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BackgroundRobotic-assisted neurointervention was recently introduced, with implications that it could be used to treat neurovascular diseases.ObjectiveTo evaluate the effectiveness and safety of the robotic-assisted platform CorPath GRX for treating cerebral aneurysms.MethodsThis prospective, international, multicenter study enrolled patients with brain aneurysms that required endovascular coiling and/or stent-assisted coiling. The primary effectiveness endpoint was defined as successful completion of the robotic-assisted endovascular procedure without any unplanned conversion to manual treatment with guidewire or microcatheter navigation, embolization coil(s) or intracranial stent(s) deployment, or an inability to navigate vessel anatomy. The primary safety endpoint included intraprocedural and periprocedural events.ResultsThe study enrolled 117 patients (74.4% female) with mean age of 56.6 years from 10 international sites. Headache was the most common presenting symptom in 40/117 (34.2%) subjects. Internal carotid artery was the most common location (34/122, 27.9%), and the mean aneurysm height and neck width were 5.7±2.6 mm and 3.5±1.4 mm, respectively. The overall procedure time was 117.3±47.3 min with 59.4±32.6 min robotic procedure time. Primary effectiveness was achieved in 110/117 (94%) subjects with seven subjects requiring conversion to manual for procedure completion. Only four primary safety events were recorded with two intraprocedural aneurysm ruptures and two strokes. A Raymond-Roy Classification Scale score of 1 was achieved in 71/110 (64.5%) subjects, and all subjects were discharged with a modified Rankin Scale score of ≤2.ConclusionsThis first-of-its-kind robotic-assisted neurovascular trial demonstrates the effectiveness and safety of the CorPath GRX System for endovascular embolization of cerebral aneurysm procedures.Trial registration numberNCT04236856

Microbial nanotechnology is an expanding research area devoted to producing biogenic metal and metalloid nanomaterials (NMs) using microorganisms. Often, biogenic NMs are explored as antimicrobial, anticancer, or antioxidant agents. Yet, most studies focus on their applications rather than the underlying mechanism of action or toxicity. Here, we evaluate the toxicity of our well-characterized biogenic selenium nanoparticles (bSeNPs) produced by the Stenotrophomonas maltophiliastrain SeITE02 against the model yeast Saccharomyces cerevisiaecomparing it with chemogenic SeNPs (cSeNPs). Knowing from previous studies that the biogenic extract contained bSeNPs in an organic material (OM) and supported here by Fourier transform infrared spectroscopy, we removed and incubated it with cSeNPs (cSeNPs_OM) to assess its influence on the toxicity of these formulations. Specifically, we focused on the first stages of the eukaryotic cell exposure to these samples─i.e., their interaction with the cell lipid membrane, which was mimicked by preparing vesicles from yeast polar lipid extract or phosphatidylcholine lipids. Fluidity changes derived from biogenic and chemogenic samples revealed that the bSeNP extract mediated the overall rigidification of lipid vesicles, while cSeNPs showed negligible effects. The OM and cSeNPs_OM induced similar modifications to the bSeNP extract, reiterating the need to consider the OM influence on the physical–chemical and biological properties of bSeNP extracts.

BackgroundThe use of robotics in medicine may enable increased technical accuracy, reduced procedural time and radiation exposure, and remote completion of procedures. We have previously described the first-in-human, robotic-assisted cerebral aneurysm treatment using the CorPath GRX Robotic System. In this report we discuss our early experiences and outcomes using this robotic device for endovascular treatment of intracranial aneurysms using stent-assisted coil embolization and flow diversion.MethodsThe patient and disease characteristics, procedural details, and follow-up imaging and clinical outcomes of consecutive patients undergoing robotically-assisted intracranial aneurysm embolization between November 2019 and February 2020 are presented.ResultsSix patients underwent robotically-assisted embolization of intracranial aneurysms. Four of the patients were treated with a neck-bridging stent (with or without coiling) and two patients were treated with a flow-diverting stent. Two patients were treated in the subacute period of subarachnoid hemorrhage and four patients were treated electively. All of the procedures could be completed robotically and there was no need for unplanned manual intervention. The technical success rate of the procedures was 100%. There was no morbidity or mortality associated with the procedures. One year follow-up imaging showed that four aneurysms were completely obliterated (Raymond-Roy Occlusion Classification (RROC) class I) and the remaining two were occluded with a residual neck (RROC class II).ConclusionsThe Corpath GRX Robotic System demonstrated a precise control over the microcatheter, wire and stent during aneurysm treatment. Robotic neuro-procedures seem to be safe and effective and demonstrate stable occlusion results in the midterm follow-up.

BackgroundThe use of a balloon-guide catheter (BGC) in acute stroke treatment has been widely adopted after demonstrating optimized procedure metrics and outcomes. Initial technical constraints of previous devices included catheter stiffness and smaller inner diameters. We aim to evaluate the performance and safety of the Walrus BGC, a variable stiffness catheter with a large bore 0.087 inch inner diameter (ID), via the the WICkED study (Walrus Large Bore guide Catheter Impact on reCanalization first pass Effect anDoutcomes).MethodsThis is a retrospective, site adjudicated, multicenter study on consecutive patients with large vessel occlusion treated with the Walrus BGC. Baseline characteristics, procedural outcomes and functional outcomes were analyzed.ResultsA total of 338 patients met the inclusion criteria. The Walrus was successfully tracked into distal vasculature and allowed therapeutic device delivery in all but 3 cases (0.9%). Large aspiration catheters ≥0.070 inch ID were used in 71.9% of cases. Stent retriever thrombectomy was used as the first-line modality in 59.2% and thromboaspiration in 40.8% of cases. The successful recanalization rate (modified treatment in cerebral ischemia (mTICI) 2b/3) was 94.4%, with 64.8% of the patients achieving mTICI 2b/3 after the first pass. The Walrus-related adverse event rate was 0.6%, corresponding to two vessel dissections. Functional independence was 50% (126/252) and mortality 25% (63/252). Unfavorable outcomes were more likely in older patients, who had unsuccessful reperfusion, longer procedure times, and a higher mean number of passes.ConclusionIn acute ischemic stroke patients presenting with large vessel occlusion, the Walrus BGC demonstrated excellent navigability and safety profile, allowed the accommodation of leading large bore aspiration catheters, and demonstrated high vessel recanalization rates.

