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Objective A high rate of cerebral aneurysm recurrence following endovascular coiling has prompted the use of digital subtraction angiography (DSA) for interval follow-up. However, the utility of skull x-rays as an alternative screening method for aneurysm recurrence is unproperly characterized. Methods Retrospective review of a prospective registry of ruptured and unruptured cerebral aneurysms. Anteroposterior and lateral skull x-rays were obtained immediately at the end of the procedure and at 6-month follow-up. Aneurysm recurrence was defined by comparing post-procedure and 6-month DSA imaging. A true positive was defined as a change in coil mass morphology on at least one projection with aneurysm recurrence on DSA, and a true negative defined as a stable coil mass on both projections and no recurrence on DSA. Receiver operating characteristic area under the curve (AUC) statistics was used to assess the performance of skull x-rays in identifying aneurysm recurrence. Results A total of 118 cerebral aneurysms were evaluated with DSA imaging and skull x-rays. A change in coil mass morphology on one projection of skull x-rays correctly detected all true recurrences with a sensitivity of 100% (95% confidence interval [CI], 91-100%). Skull x-rays failed to identify a stable aneurysm coil mass in 15 cases, with a specificity of 79% (68-88%). Skull x-rays performed with AUC 0.8958 (95% CI, 0.8490-0.9431) in identifying aneurysm recurrence. Conclusions The findings of our study suggest that skull x-rays may represent a low-cost, non-invasive screening tool to rule out aneurysm recurrence, which can potentially aid in decreasing the utilization of DSA in the follow-up of patients with coiled cerebral aneurysms.

Objective Brain arteriovenous malformations (bAVMs) are a leading cause of hemorrhagic stroke and neurological deficits in children and young adults, however, no pharmacological intervention is available to treat these patients. Although more than 95% of bAVMs are sporadic without family history, the pathogenesis of sporadic bAVMs is largely unknown, which may account for the lack of therapeutic options. KRAS mutations are frequently observed in cancer, and a recent unprecedented finding of these mutations in human sporadic bAVMs offers a new direction in the bAVM research. Using a novel adeno-associated virus targeting brain endothelium (AAV-BR1), the current study tested if endothelial KRASG12V mutation induces sporadic bAVMs in mice. Methods Five-week-old mice were systemically injected with either AAV-BR1-GFP or -KRASG12V . At 8 weeks after the AAV injection, bAVM formation and characteristics were addressed by histological and molecular analyses. The effect of MEK/ERK inhibition on KRASG12V -induced bAVMs was determined by treatment of trametinib, a US Food and Drug Administration (FDA)-approved MEK/ERK inhibitor. Results The viral-mediated KRASG12V overexpression induced bAVMs, which were composed of a tangled nidus mirroring the distinctive morphology of human bAVMs. The bAVMs were accompanied by focal angiogenesis, intracerebral hemorrhages, altered vascular constituents, neuroinflammation, and impaired sensory/cognitive/motor functions. Finally, we confirmed that bAVM growth was inhibited by trametinib treatment. Interpretation Our innovative approach using AAV-BR1 confirms that KRAS mutations promote bAVM development via the MEK/ERK pathway, and provides a novel preclinical mouse model of bAVMs which will be useful to develop a therapeutic strategy for patients with bAVM. ANN NEUROL 2021;89:926-941.

Background and Purpose: The optimal endovascular stroke therapy (EVT) care delivery structure is unknown. Here, we present our experience in creating an integrated stroke system (ISS) to expand EVT availability throughout our region while maintaining hospital and physician quality standards. Methods: We identified all consecutive patients with large vessel occlusion acute ischemic stroke treated with EVT from January 2014 to February 2019 in our health care system. In October 2017, we implemented the ISS, in which 3 additional hospitals (4 total) became EVT-performing hospitals (EPHs) and physicians were rotated between all centers. The cohort was divided by time into pre-ISS and post-ISS, and the primary outcome was time from stroke onset to EPH arrival. Secondary outcomes included hospital and procedural quality metrics. We performed an external validation using data from the Southeast Texas Regional Advisory Council. Results: Among 513 patients with large vessel occlusion acute ischemic stroke treated with EVT, 58% were treated pre-ISS and 43% post-ISS. Over the study period, EVT procedural volume increased overall but remained relatively low at the 3 new EPHs (P P P Conclusions: In our system, increasing EVT availability decreased time from stroke onset to EPH arrival. The ISS provides a framework to maintain quality in lower volume hospitals.

OBJECTIVETraditionally, stent-assisted coiling and balloon remodeling have been the primary endovascular treatments for wide-necked intracranial aneurysms with complex morphologies. PulseRider is an aneurysm neck reconstruction device that provides parent vessel protection for aneurysm coiling. The objective of this study was to report early postmarket results with the PulseRider device.METHODSThis study was a prospective registry of patients treated with PulseRider at 13 American neurointerventional centers following FDA approval of this device. Data collected included clinical presentation, aneurysm characteristics, treatment details, and perioperative events. Follow-up data included degree of aneurysm occlusion and delayed (> 30 days after the procedure) complications.RESULTSA total of 54 aneurysms were treated, with the same number of PulseRider devices, across 13 centers. Fourteen cases were in off-label locations (7 anterior communicating artery, 6 middle cerebral artery, and 1 A1 segment anterior cerebral artery aneurysms). The average dome/neck ratio was 1.2. Technical success was achieved in 52 cases (96.2%). Major complications included the following: 3 procedure-related posterior cerebral artery strokes, a device-related intraoperative aneurysm rupture, and a delayed device thrombosis. Immediately postoperative Raymond-Roy occlusion classification (RROC) class 1 was achieved in 21 cases (40.3%), class 2 in 15 (28.8%), and class 3 in 16 cases (30.7%). Additional devices were used in 3 aneurysms. For those patients with 3- or 6-month angiographic follow-up (28 patients), 18 aneurysms (64.2%) were RROC class 1 and 8 (28.5%) were RROC class 2.CONCLUSIONSPulseRider is being used in both on- and off-label cases following FDA approval. The clinical and radiographic outcomes are comparable in real-world experience to the outcomes observed in earlier studies. Further experience is needed with the device to determine its role in the neurointerventionalist’s armamentarium, especially with regard to its off-label use.

Despite the increasing evidence of the association between breast cancer and meningioma in women, the relationship between these tumors remains improperly examined. In this study, we aim to identify the sociodemographic and clinicopathologic features of women with breast cancer associated with a higher risk of developing a meningioma.The SEER (Surveillance Epidemiology and End Results) database (18 registries) was used to identify women with breast cancer as their first neoplasm. The risk of subsequent meningioma was reported as the standardized incidence ratio (SIR) and was analyzed by sociodemographic and clinicopathologic subgroups. Results are given as SIR (95% confidence interval [CI]).A total of 564,516 women diagnosed with breast cancer between 2004 and 2016 were included for analysis. A 26% increased risk of meningioma development (SIR, 1.26; 95% CI, 1.19-1.33; P0.05) was found in the cohort compared with the general population. Patients aged between 18 and 49 years (SIR, 2.16; 95% CI, 1.78-2.61; P0.05) and those with a more advanced tumor stage (stage IV; SIR, 2.39; 95% CI, 1.71-3.25; P0.05) were at a higher risk. Hormone receptor expression and treatment modality subgroups were at a similar risk compared with the general population.Our study corroborated the known association between these tumors and found a 26% risk of meningioma development in women with breast cancer, with younger patients and those with a more aggressive disease having a higher than expected risk.

Patients with cerebral vasospasm caused by aneurysmal subarachnoid hemorrhage (aSAH) are often treated with intra-arterial (IA) vasodilator infusion. However, the optimal drug regimen is yet to be elucidated. A retrospective review of patients with aSAH and cerebral vasospasm treated with IA vasodilator infusion was performed. Patients in group 1 (2008–2011) were treated with a single agent, either nicardipine or verapamil, and patients in group 2 (2010–2016) were treated with a regimen of nitroglycerin, verapamil, and nicardipine. The post-infusion improvement ratio (PIIR) was compared between groups. Adjusted multivariate logistic regression models were utilized to determine whether patients treated with multiple vasodilators had an improved functional outcome, defined by the modified Rankin Scale, at discharge and 90-day follow-up. Among 116 patients from group 1 (N = 47) and group 2 (N = 69), the median age was 54.5 years [IQR, 46–53 years] and 78% were female. Use of multiple-agent therapy resulted in a 24.36% improvement in vessel diameter over single-agent therapy (median PIIR: group 1, 10.5% [IQR, 5.3–21.1%] vs group 2, 34.9% [IQR, 21.4–66.0%]; p < 0.0001). In the adjusted multivariate logistic regression, the use of multiple-agent therapy was associated with a better functional outcome at discharge (OR 0.15, 95% CI [0.04–0.55]; p < 0.01) and at 90-day follow-up (OR 0.20, 95% CI [0.05–0.77]; p < 0.05) when compared to single-agent therapy. In this study, we found that patients treated for cerebral vasospasm with IA infusion of multiple vasodilators had an increased vessel response and better functional outcomes compared to those treated with a single agent.

