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Objective: The objective of this study was to identify place features associated with increased risk of drug-involved fatalities and generate a composite score measuring risk based on the combined effects of features of the built environment., Methods: We conducted a geospatial analysis of overdose data from 2022 to 2023 provided by the St. Louis County Medical Examiner's Office to test whether drug-involved deaths were more likely to occur near 54 different place features using Risk Terrain Modeling (RTM). RTM was used to identify features of the built environment that create settings of heightened overdose risk. Risk was estimated using Relative Risk Values (RRVs) and a composite score measuring Relative Risk Scores (RRS) across the county was produced for drugs, opioids, and stimulants, as well as by Black and White decedents., Results: In the model including all drugs, deaths were more likely to occur in close proximity to hotels/motels (RRV=39.65, SE=0.34, t-value=10.81 p<.001), foreclosures (RRV=4.42, SE=0.12, t-value = 12.80, p<.001), police departments (RRV=3.13, SE=0.24, t-score=4.86, p<.001), and restaurants (RRV=2.33, SE=0.12, t-value=7.16, p<.001). For Black decedents, deaths were more likely to occur near foreclosures (RRV=9.01, SE=0.18, t-value =11.92, p<.001), and places of worship (RRV= 2.51, SE=0.18, t-value = 11.92, p<.001). For White decedents, deaths were more likely to occur in close proximity to hotels/motels (RRV=38.97, SE=0.39, t-value=9.30, p<.001) foreclosures (RRV=2.57, SE=0.16, t-value =5.84, p<.001), restaurants (RRV=2.52, SE=0.17, t-value=5.33, p<.001) and, auto painting/repair shops (RRV=0.04, SE=0.18, t-value =3.39, p<.001)., Conclusion: These findings suggest that places of worship, the hospitality industry, and housing authorities may be physical features of the environment that reflect social conditions that are conducive to overdose. The scaling up of harm reduction strategies could be enhanced by targeting places where features are co-located., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Non-Hispanic Black (NHB) patients experience increased prevalence of stroke risk factors and stroke incidence compared with non-Hispanic White (NHW) patients. However, little is known about >90-day post-stroke functional outcomes following mechanical thrombectomy., Objective: To describe patient characteristics, evaluate stroke risk factors, and analyze the adjusted impact of race on long-term functional outcomes to better identify and limit sources of disparity in post-stroke care., Methods: We retrospectively reviewed 326 patients with ischemic stroke who underwent thrombectomy at two centers between 2019 and 2022. Race was self-reported as NHB, NHW, or non-Hispanic Other. Stroke risk factors, insurance status, procedural parameters, and post-stroke functional outcomes were collected. Good outcomes were defined as modified Rankin Scale score ≤2 and/or discharge disposition to home/self-care. To assess the impact of race on outcomes at 3-, 6-, and 12-months' follow-up, we performed univariate and multivariate logistic regression., Results: Patients self-identified as NHB (42%), NHW (53%), or Other (5%). 177 (54.3%) patients were female; the median (IQR) age was 67.5 (59-77) years. The median (IQR) National Institutes of Health Stroke Scale score was 15 (10-20). On univariate analysis, NHB patients were more likely to have poor short- and long-term functional outcomes, which persisted on multivariate analysis as significant at 3 and 6 months but not at 12 months (3 months: OR=2.115, P=0.04; 6 months: OR=2.423, P=0.048; 12 months: OR=2.187, P=0.15). NHB patients were also more likely to be discharged to rehabilitation or hospice/death than NHW patients after adjusting for confounders (OR=1.940, P=0.04)., Conclusions: NHB patients undergoing thrombectomy for ischemic stroke experience worse 3- and 6-month functional outcomes than NHW patients after adjusting for confounders. Interestingly, this disparity was not detected at 12 months. Future research should focus on identifying social determinants in the short-term post-stroke recovery period to improve parity in stroke care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Postoperative stroke is a potentially devastating neurological complication following surgical revascularization for Moyamoya disease. We sought to evaluate whether peri-operative hemoglobin levels were associated with the risk of early post-operative stroke following revascularization surgery in adult Moyamoya patients., Methods: Adult patients having revascularization surgeries for Moyamoya disease between 1999-2022 were identified through single institutional retrospective review. Logistic regression analysis was used to test for the association between hemoglobin drop and early postoperative stroke., Results: In all, 106 revascularization surgeries were included in the study. A stroke occurred within 7 days after surgery in 9.4% of cases. There were no significant associations between the occurrence of an early postoperative stroke and patient age, gender, or race. Mean postoperative hemoglobin drop was greater in patients who suffered an early postoperative stroke compared with patients who did not (2.3±1.1 g/dL vs. 1.3±1.1 g/dL, respectively; P=0.034). Patients who experienced a hemoglobin drop post-operatively had 2.03 times greater odds (95% confidence interval, 1.06-4.23; P=0.040) of having a stroke than those whose hemoglobin levels were stable. Early postoperative stroke was also associated with an increase in length of hospital stay (P<0.001), discharge to a rehabilitation facility (P=0.014), and worse modified Rankin scale at 1 month (P=0.001)., Conclusion: This study found a significant association between hemoglobin drop and early postoperative stroke following revascularization surgery in adult patients with Moyamoya disease. Based on our findings, it may be prudent to avoid hemoglobin drops in Moyamoya patients undergoing surgical revascularization., Competing Interests: J.H. owns stock in Longevit. The remaining authors have no conflicts of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Although pretreatment radiographic biomarkers are well established for hemorrhagic transformation (HT) following successful mechanical thrombectomy (MT) in large vessel occlusion (LVO) strokes, they are yet to be explored for medium vessel occlusion (MeVO) acute ischemic strokes. We aim to investigate pretreatment imaging biomarkers representative of collateral status, namely the hypoperfusion intensity ratio (HIR) and cerebral blood volume (CBV) index, and their association with HT in successfully recanalized MeVOs. A prospectively collected registry of acute ischemic stroke patients with MeVOs successfully recanalized with MT between 2019 and 2023 was retrospectively reviewed. A multivariate logistic regression for HT of any subtype was derived by combining significant univariate predictors into a forward stepwise regression with minimization of Akaike information criterion. Of 60 MeVO patients successfully recanalized with MT, HT occurred in 28.3% of patients. Independent factors for HT included: diabetes mellitus history (p = 0.0005), CBV index (p = 0.0071), and proximal versus distal occlusion location (p = 0.0062). A multivariate model with these factors had strong diagnostic performance for predicting HT (area under curve [AUC] 0.93, p < 0.001). Lower CBV indexes, distal occlusion location, and diabetes history are significantly associated with HT in MeVOs successfully recanalized with MT. Of note, HIR was not found to be significantly associated with HT., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Poor venous outflow (VO) profiles are associated with unfavorable outcomes in patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO), despite achieving successful reperfusion. The objective of this study is to assess the association between mortality and prolonged venous transit (PVT), a novel visual qualitative VO marker on CT perfusion (CTP) time to maximum (Tmax) maps., Methods: We performed a retrospective analysis of prospectively collected data from consecutive adult patients with AIS-LVO with successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b/2c/3). PVT+ was defined as Tmax ≥10 s timing on CTP Tmax maps in at least one of the following: superior sagittal sinus (proximal venous drainage) and/or torcula (deep venous drainage). PVT- was defined as lacking this in both regions. The primary outcome was mortality at 90 days. In a 1:1 propensity score-matched cohort, regressions were performed to determine the effect of PVT on 90-day mortality., Results: In 127 patients of median (IQR) age 71 (64-81) years, mortality occurred in a significantly greater proportion of PVT+ patients than PVT- patients (32.5% vs 12.6%, P=0.01). This significant difference persisted after matching (P=0.03). PVT+ was associated with a significantly increased likelihood of 90-day mortality (OR 1.22 (95% CI 1.02 to 1.46), P=0.03) in the matched cohort., Conclusions: PVT+ was significantly associated with 90-day mortality despite successful reperfusion therapy in patients with AIS-LVO. PVT is a simple VO profile marker with potential as an adjunctive metric during acute evaluation of AIS-LVO patients. Future studies will expand our understanding of using PVT in the evaluation of patients with AIS-LVO., Competing Interests: Competing interests: VSY, JJH and GWA are consultants for iSchemaView (Menlo Park, California, USA) not related to the submitted work., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: In large vessel occlusion (LVO) stroke patients, relative cerebral blood flow (rCBF)<30% volume thresholds