BackgroundMost conventional 0.088 inch guide catheters cannot safely navigate intracranial vasculature. The objective of this study is to evaluate the safety of stroke thrombectomy using a novel 0.088 inch guide catheter designed for intracranial navigation.MethodsThis is a multicenter retrospective study, which included patients over 18 years old who underwent thrombectomy for anterior circulation large vessel occlusions. Technical outcomes for patients treated using the TracStar Large Distal Platform (TracStar LDP) or earlier generation TRX LDP were compared with a matched cohort of patients treated with other commonly used guide catheters. The primary outcome measure was device-related complications. Secondary outcome measures included guide catheter failure and time between groin puncture and clot engagement.ResultsEach study arm included 45 patients. The TracStar group was non-inferior to the control group with regard to device-related complications (6.8% vs 8.9%), and the average time to clot engagement was 8.89 min shorter (14.29 vs 23.18 min; p=0.0017). There were no statistically significant differences with regard to other technical outcomes, including time to recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2B). The TracStar was successfully advanced into the intracranial internal carotid artery in 33 cases (73.33%); in three cases (6.67%), it was swapped for an alternate catheter. Successful reperfusion (mTICI 2B-3) was achieved in 95.56% of cases. Ninety-day follow-up data were available for 86.67% of patients, among whom 46.15% had an modified Rankin Score of 0–2%, and 10.26% were deceased.ConclusionsTracstar LDP is safe for use during stroke thrombectomy and was associated with decreased time to clot engagement. Intracranial access was regularly achieved.

BackgroundDirect aspiration thrombectomy techniques use large bore aspiration catheters for mechanical thrombectomy. Several aspiration catheters are now available. We report a bench top exploration of a novel beveled tip catheter and our experience in treating large vessel occlusions (LVOs) using next-generation aspiration catheters.MethodsA retrospective analysis from a prospectively maintained database comparing the bevel shaped tip aspiration catheter versus non-beveled tip catheters was performed. Patient demographics, periprocedural metrics, and discharge and 90-day modified Rankin Scale (mRS) scores were collected. Patients were divided into two groups based on which aspiration catheter was used.ResultsOur data showed no significant difference in age, gender, IV tissue plasminogen activator administration, admission NIH Stroke Scale score, baseline mRS, or LVO location between the beveled tip and flat tip groups. With the beveled tip, Thrombolysis in Cerebral Infarction (TICI) 2C or better recanalization was more frequent overall (93.2% vs 74.2%, p=0.017), stent retriever usage was lower (9.1% vs 29%, p=0.024), and patients had lower mRS on discharge (median 3 vs 4, p<0.001) and at 90 days (median 2 vs 4, p=0.008).ConclusionPatients who underwent mechanical thrombectomy with the beveled tip catheter had a higher proportion of TICI 2C or better and had a significantly lower mRS score on discharge and at 90 days.

The core entities of computer science include formal languages, spec-ifications, models, programs, implementations, semantic theories, type inference systems, abstract and physical machines. While there are conceptual questions concerning their nature, and in particular ontological ones (Turner 2018), our main focus here will be on the relationships between them. These relationships have an extensional aspectthat articulates the propositional connection between the two entities, and an intentionalone that fixes the direction of governance. An analysis of these two aspects will drive our investigation; an investigation that will touch upon some of the central concerns of the philosophy of computer science (Turner 2017).

Various technological and biomedical applications rely on the ability of materials to emit light (photoluminescence [PL]), and, among them, metal nanoparticles (NPs) and semi-conductor Quantum Dots (QDs) represent ideal candidates as sensing probes and imaging tools, portraying better PL features than conventional organic dyes. However, the knowledge of PL behavior of semiconductor NPs – i.e., selenium; SeNPs – is still in its infancy, especially for those synthesized by microorganisms. Considering the essential role played by biogenic SeNPs as antimicrobial, anticancer, and antioxidant agents, or food supplements, their PL properties must be explored to take full advantage of them as eco-friendly and versatile tools. Here, PL features of SeNPs produced by the Se-tolerant Stenotrophomonas maltophiliaSeITE02 strain, compared with chemogenic ones, are investigated, highlighting the PL dependency on the NP size. Indeed, PL emission shifted from indigo-blue (emission wavelength λem400–450 nm) to green-yellow (λem480–570 nm) and orange-red (λem580–700 nm) for small (ca. 50 nm) and big (ca. 100 nm) SeNPs respectively, revealing the versatility of an environmental bacterial isolate to synthesize diverse PL probes. Besides, biogenic SeNPs show PL lifetime comparable to those of the most used fluorophores, supporting their potential application as markers for (bio)imaging.

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IntroductionThe endovascular stent-assisted coiling approach for the treatment of cerebral aneurysms is evolving rapidly with the availability of new stent devices. It remains unknown how each type of stent affects the safety and efficacy of the stent-coiling procedure.MethodsThis study compared the outcomes of endovascular coiling of cerebral aneurysms using Neuroform (NEU), Enterprise (EP), and Low-profile Visualized Intraluminal Support (LVIS) stents. Patient characteristics, treatment details and angiographic results using the Raymond–Roy grade scale (RRGS), and procedural complications were analyzed in our study.ResultsOur study included 659 patients with 670 cerebral aneurysms treated with stent-assisted coiling (NEU, n=182; EP, n=158; LVIS, n=330) that were retrospectively collected from six academic centers. Patient characteristics included mean age 56.3±12.1 years old, female prevalence 73.9%, and aneurysm rupture on initial presentation of 18.8%. We found differences in complete occlusion on baseline imaging, defined as RRGS I, among the three stents: LVIS 64.4%, 210/326; NEU 56.2%, 95/169; EP 47.6%, 68/143; P=0.008. The difference of complete occlusion on 10.5 months (mean) and 8 months (median) angiographic follow-up remained significant: LVIS 84%, 251/299; NEU 78%, 117/150; EP 67%, 83/123; P=0.004. There were 7% (47/670) intra-procedural complications and 11.5% (73/632) post-procedural-related complications in our cohort. Furthermore, procedure-related complications were higher in the braided-stents vs laser-cut, P=0.002.ConclusionsThere was a great variability in techniques and choice of stent type for stent-assisted coiling among the participating centers. The type of stent was associated with immediate and long-term angiographic outcomes. Randomized prospective trials comparing the different types of stents are warranted.