Brain arteriovenous malformations (bAVMs) have long been considered to be congenital, developing between the third and eighth weeks of embryogenesis. However, cases reporting their de novo formation suggest that these lesions can develop after birth and have challenged this concept. We present a case of a 6-year-old boy with a history of a brainstem cavernous malformation diagnosed after birth who later developed a de novo bAVM. The de novo occurrence of this bAVM distant to the site of the cavernous malformation and a prior negative catheter angiography contributes to the uncertainty of the dynamics and pathophysiology of bAVMs.

Background and Purpose— Mechanical thrombectomy (MT) devices have led to improved reperfusion and clinical outcomes in acute ischemic stroke patients with emergent large vessel occlusions; however, less than one-third of patients achieve complete reperfusion. Use of intraarterial thrombolysis in the context of MT may provide an opportunity to enhance these results. Here, we evaluate the use of intraarterial rtPA (recombinant tissue-type plasminogen activator) as rescue therapy (RT) after failed MT in the North American Solitaire Stent-Retriever Acute Stroke registry. Methods— The North American Solitaire Stent-Retriever Acute Stroke registry recruited sites within North America to submit data on acute ischemic stroke patients treated with the Solitaire device. After restricting the population of 354 patients to use of RT and anterior emergent large vessel occlusions, we compared patients who were treated with and without intraarterial rtPA after failed MT. Results— A total of 37 and 44 patients was in the intraarterial rtPA RT and the no intraarterial rtPA RT groups, respectively. Revascularization success (modified Thrombolysis in Cerebral Infarction ≥2b) was achieved in more intraarterial rtPA RT patients (61.2% versus 46.6%; P =0.13) with faster times to recanalization (100±85 versus 164±235 minutes; P =0.36) but was not statistically significant. The rate of symptomatic intracranial hemorrhage (13.9% versus 6.8%; P =0.29) and mortality (42.9% versus 44.7%; P =0.87) were similar between the groups. Good functional outcome (modified Rankin Scale score of ≤2) was numerically higher in intraarterial rtPA patients (22.9% versus 18.4%; P =0.64). Further restriction of the RT population to M1 occlusions only and time of onset to groin puncture ≤8 hours, resulted in significantly higher successful revascularization rates in the intraarterial rtPA RT cohort (77.8% versus 38.9%; P =0.02). Conclusions— Intraarterial rtPA as RT demonstrated a similar safety and clinical outcome profile, with higher reperfusion rates achieved in patients with M1 occlusions. Prospective studies are needed to delineate the role of intraarterial thrombolysis in MT.

Background and Purpose— Mechanical thrombectomy has been shown to improve clinical outcomes in patients with acute ischemic stroke. However, the impact of balloon guide catheter (BGC) use is not well established. Methods— STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter study of patients with large vessel occlusion treated with the Solitaire stent retriever as first-line therapy. In this study, an independent core laboratory, blinded to the clinical outcomes, reviewed all procedures and angiographic data to classify procedural technique, target clot location, recanalization after each pass, and determine the number of stent retriever passes. The primary clinical end point was functional independence (modified Rankin Scale, 0–2) at 3 months as determined on-site, and the angiographic end point was first-pass effect (FPE) success rate from a single device attempt (modified Thrombolysis in Cerebral Infarction, ≥2c) as determined by a core laboratory. Achieving modified FPE (modified Thrombolysis in Cerebral Infarction, ≥2b) was also assessed. Comparisons of clinical outcomes were made between groups and adjusted for baseline and procedural characteristics. All participating centers received institutional review board approval from their respective institutions. Results— Adjunctive technique groups included BGC (n=445), distal access catheter (n=238), and conventional guide catheter (n=62). The BGC group had a higher rate of FPE following first pass (212/443 [48%]) versus conventional guide catheter (16/62 [26%]; P =0.001) and distal access catheter (83/235 [35%]; P =0.002). Similarly, the BGC group had a higher rate of modified FPE (294/443 [66%]) versus conventional guide catheter (26/62 [42%]; P P =0.003). The BGC group achieved the highest rate of functional independence (253/415 [61%]) versus conventional guide catheter (23/55 [42%]; P =0.007) and distal access catheter (113/218 [52%]; P =0.027). Final revascularization and mortality rates did not differ across the groups. Conclusions— BGC use was an independent predictor of FPE, modified FPE, and functional independence, suggesting that its routine use may improve the rates of early revascularization success and good clinical outcomes. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

Background: Ischemic stroke has no approved treatments to enhance recovery. ALD-401 is an enriched population of aldehyde dehydrogenase-bright stem cells, capable of reducing neurological deficits in animal models. The primary objective of this trial was to determine the safety of internal carotid artery, intra-arterially delivered autologous bone marrow–derived ALD-401 in patients with disabling middle cerebral artery stroke in comparison with sham harvest with sham infusion. Secondary objectives were to determine feasibility and efficacy. Methods: This was a prospective phase 2, industry-funded, randomized, sham-controlled, parallel-group, multicenter study with blinded assessments. One hundred subjects were planned, aged 30 to 83 years, with confirmed first-time middle cerebral artery ischemic stroke with modified Rankin scale ≥3. Study patients were randomly assigned 3:2 to bone marrow harvest at 11 to 17 days after stroke followed 2 days later by intracarotid infusion of ALD-401 versus sham harvest and then sham infusion in the same timeframe. The primary study outcome was safety based on the incidence of a 4-point National Institutes of Health Stroke Scale worsening and the proportion of serious adverse events. Efficacy was based on modified Rankin scale change at 90 days. Other secondary outcomes were the proportions of patients experiencing adverse events, disability by Barthel Index, quality of life using EQ-5D, rehabilitation utilization, disability at 1 year, and MRI evidence of complications. Results: There were no infusional or allergic reactions and no difference in treatment emergent adverse events. Four patients had small areas of asymptomatic restricted diffusion on MRI in the treatment group. There was no significant difference between the ALD-401 and placebo groups on the modified Rankin scale for the intent-to-treat population at day 90 (mean difference, 0.3; 95% CI, –0.3 to 0.8; P =0.330). There were no significant differences between the groups on any of the secondary efficacy measures. Conclusions: Intracarotid infusion of ALD-401 does not lead to clinical adverse events in patients with subacute ischemic stroke, although there was a higher incidence of small lesions on MRI in the treatment group. There was no difference in the primary efficacy end point between the groups. The study provides a framework for the design and conduct of future intra-arterial cell therapy trials in stroke. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01273337.

Objective Carotid blister aneurysms remain a formidable surgical challenge with varied surgical options. There have been significant advancements in the endovascular management of these aneurysms with the introduction of flow diverters. The comparative risk profiles for different endovascular options compared to surgical management of these lesions is not completely understood. Methods The study is a comprehensive systematic review and meta-analysis on the treatment of carotid blood blister aneurysms. Pubmed searches were used to identify relevant articles and patient level data was extracted. Two and three group analyses were conducted comparing surgical and endovascular strategies and surgical, stent coil and flow diversion techniques respectively. Patient outcomes were graded on the modified Rankin Scale with a score of 2 or less defined as favorable. Results In total, 83 studies (41 and 42 studies on surgical and endovascular interventions, respectively) with 1119 patients met our inclusion criteria. A statistically significant difference (at the 5% level of significance) in the effect among three different interventions was not found (Q = 3.41, p = 0.1815) under the random-effect model. Our results did show summary proportions of favorable outcomes were higher in the stent coil (0.87, 95% CI: 0.79 – 0.94) and flow diversion (0.87, 95% CI: 0.75 – 0.96) than that of surgery (0.76, 95% CI: 0.71 – 0.83). Conclusions Our results suggest a trend towards improved patient outcomes with endovascular techniques compared to surgical strategies but statistical significance was not achieved. We also found that endovascular techniques compare favorably. Increasing retreatments were found to negatively affect patient outcomes.