are commonly used in treatment decisions. In the early time window, nearly infarcted but salvageable tissue volumes may lead to pretreatment overestimates of infarct volume, and thus potentially exclude patients who may otherwise benefit from intervention. Our multisite analysis aims to explore the strength of relationships between widely used pretreatment CT parameters and clinical outcomes for early window stroke patients., Methods: Patients from two sites in a prospective registry were analyzed. Patients with LVOs, presenting within 3 hours of last known well, and who were successfully reperfused were included. Primary short-term neurological outcome was percent National Institutes of Health Stroke Scale (NIHSS) change from admission to discharge. Secondary long-term outcome was 90-day modified Rankin score. Spearman's correlations were performed. Significance was attributed to p-value ≤.05., Results: Among 73 patients, median age was 66 (interquartile range 54-76) years. Among all pretreatment imaging parameters, rCBF<30%, rCBF<34%, and rCBF<38% volumes were significantly, inversely correlated with percentage NIHSS change (p<.048). No other parameters significantly correlated with outcomes., Conclusions: Our multisite analysis shows that favorable short-term neurological recovery was significantly correlated with rCBF volumes in the early time window. However, modest strength of correlations provides supportive evidence that the applicability of general ischemic core estimate thresholds in this subpopulation is limited. Our results support future larger-scale efforts to liberalize or reevaluate current rCBF parameter thresholds guiding treatment decisions for early time window stroke patients., (© 2023 American Society of Neuroimaging.)

Acute cerebral ischemia triggers a profound inflammatory response. While macrophages polarized to an M2-like phenotype clear debris and facilitate tissue repair, aberrant or prolonged macrophage activation is counterproductive to recovery. The inhibitory immune checkpoint Programmed Cell Death Protein 1 (PD-1) is upregulated on macrophage precursors (monocytes) in the blood after acute cerebrovascular injury. To investigate the therapeutic potential of PD-1 activation, we immunophenotyped circulating monocytes from patients and found that PD-1 expression was upregulated in the acute period after stroke. Murine studies using a temporary middle cerebral artery (MCA) occlusion (MCAO) model showed that intraperitoneal administration of soluble Programmed Death Ligand-1 (sPD-L1) significantly decreased brain edema and improved overall survival. Mice receiving sPD-L1 also had higher performance scores short-term, and more closely resembled sham animals on assessments of long-term functional recovery. These clinical and radiographic benefits were abrogated in global and myeloid-specific PD-1 knockout animals, confirming PD-1+ monocytes as the therapeutic target of sPD-L1. Single-cell RNA sequencing revealed that treatment skewed monocyte maturation to a non-classical Ly6C lo , CD43 hi , PD-L1+ phenotype. These data support peripheral activation of PD-1 on inflammatory monocytes as a therapeutic strategy to treat neuroinflammation after acute ischemic stroke., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HB has received research funding from the National Institutes of Health, Khatib Foundation, NICO Myriad Corporation, and philanthropy. He is the Chairman of the Medical Advisory Board for Insightec, which is developing focused ultrasound treatments for brain tumors. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict-of-interest policies. He has consultation agreements with Accelerating Combination Therapies, Insightec, Candel Therapeutics, Inc., Catalio Nexus Fund II, LLC, LikeMinds, Inc*, Galen Robotics, Inc.*, CraniUS*, and Nurami Medical* (Includes equity or options). ML has received research funding from Arbor, Bristol Myers Squibb, Accuray, Biohaven, and Urogen. He is a consultant for VBI, InCephalo Therapeutics, Merck, Pyramid Bio, Insightec, Biohaven. Sanianoia, Novocure, Noxxon, Hemispherian, InCando, Century Therapeutics, CraniUs, MediFlix, and XSense. He is a shareholder in Egret Therapeutics. He is an inventor on patents for focused radiation + checkpoint inhibitors, local chemotherapy + checkpoint inhibitors, and checkpoints and Neuro-inflammation. He is a non-research consultant for Stryker and on the DSMB for Cellularity. RJT is an inventor on patents for immune checkpoints and neuroinflammation. CMJ has received research support from Biohaven, InCephalo, the Goldhirsh-Yellin Foundation, the Brain Aneurysm Foundation, and philanthropy. He is an inventor on patents for immune checkpoints and neuroinflammation. He is the co-founder and owns equity interest in Egret Therapeutics. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict-of-interest policies., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Nosocomial infections are the most common complication among critically ill patients and contribute to poor long-term outcomes. Patients with aneurysmal subarachnoid hemorrhage (aSAH) are highly susceptible to perioperative infections, yet it is unclear what factors influence infection onset and functional recovery. The objective was to investigate risk factors for perioperative infections after aSAH and relate causative pathogens to patient outcomes., Methods: Clinical records were obtained for 194 adult patients with aSAH treated at our institution from 2016 to 2020. Demographics, clinical course, complications, microbiological reports, and outcomes were collected. χ 2 , univariate, and multivariate logistic regression analyses were used to analyze risk factors., Results: Nearly half of the patients developed nosocomial infections, most frequently pneumonia and urinary tract infection. Patients with infections had longer hospital stays, higher rates of delayed cerebral ischemia, and worse functional recovery up to 6 months after initial hemorrhage. Independent risk factors for pneumonia included male sex, comatose status at admission, mechanical ventilatory use, and longer admission, while those for urinary tract infection included older age and longer admission. Staphylococcus , Klebsiella , and Enterococcus spp. were associated with poor long-term outcome. Certain pathogenic organisms were associated with delayed cerebral ischemia., Conclusion: Perioperative infections are highly prevalent among patients with aSAH and are related to adverse outcomes. The risk profiles for nosocomial infections are distinct to each infection type and causative organism. Although strong infection control measures should be universally applied, patient management must be individualized in the context of specific infections., (Copyright © Congress of Neurological Surgeons 2023. 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: Treatment decision-making for brain arteriovenous malformations (bAVMs) with microsurgery or stereotactic radiosurgery (SRS) is controversial., Objective: To conduct a systematic review and meta-analysis to compare microsurgery vs SRS for bAVMs., Method: Medline and PubMed were searched from inception to June 21, 2022. The primary outcomes were obliteration and follow-up hemorrhage, and secondary outcomes were permanent neurological deficit, worsened modified Rankin scale (mRS), follow-up mRS > 2, and mortality. The GRADE approach was used for grading the level of evidence., Results: Eight studies were included, which yielded 817 patients, of which 432 (52.8%) and 385 (47.1%) patients underwent microsurgery and SRS, respectively. Two cohorts were comparable in age, sex, Spetzler-Martin grade, nidus size, location, deep venous drainage, eloquence, and follow-up. In the microsurgery group, the odds ratio (OR) of obliteration was higher (OR = 18.51 [11.05, 31.01], P < .000001, evidence: high) and the hazard ratio of follow-up hemorrhage was lower (hazard ratio = 0.47 [0.23, 0.97], P = .04, evidence: moderate). The OR of permanent neurological deficit was higher with microsurgery (OR = 2.85 [1.63, 4.97], P = .0002, evidence: low), whereas the OR of worsened mRS (OR = 1.24 [0.65, 2.38], P = .52, evidence: moderate), follow-up mRS > 2 (OR = 0.78 [0.36, 1.7], P = .53, evidence: moderate), and mortality (OR = 1.17 [0.41, 3.3], P = .77, evidence: moderate) were comparable between the groups., Conclusion: Microsurgery was superior at obliterating bAVMs and preventing further hemorrhage. Despite a higher rate of postoperative neurological deficit with microsurgery, functional status and mortality were comparable with patients who underwent SRS. Microsurgery should remain a first-line consideration for bAVMs, with SRS reserved for inaccessible locations, highly eloquent areas, and medically high-risk or unwilling patients., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Introduction: Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality among patients recovering from aneurysmal subarachnoid hemorrhage (aSAH). Prophylactic heparin reduces the risk of VTE, but the optimal timing for its initiation among aSAH patients remains unclear., Objective: To conduct a retrospective study assessing risk factors for VTE and optimal timing of chemoprophylaxis in patients treated for aSAH., Methods: From 2016-2020, 194 adult patients were treated for aSAH at our institution. Patient demographics, clinical diagnoses, complications, pharmacologic interventions, and outcomes were recorded. Risk factors for symptomatic VTE (sVTE) were analyzed via Chi-squared, univariate, and multivariate regression., Results: In total 33 patients presented with sVTE (25 DVT, 14 PE). Patients with sVTE had longer hospital stays (p < 0.01) and worse outcomes at one-month (p < 0.01) and three-month