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Background and purposeThe ability of polymer-modified coils to promote stable aneurysm occlusion after endovascular treatment is not well-documented. Angiographic aneurysm recurrence is widely used as a surrogate for treatment failure, but studies documenting the correlation of angiographic recurrence with clinical failure are limited. This trial compares the effectiveness of Matrix(2) polyglycolic/polylactic acid biopolymer-modified coils with bare metal coils and correlates the angiographic findings with clinical failure (ie, target aneurysm recurrence), a composite end point that includes any incident of posttreatment aneurysm rupture, retreatment, or unexplained death.Materials and methodsThis was a multicenter randomized noninferiority trial with blinded end point adjudication. We enrolled 626 patients, divided between Matrix(2) and bare metal coil groups. The primary outcome was target aneurysm recurrence at 12 ± 3 months.ResultsAt 455 days, at least 1 target aneurysm recurrence event had occurred in 14.6% of patients treated with bare metal coils and 13.3% of Matrix(2) (P = .76, log-rank test) patients; 92.8% of target aneurysm recurrence events were re-interventions for aneurysms that had not bled after treatment, and 5.8% of target aneurysm recurrence events resulted from hemorrhage or rehemorrhage, with or without retreatment. Symptomatic re-intervention occurred in only 4 (0.6%) patients. At 455 days, 95.8% of patients with unruptured aneurysms and 90.4% of those with ruptured aneurysms were independent (mRS ≤ 2). Target aneurysm recurrence was associated with incomplete initial angiographic aneurysm obliteration, presentation with rupture, and a larger aneurysmal dome and neck size.ConclusionsTested Matrix(2) coils were not inferior to bare metal coils. Endovascular coiling of intracranial aneurysms was safe, and the rate of technical success was high. Target aneurysm recurrence is a promising clinical outcome measure that correlates well with established angiographic measurements.

Background and purposeDistal ACA aneurysms remain difficult to treat with endovascular therapy, but improved technology and experience allows for the treatment of some of these aneurysms with excellent results. The purpose of this study was to assess the status of endovascular treatment of distal ACA aneurysms by comparing our results with recent endovascular and microsurgical series of distal ACA aneurysms.Materials and methodsBetween 2000 and 2008, a total of 22 consecutive patients (14 women; mean age, 58.4 years) with distal ACA aneurysms underwent coil placement at Barrow Neurological Institute. Clinical presentations, radiographic findings, endovascular management, and outcomes were reviewed retrospectively.ResultsOf the 22 patients, 13 (59%) presented with subarachnoid hemorrhage. Six patients were HH grade I or II, 1 was grade III, 5 were grade IV, and 1 was grade V. Frontal lobe hematomas occurred in 5 patients with ruptured aneurysms. The mean aneurysm size was 7.5 mm (range, 2.8-25 mm); 55% were smaller than 7 mm. Twelve aneurysms (55%) arose from the origin of the callosomarginal artery (55%). Complete occlusion was achieved in 50% of the cases and near-complete occlusion in 45%. The few periprocedural complications included 1 retroperitoneal hematoma and 1 intraoperative rupture. Four patients had thromboembolic events adequately treated intraprocedurally with abciximab. No deaths occurred in the patients treated.ConclusionsThe characteristics of the patients and aneurysms treated in our series were comparable to previous reports of endovascular treatment of ACA aneurysms with respect to rupture status. Periprocedural morbidity and mortality rates in our series fared well compared with previous reports, as did our combined rate of complete or near-complete occlusions. Recent advances in endovascular devices and techniques have improved outcomes of distal ACA aneurysms.

Background: Acute ischemic stroke (AIS) is the second leading cause of death globally. Mechanical thrombectomy (MT) has improved patient prognosis but expedient treatment is still necessary to minimize anoxic injury. Lower intraoperative body temperature decreases cerebral oxygen demand, but the role of hypothermia in treatment of AIS with MT is unclear., Methods: We retrospectively reviewed patients undergoing MT for AIS from 2014 to 2020 at our institution. Patient demographics, comorbidities, intraoperative parameters, and outcomes were collected. Maximum body temperature was extracted from minute-by-minute anesthesia readings, and patients with maximal temperature below 36°C were considered hypothermic. Risk factors were assessed by χ 2 and multivariate ordinal regression., Results: Of 68 patients, 27 (40%) were hypothermic. There was no significant association of hypothermia with patient age, comorbidities, time since last known well, number of passes intraoperatively, favorable revascularization, tissue plasminogen activator use, and immediate postoperative complications. Hypothermic patients exhibited better neurologic outcome at 3-month follow-up (P = 0.02). On multivariate ordinal regression, lower maximum intraoperative body temperature was associated with improved 3-month outcomes (P < 0.001), when adjusting for other factors influencing neurological outcomes. Other significant protective factors included younger age (P = 0.03), better revascularization (P = 0.03), and conscious sedation (P = 0.02)., Conclusions: Lower intraoperative body temperature during MT was independently associated with improved neurological outcome in this single center retrospective series. These results may help guide clinicians in employing therapeutic hypothermia during MT to improve long-term neurologic outcomes from AIS, although larger studies are needed., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Objectives: Flow diversion of intracranial aneurysms results in high occlusion rates. However, 10% to 20% remain persistently filling at 1 year. Often, these are retreated, but benefits of retreatment are not well established. A better understanding of the long-term rupture risk of persistently filling aneurysms after flow diversion is needed., Methods: Our institutional database of 974 flow diversion cases was queried for persistently filling saccular aneurysms of the clinoidal, ophthalmic, and communicating segments of the internal carotid artery treated with the pipeline embolization device (PED, Medtronic). Persistent filling was defined as continued flow into the aneurysm on 1 year catheter angiogram. The clinical record was queried for retreatments and delayed ruptures. Clinical follow-up was required for at least 2 years., Results: Ninety-four persistent aneurysms were identified. The average untreated aneurysm size was 5.6 mm. A branch vessel originated separately in 55% of cases from the body of the aneurysm in 10.6% of cases and from the neck in 34% of cases. Eighteen percent of aneurysms demonstrated >95% filling at 1 year, and 61% were filling 5% to 95% of their original size. The mean follow-up time was 4.9 years, including 41 cases with >5 years. No retreatment was undertaken in 91.5% of aneurysms. There were no cases of delayed subarachnoid hemorrhage., Conclusion: Among saccular internal carotid artery aneurysms treated with PED that demonstrated persistent aneurysm filling at 1 year, there were no instances of delayed rupture on long-term follow-up. These data suggest that observation may be appropriate for continued aneurysm filling at least in the first several years after PED placement., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Vertebral-venous fistulas (VVFs) are rare. Scarce literature exists to guide our understanding and management. We report our experience and propose a classification based on flow, feeder number, and involvement of accessible veins. Additionally, we include a practical treatment approach., Methods: Retrospective chart and imaging review of cerebrovascular arteriovenous fistulas treated in our center between July 2013 and April 2022. We reviewed patient demographics, presentation, imaging, treatment strategies, and outcomes., Results: Nine patients with VVFs were identified, six were females. Ages ranged between 38-83 years. There were six high-flow and three low-flow. Most VVFs originated at the level of V3. Additional feeders from the internal carotid artery, external carotid artery, and/or subclavian artery were present in four cases (two were high-flow). Four cases had multiple arterial feeders. All cases were symptomatic. Origin was spontaneous in eight and iatrogenic in one case. Most common presenting symptoms were pain (7) and pulsatile tinnitus (4). Neurological deficits were present in two cases (1 high- and 1 low-flow). Four cases were treated with vertebral artery segmental sacrifice alone, three required multiple transarterial embolizations with or without VA sacrifice, one case had single transvenous approach, and one was treated with single targeted transarterial embolization. One patient had a minor transient neurological complication. No treatment-related mortality was seen., Conclusion: Treatment of high-flow and symptomatic low-flow VVFs is feasible and safe. Our classification and treatment approach might help guide patient selection and choice of endovascular approach. However, our approach warrants further validation with a larger number of patients.