The apoptosis of proximal tubule epithelial cells (PTECs) is a critical event of acute kidney injury (AKI). Tetratricopeptide repeat domain 36 (TTC36) with three tetratricopeptide repeats is evolutionarily conserved across mammals, which functions as a chaperone for heat shock protein 70. We have revealed that TTC36 is specifically expressed in PTECs in our previous work. There are few studies about the role TTC36 played in AKI. Therefore, in this study, we investigated the function of TTC36 in the apoptosis of HK2 cells, which are derived from the human proximal tubule. Firstly, we observed that TTC36 was obviously down-regulated and was negatively related to the kidney damage degree in a mouse model of acute kidney injury established by ischemia/reperfusion. In addition, TTC36 overexpression protected HK2 cells against cisplatin-induced apoptosis. Moreover, we discovered the mechanism that TTC36 mitigated cisplatin-triggered mitochondrial disorder via sustaining the membrane potential of mitochondria and mitochondrial autophagy-related gene expression. Collectively, these results suggested that TTC36 plays a protective role in the cisplatin-induced apoptosis of renal tubular cells through maintaining the mitochondrial potential and mitochondrial autophagy-related gene expression. These observations highlight the essential role of TTC36 in regulating PTEC apoptosis and imply TTC36/mitochondrial homeostasis axis as a potential target for the therapeutic intervention in AKI.

Endovascular coiling (EC) is a vital procedure that treats intracranial aneurysms (IA) but a common complication is aneurysm recurrence as a result of coil compaction, when the implanted coil fails to isolate IA from cerebrovascular circulation. Such an event may lead to devastating hemorrhages. Hence, frequent follow-up imaging sessions using Digital Subtraction Angiography (DSA) are critical. However, DSA is invasive, expensive and not widely available. Recently, it has been shown that skull X-rays could be used as a proxy. In this work, we present a new pipeline that enables the semi-automatic evaluation of coil compaction based on X-ray images. Our pipeline involves coil segmentation with GrabCut and an autoencoder that learns image embeddings with a location-sensitive loss function. This approach generates efficient representations without training on image labels. We show that the image embeddings capture information relevant to coil compaction and that a simple distance measure between embeddings outperforms other baseline methods including a Siamese network.

Background: Foramen ovale is a residual cavity in the developing heart in the fetus. At present, the standard methods for the diagnosis of PFO-right-to-left-shunting (PFO-RLS) include transesophageal echocardiography (TEE), contrast-transcranial Doppler echocardiography (C-TCD), and contrast-transthoracic echocardiography (C-TTE), each of them having its advantages and disadvantages.However, there are no data allowing the comparison of these three methods. Methods: We systematically reviewed all published studies on patients with cryptogenic cerebral ischemia. The sensitivity, specificity, and other indexes of C-TCD and C-TTE in the diagnosis of PFO-RLS were calculated using the Stata 16.0 software. The area under the summary receiver operating curve（SROC) was calculated. Results: Twenty-five 25 controlled studies involving a total of 2282 patients were analyzed. There was considerable heterogeneity between C-TCD and C-TTE sensitivity and specificity among the studies. The combined sensitivity and specificity of C-TCD and C-TTE were 0.95 (95%CI, 0.93-0.97) and 0.86(95%CI, 0.78-0.91), and 0.88 (95%CI, 0.69-0.96) and 0.99 (95%CI, 0.67-1.00). The positive likelihood ratio and negative likelihood ratio of C-TCD and C-TTE were 6.81 (95%CI, 4.42-10.48) and 0.05 (95%CI, 0.03-0.08), and 82.31(95%CI, 2.03-3341.00) and 0.12 (95%CI, 0.04-0.34). The areas under the SROC for C-TCD and C-TTE were 0.97 (95%CI, 0.95–0.98) and 0.98 (95%CI, 0.96–0.99), respectively, and were not significantly different by the Z test (z=-0.17, p=0.86). Conclusion: C-TCD and C-TTE have advantages in diagnosing PFO-RTL. The combination of C-TCD and C-TTE improves the detection rate and reduces the misdiagnosis rate. Key words: patent foramen ovale, cryptogenic cerebral ischemia, contrast-transthoracic echocardiography, contrast-transthoracic echocardiography

INTRODUCTION: Prior retrospective and case-control studies have shown that the use of general anesthesia (GA) during endovascular therapy (EVT) for acute ischemic stroke with large vessel occlusion (AIS-LVO) was independently associated with poor clinical outcomes compared with cases performed under conscious sedation (CS). Conversely, recent small randomized clinical trials (RCT) demonstrated a trend toward better outcome in cases performed under GA. METHODS: We submitted an online survey to 193 Society of Vascular Interventional Neurology and 78 American Association of Neurological Surgeons and Congress of Neurological Surgeons – Cerebrovascular Section neuroendovascular practitioners. Questions were aimed at understanding the current state of anesthesia practice during EVT, and to determine if there is clinical equipoise for a large multicenter RCT comparing GA versus CS during EVT. RESULTS: Between March and May of 2017, we received 116 (43%) responses. Anesthesiologists were responsible for managing 96% of the GA cases as compared to only 51% of the CS cases (P < 0.0001). Notable 56% of providers reported performing less than a quarter of their cases under GA. Only 7% performed all cases under GA compared with 17% who used solely CS (P = 0.048). More than half of respondents thought a new RCT was necessary, of whom 61% were interested in participating. Among interested responders, 59% were located in centers with 3 or more neurointerventionalists. CONCLUSION: The significant variation among neuroendovascular providers, added with the lack of consensus among recent trials and meta-analyses, demonstrate clinical equipoise for further studies to explore the effects of anesthesia during EVT in AIS-LVO.

Introduction: Although stroke severity is increased in patients with diabetes (e.g., higher mortality, larger infarcts, and worse neurological deficits), the underlying mechanism(s) of the worse outcomes is not clear. Evidence shows that hypothalamic-pituitary-adrenal (HPA) axis is dysregulated and cortisol levels are increased in diabetes. Based on the role of HPA axis in immunity, we hypothesized that diabetes-enhanced stress response contributes to stroke injury via regulating inflammation. Methods: Diabetes was induced in C57BL/6 mice by feeding a diabetogenic diet and injecting streptozotocin. Mice were subjected to 30 min middle cerebral artery occlusion. Infarct volume and neurological scores were measured at 24h-post stroke. We measured expression of factors related to stress response, plasma corticosterone, c-Fos and corticotropin-releasing factor (CRH) in hypothalamus, and proopiomelanocortin (POMC) and corticotropin-releasing hormone receptor 1 (CRHR1) in pituitary. Inflammatory cytokine levels were also determined in the ischemic brain. Results: Diabetic mice showed hyperglycemia and delayed glucose clearance in blood. At 1d-post stroke, diabetic mice showed larger infarct and worse neurological score. Plasma corticosterone levels were significantly increased in diabetic mice. We also found increased c-Fos in hypothalamus, and CRHR1 and POMC in pituitary. These were accompanied by increased IL-1β, TNF-α, and IL-6 mRNA in the ischemic brain. Conclusion: Our results indicate that stress response is enhanced in diabetic conditions, and associated with increased inflammation in ischemic brain and worse stroke outcomes. It suggests that regulation of stress response may improve stroke outcomes in diabetic conditions.

