents. Methods A retrospective review of a multicenter aneurysm database from 2012 to 2020 was performed to identify saccular aneurysms treated initially with single and multiple flow‐diverting stents with ≥12‐month angiographic and clinical follow‐up. Aneurysm occlusion rates as a function of stent number served as a primary outcome measure with iatrogenic complications serving as a secondary outcome measure. Results A total of 250 patients were initially treated with a single Pipeline embolization device (PED), and 48 patients were initially treated with multiple PEDs. There was no significant difference in aneurysm size, morphology, or dual‐antiplatelet therapy regimen used between groups. There was no significant difference in the aneurysm occlusion (single, 83.6%, versus multiple, 83.4%; P=0.65) or retreatment rates (single, 8.0%, versus multiple, 10.4%; P=0.58) between groups. There was no significant difference in the number of procedure‐related complications between groups (single, 8.0%, versus multiple, 4.2%; P=0.42), with 0.8% of patients treated with a single PED and 2.1% of patients treated with multiple PEDs experiencing a procedure‐related ischemic stroke. Conclusions There is no significant difference in overall aneurysm occlusion rates between aneurysms treated initially with single versus multiple overlapping PEDs nor are there significant differences in procedure‐related complications. Single PED flow diversion may be preferred whenever possible, with multiple PED constructs reserved for extenuating clinical circumstances as may be encountered with giant aneurysms.

A stroke volume of arterial blood that arrives to the brain housed in the rigid cranium must be matched over the cardiac cycle by an equivalent volume of ejected venous blood. We hypothesize that the brain maintains this equilibrium by organizing coherent arterial and venous pulse waves. To test this hypothesis, we applied wavelet computational methods to diagnostic cerebral angiograms in four human patients, permitting the capture and analysis of cardiac frequency phenomena from fluoroscopic images acquired at faster than cardiac rate. We found that the cardiac frequency reciprocal phase of a small region of interest (ROI) in a named artery predicts venous anatomy pixel-wise and that the predicted pixels reconstitute venous bolus passage timing. Likewise, a small ROI in a named vein predicts arterial anatomy and arterial bolus passage timing. The predicted arterial and venous pixel groups maintain phase complementarity across the bolus travel. We thus establish a novel computational method to analyze vascular pulse waves from minimally invasive cerebral angiograms and provide the first direct evidence of arteriovenous coupling in the intact human brain. This phenomenon of arteriovenous coupling may be a physiologic mechanism for how the brain precisely maintains mechanical equilibrium against volume displacement and kinetic energy transfer resulting from cyclical deformations with each heartbeat. The study also paves the way to study deranged arteriovenous coupling as an underappreciated pathophysiologic disturbance in a myriad of neurological pathologies linked by mechanical disequilibrium.

PurposeIn recent years, metabolic syndrome has risen in prevalence and brought a heavy disease burden to modern society. As the representative aspect of metabolic syndrome, obesity has been shown to be related to an increased risk of stroke. Given that visceral adipose tissue (VAT) forms the fundamental basis of central obesity, we sought to explore a causal relationship between VAT and stroke by using mendelian randomization (MR) methods.MethodsBased on two large genome-wide association studies (GWAS) including 325,153 and 35,762 cases of VAT and stroke, respectively, we conducted a MR study which has the inherent advantage of reducing the noise of confounding and reverse causation.ResultsVAT had a significant causal association with ischemic stroke (OR, per 1kg increase in VAT mass, 1.30; 95% CI, 1.18 ~ 1.45; P = 5.87E-07) as opposed to intracranial hemorrhage (ICH) (OR, 1.15; 95% CI, 0.70 ~ 1.88, P = 5.81E-01) as evaluated with inverse-variance weighting (IVW). Regarding subtypes of ischemic stroke, there was a significant causal effect for cardioembolic stroke (OR, 1.34; 95% CI, 1.13 ~ 1.58, P = 8.07E-04), and potential causal effect for small-vessel stroke (OR, 1.32; 95% CI, 1.06 ~ 1.65, P = 1.39E-02) and large-artery atherosclerotic stroke (OR, 1.33; 95% CI, 1.03 ~ 1.70, P = 2.59E-02).ConclusionsThis study provides potential evidence for a causal role of VAT in ischemic stroke and could suggest novel genetical therapeutic strategies for distinct subtypes of ischemic stroke.