The nonmetabolizable lysophosphatidylcholine (LysoPC) analogue edelfosine is the prototype of a class of compounds being investigated for their potential as selective chemotherapeutic agents. Edelfosine targets membranes, disturbing cellular homeostasis. Is not clear at this point how membrane alterations are communicated between intracellular compartments leading to growth inhibition and eventual cell death. In the present study, a combined metabolomics/lipidomics approach for the unbiased identification of metabolic pathways altered in yeast treated with sublethal concentrations of the LysoPC analogue was employed. Mass spectrometry of polar metabolites, fatty acids, and lipidomic profiling was used to study the effects of edelfosine on yeast metabolism. Amino acid and sugar metabolism, the Krebs cycle, and fatty acid profiles were most disrupted, with polar metabolites and short–medium chain fatty acid changes preceding long and very long-chain fatty acid variations. Initial increases in metabolites such as trehalose, proline, and γ-amino butyric acid with a concomitant decrease in metabolites of the Krebs cycle, citrate and fumarate, are interpreted as a cellular attempt to offset oxidative stress in response to mitochondrial dysfunction induced by the treatment. Notably, alanine, inositol, and myristoleic acid showed a steady increase during the period analyzed (2, 4, and 6 h after treatment). Of importance was the finding that edelfosine induced significant alterations in neutral glycerolipid metabolism resulting in a significant increase in the signaling lipid diacylglycerol.

Background There is a clinical need for a guide catheter with combined stability and navigability, which can be used in a biaxial system for neuroendovascular procedures in place of triaxial systems.Objective To assess the safety and feasibility of the Q’Apel Medical Wahoo Hybrid Access System, a dual-mode 0.072″ internal diameter guide catheter, in a range of neuroendovascular procedures.Methods We performed a retrospective analysis of consecutive cases from a high-volume tertiary center in which the Wahoo Hybrid Access System was used as the guide catheter. Characteristics of the patients, vascular lesions, procedure, and procedural complications were assessed.Results A total of 102 patients were included for analysis. Vascular lesions were in the anterior circulation in 90 of 102 (88%), and posterior circulation in 12 of 102 (12%). Eighty-four cases were ruptured or unruptured aneurysm embolization procedures, the majority being balloon-assisted coiling (42%) and flow diversion (42%). All cases, including flow diversion, were performed as a biaxial system. There were no instances of prolapse of the catheter beyond the arterial segment in which it was initially placed. The procedure was able to be performed to completion in 101 of 102 (99%) cases. Thromboembolic complications occurred in 5 of 102 (5%); causality in two cases was unrelated to the guide catheter, and three were indeterminate.Conclusions The Wahoo guide catheter is safe and feasible when used in a variety of neuroendovascular procedures. It can accommodate a range of devices, can be safely navigated into distal vasculature, and provides support for a range of procedures, including those which traditionally require triaxial support.

Background The antiplatelet management in acute ischemic stroke requiring carotid artery stenting is heterogenous, with no clear guidelines to direct management.Objective To evaluate the safety and efficacy of an intravenous eptifibatide protocol in the management of acute ischemic stroke requiring emergent carotid artery stenting.Methods We performed a retrospective analysis of consecutive patients who underwent carotid artery stenting for acute ischemic stroke at a high-volume tertiary neuroscience center, who were managed with an intravenous eptifibatide protocol. The protocol consists of an intravenous loading eptifibatide bolus (180 mcg/kg) at the time of stenting, followed by a maintenance infusion of 1 mcg/kg/min, then oral or nasogastric loading of dual antiplatelet agents.Results 80 patients were included for analysis. Median presenting NIHSS was 17. Sixty-six patients (83%) had a tandem intracranial occlusion. Six (7.5%) patients developed symptomatic intracranial hemorrhage (sICH). Those who received intravenous thrombolysis were not more likely to develop sICH (10% vs 5%, p = 0.40). Those patients with a presenting ASPECTS <8 were significantly more likely to develop sICH than those with ASPECTS 8–10 (25% vs 3%, p = 0.004).Conclusions Eptifibatide may have a role in the management of acute stroke requiring carotid stenting. Caution may be required in those with established infarct on presentation imaging.

Environmental contextAlthough tellurium is a relatively rare element in the earth’s crust, its concentration in some niches can be naturally high owing to unique geology. Tellurium, as the oxyanion, is toxic to prokaryotes, and although prokaryotes have evolved resistance to tellurium, no universal mechanism exists. We review the interaction of tellurite with prokaryotes with a focus on those unique strains that thrive in environments naturally rich in tellurium. AbstractThe timeline of tellurite prokaryotic biology and biochemistry is now over 50 years long. Its start was in the clinical microbiology arena up to the 1970s. The 1980s saw the cloning of tellurite resistance determinants while from the 1990s through to the present, new strains were isolated and research into resistance mechanisms and biochemistry took place. The past 10 years have seen rising interest in more technological developments and considerable advancement in the understanding of the biochemical mechanisms of tellurite metabolism and biochemistry in several different prokaryotes. This research work has provided a list of genes and proteins and ideas about the fundamental metabolism of Te oxyanions. Yet the biomolecular mechanisms of the tellurite resistance determinants are far from established. Regardless, we have begun to see a new direction of Te biology beyond the clinical pathogen screening approaches, evolving into the biotechnology fields of bioremediation, bioconversion and bionanotechnologies and subsequent technovations. Knowledge on Te biology may still be lagging behind that of other chemical elements, but has moved beyond its dark ages and is now well into its renaissance.

Pediatric stroke presents with a variety of signs and symptoms. Correct modality of imaging is essential in decreasing the time from symptom onset to appropriate management. Evaluation of pediatric stroke should include both blood work as well as imaging in a parallel rather than a sequential matter. We report a case of a child with a bow hunter’s stroke that was challenging to diagnose. This type of stroke happens when the vertebral artery is occluded at the atlantoaxial or subaxial level during neck rotation. This case demonstrates that workup of stroke should be comprehensive to include all mechanical and anatomic possibilities before investigating rarer hypercoagulable disorders.