Objective: To evaluate the safety and effectiveness of the Flow Redirection Endoluminal Device (FRED) flow diverter in support of an application for Food and Drug Administration approval in the USA., Methods: 145 patients were enrolled in a prospective, single-arm multicenter trial. Patients with aneurysms of unfavorable morphology for traditional endovascular therapies (large, wide-necked, fusiform, etc) were included. The trial was designed to demonstrate non-inferiority in both safety and effectiveness, comparing trial results with performance goals (PGs) established from peer-reviewed published literature. The primary safety endpoint was death or major stroke (National Institutes of Health Stroke Scale score ≥4 points) within 30 days of the procedure, or any major ipsilateral stroke or neurological death within the first year. The primary effectiveness endpoint was complete occlusion of the target aneurysm with ≤50% stenosis of the parent artery at 12 months after treatment, and in which an alternative treatment of the target intracranial aneurysm had not been performed., Results: 145 patients underwent attempted placement of a FRED device, and one or more devices were placed in all 145 patients. 135/145 (93%) had a single device placed. Core laboratory adjudication deemed 106 (73.1%) of the aneurysms large or giant. A safety endpoint was experienced by 9/145 (6.2%) patients, successfully achieving the safety PG of <15%. The effectiveness PG of >46% aneurysm occlusion was also achieved, with the effectiveness endpoint being met in 80/139 (57.6%) CONCLUSION: As compared with historically derived performance benchmarks, the FRED flow diverter is both safe and effective for the treatment of appropriately selected intracranial aneurysms., Clinical Registration Number: NCT01801007., Competing Interests: Competing interests: CGM: consultant to Microvention and Medtronic OOD: proctor for FRED/Microvention. AB: consultant to Microvention and Vesalio. AHS:SNIS Board of Directors; current research grants: co-investigator: NIH/NINDS 1R01NS091075 Virtual intervention of intracranial aneurysms; role: co-principal investigator NIH-NINDS R21 NS109575-01 Optimizing approaches to endovascular therapy of acute ischemic stroke; financial interest: Adona Medical, Inc., Amnis Therapeutics, Bend IT Technologies, Ltd., BlinkTBI, Inc, Boston Scientific Corp (for purchase of Claret Medical), Buffalo Technology Partners, Inc., Cardinal Consultants, LLC, Cerebrotech Medical Systems, Inc, Cognition Medical, Endostream Medical, Ltd, Imperative Care, Inc., Instylla, Inc., International Medical Distribution Partners, IRRAS, LaunchNY Seed Fund Management, LLC, NeuroRadial Technologies, Inc., Neurovascular Diagnostics, Inc., Perflow Medical, Ltd., Q’Apel Medical, Inc., Radical Catheter Technologies, Inc., Rebound Therapeutics Corp. (purchased 2019 by Integra Lifesciences, Corp), Rist Neurovascular, Inc., Sense Diagnostics, Inc., Serenity Medical, Inc., Silk Road Medical, Spinnaker Medical, Inc., StimMed, Synchron, Three Rivers Medical, Inc., Truvic Medical, Inc, Vastrax, LLC, VICIS, Inc., Viseon, Inc., Viz.ai, Inc; consultant/advisory board: Amnis Therapeutics, Apellis Pharmaceuticals, Inc., Boston Scientific, Canon Medical Systems USA, Inc., Cerebrotech Medical Systems, Inc., Cerenovus, Corindus, Inc., Endostream Medical, Ltd, Imperative Care, Inc., Integra LifeSciences Corp., IRRAS, Medtronic, MicroVention, Minnetronix Neuro, Inc., Northwest University – Data Safety Monitoring Board chair for HEAT Trial, Penumbra, Perflow Medical, Ltd., Q’Apel Medical, Inc., Rapid Medical, Rebound Therapeutics Corp., Serenity Medical, Inc., Silk Road Medical, StimMed, Stryker, Three Rivers Medical, Inc., VasSol, Viz.ai, Inc., W.L. Gore & Associates; national PI/steering committees: Cerenovus NAPA Trial and ARISE II Trial; Medtronic SWIFT PRIME and SWIFT DIRECT Trials; MicroVention FRED Trial and CONFIDENCE Study; MUSC POSITIVE Trial; Penumbra 3D Separator Trial, COMPASS Trial, INVEST Trial;· No consulting salary arrangements. All consulting is per project and/or per hour. JC: No disclosures. JTF: SNIS Board of Directors; consultant to Microvention and Stryker. AST: consultant to Microvention, Medtronic, Viz AI, Siemens;.chief medical officer Imperative Care. YK: consultant to Microvention, Penumbra, Medtronic. PJ: consultant to Microvention, (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The incidence of internal carotid artery (ICA) injury associated with endoscopic endonasal approaches to the pituitary is less than 1%. While parent vessel sacrifice has historically been the choice of treatment, vessel-preserving endovascular techniques have been reported. Although flow diversion offers endoluminal reconstruction, its major limitation is the delay in obtaining complete occlusion. We describe the use of a combined Pipeline embolization device (PED) with endoscopic endonasal repair using a fascia lata/muscle graft to treat an iatrogenic ICA pseudoaneurysm and report long-term radiographic follow-up. Further investigation into the utility of directed endoscopic endonasal repair of iatrogenic pseudoaneurysms initially treated with PED is necessary, especially given the need of post-PED anticoagulation and the rate of permanent neurological deficit after ICA sacrifice., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