Background: Acute ischemic stroke (AIS) caused by tandem intracranial and extracranial occlusions is not rare. However, optimal strategy between antegrade (extracranial first) or retrograde (intracranial first) approaches still remains elusive. This systematic review and meta-analysis aim to compare the two approaches to provide updated clinical evidence of strategy selection.Methods: PubMed, Ovid, Web of Science, and the Cochrane Library were searched for literature comparing antegrade and retrograde approaches for patients with AIS with concomitant tandem occlusions. Outcomes including successful reperfusion [Throbolysis in Cerebral Infarction (TICI) 2b−3] and 90-day favorable outcome [modified Rankin Scale (mRS) 0–2], any intracerebral hemorrhage, symptomatic intracerebral hemorrhage, procedural complications, and mortality were evaluated. The risk of bias was assessed using the Newcastle–Ottawa Scale and illustrated in the Funnel plot. Heterogeneity was assessed by I2 statistic. Subgroup and sensitivity analyses were also performed.Results: A total of 11 studies accounting 1,517 patients were included. 831 (55%) patients were treated with an antegrade approach and 686 (45%) patients were treated with the retrograde approach. A higher successful reperfusion rate was achieved in retrograde group than that of antegrade group [83.8 vs. 78.0%; odds ratio (OR): 0.63, 95% CI: 0.40–0.99, p = 0.04]. 90-day favorable outcome (mRS 0–2 at 90 days) also showed significantly higher in retrograde group compared with antegrade group (47.3 vs. 40.2%; OR: 0.72, 95% CI: 0.58–0.89, p = 0.002). The incidence of any intracranial hemorrhage (ICH), symptomatic intracranial hemorrhage, 90-day mortality, and other complications did not differ between two groups.Conclusion: In AIS with tandem occlusions, the retrograde approach might achieve a higher successful reperfusion rate and better functional outcome with a comparable safety profile when compared with an antegrade approach. Further prospective controlled studies with more meticulous design and a higher level of evidence are needed to confirm these results.Systematic Review Registration: “PROSPERO” database (CRD 42020199093), https://www.crd.york.ac.uk/PROSPERO/.

Background: Basilar artery fenestration has been proposed as a contributor to ischemic stroke, as unique flow patterns induced by fenestration may be related to thrombus formation or insufficiency. This study aimed to evaluate the hemodynamics of basilar artery fenestration (BAF) using computational fluid dynamics (CFD).Methods: Patients with BAF and normal vertebrobasilar system were recruited and separately evaluated using CFD. Specific geometric vascular models were reconstructed based on 3D-rotational angiography (3D-RA). Patients were divided into the BAF group and control group (i.e., patients with the normal vertebrobasilar system). Hemodynamic and geometric variables were calculated and compared between groups using Student's t-test or Wilcoxon rank-sum test.Results: Overall, 24 patients were included, with 12 patients each in the BAF group and the control group. The BAF group had a significantly smaller basilar artery diameter than the control group (3.1 ± 0.51 vs. 3.76 ± 0.4, p = 0.002). Compared to the control group, the BAF group had higher values of maxOSI (median, 0.3 vs. 0.09, p = 0.028), TAWSSG (median, 983.42 vs. 565.39, p = 0.038) in the flow confluence, higher SAR-TAWSSG in bifurcation (median, 70.22 vs. 27.65, p = 0.002) and higher SAR-TAWSSG in basilar artery (median, 48.75 vs. 16.17, p < 0.001) of the vertebrobasilar artery.Conclusions: This pilot study suggested that hemodynamic differences between BAF and normal vertebrobasilar artery across multiple shear flow parameters. The disturbed flow in the BAF may increase the risk of thrombus formation, plaque instability, and subsequent ischemic cerebrovascular events. These should be confirmed by future studies.

Symptomatic cervical spinal stenosis and carotid artery stenosis are common neurosurgical diseases, but little is known about the management of their concurrent presentation. We present a 62 year-old woman with a precipitous decline in bilateral lower extremity strength, dexterity, and gait, and a 2-year history of amaurosis fugax. She was found to have cervical stenosis at C5-C7 with cord compression, lumbar stenosis at L3-L5 with a right L4-L5 synovial cyst, and moderate right internal carotid artery stenosis of 50–70%. The patient underwent a staged procedure. Stage 1 was a simultaneous right carotid endarterectomy and C6 corpectomy with C5-C7 anterior fusion. Stage 2 was a C3-T1 posterior decompression and fusion and L3-L5 decompression with synovial cyst removal. The presentation of concurrent cervical stenosis and CAS is likely underappreciated. Deciding between simultaneous or staged CEA and spinal decompression should be based on a careful risk-benefit assessment and tailored to the relative severity of symptoms, patient anatomy and comorbidities.