EmrE is a member of the small multidrug resistance (SMR) protein family in Escherichia coli. It confers resistance to a wide variety of quaternary cation compounds (QCCs) as an efflux transporter driven by the transmembrane proton motive force. We have expressed hexahistidinyl (His6) – myc epitope tagged EmrE, extracted it from membrane preparations using the detergent n-dodecyl-β-D-maltopyranoside (DDM), and purified it using nickel-affinity chromatography. The size of the EmrE protein, in DDM environment, was then examined in the presence and absence of a range of structurally different QCC ligands that varied in their chemical structure, charge and shape. We used dynamic light scattering and showed that the size and oligomeric state distributions are dependent on the type of QCC. We also followed changes in the Trp fluorescence and determined apparent dissociation constants (Kd). Overall, our in vitro analyses of epitope tagged EmrE demonstrated subtle but significant differences in the size distributions with different QCC ligands bound.

BackgroundThe development of new revascularization devices has improved recanalization rates and time, but not clinical outcomes. We report a prospectively collected clinical experience with a new technique utilizing a direct aspiration first pass technique with large bore aspiration catheter as the primary method for vessel recanalization.Methods98 prospectively identified acute ischemic stroke patients with 100 occluded large cerebral vessels at six institutions were included in the study. The ADAPT technique was utilized in all patients. Procedural and clinical data were captured for analysis.ResultsThe aspiration component of the ADAPT technique alone was successful in achieving Thrombolysis in Cerebral Infarction (TICI) 2b or 3 revascularization in 78% of cases. The additional use of stent retrievers improved the TICI 2b/3 revascularization rate to 95%. The average time from groin puncture to at least TICI 2b recanalization was 37 min. A 5MAX demonstrated similar success to a 5MAX ACE in achieving TICI 2b/3 revascularization alone (75% vs 82%, p=0.43). Patients presented with an admitting median National Institutes of Health Stroke Scale (NIHSS) score of 17.0 (12.0–21.0) and improved to a median NIHSS score at discharge of 7.3 (1.0–11.0). Ninety day functional outcomes were 40% (modified Rankin Scale (mRS) 0–2) and 20% (mRS 6). There were two procedural complications and no symptomatic intracerebral hemorrhages.DiscussionThe ADAPT technique is a fast, safe, simple, and effective method that has facilitated our approach to acute ischemic stroke thrombectomy by utilizing the latest generation of large bore aspiration catheters to achieve previously unparalleled angiographic outcomes.

BackgroundThe development of new revascularization devices has improved recanalization rates and time but not clinical outcomes. We report our initial results with a new technique utilizing a direct aspiration first pass technique with a large bore aspiration catheter as the primary method for vessel recanalization.MethodsA retrospective evaluation of a prospectively captured database of 37 patients at six institutions was performed on patients where the ADAPT technique was utilized. The data represent the initial experience with this technique.ResultsThe ADAPT technique alone was successful in 28 of 37 (75%) cases although six cases had large downstream emboli that required additional aspiration. Nine cases required the additional use of a stent retriever and one case required the addition of a Penumbra aspiration separator to achieve recanalization. The average time from groin puncture to at least Thrombolysis in Cerebral Ischemia (TICI) 2b recanalization was 28.1 min, and all cases were successfully revascularized. TICI 3 recanalization was achieved 65% of the time. On average, patients presented with an admitting National Institutes of Health Stroke Scale (NIHSS) score of 16.3 and improved to an NIHSS score of 4.2 by the time of hospital discharge. There was one procedural complication.DiscussionThis initial experience highlights the fact that the importance of the technique with which new stroke thrombectomy devices are used may be as crucial as the device itself. The ADAPT technique is a simple and effective approach to acute ischemic stroke thrombectomy. Utilizing the latest generation of large bore aspiration catheters in this fashion has allowed us to achieve excellent clinical and angiographic outcomes.

BackgroundWhile mechanical thrombectomy (MT) has become the standard of care for patients with acute ischemic stroke (AIS) with emergent large-vessel occlusions (ELVO), recently published guidelines appropriately award top-tier evidence to the same selective criteria that were employed in completed clinical trials. We sought to evaluate the safety and effectiveness of MT in patients with AIS with ELVO who do not meet top-tier evidence criteria (TTEC).MethodsWe conducted an observational study on consecutive patients with AIS with ELVO who underwent MT at six high-volume endovascular centers. Standard safety outcomes (3-month mortality, symptomatic intracranial hemorrhage) and effectiveness outcomes (3-month functional independence: modified Rankin Scale scores of 0–2) were compared between patients meeting and failing TTEC.ResultsThe sample consisted of 349 (60%) controls fulfilling TTEC and 234 (40%) non-TTEC patients. Control patients meeting TTEC for MT tended to have higher functional independence rates at 3 months (47% vs 39%; p=0.055), while the rates of symptomatic intracerebral hemorrhage (sICH) were similar (9%) in both groups (p=0.983). In multivariable logistic regression models, adherence to TTEC for MT was not independently related to any safety outcome (sICH: OR 0.71, 95% CI 0.30 to 1.68, p=0.434; 3-month mortality: OR 1.27, 95% CI 0.69 to 2.33, p=0.448) or effectiveness outcome (3-month functional independence: OR 0.81, 95% CI 0.48 to 1.37, p=0.434; 3-month functional improvement: OR 0.73, 95% CI 0.48 to 1.11, p=0.138) after adjusting for potential confounders.ConclusionsApproximately 40% of patients with AIS with ELVO offered MT do not fulfill TTEC for MT. Patients who did not meet TTEC had high rates of good clinical outcome and low complication rates.

Infectious intracranial aneurysms (IIAs) are a rare cerebrovascular complication of systemic infections induced by microbial infiltration and degradation of the arterial vessel wall. Studies on the epidemiology and management of IIAs are limited to case reports and retrospective single-center studies, and report a large variability in epidemiological features, management, and outcomes due to the limited sample size. We conducted a systematic review of all published papers on IIAs in the English literature using MEDLINE and SCOPUS database from January 1950 to June 2017. A total of 288 publications describing 1191 patients with IIA (1398 aneurysms) were included and reviewed for epidemiological features, disease features, treatment and outcome. All patients were merged into a single cohort and summary data are presented. The majority of reported IIAs are distally located, relatively small (<5 mm), involve the anterior circulation, are associated with a relatively high rate of rupture, and demonstrate a propensity to multiplicity of aneurysms. Sensitive diagnosis of IIAs requires digital subtraction angiography and not CT angiography or MR angiography. Treatment of ruptured, symptomatic, or enlarging IIAs has evolved over the last 50 years. Endovascular therapy is associated with a high success rate and low morbidity compared with microsurgical and medical management. A treatment algorithm for the management of patients with IIA in various contexts is proposed and the need for prospective multicenter studies is emphasized.