follow-up (p = 0.02). Univariate predictors of sVTE included male sex (p = 0.03), Hunt Hess score (p = 0.01), Glasgow Coma scale (p = 0.02), intracranial hemorrhage (p = 0.03), hydrocephalus requiring external ventricular drain (EVD) placement (p < 0.01), and mechanical ventilation (p < 0.01). Only hydrocephalus requiring EVD (p = 0.01) and ventilator use (p = 0.02) remained significant upon multivariate analysis. Patients with delayed heparin introduction were significantly more likely to sustain sVTE on univariate analysis (p = 0.02) with a trend-level significance on multivariate analysis (p = 0.07)., Conclusions: Patients with aSAH are more likely to develop sVTE following use of perioperative EVD or mechanical ventilation. sVTE leads to longer hospital stays and worse outcomes among patients treated for aSAH. Delayed heparin initiation increases the risk of sVTE. Our results may help guide surgical decision-making during recovery from aSAH and improve VTE-related postoperative outcomes., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: The physical environment and social determinants of health have been shown to influence health behaviors including drug use and fatal drug overdose. The current research examines the effects of the built environment, social determinants of health measures and aggregated risk from the built environment at neighborhood-level on drug overdose death locations in Miami-Dade County, Florida., Methods: Risk Terrain Modeling (RTM) was used to assess the place features risk factors that significantly increase the risk of drug overdose death spatially in Miami-Dade County ZIP Code Tabulation Areas, Florida from 2014 to 2019. An aggregated neighborhood risk of fatal drug overdose measure was developed by averaging the risk per grid cell from the RTM within census block groups each year. Six logistic and zero-inflated regression models were built to examine the effects of three indices of incident-specific social determinants of health (IS-SDH) measures and aggregated risk measures separately, and simultaneously on drug overdose death locations each year., Results: Seven place features including parks, bus stops, restaurants and grocery stores were significantly related to the occurrence of fatal drug overdoses. When examined separately, one or more indices of the IS-SDH were significant covariates of drug overdose locations in some years. When examined simultaneously, the three indices of the IS-SDH and aggregated risk of fatal drug overdose measure could be all significant in certain years., Conclusions: The patterns of high-risk areas and place features identified from the RTM related to drug overdose deaths may be used to inform the placement of treatment and prevention resources. A multi-factor approach that combines an aggregated neighborhood risk measure reflecting the risk from the built environment and the incident-specific social determinants of health measures can be used to identify the drug overdose death locations in certain years., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Objective: Although randomized controlled trials have compared surgery versus endovascular treatment for intracranial aneurysms, the literature is sparse in terms of subgroup analysis for anterior communicating artery (ACoA) aneurysm management. This systematic review and meta-analysis sought to compare surgical versus endovascular treatment for ACoA aneurysms., Methods: Medline, PubMed, and Embase were searched from inception to December 12, 2022. Primary outcomes were post-treatment modified Rankin Scale (mRS) >2 and mortality. Secondary outcomes were aneurysm obliteration, retreatment and recurrence, rebleeding, technical failure, vessel rupture, aneurysmal subarachnoid hemorrhage-related hydrocephalus, symptomatic vasospasm, and stroke., Results: Eighteen studies yielded 2368 patients, from which 1196 (50.5%) and 1172 (49.4%) patients underwent surgery and endovascular treatment, respectively. The odds ratio (OR) of mortality was similar in total (OR = 0.92 [0.63-1.37], P = 0.69), ruptured (OR = 0.92 [0.62-1.36], P = 0.66), and unruptured cohorts (OR = 1.58 [0.06-39.60], P = 0.78). The OR of mRS > 2 was similar in total (OR = 0.75 [0.50-1.13], P = 0.17), ruptured (OR = 0.77 [0.49-1.20], P = 0.25), and unruptured cohorts (OR = 0.64 [0.21-1.96], P = 0.44). The OR of obliteration was higher with surgery in the total (OR = 2.52 [1.49-4.27], P = 0.0008) and ruptured cohorts (OR = 2.61 [1.33-5.10], P = 0.005) and unruptured group (OR = 3.46 [1.30-9.20], P = 0.01). The OR of retreatment was lower with surgery in the total (OR = 0.37 [0.17-0.76], P = 0.007) and ruptured cohorts (OR = 0.31 [0.11-0.89], P = 0.03), thought it was similar in the unruptured group (OR = 0.51 [0.08-3.03], P = 0.46). The OR of recurrence was lower with surgery in the total (OR = 0.22 [0.10, 0.47], P = 0.0001), ruptured (OR = 0.16 [0.03, 0.90], P = 0.04), and mixed (un) ruptured cohorts (OR = 0.22 [0.09-0.53], P = 0.0009). The OR of rebleeding in ruptured group was similar (OR = 0.66 [0.29-1.52], P = 0.33). The ORs of other outcomes were similar., Conclusions: ACoA aneurysms may be safely treated with either surgery or endovascular treatment, although microsurgical clipping demonstrates higher obliteration rates and lower rates of retreatment and recurrence., (Published by Elsevier Inc.)