Introduction: The care of emergent large vessel occlusion (ELVO) stroke patients has been revolutionized by endovascular thrombectomy (EVT). Given its robust efficacy, it is crucial to optimize delivery to eligible patients. Within hub‐and‐spoke hospital system models, some patients first present to distant spoke hospitals and require transfer to hub hospitals for EVT. We sought to understand reasons EVT candidates become ineligible after transfer for treatment. Methods: Consecutive EVT candidates presenting to 25 spokes from 2018 to 2020 with pre‐transfer CTA‐defined ELVO and Alberta Stroke Program Early CT Score ≥6 were identified from a prospectively maintained database. Outcomes of interest included hub EVT, reasons for EVT ineligibility, and 90‐day functional independence (modified Rankin Scale, mRS ≤2). Results: 258 patients were identified with median age 70 years (IQR 60–81) and 50% female. 44% underwent EVT upon hub arrival, of which 87% achieved Thrombolysis in Cerebral Infarction 2b‐3 reperfusion. Compared to EVT‐eligible patients, ineligible patients were older (73 vs 68 years, p = 0.04), had lower NIH Stroke Scale (NIHSS, 10 vs 16, p

Background Acute ischemic stroke (AIS) in the context of COVID‐19 has received considerable attention for its propensity to affect patients of all ages. We aimed to evaluate the effect of age on functional outcome and mortality following an acute ischemic event. Methods and Results A prospectively maintained database from comprehensive stroke centers in Canada and the United States was analyzed for patients with AIS from March 14 to September 30, 2020 who tested positive for SARS‐CoV‐2. The primary outcome was Modified Rankin Scale score at discharge, and the secondary outcome was mortality. Baseline characteristics, laboratory values, imaging, and thrombectomy workflow process times were assessed. Among all 126 patients with COVID‐19 who were diagnosed with AIS, the median age was 63 years (range, 27–94). There were 35 (27.8%) patients with AIS in the aged ≤55 years group, 47 (37.3%) in the aged 56 to 70 group, and 44 (34.9%) in the aged >70 group. Intravenous tissue plasminogen activator and thrombectomy rates were comparable across these groups, (P=0.331 and 0.212, respectively). There was a significantly lower rate of mortality between each group favoring younger age (21.9% versus 45.0% versus 48.8%, P=0.047). After multivariable adjustment for possible confounders, a 1‐year increase in age was significantly associated with fewer instances of a favorable outcome of Modified Rankin Scale 0 to 2 (odds ratio [OR], 0.95; 95 CI%, 0.90–0.99; P=0.048) and higher mortality (OR, 1.06; 95 CI%, 1.02–1.10; P=0.007). Conclusions AIS in the context of COVID‐19 affects young patients at much greater rates than pre‐pandemic controls. Nevertheless, instances of poor functional outcome and mortality are closely tied to increasing age.

Introduction: The weekend effect is a well-recognized phenomenon in which patient outcomes worsen for acute strokes presenting outside routine business hours. This is attributed to non-uniform availability of services throughout the week and evenings and, though described for intravenous thrombolysis candidates, is poorly understood for endovascular stroke care. We evaluated the impact of institutional protocols on the weekend effect, and the speed and outcome of endovascular therapy as a function of time of presentation.Method: This study assesses a prospective observational cohort of 129 consecutive patients. Patients were grouped based on the time of presentation during regular work hours (Monday through Friday, 07:00–19:00 h) vs. off-hours (overnight 19:00–07:00 h and weekends) and assessed for treatment latency and outcome.Results: Treatment latencies did not depend on the time of presentation. The door to imaging interval was comparable during regular and off-hours (median time 21 vs. 19 min, respectively, p < 0.50). Imaging to groin puncture was comparable (71 vs. 71 min, p < 1.0), as were angiographic and functional outcomes. Additionally, treatment intervals decreased with increased protocol experience; door-to-puncture interval significantly decreased from the first to the fourth quarters of the study period (115 vs. 94 min, respectively, p < 0.006), with the effect primarily seen during off-hours with a 28% reduction in median door-to-puncture times.Conclusions: Institutional protocols help diminish the weekend effect in endovascular stroke treatment. This is driven largely by improvement in off-hours performance, with protocol adherence leading to further decreases in treatment intervals over time.