ObjectiveThis study retrospectively compared the clinical and angiographic outcomes of treating cerebral aneurysms with Neuroform (NEU), Enterprise (EP), and Low-profile Visualized Intraluminal Support (LVIS/LVIS Jr) stents.Materials and methodsWe conducted a retrospective analysis of a procedural database. All aneurysm procedures using any of the three types of self-expanding nitinol stents (NEU, EP and LVIS/LVIS Jr) were included. Intra-procedure complications, post-procedure complications, and angiographic results (Raymond–Roy grade scale, RRGS) were analyzed retrospectively. A multivariate logistic regression analysis was conducted to identify predictors of intra-procedure and post-procedure complications.ResultsTwo hundred and forty-three aneurysms in 229 patients treated with stent-assisted coiling were included (NEU group: 109 aneurysms; EP group: 61 aneurysms; LVIS/LVIS Jr: 73 aneurysms). The LVIS/LVIS Jr group was associated with the lowest rate of initial complete occlusion (RRGS I: 47.9%; 35/73). Follow-up showed the proportion of RRGS I increased for all stent groups but was greatest in the LVIS/LVIS Jr group. Overall, 17 intra-procedural complications were seen in 229 patients (7.4%) and 15 post-procedural complications were found in 198 patients at follow-up (7.6%), with no differences between stent groups. Thrombotic events were the most common complications and occurred in 13 patients (13/229, 5.7%).ConclusionsAll three types of stents used to treat cerebral aneurysms with unfavorable neck were safe and effective, providing suitable support for the coil mass. LVIS/LVIS Jr promotes better progressive aneurysm complete occlusion than the other two stents but seems to cause more common intra-procedural stent-related thrombotic events and fewer post-procedural complications.

BackgroundThe angiographic evaluation of previously coiled aneurysms can be difficult yet remains critical for determining re-treatment.ObjectiveThe main objective of this study was to determine the inter-rater reliability for both the Raymond Scale and per cent embolization among a group of neurointerventionalists evaluating previously embolized aneurysms.MethodsA panel of 15 neurointerventionalists examined 92 distinct cases of immediate post-coil embolization and 1 year post-embolization angiographs. Each case was presented four times throughout the study, along with alterations in demographics in order to evaluate intra-rater reliability. All respondents were asked to provide the per cent embolization (0–100%) and Raymond Scale grade (1-3) for each aneurysm. Inter-rater reliability was evaluated by computing weighted kappa values (for the Raymond Scale) and intraclass correlation coefficients (ICC) for per cent embolization.Results10 neurosurgeons and 5 interventional neuroradiologists evaluated 368 simulated cases. The agreement among all readers employing the Raymond Scale was fair (κ=0.35) while concordance in per cent embolization was good (ICC=0.64). Clinicians with fewer than 10 years of experience demonstrated a significantly greater level of agreement than the group with greater than 10 years (κ=0.39 and ICC=0.70 vs κ=0.28 and ICC=0.58). When the same aneurysm was presented multiple times, clinicians demonstrated excellent consistency when assessing per cent embolization (ICC=0.82), but moderate agreement when employing the Raymond classification (κ=0.58).ConclusionsIdentifying the per cent embolization in previously coiled aneurysms resulted in good inter- and intra-rater agreement, regardless of years of experience. The strong agreement among providers employing per cent embolization may make it a valuable tool for embolization assessment in this patient population.

IntroductionIn acute ischemic stroke (AIS), extending mechanical thrombectomy procedural times beyond 60 min has previously been associated with an increased complication rate and poorer outcomes.ObjectiveAfter improvements in thrombectomy methods, to reassess whether this relationship holds true with a more contemporary thrombectomy approach: a direct aspiration first pass technique (ADAPT).MethodsWe retrospectively studied a database of patients with AIS who underwent ADAPT thrombectomy for large vessel occlusions. Patients were dichotomized into two groups: ‘early recan’, in which recanalization (recan) was achieved in ≤35 min, and ‘late recan’, in which procedures extended beyond 35 min.Results197 patients (47.7% women, mean age 66.3 years) were identified. We determined that after 35 min, a poor outcome was more likely than a good (modified Rankin Scale (mRS) score 0–2) outcome. The baseline National Institutes of Health Stroke Scale (NIHSS) score was similar between ‘early recan’ (n=122) (14.7±6.9) and ‘late recan’ patients (n=75) (15.9±7.2). Among ‘early recan’ patients, recanalization was achieved in 17.8±8.8 min compared with 70±39.8 min in ‘late recan’ patients. The likelihood of achieving a good outcome was higher in the ‘early recan’ group (65.2%) than in the ‘late recan’ group (38.2%; p<0.001). Patients in the ‘late recan’ group had a higher likelihood of postprocedural hemorrhage, specifically parenchymal hematoma type 2, than those in the ‘early recan’ group. Logistic regression analysis showed that baseline NIHSS, recanalization time, and atrial fibrillation had a significant impact on 90-day outcomes.ConclusionsOur findings suggest that extending ADAPT thrombectomy procedure times beyond 35 min increases the likelihood of complications such as intracerebral hemorrhage while reducing the likelihood of a good outcome.