The predictive values of current risk stratification scales such as the Unruptured Intracranial Aneurysm Treatment Score (UIATS) and the PHASES score are debatable. We evaluated these scores using a cohort of ruptured intracranial aneurysms to simulate their management recommendations had the exact same patients presented prior to rupture. A prospectively maintained database of ruptured saccular aneurysm patients presenting to our institution was used. The PHASES score was calculated for 992 consecutive patients presenting between January 2002 and December 2018, and the UIATS was calculated for 266 consecutive patients presenting between January 2013 and December 2018. A shorter period was selected for the UIATS cohort given the larger number of variables required for calculation. Clinical outcomes were compared between UIATS-recommended "observation" aneurysms and all other aneurysms. Out of 992 ruptured aneurysms, 54% had a low PHASES score (≤5). Out of the 266 ruptured aneurysms, UIATS recommendations were as follows: 68 (26%) "observation," 97 (36%) "treatment," and 101 (38%) "non-definitive." The UIATS conservative group of patients developed more SAH-related complications (78% vs. 65%, p=0.043), had a higher rate of non-home discharge (74% vs. 46%, p<0.001), and had a greater incidence of poor functional status (modified Rankin scale >2) after 12-18 months (68% vs. 51%, p=0.014). Current predictive scoring systems for unruptured aneurysms may underestimate future rupture risk and lead to more conservative management strategies in some patients. Patients that would have been recommended for conservative therapy were more likely to have a worse outcome after rupture., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The contribution of specific immune cell populations to the post-hemorrhagic inflammatory response in aneurysmal subarachnoid hemorrhage (aSAH) and correlations with clinical outcomes, such as vasospasm and functional status, remains unclear. We aimed to compare the predictive value of leukocyte ratios that include monocytes as compared to the neutrophil-to-lymphocyte ratio (NLR) in aSAH. A prospectively accrued database of consecutive patients presenting to our institution with aSAH between January 2013 and December 2018 was used. Patients with signs and symptoms of infection (day 1-3) were excluded. Admission values of the NLR, monocyte-neutrophil-to-lymphocyte ratio (M-NLR), and lymphocyte-to-monocyte ratio (LMR) were calculated. Associations with functional status, the primary outcome, and vasospasm were evaluated using univariable and multivariable logistic regression analyses. In the cohort of 234 patients with aSAH, the M-NLR and LMR, but not the NLR, were significantly associated with poor functional status (modified Rankin scale > 2) at 12-18 months following discharge (p = 0.001, p = 0.023, p = 0.161, respectively). The area under the curve for predicting poor functional status was significantly lower for the NLR (0.543) compared with the M-NLR (0.603, p = 0.024) and LMR (0.608, p = 0.040). The M-NLR (OR = 1.01 [1.01-1.02]) and LMR (OR = 0.88 [0.78-0.99]) were independently associated with poor functional status while controlling for age, hypertension, Fisher grade, and baseline clinical status. The LMR was significantly associated with vasospasm (OR = 0.84 [0.70-0.99]) while adjusting for age, hypertension, Fisher grade, aneurysm size, and current smoking. Inflammatory indices that incorporate monocytes (e.g., M-NLR and LMR), but not those that include only neutrophils, predict outcomes after aSAH., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Efforts to develop effective neuroprotective therapies for ischemic stroke have had little success to date. One promising approach to neuroprotection is ischemic postconditioning, which utilizes brief bouts of ischemia after acute ischemic stroke to elicit neuroprotection, although the mechanism is largely unknown. As the primary components of transient ischemia are local hypoxia and acidosis, and hypoxic postconditioning has had little success, it is possible that the acidosis component may be the primary driver. To address the evidence behind this, we performed a systematic review of preclinical studies focused on the neuroprotective role of transient acidosis after ischemia. Animal studies demonstrated that mild-to-moderate acidosis after ischemic events led to better functional neurologic outcomes with reduced infarct volumes, while severe acidosis often led to cerebral edema and worse functional outcomes. In vitro studies demonstrated that mild-to-moderate acidosis improves neuronal survival largely through two means: (1) inhibition of harmful superoxide formation in the excitotoxic pathway and (2) remodeling neuronal mitochondria to allow for efficient ATP production (i.e., oxidative phosphorylation), even in the absence of oxygen. Similar to the animal studies, acidotic postconditioning in humans would entail short cycles of carbon dioxide inhalation, which has already been demonstrated to be safe as part of a hypercapnic challenge when measuring cerebrovascular reactivity. Due to the preclinical efficacy of acidotic postconditioning, its relatively straightforward translation into humans, and the growing need for neuroprotective therapies, future preclinical studies should focus on filling the current knowledge gaps that are currently restricting the development of phase I/II clinical trials., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: No randomized trial of intracranial aneurysm coiling has compared long-term efficacy of polymer-modified coils to bare metal coils (BMCs). We report 5-year results comparing Matrix 2 coils to BMCs. The primary objective was to compare the rates of target aneurysm recurrence (TAR) at 12 months. Secondary objectives included angiographic outcomes at TAR or 12 months and TAR at 5 years., Methods: A total of 626 patients were randomized to BMCs or Matrix 2 coils. Detailed methods and 1-year results have been published previously., Results: Of 580 patients eligible for 5-year follow-up, 431 (74.3%) completed follow-up or reached TAR. Matrix 2 coils were non-inferior to BMCs (P=0.8) but did not confer any benefit. Core lab reported post-treatment residual aneurysm filling (Raymond III) correlated with TAR (P<0.0001) and with aneurysm hemorrhage after treatment (P<0.008). Repeat aneurysmal hemorrhage after treatment, but before hospital discharge, occurred in three patients treated for acutely ruptured aneurysms. Additionally, two patients treated for unruptured aneurysms experienced a first hemorrhage during follow-up. All five hemorrhages resulted from aneurysms with Raymond III residual aneurysm filling persisting after initial treatment. After 5 years follow-up, 2/626 (0.3%) patients are known to have had target aneurysm rupture following hospital discharge. The annualized rate of delayed hemorrhage after coiling was 2/398/5=0.001 (0.1%) per year for unruptured aneurysms and 0 for ruptured aneurysms., Conclusions: After 5 years Matrix 2 coils were non-inferior to BMCs but no benefit was demonstrated. Post-treatment residual angiographic aneurysm filling (Raymond III) is strongly associated with TAR (P<0.0001) and post-treatment aneurysmal hemorrhage (P=0.008)., Competing Interests: Competing interests: SWH: core lab services for Stryker and MicroVention Terumo (money paid to UCSF, over $5K); consulting for Microvention Terumo (money paid to Dr Hetts, under $5K). CGM: consultant for Medtronic and Microvention. JCC: consultant for Stryker. AB: consultant for Stryker, Microvention, Balt, and Phenox. AKW: research grant from Philips Medical; serves as a consultant for Stryker and Phenox; is a stockholder of InNeuroCo, EpiEP, Neural Analytics, Rist, Analytics 4 Life, and ThrombX; and is on the Speakers’ Bureau for SCENT trial (Surpass Intracranial Aneurysm Embolization System Pivotal Trial to Treat Large or Giant Wide Neck Aneurysms) presentations. AG: consultant for Microvention and emeritus consultant at Newcastle upon Tyne Hospitals NHS Trust. CFD: chief adjudicator, Stryker EVOLVE Trial Core Angiography Lab (salary support to department)., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Concordance between the Unruptured Intracranial Aneurysm Treatment Score (UIATS), Earlier Subarachnoid Hemorrhage, Location, Age, Population, Size, Shape (ELAPSS) score, and Population, Hypertension, Age, Size, Earlier Subarachnoid Hemorrhage, Site (PHASES) score with real-world management decisions in unruptured intracranial aneurysms (UIAs) remains unclear, especially in current practice. This study aimed to investigate this concordance, while developing an optimal model predictive of recent decision practices at a quaternary referral center. A prospective database of patients presenting with UIAs to our institution from January 1 to December 31, 2018, was used. Concordance between the scores and real-world management decisions on every UIA was assessed. Complications and length of stay (LOS) were compared between aneurysms in the UIATS-recommended treatment and observation groups. A subgroup analysis of concordance was also conducted among junior and senior surgeons. An optimal logistic regression model predictive of real-world decisions was also derived. The cohort consisted of 198 patients with 271 UIAs, of which 42% were treated. The UIATS demonstrated good concordance with an AUC of 0.765. Of the aneurysms in the UIATS-recommended "observation" group, 22% were discordantly treated. The ELAPSS score demonstrated good discrimination (AUC = 0.793), unlike the PHASES score (AUC = 0.579). Endovascular treatment rates, complications, and LOS were similar between aneurysms in the UIATS-recommended treatment and observation groups. Similar concordance was obtained among junior and senior surgeons. The optimal predictive model consisted of several significantly associated variables and had an AUC of 0.942. Cerebrovascular specialists may be treating aneurysms slightly more than these scores would recommend, independently of years in practice. Wide variation still exists in management practices of UIAs.

Background: Cerebral vasospasm is a major source of morbidity and mortality following aneurysm rupture and has limited treatment options., Objective: To evaluate the role of programmed death-1 (PD-1) in cerebral vasospasm., Methods: Endovascular internal carotid artery perforation (ICAp) was used to induce cerebral vasospasm in mice. To evaluate the therapeutic potential of targeting PD-1, programmed death ligand-1 (PD-L1) was administered 1 h after ICAp and vasospasm was measured histologically at the level of the ICA bifurcation bilaterally. PD-1 expressing immune cell populations were evaluated by flow cytometry. To correlate these findings to patients and evaluate the potential of PD-1 as a biomarker, monocytes were isolated from the peripheral blood and analyzed by flow cytometry in a cohort of patients with ruptured cerebral aneurysms. The daily frequency of PD-1+ monocytes in the peripheral blood was correlated to transcranial Doppler velocities as well as clinical and radiographic vasospasm., Results: We found that PD-L1 administration prevented cerebral vasospasm by inhibiting ingress of activated Ly6c+ and CCR2+ monocytes into the brain. Human correlative studies confirmed the presence of PD-1+ monocytes in the peripheral blood of patients with ruptured aneurysms and the frequency of these cells corresponded with cerebral blood flow velocities and clinical vasospasm., Conclusion: Our results identify PD-1+ monocytes as mediators of cerebral vasospasm and support PD-1 agonism as a novel therapeutic strategy., (© Congress of Neurological Surgeons 2020.)

Background: Given increasing life expectancy in the United States and worldwide, the proportion of elderly patients affected by aneurysmal subarachnoid hemorrhage (aSAH) would be expected to increase., Objective: To determine whether an aging trend exists in the population of aSAH patients presenting to our institution over a 28-yr period., Methods: A prospectively maintained database of consecutive patients presenting to our institution with subarachnoid hemorrhage between January 1991 and December 2018 was utilized. The 28-yr period was categorized into 4 successive 7-yr quarter intervals. The age of patients was compared among these intervals, and yearly trends were derived using linear regression., Results: The cohort consisted of 1671 ruptured aneurysm patients with a mean age of 52.8 yr (standard deviation = 15.0 yr). Over the progressive 7-yr time intervals during the 28-yr period, there was an approximately 4-fold increase in the proportion of patients aged 80 yr or above (P < .001) and an increase in mean patient age from 51.2 to 54.6 yr (P = .002). Independent of this trend but along the same lines, there was a 29% decrease in the proportion of younger patients (<50 yr) from 49% to 35%. On linear regression, there was 1-yr increase in mean patient age per 5 calendar years (P < .001)., Conclusion: Analyses of aSAH patients demonstrate an increase in patient age over time with a considerable rise in the proportion of octogenarian patients and a decrease in patients younger than 50 yr. This aging phenomenon presents a challenge to the continued improvement in outcomes of aSAH patients., (© Congress of Neurological Surgeons 2020.)