Background: Knowledge on the pharmacodynamic effects of antiplatelet drugs including clopidogrel and ticagrelor on Asian patients is scarce. We aim to evaluate the effects of the two drugs on platelet reactivity in the treatment of Chinese patients who underwent percutaneous coronary intervention (PCI), using two platelet function tests (PFT). Meanwhile, the relationship between mean platelet volume (MPV), a routine index of platelet size, and high on-treatment platelet reactivity (HPR) is also investigated.Methods: Patients receiving dual antiplatelet therapy (DAPT) were scheduled for the assessment of platelet reactivity at 2–3 days after PCI. Two PFTs, light transmission aggregometry (LTA) and vasodilator-stimulated phosphoprotein (VASP)-FCM assay, were applied in the evaluation of platelet reactivity. The MPV was measured simultaneously with EDTA plasma using a Sysmex XN 2000 automated hematology analyzer.Results: The final study population included the aspirin + clopidogrel group (n = 46) and the aspirin + ticagrelor group (n = 66). In the aspirin + ticagrelor group, the maximal light transmittance (LT) changes in response to 5 µM ADP assessed by LTA was obviously lower than that in the aspirin + clopidogrel group (P < 0.001). The platelet reactivity index (PRI) level in the VASP test was also markedly lower in the group given aspirin and ticagrelor (P < 0.001). There was a significant difference in HPR between the two groups. MPV showed a potent ability to predict the presence of HPR at VASP assay (AUC = 0.788, 95% CI: 0.701–0.875, P < 0.001) in receiver-operating characteristic curve analysis.Conclusions: Compared with clopidogrel, ticagrelor has dramatically greater antiplatelet effect, with a superiority in suppressing platelet function and a lower HPR rate. In addition, there existed a significant independent association between MPV and high prevalence of HPR in the VASP assay.

Background Venous stenting (VS) for venous sinus stenosis in the setting of idiopathic intracranial hypertension has been increasing in acceptance by neurointerventionalists. Stent-adjacent stenosis (SAS) and in-stent stenosis leading to symptom recurrence and the need for retreatment are known delayed complications. However, the effect of the dual antiplatelet therapy (DAPT) duration on these complications has remained poorly characterized. Methods An extensive literature search was performed to identify reports of VS for patients with idiopathic intracranial hypertension from 2000 to 2020. The primary outcome was the occurrence of SAS. The secondary outcomes included the occurrence of composite stenosis (in-stent stenosis and SAS) and stent survival, defined as the need for retreatment or other surgical management. Generalized linear mixed models were used to explore the effects of DAPT duration (3 vs ≥6 months) on the primary and secondary outcomes. Results A total of 325 patients met the inclusion criteria and were included in our analysis. SAS occurred in 9% (95% confidence interval, 6%-15%) of the patients, and stent survival was 90% (95% confidence interval, 84%-93%) in the cohort. With every 1-mm Hg increase in the venous pressure gradient, an 8% decrease was found in the odds of stent survival (P = 0.043). The meta-regression revealed no association between the DAPT duration and the primary outcome or the odds of composite stenosis and stent survival. Conclusions We found no differences between 3 and ≥6 months of DAPT in terms of the risk of stent stenosis or stent survival. However, patients with a higher venous pressure gradient before VS had a greater risk of stent failure.

BackgroundPrior studies on rupture risk of brain arteriovenous malformations (AVMs) in women undergoing pregnancy and delivery have reported conflicting findings, but also have not accounted for AVM morphology and heterogeneity. Here, we assess the association between pregnancy and the risk of intracranial hemorrhage (ICH) in women with AVMs using a cohort-crossover design in which each woman serves as her own control.MethodsWomen who underwent pregnancy and delivery were identified using DRG codes from the Healthcare Cost and Utilization Project State Inpatient Databases for California (2005–2011), Florida (2005–2014), and New York (2005–2014). The presence of AVM and ICH was determined using ICD 9 codes. Pregnancy was defined as the 40 weeks prior to delivery, and postpartum as 12 weeks after. We defined a non-exposure control period as a 52-week period prior to pregnancy. The relative risks of ICH during pregnancy were compared against the non-exposure period using conditional Poisson regression.ResultsAmong 4 022 811 women identified with an eligible delivery hospitalization (median age, 28 years; 7.3% with gestational diabetes; 4.5% with preeclampsia/eclampsia), 568 (0.014%) had an AVM. The rates of ICH during pregnancy and puerperium were 6355.4 (95% CI 4279.4 to 8431.5) and 14.4 (95% CI 13.3 to 15.6) per 100 000 person-years for women with and without AVM, respectively. In cohort-crossover analysis, in women with AVMs the risk of ICH increased 3.27-fold (RR, 95% CI 1.67 to 6.43) during pregnancy and puerperium compared with a non-pregnant period.ConclusionsAmong women with AVM, pregnancy and puerperium were associated with a greater than 3-fold risk of ICH.

Background and Purpose: Noncontrast head CT and CT perfusion (CTP) are both used to screen for endovascular stroke therapy (EST), but the impact of imaging strategy on likelihood of EST is undetermined. Here, we examine the influence of CTP utilization on likelihood of EST in patients with large vessel occlusion (LVO). Methods: We identified patients with acute ischemic stroke at 4 comprehensive stroke centers. All 4 hospitals had 24/7 CTP and EST capability and were covered by a single physician group (Neurology, NeuroIntervention, NeuroICU). All centers performed noncontrast head CT and CT angiography in the initial evaluation. One center also performed CTP routinely with high CTP utilization (CTP-H), and the others performed CTP optionally with lower utilization (CTP-L). Primary outcome was likelihood of EST. Multivariable logistic regression was used to determine whether facility type (CTP-H versus CTP-L) was associated with EST adjusting for age, prestroke mRS, National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, LVO location, time window, and intravenous tPA (tissue-type plasminogen activator). Results: Among 3107 patients with acute ischemic stroke, 715 had LVO, of which 403 (56%) presented to CTP-H and 312 (44%) presented to CTP-L. CTP utilization among LVO patients was greater at CTP-H centers (72% versus 18%, CTP-H versus CTP-L, P Conclusions: We identified an increased likelihood for undergoing EST in centers with lower CTP utilization, which was not associated with worse clinical outcomes or increased hemorrhage. These findings suggest under-treatment bias with routine CTP.

Background Ischemic stroke is increasingly being realized to be an inflammatory disease. Post stroke peripheral leukocyte recruitment to the brain has been well studied in preclinical models of ischemic stroke. Limited studies have examined the intravascular inflammatory milieu in the brain during ischemia. Thrombi collected from ischemic stroke thrombectomy patients can be valuable resources for these studies. There are a handful of studies focusing on the role of inflammation in clot pathology. Small studies have demonstrated that higher thrombus leukocyte fraction and neutrophil to lymphocyte ratios are associated with technically challenging procedures and a trend to worse long term outcomes. Methods We prospectively collected 44 thrombi obtained during mechanical thrombectomy in patients with LVO ischemic strokes. Data on demographics, clinical, procedural and clot composition were collected. These thrombi were paraffin embedded, sliced and stained with Hematoxylin and Eosin. Images were taken using a light microscope,20 and 40x magnification. Image J was used to quantify the leukocytes using previously described methods. The median and maximum leukocyte count of the 5 analyzed images for each patient was used for analysis. Outcome was defined as location at discharge with discharge to home or rehab considered favorable. Fisher’s exact and Mann-Whitney U tests were used for comparison of categorical and continuous variables, respectively. Multivariate logistic regression was then performed. Pearson’s correlation coefficient was used to assess the relationship of leukocytes to NIHSS and time from symptom onset to groin puncture. Results Among 44 patients with large vessel occlusion, median age was 65.5 years [59–73 years], 15 (35%) were women, 84% had hypertension, 43% had atrial fibrillation, and 24% had hyperlipidemia. Median NIHSS was 18 [14–22] and median leukocyte count in the thrombi was 537 [397–794.5]. NIHSS on admission had a negative correlation with favorable discharge outcome as defined by discharge to home or rehab (OR=0.44, p=0.021). Total leukocyte count did not correlate with NIHSS at arrival (r=-0.0086; P=0.9560), number of passes, TICI score nor with time from last seen well to groin puncture (r=0.1937; P=0.2134). On multivariate analysis, there was a negative correlation between maximum thrombus leukocyte count and discharge outcome (OR=0.066, p=0.048) after accounting for age and NIHSS on admission. Conclusion Leukocyte count in thrombi retrieved post mechanical thrombectomy shows a significant negative correlation with discharge outcome in patients with ischemic stroke. Our study focused on total leukocyte count and corroborates with previous studies which focused on leukocyte fraction. Further studies using flow cytometry and concomitant peripheral blood analysis along with long term outcome measures are necessary to better define this relationship and understand role of inflammation in LVO stroke. Disclosures P. Chen: None. F. Sheriff: None. M. Inam: None. V. Lopez-Rivera: None. E. Lekka: None. A. Oni-Orisan: None. C. Finger: None. J. Hudobenko: None. D. Morales: None. S. Seth: None. B. Manwani: None.