BackgroundBlood blister aneurysms (BBA) are a rare subset of intracranial aneurysms that represent a therapeutic challenge from both a surgical and endovascular perspective.ObjectiveTo report multicenter experience with flow diversion exclusively for BBA, located at non-branching segments along the anteromedial wall of the supraclinoidal internal carotid artery (ICA).MethodsConsecutive cases of BBA located at non-branching segments along the anteromedial wall of the supraclinoidal ICA treated with flow diversion were included in the final analysis.Results49 patients with 51 BBA of the ICA treated with devices to achieve the flow diversion effect were identified. 43 patients with 45 BBA of the ICA were treated with the pipeline embolization device and were included in the final analysis. Angiographic follow-up data were available for 30 patients (32 aneurysms in total); 87.5% of aneurysms (28/32) showed complete obliteration, 9.4% (3/32) showed reduced filling, and 3.1% (1/32) persistent filling. There was no difference between the size of aneurysm (≤2 mm vs >2 mm) or the use of adjunct coiling and complete occlusion of the aneurysm on follow-up (P=0.354 and P=0.865, respectively). Clinical follow-up data were available for 38 of 43 patients. 68% of patients (26/38) had a good clinical outcome (modified Rankin scale score of 0–2) at 3 months. There were 7 (16%) immediate procedural and 2 (5%) delayed complications, with 1 case of fatal delayed re-rupture after the initial treatment.ConclusionsOur data support the use of a flow diversion technique as a safe and effective therapeutic modality for BBA of the supraclinoid ICA.

IntroductionEffective triage of patients with emergent large vessel occlusion (ELVO) to endovascular therapy capable centers may decrease time to treatment and improve outcome for these patients. Here we performed a derivation study to evaluate the accuracy of a portable, non-invasive, and easy to use severe stroke detector.MethodsThe volumetric impedance phase shift spectroscopy (VIPS) device was used to assign a bioimpedance asymmetry score to 248 subjects across three cohorts, including 41 subjects presenting as acute stroke codes at a major comprehensive stroke center (CSC), 79 healthy volunteers, and 128 patients presenting to CSCs with a wide variety of brain pathology including additional stroke codes. Diagnostic parameters were calculated for the ability of the device to discern (1) severe stroke from minor stroke and (2) severe stroke from all other subjects. Patients with intracranial hardware were excluded from the analysis.ResultsThe VIPS device was able to differentiate severe stroke from minor strokes with a sensitivity of 93% (95% CI 83 to 98), specificity of 92% (95% CI 75 to 99), and an area under the curve (AUC) of 0.93 (95% CI 0.85 to 0.97). The device was able to differentiate severe stroke from all other subjects with a sensitivity of 93% (95% CI 83 to 98), specificity of 87% (95% CI 81 to 92), and an AUC of 0.95 (95% CI 0.89 to 0.96).ConclusionThe VIPS device is a portable, non-invasive, and easy to use tool that may aid in the detection of severe stroke, including ELVO, with a sensitivity of 93% and specificity of 92% in this derivation study. This device has the potential to improve the triage of patients suffering severe stroke.

IntroductionIn acute ischemic stroke (AIS), posterior circulation large vessel occlusions (LVOs) have been associated with poorer outcomes compared with anterior circulation LVOs. The outcomes of anterior versus posterior circulation thrombectomy for LVOs were compared at a high volume center employing a direct aspiration first pass technique (ADAPT).MethodsWe retrospectively studied a database of AIS cases that underwent ADAPT thrombectomy for LVOs. Cases were grouped by anatomical location of thrombectomy (posterior vs anterior circulation), and analysis was performed on both entire sample size.ResultsA total of 436 AIS patients (50.2% women, mean age 67.3 years) underwent ADAPT thrombectomy for LVO during the study period, of whom 13% of had posterior circulation thrombectomy. Patients with posterior circulation thrombectomy did not show a significant difference in preprocedural variables, including age, baseline National Institutes of Health Stroke Scale (NIHSS), and onset to groin time, compared with anterior circulation (P>0.05). There were also no differences in procedural variables between the two groups. Patients in the posterior group were found to have a similar likelihood of good outcome (modified Rankin Scale score 0—2) at 90 days compared with the anterior group (42.9% vs 43.2%, respectively), and a small but not significant increase in mortality at 90 days. Multilogistic regression analysis showed that the anatomical location (anterior vs posterior) was not an independent predictor of good outcome or mortality after thrombectomy. Prominent predictors of outcome/mortality included age, female gender, procedure time, and baseline NIHSS.ConclusionsOur findings demonstrate that when patients are carefully selected for thrombectomy, those with posterior circulation LVOs can achieve similar outcomes compared with anterior circulation thrombectomy, indicating comparable safety and efficacy profiles.

IntroductionCompleted randomized trials on endovascular thrombectomy (ET) did not independently assess the efficacy of ET in the elderly (≥80 years old) who were often excluded or under-represented in trials. There were also inconsistent criteria for patient selection in this population across the different trials. This work evaluates outcomes after ET for acute ischemic stroke (AIS) in the elderly at a high volume stroke center.MethodsWe reviewed all cases of AIS that underwent a direct aspiration first pass technique (ADAPT) thrombectomy for large vessel occlusions between March 2013 and October 2017 while comparing outcomes in the elderly with younger counterparts. We also reviewed AIS cases in elderly patients undergoing medical management who were matched to the ET counterparts by demographics, comorbidities, baseline deficits, and stroke severity.ResultsOf 560 patients undergoing ET for AIS, 108 patients were in the elderly group (≥80 years of age), and had a significantly lower likelihood of functional independence (defined as a modified Rankin Scale score of 0–2) at 90 days compared with younger patients (20.5% vs 44.4%, P<0.001), and higher mortality rates (34.3% vs 20%, P<0.001). When compared with patients undergoing medical management, elderly patients did not have a significant improvement in rates of good outcomes (20.5% vs 19.5%, P>0.05), and had significantly higher rates of hemorrhage (40.7% vs 9.3%, P<0.001). We also identified baseline stroke severity and the incidence of hemorrhage as two independent predictors of outcome in the elderly patients.ConclusionsET in the elderly did not show a similar benefit to younger patients when compared with medical management. These findings emphasize the need for more optimal selection criteria for the elderly population to improve the risk to benefit ratio of ET.

AbstractObjective: Clinical observation and anecdotal reports suggest changes can occur to dental occlusion following intervention with the National Upper Cervical Chiropractic Association (NUCCA) procedure. This case controlled study discerned if occlusion changes are measurable using a dental force plate (T-Scan®) following an adjustment to the craniocervical junction (CCJ).Methods: A degree of case control was established by active patients being assessed twice prior to and following intervention. Before–after intervention assessment included posture evaluation and dental occlusion (T-Scan®).Results: Findings suggest that changes in posture and occlusion can be observed after the NUCCA chiropractic procedure. Not all patients demonstrated a more balanced contact pattern following the adjustment, indicating a need for further investigation.Discussion: These findings may suggest interconnectivity between the CCJ and an individual’s occlusal contacts and support the need for further integration between chiropractors and dentists seeking to co-manage temporomandibular joint disorders.