The use of mechanical thrombectomy for the treatment of acute childhood arterial ischemic stroke with large vessel occlusion is increasing, with mounting evidence for its feasibility and safety. Despite this emerging evidence, clear guidelines for patient selection, thrombectomy technique, and postprocedure care do not exist for the pediatric population. Due to unique features of stroke in children, neurologists and interventionalists must consider differences in patient size, anatomy, collateral vessels, imaging parameters, and expected outcomes that may impact appropriate patient selection and timing criteria. In addition, different causes of stroke and comorbidities in children must be considered and may alter the safety and efficacy of thrombectomy. To optimize the success of endovascular intervention in children, a multidisciplinary team should take into account these nuanced considerations when determining patient eligibility, developing a procedural approach, and formulating a postprocedure neurological monitoring and therapeutic plan.

Objective: Although previous studies have explored factors that predict an academic career among neurosurgery residents in general, such predictors have yet to be determined within specific neurosurgical subspecialties. The authors report on predictors they identified as correlating with academic placement among fellowship-trained vascular neurosurgeons., Methods: A database was created that included all physicians who graduated from ACGME (Accreditation Council for Graduate Medical Education)-accredited neurosurgery residency programs between 1960 and 2018 using publicly available online data. Neurosurgeons who completed either open vascular or endovascular fellowships were identified. Subsequent employment of vascular or endovascular neurosurgeons in academic centers was determined. A position was considered academic if the hospital of employment was affiliated with a neurosurgery residency program; all other positions were considered non-academic. Bivariate analyses were conducted using Fisher's exact test or the Mann-Whitney U-test, and multivariate analysis was performed using a logistic regression model., Results: A total of 83 open vascular neurosurgeons and 115 endovascular neurosurgeons were identified. In both cohorts, the majority of neurosurgeons were employed in academic positions after training. In bivariate analysis, only 2 factors were significantly associated with a career in academic neurosurgery for open vascular neurosurgeons: 1) an h-index of ≥ 2 during residency (OR 3.71, p = 0.016), and 2) attending a top 10 residency program based on U.S. News and World Report rankings (OR 4.35, p = 0.030). In bivariate analysis, among endovascular neurosurgeons, having an h-index of ≥ 2 during residency (OR 4.35, p = 0.0085) and attending a residency program affiliated with a top 10 U.S. News and World Report medical school (OR 2.97, p = 0.029) were significantly associated with an academic career. In multivariate analysis, for both open vascular and endovascular neurosurgeons, an h-index of ≥ 2 during residency was independently predictive of an academic career. Attending a residency program affiliated with a top 10 U.S. News and World Report medical school independently predicted an academic career among endovascular neurosurgeons only., Conclusions: The authors report that an h-index of ≥ 2 during residency predicts pursuit of an academic career among vascular and endovascular neurosurgeons. Additionally, attendance of a residency program affiliated with a top research medical school independently predicts an academic career trajectory among endovascular neurosurgeons. This result may be useful to identify and mentor residents interested in academic vascular neurosurgery.

Background: Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke., Methods: For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1:1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0-1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018., Findings: Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups., Interpretation: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo., Funding: Canadian Institutes for Health Research, Alberta Innovates, and NoNO., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The Subarachnoid Hemorrhage International Trialists (SAHIT) repository is a collection of randomized clinical trials, prospective observational studies, and hospital registries that was used to create a predictive model of unfavorable outcome/mortality following aneurysmal SAH., Objective: To externally validate the SAHIT model using Barrow Ruptured Aneurysm Trial (BRAT) data, which was not included in the SAHIT repository., Methods: This is a post hoc analysis of the prospective, randomized BRAT. Three models were created: (1) Core (age, hypertension, World Federation of Neurosurgical Societies grade), (2) neuroimaging (aneurysm size/location, Fisher score), and (3) full model (model 1 and 2 plus treatment type). The performance of the models was evaluated by measures of model discrimination (area under the curve [AUC]) and model calibration (goodness of fit test, calibration in-the-large, calibration slope)., Results: A total of 338 patients (average age 54 years; 67.7% good clinical grade; average aneurysm size 6.7 mm; 84.1% anterior circulation) were included. Due to a large number of crossovers, more aneurysms were clipped than coiled (67.5% vs 32.5%, respectively). A total of 10.1% of the patients died and 29.6% experienced an unfavorable outcome. For unfavorable outcome, the AUCs for the three models were: 0.728, 0.732, and 0.734, respectively. For mortality, the AUCs for the three models were: 0.721, 0.739, and 0.744, respectively. Overall, all models showed good calibration, and the measures of calibration fell within 95% CI of those produced in the SAHIT study., Conclusion: Using the BRAT data, we have externally validated the SAHIT model for predicting unfavorable outcome and mortality after SAH. The model may be used to counsel patients and families on prognosis following aneurysmal SAH., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Background and Purpose- The management of unruptured brain arteriovenous malformations remains unclear. Using a large cohort to determine risk factors predictive of hemorrhagic presentation of arteriovenous malformations, this study aims to develop a predictive tool that could guide hemorrhage risk stratification. Methods- A database of 789 arteriovenous malformation patients presenting to our institution between 1990 and 2017 was used. A hold-out method of model validation was used, whereby the data was randomly split in half into training and validation data sets. Factors significant at the univariable level in the training data set were used to construct a model based on multivariable logistic regression. Model performance was assessed using receiver operating curves on the training, validation, and complete data sets. The predictors and the complete data set were then used to derive a risk prediction formula and a practical scoring system, where every risk factor was worth 1 point except race, which was worth 2 points (total score varies from 0 to 6). The factors are summarized by R 2 eD arteriovenous malformation (acronym: R 2 eD AVM). Results- In 755 patients with complete data, 272 (36%) presented with hemorrhage. From the training data set, a model was derived containing the following risk factors: nonwhite race (odds ratio [OR]=1.8; P=0.02), small nidus size (OR=1.47; P=0.14), deep location (OR=2.3; P<0.01), single arterial feeder (OR=2.24; P<0.01), and exclusive deep venous drainage (OR=2.07; P=0.02). Area under the curve from receiver operating curve analysis was 0.702, 0.698, and 0.685 for the training, validation, and complete data sets, respectively. In the entire study population, the predicted probability of hemorrhagic presentation increased in a stepwise manner from 16% for patients with no risk factors (score of 0) to 78% for patients having all the risk factors (score of 6). Conclusions- The final model derived from this study can be used as a predictive tool that supplements clinical judgment and aids in patient counseling.

Objective: The authors present the 10-year results of the Barrow Ruptured Aneurysm Trial (BRAT) for saccular aneurysms. The 1-, 3-, and 6-year results of the trial have been previously reported, as have the 6-year results with respect to saccular aneurysms. This final report comparing the safety and efficacy of clipping versus coiling is limited to an analysis of those patients presenting with subarachnoid hemorrhage (SAH) from a ruptured saccular aneurysm., Methods: In the study, 362 patients had saccular aneurysms and were randomized equally to the clipping and the coiling cohorts (181 each). The primary outcome analysis was based on the assigned treatment group; poor outcome was defined as a modified Rankin Scale (mRS) score > 2 and was independently adjudicated. The extent of aneurysm obliteration was adjudicated by a nontreating neuroradiologist., Results: There was no statistically significant difference in poor outcome (mRS score > 2) or deaths between these 2 treatment arms during the 10 years of follow-up. Of 178 clip-assigned patients with saccular aneurysms, 1 (< 1%) was crossed over to coiling, and 64 (36%) of the 178 coil-assigned patients were crossed over to clipping. After the initial hospitalization, 2 of 241 (0.8%) clipped saccular aneurysms and 23 of 115 (20%) coiled saccular aneurysms required retreatment (p < 0.001). At the 10-year follow-up, 93% (50/54) of the clipped aneurysms were completely obliterated, compared with only 22% (5/23) of the coiled aneurysms (p < 0.001). Two patients had documented rebleeding, both died, and both were in the assigned and treated coiled cohort (2/83); no patient in the clipped cohort (0/175) died (p = 0.04). In 1 of these 2 patients, the hemorrhage was not from the target aneurysm but from an incidental basilar artery aneurysm, which was coiled at the same time., Conclusions: There was no significant difference in clinical outcomes between the 2 assigned treatment groups as measured by mRS outcomes or deaths. Clinical outcomes in the patients with posterior circulation aneurysms were better in the coiling group at 1 year, but after 1 year this difference was no longer statistically significant. Rates of complete aneurysm obliteration and rates of retreatment favored patients who actually underwent clipping compared with those who underwent coiling.Clinical trial registration no.: NCT01593267 (clinicaltrials.gov).