Treatment of ependymoma (EPN) is guided by associated tumor features, such as grade and location. However, the relationship between these features with treatments and overall survival in EPN patients remains uncharacterized. Here, we describe the change over time in treatment strategies and identify tumor characteristics that influence treatment and survival in EPN.Using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 18 Registries (1973-2016) database, we identified patients with EPN microscopically confirmed to be grade II (EPN-GII) or III (EPN-GIII) tumors between 2004-2016. Overall survival (OS) was analyzed using Kaplan-Meier survival estimates and multivariable Cox proportional hazard models. A sub-analysis was performed by tumor location (supratentorial, posterior fossa, and spine). Change over time in rates of gross total resection (GTR), radiotherapy (RT), and chemotherapy (CS) were analyzed using linear regression, and predictors of treatment were identified using multivariable logistic regression models.Between 2004-2016, 1,671 patients were diagnosed with EPN, of which 1,234 (74 %) were EPN-GII and 437 (26 %) EPN-GIII. Over the study period, EPN-GII patients underwent a less aggressive treatment (48 % vs 27 %, GTR; 60 % vs 30 %, RT; 22 % vs 2%, CS; 2004 vs 2016; p 0.01 for all). Age, tumor size, location, and grade were positive predictors of undergoing treatment. Univariate analysis revealed that tumor grade and location were significantly associated with OS (p 0.0001 for both). In multivariable Cox regression, tumor grade was an independent predictor of OS among patients in the cohort (grade III, HR 3.89 [2.84-5.33]; p 0.0001), with this finding remaining significant across all tumor locations.In EPN, tumor grade and location are predictors of treatment and overall survival. These findings support the importance of histologic WHO grade and location in the decision-making for treatment and their role in individualizing treatment for different patient populations.

Background: The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Methods: In the prospective multicenter cohort study of imaging selection for EVT (SELECT), patients were stratified based on their anesthesia type into general anesthesia (GA) and conscious sedation (CS). EVT times and outcomes were compared. Further we assessed the impact of ischemic core size (rCBF Results: Of 361 enrolled, 285 received EVT. 129 (45%%) received GA and 156 (54%) CS. The baseline characteristics were similar, except for presentation NIHSS (GA 17(13-21), CS 15(11-20), p=0.027) and ischemic core volume (GA 14.1 cc (0-38) vs CS 6.3(0-26.1), p=0.034). GA was associated with numerically longer arrival to GP times 92 (68—115) vs. 85(60-117) mins, p=0.58. After adjustment for baseline imbalances, patients who received CS had a shift toward better outcome (adj cOR 1.72, 95% CI=1.08-2.75, p=0.022) with higher functional independence rates 56.8% vs 48.8%, p=0.75. Furthermore, GA was associated with higher mortality rates (19% vs 9%, p=0.017), figure 1A. In patients with core volume ≥ 50 cc, there was a trend for a shift towards better outcomes (adj cOR=5.84, 95%CI= 0.90-38.00, P=0.065), figure 1B while there was no difference in patients with core volume < 50 cc (adj cOR=1.01 (95%CI 0.53-1.94, P=0.96), figure 1C. There was an interaction between core volume size and anesthesia type on functional outcome (p=0.042). For every 10cc increase in the core volume, the odds of attaining better functional outcome decreased by 29% (adjusted cOR: 0.71, 95% CI=0.61-0.83, p Conclusion: Conscious sedation was associated with a shift towards better EVT outcomes. This effect was driven by patients with larger ischemic core volumes and has implications for randomized trials of conscious sedation vs general anesthesia.

Introduction: Prior studies suggest that patients with large vessel occlusion (LVO) who undergo endovascular stroke therapy (EST) after inter-hospital transfer (IHT) have worse outcomes than those who present directly to EST centers. However, these studies were largely derived from clinical trials or registries and may not be representative of real-world clinical practice. Methods: We performed a multicenter, observational cohort study on acute ischemic stroke (AIS) patients with LVO that presented to EST-capable centers directly (LVO-D) or after IHT (LVO-T) between 1/1/2018 to 2/1/2019. The study included 11 hospitals in the Houston area, of which 4 are EST-capable. Clinical data were collected using our cerebrovascular data registry. All transfers were from non-EST capable hospitals to EST-capable hospitals. Logistic regression adjusted for age, NIHSS, occlusion location and direct vs transfer arrival was used to assess the likelihood of good outcome, defined as discharge to home or rehabilitation. Results are given as median [IQR] and OR [95% CI]. Results: Among 4,313 patients with AIS, 772 (18%) patients had LVO. Among LVO patients, median age was 68 [59-79], 47% were female, 51% were white, 378 (49%) were LVO-D and 394 (51%) were LVO-T. Median IHT time was 152 min [114-198]. LVO-D patients arrived at EST-treating hospitals with superior ASPECTS compared to LVO-T (9 [7-10] vs 7 [6-9], p Conclusion: In this real-world cohort of a multi-center stroke network, IHT was not associated with worse outcomes for patients with LVO, for both patients who did receive EST and those that did not.

Background: Whether IV tPA has adjunctive benefit to endovascular thrombectomy (EVT) is unclear. Methods: In a prospective multicenter cohort study of imaging selection for EVT (SELECT), patients who received IV tPA vs. no IV tPA were compared stratified by stroke severity and ischemic core size (rCBF Results: Of 361 enrolled, 285 received EVT; 226 presented within 4.5 hrs, 162 (72%) received IV tPA. IV tPA patients had lower median ASPECTS (8 vs 9, p=0.007) and larger ischemic core size (11.4 (1.5-37) vs 3.9 (0-32.15), p=0.042, otherwise similar at baseline. There were no delays in EVT delivery associated with tPA: median time (IQR) from arrival to groin puncture 95.0 min (66.0, 118.0) tPA vs 81.5 (63.5, 107.5) no tPA, p=0.21. IV tPA use was associated with higher mRS 0-2 rates (57% vs 44%), aOR 2.02 (95% CI 1.01-4.03, p=0.046) after adjustment for baseline differences with a shift towards better outcomes on all mRS levels (cOR 2.06, 95% CI 1.18-3.59, p=0.01) with lower mortality (11% vs 22%, p=0.026) and similar sICH rates (and 6% vs 6%, p=1.0). In patients with NIHSS Conclusion: IV tPA did not result in thrombectomy delivery delays and may result in better outcomes. Patients with less severe strokes and smaller infarct size had a stronger association between the use of IV tPA and favorable outcomes.

Background: Whether Endovascular Thrombectomy (EVT) is cost-effective in large ischemic core infarcts is unknown. Methods: In the prospective multicenter cohort study of imaging selection study (SELECT), large core was defined as CT ASPECTS < 6 or CTP ischemic core volume (rCBF Results: Of 361 enrolled, 105 had large core on CT or CTP (EVT 62, MM 43). 19 (31%) EVT patients achieved mRS 0-2 vs 6 (14%) MM (aOR: 3.27, 95% CI: 1.11-9.62; P = .03) with a shift towards better mRS (adj cOR: 2.12, 95% CI: 1.05-4.31, P = .04). Over 20 years EVT was associated with $26589 (C.I. $8672- $43978) incremental costs and a gain of 1.18 QALYs (C.I. 0.091- 2.2) per patient. EVT could avert 75 deaths over a theoretical cohort of 1000 patients (MM 861 vs EVT 786) thus the ICER of EVT compared to MM was $22400 per QALY (CI. $10109 - $66140), which is EVT has a higher NMB compared to MM at the lower and upper WTP thresholds (EVT $86,3 and 271,4 million vs MM $53,6-$179,3 million), Tab 2. The PSA confirmed the results (fig 1). The CEAC showed 94% and 97% cost-effectiveness probability of EVT at the lower and upper values respectively of the maximum WTP, fig 2. EVT ICER in SELECT large core ($22400/QALY) was higher but still comparable to those in HERMES ($16882/QALY), DAWN ($7335/QALY) and DEFUSE3 ($14673/QALY), Tab 3. Conclusion: EVT may result in better outcomes and more lives saved in large core patients with higher QALYs, NMB and an acceptable ICER. The results were comparable to other EVT RCTs.