BACKGROUND:The safety and probable benefit of the PulseRider (Pulsar Vascular, Los Gatos, California) for the treatment of broad-necked, bifurcation aneurysms was studied in the context of the prospective, nonrandomized, single arm clinical trial—the Adjunctive Neurovascular Support of Wide-neck aneurysm Embolization and Reconstruction (ANSWER) Trial.OBJECTIVE:To present the results of the United States cases employing the PulseRider device as part of the ANSWER clinical trial.METHODS:Aneurysms treated with the PulseRider device among sites enrolling in the ANSWER trial were prospectively studied and the results are summarized. Aneurysms arising at either the carotid terminus or basilar apex that were relatively broad necked were considered candidates for inclusion into the ANSWER study.RESULTS:Thirty-four patients were enrolled (29 female and 5 male) with a mean age of 60.9 years (27 basilar apex and 7 carotid terminus). Mean aneurysm height ranged from 2.4 to 15.9 mm with a mean neck size of 5.2 mm (range 2.3-11.6 mm). In all patients, the device was delivered and deployed. Immediate Raymond I or II occlusion was achieved in 82.4% and progressed to 87.9% at 6-month follow-up. A modified Rankin Score of 2 or less was seen in 94% of patients at 6 months.CONCLUSION:The results from the ANSWER trial demonstrate that the PulseRider device is safe and offers probable benefit as for the treatment of bifurcation aneurysms arising at the basilar apex or carotid terminus. As such, it represents a useful addition to the armamentarium of the neuroendovascular specialist.

IntroductionThe direct aspiration first pass technique (ADAPT) has been introduced as a simple and fast method for achieving good angiographic and clinical outcomes using large bore aspiration catheters for the treatment of acute ischemic stroke (AIS). We present a single center's long term experience with ADAPT.MethodsRetrospective analysis of a database was gathered on patients undergoing stroke thrombectomy with ADAPT at a stroke center. Specific parameters captured included age, gender, National Institutes of Health Stroke Scale (NIHSS) score at presentation, time to presentation from last normal, and modified Rankin Scale (mRS) score at the 90 day follow-up. Radiological and angiographic imaging was reviewed to document the location of the vascular occlusion, Thrombolysis in Cerebral Infarction (TICI) flow postprocedure, and procedural complications.Results191 consecutive patients who suffered an AIS treated with ADAPT were reviewed; 91 were women, and mean age was 67 years. Patients presented with a mean NIHSS score of 15.4, and 71 patients received intravenous tissue plasminogen activator. The average time from onset to puncture was 7.8 h. The average time for recanalization was 37.3 min. TICI 2B or better recanalization was achieved in 180 (94.2%) patients. 98 (54.1%) patients had an mRS of 0–2 at 90 days. Direct aspiration alone was performed in 145 cases, and 43 cases required the additional use of a stent retriever. There was no significant difference in presenting NIHSS score, average time to presentation, average mRS at 90 days, or 90 day mortality between the two groups. Time to recanalization was 29.6 min for direct aspiration compared with 61.4 min in cases that required adjunct devices (p=0.00000201). 79 (57.7%) patients who underwent direct aspiration only achieved a good outcome at 90 days (mRS 0–2) compared with 19 (43.2%) who underwent adjunct therapies (p=0.12).ConclusionsADAPT is an effective method to achieve good clinical and angiographic outcomes, and serves as a useful firstline method for revascularization.

BackgroundThe effect of the five positive randomized controlled trials on thrombectomy practices and procedural volume has yet to be defined. Further, few studies have attempted to define modern thrombectomy practices in terms of selection criteria and devices used.MethodsA 21 question survey of Society of Neurointerventional Surgery (SNIS) physicians was administered using the SurveyMonkey website, addressing current practices as well as changes from before January 1, 2015 to the months after this date.ResultsA total of 78 responses were obtained (approximately 10% of SNIS membership). Prior to January 2015, two-thirds of respondents reported performing 1–5 thrombectomies per month (67%), with 31% performing more than 5 per month. Following January 2015, 62% of respondents reported performing more than 5 thrombectomies per month; 45% of respondents reported a higher number of thrombectomies after trial publication. 73% and 80% of respondents indicated that inpatient consultations and hospital to hospital transfers for thrombectomy have increased, respectively. A plurality of respondents reported using A Direct Aspiration First Pass Technique (40%) as the first strategy for revascularization. Most commonly, neurointerventionalists reported using conscious sedation (56%) for anesthesia. 74% of respondents indicated being successful with their primary technique in at least 70% of cases.ConclusionsThis survey of predominantly academic SNIS physicians indicates that inpatient consultations, hospital to hospital transfers, and thrombectomy procedural volumes have increased modestly since the publication of the five major stroke trials this year. In addition, many respondents indicated an increase in aggressiveness in pursuing thrombectomy based on selection criteria.

IntroductionVenous sinus stenting is a popular treatment strategy for patients with high venous sinus pressure gradients across a site of outflow obstruction. Little is known about the effect of anesthesia on venous sinus pressure measurements.ObjectiveTo compare venous manometry performed in patients under general anesthesia and while awake.MethodsA prospective database was accessed to retrospectively identify patients who had undergone venous sinus stenting. Pressure gradients were compared between those patients who underwent manometry while awake and before stenting under general anesthesia.ResultsThirty patients with both general anesthesia and awake pressure recordings were identified. Pressure measurements were highly variable but overall were higher under general anesthesia by an average of 5.8 mm Hg (1.7; p=0.002). A significant difference between awake and general anesthesia pressure measurements was detected in the sigmoid sinus (5.8 mm Hg (2.0); p=0.005) and the jugular vein (8.1 mm Hg (3.9); p=0.040). Only 11/30 (36.7%) pressure gradients remained within 5 mm Hg of the original awake gradient when repeated under general anesthesia; 9/30 (30%) patients had gradients that were at least 10 mm Hg different across procedures.ConclusionsCalculated pressure gradients were markedly affected by anesthesia. These findings suggest that candidacy for stenting should be determined with venous manometry while patients are awake owing to the unpredictable and highly variable effect of general anesthesia on pressure measurements and an apparent tendency to underestimate the degree of venous outflow obstruction.