The authors attempted to better delineate the natural course of untreated cerebral dural arteriovenous fistulas. For a group of 295 fistulas, drainage pattern was most important in predicting the risk of future neurological events or bleeding. Moreover, presentation with a neurological event or hemorrhage was an independent risk factor for future neurological events or hemorrhage, respectively. The authors provided hemorrhage rates for various subclasses of dural arteriovenous fistulas to facilitate risk stratification, excluding partially treated lesions.

Endovascular, endosaccular, coil embolization has emerged as an established therapy for both ruptured and unruptured cerebral aneurysms. However, many aneurysms are not cured using conventional endovascular techniques. Coil embolization often results in incomplete aneurysm occlusion or recanalization in the ensuing months after treatment. The Pipeline embolization device (PED; Chestnut Medical) represents a new generation endoluminal implant which is designed to treat aneurysms by reconstructing the diseased parent artery. Immediately after implantation, the PED functions to divert flow from the aneurysm, creating an environment conducive to thrombosis. With time, the PED is incorporated into the vessel wall as neointimal-endothelial overgrowth occurs along the construct. Ultimately, this process results in the durable complete exclusion of the aneurysm from the cerebrovasculature and a definitive endoluminal reconstruction of the diseased parent artery., Competing Interests: Competing interests: PN is a consultant and stockholder in Chestnut Medical., (© 2009, Society of NeuroInterventional Surgery.)

Intracranial endovascular interventions provide effective and minimally invasive treatment of a broad spectrum of diseases. This area of expertise has continued to gain both wider application and greater depth as new and better techniques are developed and as landmark clinical studies are performed to guide their use. Some of the greatest advances since the last American Heart Association scientific statement on this topic have been made in the treatment of ischemic stroke from large intracranial vessel occlusion, with more effective devices and large randomized clinical trials showing striking therapeutic benefit. The treatment of cerebral aneurysms has also seen substantial evolution, increasing the number of aneurysms that can be treated successfully with minimally invasive therapy. Endovascular therapies for such other diseases as arteriovenous malformations, dural arteriovenous fistulas, idiopathic intracranial hypertension, venous thrombosis, and neoplasms continue to improve. The purpose of the present document is to review current information on the efficacy and safety of procedures used for intracranial endovascular interventional treatment of cerebrovascular diseases and to summarize key aspects of best practice., Competing Interests: The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest., (© 2018 American Heart Association, Inc.)

OBJECTIVE Fusiform dolichoectatic vertebrobasilar aneurysms are rare, challenging lesions. The natural history of these lesions and medium- and long-term patient outcomes are poorly understood. The authors sought to evaluate patient prognosis after diagnosis of fusiform dolichoectatic vertebrobasilar aneurysms and to identify clinical and radiographic predictors of neurological deterioration. METHODS The authors reviewed multiple, prospectively maintained, single-provider databases at 3 large-volume cerebrovascular centers to obtain data on patients with unruptured, fusiform, basilar artery dolichoectatic aneurysms diagnosed between January 1, 2000, and January 1, 2015. RESULTS A total of 50 patients (33 men, 17 women) were identified; mean clinical follow-up was 50.1 months and mean radiographic follow-up was 32.4 months. At last follow-up, 42% (n = 21) of aneurysms had progressed and 44% (n = 22) of patients had deterioration of their modified Rankin Scale scores. When patients were dichotomized into 2 groups- those who worsened and those who did not-univariate analysis showed 5 variables to be statistically significantly different: sex (p = 0.007), radiographic brainstem compression (p = 0.03), clinical posterior fossa compression (p < 0.001), aneurysmal growth on subsequent imaging (p = 0.001), and surgical therapy (p = 0.006). A binary logistic regression was then created to evaluate these variables. The only variable found to be a statistically significant predictor of clinical worsening was clinical symptoms of posterior fossa compression at presentation (p = 0.01). CONCLUSIONS Fusiform dolichoectatic vertebrobasilar aneurysms carry a poor prognosis, with approximately one-half of the patients deteriorating or experiencing progression of their aneurysm within 5 years. Despite being high risk, intervention-when carefully timed (before neurological decline)-may be beneficial in select patients.

OBJECTIVE The Barrow Ruptured Aneurysm Trial (BRAT) is a prospective, randomized trial in which treatment with clipping was compared to treatment with coil embolization. Patients were randomized to treatment on presentation with any nontraumatic subarachnoid hemorrhage (SAH). Because all other randomized trials comparing these 2 types of treatments have been limited to saccular aneurysms, the authors analyzed the current BRAT data for this subgroup of lesions. METHODS The primary BRAT analysis included all sources of SAH: nonaneurysmal lesions; saccular, blister, fusiform, and dissecting aneurysms; and SAHs from an aneurysm associated with either an arteriovenous malformation or a fistula. In this post hoc review, the outcomes for the subgroup of patients with saccular aneurysms were further analyzed by type of treatment. The extent of aneurysm obliteration was adjudicated by an independent neuroradiologist not involved in treatment. RESULTS Of the 471 patients enrolled in the BRAT, 362 (77%) had an SAH from a saccular aneurysm. Patients with saccular aneurysms were assigned equally to the clipping and the coiling cohorts (181 each). In each cohort, 3 patients died before treatment and 178 were treated. Of the 178 clip-assigned patients with saccular aneurysms, 1 (1%) was crossed over to coiling, and 64 (36%) of the 178 coil-assigned patients were crossed over to clipping. There was no statistically significant difference in poor outcome (modified Rankin Scale score > 2) between these 2 treatment arms at any recorded time point during 6 years of follow-up. After the initial hospitalization, 1 of 241 (0.4%) clipped saccular aneurysms and 21 of 115 (18%) coiled saccular aneurysms required retreatment (p < 0.001). At the 6-year follow-up, 95% (95/100) of the clipped aneurysms were completely obliterated, compared with 40% (16/40) of the coiled aneurysms (p < 0.001). There was no difference in morbidity between the 2 treatment groups (p = 0.10). CONCLUSIONS In the subgroup of patients with saccular aneurysms enrolled in the BRAT, there was no significant difference between modified Rankin Scale outcomes at any follow-up time in patients with saccular aneurysms assigned to clipping compared with those assigned to coiling (intent-to-treat analysis). At the 6-year follow-up evaluation, rates of retreatment and complete aneurysm obliteration significantly favored patients who underwent clipping compared with those who underwent coiling. Clinical trial registration no.: NCT01593267 (clinicaltrials.gov).