Background: The efficacy of endovascular thrombectomy (EVT) in M2 occlusions is uncertain. Methods: In a prospective multicenter cohort study of imaging selection (SELECT), EVT outcomes were compared to medical managment (MM) in M2 occlusions. Further, we assessed for potential treatment benefit in patients with higher stroke severity (NIHSS) and a larger perfusion deficit on CTP (Tmax > 6 sec - ischemic core volume)The primary outcome was excellent outcome (mRS 0-1). Results: of 361 patients enrolled in SELECT, 87 had isolated M2 occlusion (EVT 59, MM 28). Baseline NIHSS median (IQR) (EVT 14 (10-20), MM 15 (9.5-19.5), p=0.72) and infarct volume rCBF10 had better outcomes with EVT (46%) vs MM (10%), aOR=11.39, 95% CI=1.80-72.11, p=0.01 as shown in figure 1. As perfusion deficit lesion size increased, the odds of achieving excellent outcomes was reduced (for each 10cc by 11%, aOR: 0.89, 95% CI=0.79-1.00, p=0.05). Excellent outcomes declined in patients with MM as perfusion deficit lesion size increased, yet in the EVT they were maintained as shown in figure 2. Similar results were obtained for mRS 0-2. Conclusion: EVT may result in better rates of excellent outcomes in isolated M2 occlusions, especially those with more severe strokes and larger perfusion deficits who are more likely to have worse outcomes without emergent reperfusion.

A carotid-cavernous fistula (CCF) is an abnormal connection between the carotid circulation and the cavernous sinus. Treatment of CCFs often consists of obliteration of the fistula by a transarterial or transvenous endovascular approach using embolic agents. However, fistula embolization is often halted due to the potential embolic complications that may arise from the retrograde flow of the embolic agents into the arterial circulation, which often leads to the development of fistula recurrence. Moreover, retreatment of a CCF recurrence is challenging and more complex approaches may be required. In this technical note, we describe our experience with CCF embolization in 25 patients treated at a single center. We utilized a transvenous approach for CCF embolization with simultaneous balloon occlusion of the internal carotid artery during the infusion of the embolic material into the fistula. In our series, this simultaneous protection of the internal carotid artery showed to be a safe technique to prevent embolic complications and to achieve successful obliteration of the fistula. On follow-up, 2 cases presented a recurrence, one due to technical difficulties and the other related to an undetected vascular injury. In conclusion, this technique provides a safe approach in the treatment of CCFs by decreasing the risk of embolic complications and increasing the effectiveness of the embolic agents in accomplishing the obliteration of the CCF.

Intra-arterial embolization of juvenile nasopharyngeal angiofibroma (JNA) prior to surgical resection is the preferred approach to minimize blood loss during surgical resection of the tumor. However, the presence of external carotid artery-internal carotid artery (ECA-ICA) anastomoses may hinder complete tumor embolization due to the associated risk for embolic complications. Here, we evaluate the use of a balloon-assisted embolization (BAE) technique in the treatment of JNA. We conducted a retrospective review of JNA patients who underwent tumor embolization with injection of Onyx in a single session between 2013-2018. All cases displayed tumor arterial supply from ECA and ICA circulations on 2-D catheter angiograms. Procedural and surgical outcome data were analyzed. Results are given as mean±standard deviation (range). Among 9 patients with JNA, all were males and mean age was 14.1±6.3 years (range, 9-29 years). The mean tumor volume embolization was 84.4±12.4% (range, 60-100%) and in 89% patients ≥80% of tumor volume embolization was achieved. There were no embolization-related complications reported. During surgical resection of the tumor there was a low average surgical blood loss of 722±651.5 mL (range, 50-2,000 mL) and the mean procedure time was 282.6±85.4 mins (range, 151-403 mins). In this series, the BAE technique showed to be a safe and effective approach to achieve successful tumor embolization while avoiding embolic complications and effectively reducing the risk for blood loss during surgical resection.

Background and Purpose— In acute ischemic stroke, fast and complete recanalization of the occluded vessel is associated with improved outcomes. We describe a novel measure for newer generation devices: the first pass effect (FPE). FPE is defined as achieving a complete recanalization with a single thrombectomy device pass. Methods— The North American Solitaire Acute Stroke Registry database was used to identify a FPE subgroup. Their baseline features and clinical outcomes were compared with non-FPE patients. Clinical outcome measures included 90-days modified Rankin Scale score, National Institutes of Health Stroke Scale score, mortality, and symptomatic intracranial hemorrhage. Multivariate analyses were performed to determine whether FPE independently resulted in improved outcomes and to identify predictors of FPE. Results— A total of 354 acute ischemic stroke patients underwent thrombectomy in the North American Solitaire Acute Stroke registry. FPE was achieved in 89 out of 354 (25.1%). More middle cerebral artery occlusions (64% versus 52.5%) and fewer internal carotid artery occlusions (10.1% versus 27.7%) were present in the FPE group. Balloon guide catheters were used more frequently with FPE (64.0% versus 34.7%). Median time to revascularization was significantly faster in the FPE group (median 34 versus 60 minutes; P =0.0003). FPE was an independent predictor of good clinical outcome (modified Rankin Scale score ≤2 was seen in 61.3% in FPE versus 35.3% in non-FPE cohort; P =0.013; odds ratio, 1.7; 95% confidence interval, 1.1–2.7). The independent predictors of achieving FPE were use of balloon guide catheters and non-internal carotid artery terminus occlusion. Conclusions— The achievement of complete revascularization from a single Solitaire thrombectomy device pass (FPE) is associated with significantly higher rates of good clinical outcome. The FPE is more frequently associated with the use of balloon guide catheters and less likely to be achieved with internal carotid artery terminus occlusion.

OBJECTIVEThe most frequent procedural complication of the endovascular treatment of intracranial aneurysms is a thromboembolic event (TEE); in a subset of patients, such events will cause permanent neurological disability. In patients with unruptured aneurysms, increasing evidence supports the use of periprocedural antiplatelet therapy to prevent TEEs. The object of this study was to evaluate whether patients with ruptured aneurysms and subarachnoid hemorrhage would also benefit from periprocedural antiplatelet therapy.METHODSThe authors reviewed a prospective registry of 169 patients with endovascularly treated intracranial aneurysms to delineate angiographic features associated with periprocedural TEEs. They then performed a controlled before-and-after study in 79 patients with ruptured aneurysms who were deemed to be at high risk for TEEs (for example, patients with at least 1 angiographic feature associated with TEEs) to evaluate whether selective aspirin administration would reduce the rate of periprocedural thromboembolism without increasing major hemorrhagic complications.RESULTSSix angiographic features were associated with periprocedural TEEs in the study cohort: wide aneurysm neck, coil or loop protrusion, small parent artery diameter, an incorporated branch, intraprocedural thrombus formation, and intracranial parent vessel atherosclerosis. Aspirin administration to high-risk patients significantly decreased the rate of periprocedural TEEs, from 53.8% in the control group to 10.6% in the aspirin-treated group (p = 0.001). The reduction in TEEs in the aspirin-treated group continued to be statistically significant even when adjusted for age, sex, cardiovascular risk factors (smoking, diabetes, hypertension, dyslipidemia, coronary artery disease), and factors associated with TEEs in other large studies (wide aneurysm neck, aneurysm size ≥ 10 mm), with an adjusted OR of 0.16 (95% CI 0.03–0.8). There were no major systemic hemorrhagic complications, and aspirin did not increase the risk of aneurysm rebleeding, symptomatic intracranial hemorrhage, or major external ventricular drain (EVD)–associated hemorrhage (p = 0.3), though there was an increase in asymptomatic, minor (< 1 cm) EVD-associated hemorrhage in the aspirin-treated group (p = 0.02).CONCLUSIONSThe study findings suggest that for ruptured aneurysm patients with high-risk features, antiplatelet therapy can significantly reduce the rate of periprocedural TEE without increasing major systemic or intracranial hemorrhages.