BackgroundAcute large vessel occlusion (LVO) can result from thromboemboli or underlying intracranial atherosclerotic disease (ICAD). Although the technique for revascularization differs significantly for these two lesions (simple thrombectomy for thromboemboli and balloon angioplasty and stenting for ICAD), the underlying etiology is often unknown in acute ischemic stroke (AIS).ObjectiveTo evaluate whether procedural complications, revascularization rates, and functional outcomes differ among patients with LVO from ICAD or thromboembolism.MethodsA retrospective review of thrombectomy cases from 2008 to 2015 was carried out for cases of AIS due to underlying ICAD. Thirty-six patients were identified. A chart and imaging review was performed to determine revascularization rates, periprocedural complications, and functional outcomes. Patients with ICAD and acute LVO were compared with those with underlying thromboemboli.ResultsAmong patients with ICAD and LVO, mean National Institutes of Health Stroke Scale (NIHSS) score on admission was 12.9±8.5, revascularization (Thrombolysis In Cerebral Infarction, TICI ≥2b) was achieved in 22/34 (64.7%) patients, 11% had postprocedural intracerebral hemorrhage (PH2), and 14/33 (42.4%) had achieved a modified Rankin Scale (mRS) score of 0–2 at the 3-month follow-up. Compared with patients without underlying ICAD, there was no difference in NIHSS on presentation, or in the postprocedural complication rate. However, procedure times for ICAD were longer (98.5±59.8 vs 37.1±34.2 min), there was significant difference in successful revascularization rate between the groups (p=0.001), and a trend towards difference in functional outcome at 3 months (p=0.07).ConclusionsDespite AIS with underlying ICAD requiring a more complex, technically demanding recanalization strategy than traditional thromboembolic AIS, it appears safe, and good outcomes are obtainable.

ObjectiveTo investigate the associations between Alberta Stroke Program Early CT Score (ASPECTS) or distribution and sidedness of acute infarction and clinical outcomes following intervention with a direct aspiration first pass technique (ADAPT).MethodsA review was performed of patients who had undergone thrombectomy with ADAPT for emergent large vessel occlusions of the middle cerebral artery (MCA) between December 2012 and May 2015. Preintervention CT scans were reviewed by a blinded radiologist to calculate ASPECTS and determine the distribution of infarction. Clinical outcomes were compared for subsets of patients depending upon ASPECTS and regional infarction distribution (cortical, subcortical, or both).ResultsOne hundred and fifty-four patients (50% female, mean age 67) underwent thrombectomy using ADAPT for MCA emergent large vessel occlusion. The median presenting National Institute of Health Stroke Scale score was 15. Fifty-five per cent of patients had left-side occlusions. Similar good outcomes were achieved for patients with perfect and non-perfect ASPECTS (modified Rankin Scale (mRS) 0–2: 63% vs 51%, respectively; p=0.20). Similar outcomes were also achieved for patients with ‘poor’ ASPECTS (≤6) compared with those with ASPECTS >6 (mRS 0–2: 52% vs 53%, respectively; p=0.91). Regional distribution and sidedness of core infarction on preintervention CT also did not correlate with worse outcomes.ConclusionsPatients with moderate-sized core infarcts involving various distributions in either hemisphere can potentially achieve similar good outcomes compared with those with no core infarction at presentation. A treatment algorithm for acute ischemic stroke, which employs hardline ASPECTS thresholds or excludes patients with basal ganglia infarcts, might preclude patients who would potentially benefit from mechanical thrombectomy with ADAPT.

ObjectiveTo assess the ‘real-world’ performance of the newer generation of hydrogel coils in ruptured aneurysms.MethodsA multicenter retrospective study was carried out of angiographic and clinical outcome data on consecutive patients with ruptured aneurysms treated with at least 70% of the newer generation of hydrogel coils. Demographics and data on clinical grade, smoking, use of statins, aneurysm size, location, technique used, packing density, immediate angiographic result, angiographic follow-up, rebleeding and clinical outcome were obtained and analyzed.ResultsEighty patients (54F; 26M) with an average age of 55.1 years were entered in the study. Forty-four presented good clinical grade (Hunt and Hess 1 or 2). Forty-two (52.5%) aneurysms were ≤5 mm. 56.7% of the aneurysms were treated with simple coil embolization and 39.6% with balloon-assisted coil. The packing density ranged from 9.3% to 92.6% (mean 48.5%). Immediate occlusion rates (Raymond–Roy Scale) were: complete occlusion (class I) in 57.5%, residual neck (class II) in 32.5% and residual aneurysm (class III) in 10%. Intraoperative rupture occurred in 3 cases (3.75%). Clinical follow-up, available in 73 patients, showed a good outcome (modified Rankin Scale 0–2) in 76.3%. Preliminary data on imaging follow-up were available in 54 patients (average 6.8 months) with complete occlusion in 77.8%, residual neck in 20.3% and residual aneurysm in 1.9%. There was no re-hemorrhage.ConclusionsOur data show that the use of the newer-generation hydrogel coils in the treatment of ruptured aneurysms is feasible, safe and effective with high immediate and mid-term occlusion rates and low morbidity.

Multiple methods for quantitative proteomics are available for proteome profiling. It is unclear which methods are most useful in situations involving deep proteome profiling and the detection of subtle distortions in the proteome. Here, we compared the performance of seven different strategies in the analysis of a mouse model of Fragile X Syndrome, involving the knockout of the fmr1gene that is the leading cause of autism spectrum disorder. Focusing on the cerebellum, we show that data-independent acquisition (DIA) and the tandem mass tag (TMT)-based real-time search method (RTS) generated the most informative profiles, generating 334 and 329 significantly altered proteins, respectively, although the latter still suffered from ratio compression. Label-free methods such as BoxCar and a conventional data-dependent acquisition were too noisy to generate a reliable profile, while TMT methods that do not invoke RTS showed a suppressed dynamic range. The TMT method using the TMTpro reagents together with complementary ion quantification (ProC) overcomes ratio compression, but current limitations in ion detection reduce sensitivity. Overall, both DIA and RTS uncovered known regulators of the syndrome and detected alterations in calcium signaling pathways that are consistent with calcium deregulation recently observed in imaging studies. Data are available via ProteomeXchange with the identifier PXD039885.