Object: Despite the popularity of flow-diverting stents for the treatment of cerebral aneurysms, there is no widely accepted scale for the characterization of results. We present an outcomes-based grading scale that considers factors related to failure of flow diversion., Methods: The grading scale was developed using the results from consecutive patients at two institutions who were treated with flow diversion for a cerebral aneurysm. The initial treatment results were graded on patient, aneurysm, and treatment characteristics. A 6-point grading scale was developed based on these data., Results: One hundred and seventy-one patients were included in the patient cohort. When compared by multivariate analysis with patients without residuals, patients with aneurysm residuals were found to be older (age ≥60 years, p=0.01, OR 1.17, 95% CI 1.03 to 1.33), to have larger aneurysms (size ≥15 mm, p<0.01, OR 1.38, 95% CI 1.17 to 1.62), to have aneurysms with associated side branches (p=0.02, OR 1.17, 95% CI 1.03 to 1.33), and to have a post-treatment Raymond score of 2 or 3 (p=0.01, OR 1.28, 95% CI 1.06 to 1.56). Using the Raymond score (1-3) as the foundation for the grading scale, additional points (0 or 1) were given for the other three identified factors, creating a 6-point scale. We found that patients with residual aneurysms had statistically higher final tabulated scores (p<0.01)., Conclusions: We propose a novel straightforward outcomes-based scale to characterize results after flow diversion treatment of cerebral aneurysms. This scale may provide the basis for the common reporting of results in future studies., Competing Interests: Competing interests: PT is a consultant for Covidien and proctors physicians in the use of the PED., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Introduction: Endovascular intervention for cervical carotid artery dissection (CAD) and vertebral artery dissection (VAD) may be indicated in specific circumstances., Objective: To review our institutional experience with endovascular treatment of cervical dissections over the past 20 years to examine indications for treatment, interventional methods, and outcomes., Methods: Retrospective review of a prospectively maintained database to identify patients with extracranial dissection who underwent endovascular intervention between January 1996 and January 2016. Demographic data and details of procedures, outcomes, and complications were extracted., Results: Of 116 patients [93 CAD, 23 VAD; mean age 44.9 years (range 5-76 years)], 104 underwent stent placement; 11, coil occlusion of the parent artery; and 1, stenting with contralateral vessel occlusion. The cohorts were well matched for age, sex, dissection etiology, and admission and follow-up modified Rankin Scale (mRS) scores. Patients with CAD had significantly more stent placements (p<0.001), failure of medical therapy (p=0.004), and interventions for enlarging pseudoaneurysms (p=0.01) or thromboembolic events (p=0.004). Patients with VAD had significantly more interventions for traumatic occlusion with recanalization (p<0.001). Dissections were spontaneous (n=67), traumatic (n=36), or iatrogenic (n=13). Traumatic dissections in patients with CAD were associated with poor admission mRS scores (p=0.01). Six of 67 (9.0%) patients with spontaneous dissection reported recent chiropractic manipulation. Mean follow-up was 3.5 years (range 1-146 months). Permanent morbidity/mortality was 3.4%, including two deaths. Over a follow-up period of 364 patient-years, 1 stroke occurred (0.27% per year). At last follow-up, 41 previously disabled patients [CAD, 31/93 (33.3%); VAD, 10/23 (43.5%)] were no longer disabled; no patient reported worsened disability., Conclusions: Patients with CAD and VAD differ significantly in presentation, indications for treatment, and treatment methods. Endovascular treatment of CAD and VAD has low procedural morbidity and is associated with a low incidence of future stroke., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Approximately 17% of ruptured anterior communicating artery (ACoA) aneurysms were deemed unsuitable for coil embolization during the Barrow Ruptured Aneurysm Trial (BRAT), most commonly due to unfavorable dome-to-neck ratio or small size., Objective: To compare patients treated by coil embolization for ruptured ACoA aneurysms during the trial to those treated after the trial to determine whether advances in endovascular techniques have allowed for effective treatment of these lesions., Methods: All cases of ruptured ACoA aneurysms treated by endovascular modalities during BRAT (2003-2007) and post-BRAT (2007-2012) were reviewed for patient and aneurysm characteristics, treatment types, and clinical and angiographic outcomes at 3-yr or last follow-up., Results: The BRAT ACoA cohort included 39 patients treated with coiling (excluding those crossed over to clipping). The post-BRAT cohort included 93 patients who were significantly older (mean age, 59.5 vs 52.8 yr, P = .005) than the BRAT cohort; there were no significant cohort differences in sex, Hunt and Hess grade, or mean aneurysm size. The use of balloon remodeling was significantly higher in the post-BRAT cohort (31.2% [29/93] vs 5.1% [2/39], P = .001), as was the proportion of wide-necked aneurysms treated (66.7% [62/93] vs 30.8% [12/39], P < .001). There was no significant difference in clinical outcome or retreatment rate between the 2 cohorts (P = .90 and P = .48, respectively)., Conclusion: ACoA lesions thought unamenable to endovascular therapy in an earlier randomized trial are now successfully coiled with increased use of adjunctive techniques, without sacrificing patient outcome or treatment durability., (Copyright © 2016 by the Congress of Neurological Surgeons.)

OBJECTIVE The authors performed a pooled analysis of 3 studies-IntrePED (International Retrospective Study of the Pipeline Embolization Device), PUFS (Pipeline for Uncoilable or Failed Aneurysms Study), and ASPIRe (Aneurysm Study of Pipeline in an Observational Registry)-in order to assess angiographic outcomes and clinical safety of the Pipeline embolization device (PED). METHODS IntrePED was a retrospective study, while PUFS and ASPIRe were prospective studies. For each patient included in these studies, the authors collected baseline demographic data, aneurysm characteristics, and procedural details. The primary outcomes for this combined analysis were clinical outcomes, including neurological morbidity and mortality and major ipsilateral intracranial hemorrhage and ischemic stroke. The secondary outcomes were angiographic occlusion rates, which were available for ASPIRe and PUFS only. RESULTS A total of 1092 patients with 1221 aneurysms were included across the 3 studies. The mean aneurysm size was 12.0 ± 7.8 mm and the mean neck size was 6.6 ± 4.8 mm. The major ipsilateral ischemic stroke rate was 3.7% (40/1091). The major ipsilateral intracranial hemorrhage rate was 2.0% (22/1091). The major neurological morbidity rate was 5.7% (62/1091). The neurological mortality rate was 3.3% (36/1091). The combined major morbidity and neurological mortality rate was 7.1% (78/1091). The complete occlusion rates were 75.0% at 180 days (111/148) and 85.5% at 1 year (94/110). The overall aneurysm retreatment rate was 3.0% (33/1091) at a mean follow-up time of 10.2 ± 10.8 months. CONCLUSIONS Endovascular treatment of intracranial aneurysms with the PED is safe and effective. Angiographic occlusion rates progressed with follow-up. Rates of stroke, hemorrhage, morbidity and mortality, and retreatment were low, especially given the fact that the aneurysms treated were generally large and wide necked.

OBJECTIVE The long-term effectiveness of endovascular treatment of large and giant wide-neck aneurysms using traditional endovascular techniques has been disappointing, with high recanalization and re-treatment rates. Flow diversion with the Pipeline Embolization Device (PED) has been recently used as a stand-alone therapy for complex aneurysms, showing significant improvement in effectiveness while demonstrating a similar safety profile to stent-supported coil treatment. However, relatively little is known about its long-term safety and effectiveness. Here the authors report on the 3-year safety and effectiveness of flow diversion with the PED in a prospective cohort of patients with large and giant internal carotid artery aneurysms enrolled in the Pipeline for Uncoilable or Failed Aneurysms (PUFS) trial. METHODS The PUFS trial is a prospective study of 107 patients with 109 aneurysms treated with the PED. Primary effectiveness and safety end points were demonstrated based on independently monitored 180-day clinical and angiographic data. Patients were enrolled in a long-term follow-up protocol including 1-, 3-, and 5-year clinical and imaging follow-up. In this paper, the authors report the midstudy (3-year) effectiveness and safety data. RESULTS At 3 years posttreatment, 74 subjects with 76 aneurysms underwent catheter angiography as required per protocol. Overall, complete angiographic aneurysm occlusion was observed in 71 of these 76 aneurysms (93.4% cure rate). Five aneurysms were re-treated, using either coils or additional PEDs, for failure to occlude, and 3 of these 5 were cured by the 3-year follow-up. Angiographic cure with one or two treatments of Pipeline embolization alone was therefore achieved in 92.1%. No recanalization of a previously completely occluded aneurysm was noted on the 3-year angiograms. There were 3 (2.6%) delayed device- or aneurysm-related serious adverse events, none of which led to permanent neurological sequelae. No major or minor late-onset hemorrhagic or ischemic cerebrovascular events or neurological deaths were observed in the 6-month through 3-year posttreatment period. Among 103 surviving patients, 85 underwent functional outcome assessment in which modified Rankin Scale scores of 0-1 were demonstrated in 80 subjects. CONCLUSIONS Pipeline embolization is safe and effective in the treatment of complex large and giant aneurysms of the intracranial internal carotid artery. Unlike more traditional endovascular treatments, flow diversion results in progressive vascular remodeling that leads to complete aneurysm obliteration over longer-term follow-up without delayed aneurysm recanalization and/or growth. Clinical trial registration no.: NCT00777088 (clinicaltrials.gov).

OBJECTIVE Many small series and technical reports chronicle the evolution of endovascular techniques for cranial dural arteriovenous fistulas (dAVFs) over the past 3 decades, but reports of large patient series are lacking. The authors provide a thorough analysis of clinical and angiographic outcomes across a large patient cohort. METHODS The authors reviewed their endovascular database from January 1996 to September 2015 to identify patients harboring cranial dAVFs who were treated initially with endovascular approaches. They extracted demographic, presentation, angiographic, detailed treatment, and long-term follow-up data, and they evaluated natural history, initial angiographic occlusion, complications, recurrence, and symptomatic resolution rates. RESULTS Across a cohort of 251 patients with 260 distinct dAVFs, the overall initial angiographic occlusion rate was 70%; recurrence or occult residual lesions were seen on subsequent angiography in 3% of cases. The overall complication rate was 8%, with permanent neurological complications occurring in 3% of cases. Among 102 patients with dAVFs without cortical venous reflux, rates of resolution/improvement of pulsatile tinnitus and ocular symptoms were 79% and 78%, respectively. Following the introduction of Onyx during the latter half of the study period, the number of treated dAVFs doubled; the initial angiographic occlusion rate increased significantly from 60% before the use of Onyx to 76% after (p = 0.01). In addition, during the latter period compared with the pre-Onyx period, the rate of dAVFs obliterated via a transarterial-only approach was significantly greater (43% vs 23%, p = 0.002), as was the number of dAVFs obliterated via a single arterial pedicle (29% vs 11%, p = 0.002). CONCLUSIONS Overall, in the Onyx era, the rate of initial angiographic occlusion was approximately 80%, as was the rate of meaningful clinical improvement in tinnitus and/or ocular symptoms after initial endovascular treatment of cranial dAVFs.