Background and Purpose— Mechanical thrombectomy with stent retrievers has become standard of care for treatment of acute ischemic stroke patients because of large vessel occlusion. The STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) aimed to assess whether similar process timelines, technical, and functional outcomes could be achieved in a large real world cohort as in the randomized trials. Methods— STRATIS was designed to prospectively enroll patients treated in the United States with a Solitaire Revascularization Device and Mindframe Capture Low Profile Revascularization Device within 8 hours from symptom onset. The STRATIS cohort was compared with the interventional cohort of a previously published SEER patient-level meta-analysis. Results— A total of 984 patients treated at 55 sites were analyzed. The mean National Institutes of Health Stroke Scale score was 17.3. Intravenous tissue-type plasminogen activator was administered in 64.0%. The median time from onset to arrival in the enrolling hospital, door to puncture, and puncture to reperfusion were 138, 72, and 36 minutes, respectively. The Core lab–adjudicated modified Thrombolysis in Cerebral Infarction ≥2b was achieved in 87.9% of patients. At 90 days, 56.5% achieved a modified Rankin Scale score of 0 to 2, all-cause mortality was 14.4%, and 1.4% suffered a symptomatic intracranial hemorrhage. The median time from emergency medical services scene arrival to puncture was 152 minutes, and each hour delay in this interval was associated with a 5.5% absolute decline in the likelihood of achieving modified Rankin Scale score 0 to 2. Conclusions— This largest-to-date Solitaire registry documents that the results of the randomized trials can be reproduced in the community. The decrease of clinical benefit over time warrants optimization of the system of care. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02239640.

The protein-protein interaction between the human CMG2 receptor and the Bacillus anthracis protective antigen (PA) is essential for the transport of anthrax lethal and edema toxins into human cells. We used a genetically encoded high throughput screening platform to screen a SICLOPPS library of 3.2 million cyclic hexapeptides for inhibitors of this protein-protein interaction. Unusually, the top 3 hits all contained stop codons in the randomized region of the library, resulting in linear rather than cyclic peptides. These peptides disrupted the targeted interaction in vitro; two act by binding to CMG2 while one binds PA. The efficacy of the most potent CMG2-binding inhibitor was improved through the incorporation of non-natural phenylalanine analogues. Cell based assays demonstrated that the optimized inhibitor protects macrophages from the toxicity of lethal factor.

Background aims Extensive animal data indicate that mesenchymal stromal cells (MSCs) improve outcome in stroke models. Intra-arterial (IA) injection is a promising route of delivery for MSCs. Therapeutic effect of MSCs in stroke is likely based on the broad repertoire of secreted trophic and immunomodulatory cytokines produced by MSCs. We determined the differential effects of exposing MSCs to different types of clinically relevant vehicles, and/or different additives and passage through a catheter relevant to IA injections. Methods MSCs derived from human bone marrow were tested in the following vehicles: 5% albumin (ALB), 6% Hextend (HEX) and 40% dextran (DEX). Each solution was tested (i) alone, (ii) with low-dose heparin, (iii) with 10% Omnipaque, or (iv) a combination of heparin and Omnipaque. Cells in vehicles were collected directly or passed through an IA catheter, and MSC viability and cytokine release profiles were assessed. Results Cell viability remained above 90% under all tested conditions with albumin being the highest at 97%. Viability was slightly reduced after catheter passage or exposure to heparin or Omnipaque. Catheter passage had little effect on MSC cytokine secretion. ALB led to increased release of angiogenic factors such as vascular endothelial growth factor compared with other vehicles, while HEX and DEX led to suppression of pro-inflammatory cytokines such as interleukin-6. However, when these three vehicles were subjected to catheter passage and/or exposure to additives, the cytokine release profile varied depending on the combination of conditions to which MSCs were exposed. Discussion Exposure of MSCs to certain types of vehicles or additives changes the profile of cytokine secretion. The activation phenotype of MSCs may therefore be affected by the vehicles used for these cells or the exposure to the adjuvants used in their administration.

OBJECTIVE The primary imaging modalities used to select patients for endovascular thrombectomy (EVT) are noncontrast computed tomography (CT) and CT perfusion (CTP). However, their relative utility is uncertain. We prospectively assessed CT and CTP concordance/discordance and correlated the imaging profiles on both with EVT treatment decisions and clinical outcomes. METHODS A phase 2, multicenter, prospective cohort study of large-vessel occlusions presented up to 24 hours from last known well was conducted. Patients received a unified prespecified imaging evaluation (CT, CT angiography, and CTP with Rapid Processing of Perfusion and Diffusion software mismatch determination). The treatment decision, EVT versus medical management, was nonrandomized and at the treating physicians' discretion. An independent, blinded, neuroimaging core laboratory adjudicated favorable profiles based on predefined criteria (CT:Alberta Stroke Program Early CT Score ≥ 6, CTP:regional cerebral blood flow (

Introduction With the success of endovascular stroke therapy (EST), eligible acute ischemic stroke (AIS) patients must be appropriately screened. CT Perfusion (CTP) was the predominant imaging technique used to identify candidates in the recent trials of EST. However, the real-world utilization and availability of CTP is unknown. Methods Patients with AIS were identified by validated diagnosis codes from data on all discharges from hospitals and Emergency Departments (EDs) in Florida (FL, 2012 – 2016) and New York (NY, 2012–2014). The primary endpoint was ED imaging utilization, defined by the corresponding billing codes. CTP or EST-capable hospitals were defined as those performing at least one CTP or EST in the corresponding calendar year. Trends over time and by region were compared. Results In the FL cohort, among 226,051 admissions for stroke at 285 hospitals, median age was 72 [IQR 61–82] and 113,489 (50%) were female. 14,920 (7%) received IV tPA and 3,026 (1.3%) received EST. Nearly all strokes were treated at CTA and MRI-capable EDs, but 139,316 (62%) were treated at non-CTP-capable hospitals (figure 1). 28 (60%) of EST-capable hospitals were not CTP-capable, a trend that did not change over the study period (figure 2). In the NY cohort, among 91,193 admissions for stroke at 225 hospitals, 71,333 (78%) were evaluated at non-CTP-capable centers. 30 (13%) of hospitals treating AIS patients were CTP-capable. CTP-capable centers were concentrated in urban areas, with significant annual stroke rates in non-urban areas without CTP. Conclusions In this large cohort study, the majority of AIS patients and EDs treating AIS did not have access to CTP, a finding that did not immediately increase following 2015 trials. Use of CTP as a universal screening tool for EST may still be limited. Non-contrast CT remains the most important screening tool for EST in AIS patients under 6 hours from symptom onset. Disclosures A. Czap: None. S. Lee: None. V. Lopez-Rivera: None. J. Grotta: None. P. Chen: None. S. Blackburn: None. L. Giancardo: None. S. Savitz: None. L. McCullough: None. A. Bambhroliya: None. F. Vahidy: None. S. Sheth: None.

Background Falling is a common and devastating problem in Parkinson’s disease (PD) patients. However, the factors associated with fall among Chinese PD population remain unclear. Aim The aim of this study was to explore the prevalence and potential factors independently contribute to falls in patients with PD. Methods This cross-sectional study recruited one hundred and ninety-seven PD patients from West China Hospital. According to patients or their caregivers’ memory divided them into two different groups: fallers and non-fallers. Demographical information, clinical features and pharmacological conditions of patients were all collected. Results Out of 197 patients (mean age 63.2±9.0 years) 55.3% (110/197) patients had at least one fall in the half of year. Factors associated with falls in PD including: sex, age, co-disease condition, clinical symptoms, the severity of disease, doing activities, the function of balance, cognition, and the emotional conditions. Furthermore, statistically significant differences were found by binary regression in Hoehn and Yahr (H-Y) stage (OR = 11.500, 95% CI = 2.801-47.214, P = 0.001), the Hamilton Depression (HAMD-24) Rating Scale (OR = 1.296, 95% CI = 1.034-1.296, P = 0.011) and the Falls Efficacy (FES) Scale (OR = 1.028, 95% CI = 1.004-1.053, P = 0.021). However, doing exercise (OR = 0.159, 95% CI = 0.046-0.555, P = 0.004) is a protective factor for PD patients. Conclusions Patients with severe disease, bad psychological condition will increase the risk of falling. Monitoring disease progress and pay more attention on non-motor symptoms are needed while patients in the mild stage.