OBJECTIVE Flow diversion has proven to be an efficacious means of treating cerebral aneurysms that are refractory to other therapeutic means. Patients with tandem aneurysms treated with flow diversion have been included in larger, previously reported series; however, there are no dedicated reports on using this technique during a single session to treat this unique subset of patients. Therefore, the authors analyzed the outcomes of patients who had undergone single-session flow diversion for the treatment of tandem aneurysms. METHODS The authors conducted a retrospective review of flow diversion with the Pipeline embolization device (PED) for the treatment of tandem aneurysms in a single session at 2 participating medical centers: University of Utah, Salt Lake City, Utah, and Barrow Neurological Institute, Phoenix, Arizona. Patient demographic data, aneurysm characteristics, treatment strategy and results, complications, and follow-up data were collected from the medical record and analyzed. RESULTS Between January 2011 and December 2015, 17 patients (12 female, 5 male) with a total of 38 aneurysms (mean size 4.7 ± 2.7 mm, mean ± SD) were treated. Sixteen patients had aneurysms in the anterior circulation, and 1 patient had tandem aneurysms in the posterior circulation. Twelve patients underwent only placement of a PED, whereas 5 underwent adjunctive coil embolization of at least 1 aneurysm. One PED was used in each of 9 patients, and 2 PEDs were required in each of 8 patients. There were 2 intraprocedural complications; however, in both instances, the patients were asymptomatic at the last follow-up. The follow-up imaging studies were available for 15 patients at a mean of 7 months after treatment (216 days, range 0-540 days). The mean initial Raymond score after treatment was 2.7 ± 0.7, and the mean final score was 1.3 ± 0.7. CONCLUSIONS In this series, the use of flow diversion for the treatment of tandem cerebral aneurysms had an acceptable safety profile, indicating that it should be considered as an effective therapy for this complicated subset of patients. Further prospective studies must be performed before more definitive conclusions can be made.

Background/objective: The optimal management of residual or recurrent clipped aneurysms is infrequently addressed in the literature., Methods: We reviewed our endovascular database from January 1998 to May 2016 to identify patients with clipped aneurysms undergoing subsequent endovascular treatment, evaluating treatment approach, and clinical and angiographic outcomes., Results: 60 patients underwent endovascular treatment of residual/recurrent clipped aneurysms; 7 rebled prior to endovascular therapy. Treatment was via coiling alone (n=25, 42%), stent assisted coiling (n=15, 25%), balloon assisted coiling (n=8, 13%), flow diversion (n=8, 13%), stenting alone (n=3, 5%), or flow diversion with coiling (n=1, 2%). The procedural permanent neurological morbidity and mortality rates were 3% and 2%, respectively. Over a clinical follow-up of 253.4 patient years (median 3.9 years), there was one rebleed in a patient who had declined further treatment. For 43 patients with at least 1 month of digital subtraction angiographic follow-up (median 3.4 years), complete aneurysm occlusion was seen in 79% of cases. Neck remnants were observed in 14%, and stable small dome remnants were observed in 7% of cases. In a subgroup of 18 patients with 'clip induced' narrow neck aneurysms, all domes were initially coil occluded (Raymond 1 or 2); there was no permanent procedural morbidity and no aneurysms required retreatment or recanalized over a median follow-up of 3.9 years., Conclusions: Endovascular treatment of residual or recurrent clipped aneurysms is an excellent treatment approach in well selected patients; 'clip induced' narrow neck aneurysms fare particularly well after treatment both angiographically and clinically., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

OBJECTIVE Aneurysmal subarachnoid hemorrhage (aSAH) may be complicated by hydrocephalus in 6.5%-67% of cases. Some patients with aSAH develop shunt dependency, which is often managed by ventriculoperitoneal shunt placement. The objectives of this study were to review published risk factors for shunt dependency in patients with aSAH, determine the level of evidence for each factor, and calculate the magnitude of each risk factor to better guide patient management. METHODS The authors searched PubMed and MEDLINE databases for Level A and Level B articles published through December 31, 2014, that describe factors affecting shunt dependency after aSAH and performed a systematic review and meta-analysis, stratifying the existing data according to level of evidence. RESULTS On the basis of the results of the meta-analysis, risk factors for shunt dependency included high Fisher grade (OR 7.74, 95% CI 4.47-13.41), acute hydrocephalus (OR 5.67, 95% CI 3.96-8.12), in-hospital complications (OR 4.91, 95% CI 2.79-8.64), presence of intraventricular blood (OR 3.93, 95% CI 2.80-5.52), high Hunt and Hess Scale score (OR 3.25, 95% CI 2.51-4.21), rehemorrhage (OR 2.21, 95% CI 1.24-3.95), posterior circulation location of the aneurysm (OR 1.85, 95% CI 1.35-2.53), and age ≥ 60 years (OR 1.81, 95% CI 1.50-2.19). The only risk factor included in the meta-analysis that did not reach statistical significance was female sex (OR 1.13, 95% CI 0.77-1.65). CONCLUSIONS The authors identified several risk factors for shunt dependency in aSAH patients that help predict which patients are likely to require a permanent shunt. Although some of these risk factors are not independent of each other, this information assists clinicians in identifying at-risk patients and managing their treatment.

OBJECTIVE Cerebral venous pressure gradient (CVPG) from dural venous sinus stenosis is implicated in headache syndromes such as idiopathic intracranial hypertension (IIH). The incidence of CVPG in headache patients has not been reported. METHODS The authors reviewed all cerebral venograms with manometry performed for headache between January 2008 and May 2015. Patient demographics, headache etiology, intracranial pressure (ICP) measurements, and radiographic and manometric results were recorded. CVPG was defined as a difference ≥ 8 mm Hg by venographic manometry. RESULTS One hundred sixty-four venograms were performed in 155 patients. There were no procedural complications. Ninety-six procedures (58.5%) were for patients with IIH. The overall incidence of CVPG was 25.6% (42 of 164 procedures): 35.4% (34 of 96 procedures) in IIH patients and 11.8% (8 of 68 procedures) in non-IIH patients. Sixty procedures (36.6%) were performed in patients with preexisting shunts. Seventy-seven patients (49.7%) had procedures preceded by an ICP measurement within 4 weeks of venography, and in 66 (85.7%) of these patients, the ICP had been found to be elevated. CVPG was seen in 8.3% (n = 5) of the procedures in the 60 patients with a preexisting shunt and in 0% (n = 0) of the 11 procedures in the 77 patients with normal ICP (p < 0.001 for both). Noninvasive imaging (MR venography, CT venography) was assessed prior to venography in 112 (68.3%) of 164 cases, and dural venous sinus abnormalities were demonstrated in 73 (65.2%) of these cases; there was a trend toward CVPG (p = 0.07). Multivariate analysis demonstrated an increased likelihood of CVPG in patients with IIH (OR 4.97, 95% CI 1.71-14.47) and a decreased likelihood in patients with a preexisting shunt (OR 0.09, 95% CI 0.02-0.44). CONCLUSIONS CVPG is uncommon in IIH patients, rare in those with preexisting shunts, and absent in those with normal ICP.

Background/objective: Spinal dural arteriovenous fistulas (SDAVFs) require pretreatment angiography; embolization can be performed in the same session. To validate this approach, obliteration and morbidity rates of 'endovascular-first' (embolization and microsurgery in the case of embolization failures) must be compared with rates for 'microsurgery-first' (microsurgical ligation without attempted embolization) approaches., Methods: We reviewed our institutional database (January 1998-October 2015) for SDAVFs, performing an intention-to-treat analysis comparing endovascular-first and microsurgery-first approaches., Results: A total of 71 patients underwent surgical and/or endovascular treatment for SDAVFs. All SDAVFs were ultimately occluded. Of 35 patients under consideration for an endovascular-first approach, radicular artery anatomy or anterior spinal artery embolization risk precluded attempting embolization in seven cases (20%). Among 28 patients undergoing embolization, angiographic non-opacification of the fistula was noted in 18 (64%). Fourteen patients had obliteration with excellent casting of the draining vein (50%) and did not undergo surgery. There were no significant differences in total complications (9% vs 11%; p=1.0) or permanent complications (3% vs 4%; p=1.0) after attempted endovascular and surgical treatment. Based on an intention-to-treat analysis, there were no significant differences in total complications (11% vs 14%; p=1.0), permanent complications (6% vs 3%; p=0.61), or the symptomatic resolution/improvement rate (80% vs 78%; p=1.0) between endovascular-first and microsurgery-first groups., Conclusions: Our results support attempted embolization of SDAVFs prior to consideration of microsurgery, allowing for a less invasive treatment option in the same session as diagnostic angiography., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: With the introduction of Onyx, transarterial embolization has become the most common endovascular approach to treating dural arteriovenous fistulas (dAVFs), often via the middle meningeal or occipital arteries. The ascending pharyngeal artery (APA) is a less frequently explored transarterial route because of its small caliber, potential anastomoses to the internal carotid and vertebral arteries, and vital supply to lower cranial nerves., Objective: To review our institutional experience and highlight the prevalence of APA supply to dAVFs and cases where it is a safe and effective pedicle for embolization., Methods: We reviewed our endovascular database (January 1, 1996 to March 1, 2016) for cranial dAVFs, evaluating dAVF characteristics and embolization results for those treated transarterially via the APA., Results: Of 267 endovascularly treated dAVFs, 68 had APA supply (25%). Of these 68 dAVFs, embolization was carried out via this pedicle in 8 (12%) and 7 were ultimately occluded. No complications, including post-treatment cranial neuropathies or radiographic evidence of non-target embolization, were found. For 5 dAVFs, the APA was selected as the initial pedicle for embolization (two marginal sinus, one distal sigmoid, one cavernous, one tentorial). In four of these five cases, dAVF occlusion was achieved via the initial APA feeding artery pedicle. In one case, near-complete, stagnant occlusion was achieved after APA embolization; complete occlusion was achieved after adjunctive embolization of a single additional middle meningeal artery pedicle. In three other cases of complex transverse/sigmoid dAVFs, the APA was used after multiple attempts via middle meningeal and occipital artery pedicles. Occlusion was not achieved transarterially; two of these three dAVFs were ultimately occluded transvenously., Conclusions: In rare, select cases, the APA is an excellent route for transarterial embolization of cranial dAVFs., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Arteriovenous malformation (AVM) embolization can serve as a crucial adjunct before surgical resection, a partial approach to target high-risk features, or, rarely, as a curative approach for high-risk, surgically inaccessible lesions. Specifically, embolization is a welcome surgical adjunct to reduce the size of medium to large AVMs, to target perforator supply, and/or to target the deep portion of a nidus. In addition, a crucial role for embolization is the targeting of associated aneurysms, particularly in the setting of a ruptured lesion, regardless of the subsequent therapeutic modality. Rarely, a deep, small ruptured AVM that cannot be accessed surgically may be embolized with intent to cure. This chapter will review patient selection, technical nuances, and published results for AVM embolization. With appropriate patient selection and well-defined goals of embolization, the risk of procedural morbidity can be outweighed by its benefit., (Copyright © 2017 Cameron G. McDougall. Published by Elsevier B.V. All rights reserved.)

Patients with cavernous carotid fistulas (CCFs) can present with pituitary hypoperfusion and hypopituitarism; however, there are no previous reports of pituitary or hormonal abnormalities developing after CCF embolisation in an asymptomatic patient. We describe a patient with no hormonal abnormalities who developed syndrome of inappropriate antidiuretic hormone (SIADH) secretion after CCF embolisation. The patient had bilateral indirect CCFs, which were completely embolised via a transvenous approach, and was neurologically stable postoperatively and discharged. In the subsequent 2 weeks the patient was readmitted twice for acute hyponatraemia and a tonic-clonic seizure. Laboratory studies revealed severe SIADH. Clinical status and sodium levels improved after treatment. One year later the patient was weaned off all medications and remained neurologically stable. SIADH may be a delayed phenomenon after CCF embolisation. Given the proximity of embolised vessels to the pituitary's vascular supply, CCF treatment may result in flow disturbance, ischaemia and hormonal abnormalities., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Early and mid-term safety and efficacy of aneurysm treatment with the Pipeline Embolization Device (PED) has been well demonstrated in prior studies., Objective: To present 5-yr follow-up for patients treated in the Pipeline for Uncoilable or Failed Aneurysms clinical trial., Methods: In our prospective, multicenter trial, 109 complex internal carotid artery (ICA) aneurysms in 107 subjects were treated with the PED. Patients were followed per a standardized protocol at 180 d and 1, 3, and 5 yr. Aneurysm occlusion, in-stent stenosis, modified Rankin Scale scores, and complications were recorded., Results: The primary endpoint of complete aneurysm occlusion at 180 d (73.6%) was previously reported. Aneurysm occlusion for those patients with angiographic follow-up progressively increased over time to 86.8% (79/91), 93.4% (71/76), and 95.2% (60/63) at 1, 3, and 5 yr, respectively. Six aneurysms (5.7%) were retreated. New serious device-related events at 1, 3, and 5 yr were noted in 1% (1/96), 3.5% (3/85), and 0% (0/81) of subjects. There were 4 (3.7%) reported deaths in our trial. Seventy-eight (96.3%) of 81 patients with 5-yr clinical follow-up had modified Rankin Scale scores ≤2. No delayed neurological deaths or hemorrhagic or ischemic cerebrovascular events were reported beyond 6 mo. No recanalization of a previously occluded aneurysm was observed., Conclusion: Our 5-yr findings demonstrate that PED is a safe and effective treatment for large and giant wide-necked aneurysms of the intracranial ICA, with high rates of complete occlusion and low rates of delayed adverse events., (Copyright © 2016 by the Congress of Neurological Surgeons)

Idiopathic intracranial hypertension (IIH) occurs rarely, with severe patients recalcitrant to pharmacologic management often requiring cerebrospinal fluid diversion. We report two patients with variant IIH successfully treated with venous sinus stenting: 1) A 65-year-old man with severe vision loss, papilledema, and cognitive decline treated with four telescoped stents across a long, severely stenotic transverse-sigmoid system, and 2) a 58-year-old woman with headaches, vision loss, and papilledema secondary to a jugular paraganglioma causing severe jugular bulb stenosis that required contralateral venous sinus stenting. At 3-month and 1-month follow-up, respectively, ophthalmologic examinations showed vision improvement. The first patient also had improved cognition, and the second patient also had improved headaches., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background and Purpose: Idiopathic intracranial hypertension has been associated with dural venous sinus stenosis in some patients, but the hemodynamic environment of the dural venous sinuses has not been quantitatively described. Here, we present the first such computational fluid dynamics model by using patient-specific blood pressure measurements., Materials and Methods: Six patients with idiopathic intracranial hypertension and at least 1 stenosis or atresia at the transverse/sigmoid sinus junction underwent MR venography followed by cerebral venography and manometry throughout the dural venous sinuses. Patient-specific computational fluid dynamics models were created by using MR venography anatomy, with venous pressure measurements as boundary conditions. Blood flow and wall shear stress were calculated for each patient., Results: Computational models of the dural venous sinuses were successfully reconstructed in all 6 patients with patient-specific boundary conditions. Three patients demonstrated a pathologic pressure gradient (≥8 mm Hg) across 4 dural venous sinus stenoses. Small sample size precludes statistical comparisons, but average overall flow throughout the dural venous sinuses of patients with pathologic pressure gradients was higher than in those without them (1041.00 ± 506.52 mL/min versus 358.00 ± 190.95 mL/min). Wall shear stress was also higher across stenoses in patients with pathologic pressure gradients (37.66 ± 48.39 Pa versus 7.02 ± 13.60 Pa)., Conclusions: The hemodynamic environment of the dural venous sinuses can be computationally modeled by using patient-specific anatomy and physiologic measurements in patients with idiopathic intracranial hypertension. There was substantially higher blood flow and wall shear stress in patients with pathologic pressure gradients., (© 2016 by American Journal of Neuroradiology.)