Background and Purpose— Recent landmark trials provided overwhelming evidence for effectiveness of endovascular stroke therapy (EST). Yet, the impact of these trials on clinical practice and effectiveness of EST among lower volume centers remains poorly characterized. Here, we determine population-level patterns in EST performance in US hospitals and compare EST outcomes from higher versus lower volume centers. Methods— Using validated diagnosis codes from data on all discharges from hospitals and Emergency Rooms in Florida (2006–2016) and the National Inpatient Sample (2012–2016) we identified patients with acute ischemic stroke treated with EST. The primary end point was good discharge outcome defined as discharge to home or acute rehabilitation facility. Multivariate regressions adjusted for medical comorbidities, intravenous tPA (tissue-type plasminogen activator) usage and annual hospital stroke volume were used to evaluate the likelihood of good outcome over time and by annual hospital EST volume. Results— A total of 3890 patients (median age, 73 [61–82] years, 51% female) with EST were identified in the Florida cohort and 42 505 (median age, 69 [58–79], 50% female) in the National Inpatient Sample. In both Florida and the National Inpatient Sample, the number of hospitals performing EST increased continuously. Increasing numbers of EST procedures were performed at lower annual EST volume hospitals over the studied time period. In adjusted multivariate regression, there was a continuous increase in the likelihood of good outcomes among patients treated in hospitals with increasing annual EST procedures per year (odds ratio, 1.1; 95% CI, 1.1–1.2 in Florida and odds ratio, 1.3; 95% CI, 1.2–1.4 in National Inpatient Sample). Conclusions— Analysis of population-level datasets of patients treated with EST from 2006 to 2016 demonstrated an increase in the number of centers performing EST, resulting in a greater number of procedures performed at lower volume centers. There was a positive association between EST volume and favorable discharge outcomes in EST-performing hospitals.

Introduction: With increasing availability of endovascular aneurysm treatments away from tertiary referral centers, greater numbers of patients with aneurysmal subarachnoid hemorrhage (SAH) may be treated at lower-volume centers. This trend over time as well as its influence on patient outcomes remains poorly characterized. Methods: Using administrative data on all discharges from hospitals in New York (2005-2014) and Florida (2005-2015), we identified patients with treated aneurysmal SAH. Primary outcome was in-hospital mortality. Patients with trauma were excluded. Logistic regression adjusted for comorbidities was used to assess the relationship of hospital volume on outcome. Results are provided as median [IQR], mean ± SD and OR [95% CI]. Results: Among 12,290 patients with aneurysmal SAH, 69% were female and median age was 55 [46 - 65]. 62% were treated with endovascular coiling (EC) and 37% with surgical clipping (SC). Over the time span of the study, the number of hospitals treating SAH did not increase (88 vs. 71, 2005 vs. 2014), nor did the number of patients with SAH (1159 vs. 1212, 2005 vs. 2014). Hospitals that treated fewer numbers of patients with SAH annually were more likely to perform SC than EC (51% vs. 40%, 1-10 vs. ≥ 40 annual SAH treatments, p Conclusion: In this 10-year observational cohort, lower volume hospitals were more likely to perform SC, and fewer SAH patients were treated at the highest volume centers over time. These findings corroborate a de-centralization of SAH care, which may be associated with worse outcomes.

Background: Given the time-sensitivity of endovascular stroke therapy (EST), an increased availability of these treatments to lower-volume centers may improve patient outcomes. However, clinical trials demonstrating efficacy of EST were performed at larger volume centers, and our understanding of outcomes at lower volume centers is lacking. Methods: Using validated diagnosis codes from administrative data on all discharges from hospitals in Florida (2005-2016), and New York (2006-2014) we identified patients with acute stroke treated with EST. Primary endpoint was good outcome defined as discharge home without intracerebral hemorrhage. Descriptive statistics were used to calculate the number of EST performed. Multivariate logistic regressions adjusted for age, sex, and comorbidities were used to evaluate the association between year of treatment and hospital volume with outcome. Results: Among 5,699 patients (at 439 hospitals) treated with EST, median age was 72[60-81], 52% were female, and 54% received IV tPA. Annual EST procedures increased from 158 in 2007 to 423 in 2010 to 925 in 2014, as did the number of hospitals performing EST, from 30 in 2007 to 50 in 2010 to 68 in 2014. During the study period, an increasing proportion of total EST procedures were performed at lower volume centers ( Figure 1a ). Adjusting for age and comorbidities, the likelihood of good outcome increased yearly (OR 1.1 [1.05 -1.14]). Adjusting for age, comorbidities and year of treatment, increasing annual hospital EST volume was associated with increasing likelihood of good outcome ( Figure 1b ). Conclusions: In two large and diverse states, clinical outcomes with EST improved over time. Higher volume centers performed better than lower volume centers, a finding that persisted despite the overall trend towards improvement. These findings support the need for further study on the efficacy of EST outside of specialized centers.

Background: Whether bridging therapy with IV tPA delays endovascular thrombectomy (EVT) or alters clinical outcomes is unknown. Methods: In this prospective multicenter cohort study of imaging selection for EVT (SELECT), consecutive patients with anterior circulation (ICA, M1, M2) occlusions who presented within 24 hrs from last known well were enrolled at 9 centers. We stratified patients into those who received IV tPA prior to EVT vs those who did not. Results: Of 445 enrolled, 284 received EVT; 222 (78%) treated within 6 hrs and 62 (22%) >6-24 hrs. 65% received IV tPA. Baseline characteristics were similar between the tPA and no tPA groups. There were no workflow delays associated with IV tPA: arrival to groin puncture, median (IQR) 92 (64-117) min in the tPA group vs. 82 (64-113) no IV tPA, p=0.52. The rate of functional independence (90 day mRS 0-2) was 57% with IV tPA vs. 47% without, aOR 1.7 (95% CI 0.95-3.05), p=0.07. The ordinal analysis showed a significant shift towards better 90 day mRS scores in the tPA group, aOR 1.9, 95% CI: 1.19-3.00, p=0.007. Mortality was 11% (tPA) vs 18% (no tPA), p=0.07 and sICH rates were 7% (tPA) vs. 5% (no tPA), p=0.5. Restricting the analyses to patients presenting directly to EVT centers within 4.5 hours (N=115), no significant delays were evident; arrival to puncture with tPA 95 (76-121) min vs 86 (68-114) without tPA, p=0.4. Functional independence was 62% with tPA vs 51% without, aOR 1.73 (95% CI 0.78-3.83, p=0.18) with a statistically significant shift in favor of tPA on the ordinal analysis, aOR 1.8, 95% CI: 1.08-3.45, p=0.038. Patients with M2 occlusions, smaller baseline infarct core volume, earlier treatment, and milder strokes were most likely to have better outcomes with tPA vs no tPA (Fig 1). Conclusion: IV tPA administration did not result in delays to EVT and was associated with higher rates of good outcome. Randomized trials are required to more definitively establish the efficacy of bridging therapy with tPA prior to EVT.

Background: Large infarct cores on CT or CTP were an exclusion from most trials of Endovascular thrombectomy (EVT). However, large cores may be seen in occasional patients presenting within the early window (0-3 hours) and may not preclude potential benefit from thrombectomy. We studied clinical outcomes with thrombectomy in patients presenting with large cores measured by CT or CTP within 3 hours of last known well (LKW). Methods: From a multicenter prospective cohort study of imaging selection for EVT (SELECT), patients with a large ischemic core (CBF 50cc or ASPECT≤5 presenting within 3 hours from LKW to imaging were identified. All patients received CT and CTP with mismatch determination by RAPID software. A blinded independent core-lab adjudicated all images. Good (90 day mRS 0-2) and safety (sICH and mortality) outcomes were compared between patients who received EVT and those with medical management (MM) only. Results: Of 445 patients enrolled, 54 met criteria for large core and early presentation; 28 had ASPECT≤5 (17 EVT, 11 MM) and 40 had CTP >50 cc (26 EVT, 14 MM) and 14 on both CT and CTP. Median (IQR) age 66 years (60, 75), NIHSS 20 (18, 23), LKW to puncture 162 min (range 69-343). Baseline characteristics were similar between EVT and MM. Patients with large core whether on CT (ASPECT≤5) or CTP (CBF>50cc) had more frequent good outcome with EVT (30% overall, CT 35%, and CTP 27% vs 0% MM, p=0.04, Fig 1) Furthermore, EVT resulted in smaller average final infarcts (77 vs 202 ml, p=0.03), similar mortality (31% vs 29%, p=0.87) and sICH (16% vs 6%,p=0.34). In patients who achieved good outcome with thrombectomy, EVT resulted in smaller infarct growth 31 ml (10-58) vs 111 cc (67-233) in patients who had poor outcome, p=0.01. Outcome rates were similar if large core was defined as >70ml. Conclusion: Patients with large core infarct measured by CT or CTP presenting within 3 hours may benefit from EVT. Time may trump imaging in patients with large core who present early.