Background: The results from studies that compare middle meningeal artery (MMA) embolization vs conventional management for patients with chronic subdural hematoma are varied., Objective: To conduct a systematic review and meta-analysis on studies that compared MMA embolization vs conventional management., Methods: Medline, PubMed, and Embase databases were searched. Primary outcomes were treatment failure and surgical rescue; secondary outcomes were complications, follow-up modified Rankin scale > 2, mortality, complete hematoma resolution, and length of hospital stay (day). The certainty of the evidence was determined using the GRADE approach., Results: Nine studies yielding 1523 patients were enrolled, of which 337 (22.2%) and 1186 (77.8%) patients received MMA embolization and conventional management, respectively. MMA embolization was superior to conventional management for treatment failure (relative risk [RR] = 0.34 [0.14-0.82], P = .02), surgical rescue (RR = 0.33 [0.14-0.77], P = .01), and complete hematoma resolution (RR = 2.01 [1.10-3.68], P = .02). There was no difference between the 2 groups for complications (RR = 0.93 [0.63-1.37], P = .72), follow-up modified Rankin scale >2 (RR = 0.78 [0.449-1.25], P = .31), mortality (RR = 1.05 [0.51-2.14], P = .89), and length of hospital stay (mean difference = -0.57 [-2.55, 1.41], P = .57). For MMA embolization, the number needed to treat for treatment failure, surgical rescue, and complete hematoma resolution was 7, 9, and 3, respectively. The certainty of the evidence was moderate to high for primary outcomes and low to moderate for secondary outcomes., Conclusion: MMA embolization decreases treatment failure and the need for surgical rescue without furthering the risk of morbidity and mortality. The authors recommend considering MMA embolization in the chronic subdural hematoma management., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Randomized controlled trials comparing endovascular thrombectomy (EVT) versus EVT preceded by intravenous thrombolysis (EVT + IVT) for acute ischemic stroke due to large artery occlusion remain controversial. This systematic review and meta-analysis seek to compare these 2 modalities., Methods: Online Protocol is available at PROSPERO (york.ac.uk) (registration# CRD42022357506). MEDLINE, PubMed, and Embase were searched. The primary outcome was 90-day modified Rankin scale (mRS) ≤2. Secondary outcomes were 90-day mRS ≤1, 90-day mean mRS, National Institutes of Health Stroke Scale (NIHSS) at 1-3 and 3-7 days, 90-day Barthel Index, 90-day EQ-5D-5L (EuroQoL Group 5-Dimension 5-Level), the volume of infarction (mL), successful reperfusion, complete reperfusion, recanalization, 90-day mortality, any intracranial hemorrhage (ICH), symptomatic ICH, embolization in new territory, new infarction, puncture site complications, vessel dissection, and contrast extravasation. The certainty in the evidence was determined by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach., Results: Six randomized controlled trials yielding 2332 patients were included, of which 1163 and 1169 underwent EVT and EVT + IVT, respectively. The relative risk (RR) of 90-day mRS ≤2 was similar between the groups (RR = 0.96[0.88, 1.04]; P = 0.28). EVT was non-inferior to EVT + IVT because the lower bond of 95% confidence interval of the risk difference (RD = -0.02 [-0.06, 0.02]; P = 0.36) exceeded the -0.1 non-inferiority margin. The certainty in the evidence was high. The RR of successful reperfusion (RR = 0.96 [0.93, 0.99]; P = 0.006), any ICH (RR = 0.87 [0.77, 0.98]; P = 0.02), and puncture site complications (RR = 0.47 [0.25, 0.88]; P = 0.02) were lower with EVT. For EVT + IVT, the number needed to treat for successful reperfusion was 25, and the number needed to harm for any ICH was 20. The 2 groups were similar in other outcomes., Conclusion: EVT is non-inferior to EVT + IVT. In centers capable of both EVT and IVT, if timely EVT is feasible, it is reasonable to skip bridging IVT and keep rescue thrombolysis at the discretion of the interventionist for patients presenting within 4.5 hours of anterior ischemic stroke., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Transradial access (TRA) has gained increased usage among neurointerventionalists. However, the overall safety profile of access site complications (ASCs) and non-access site complications (NASCs) of TRA versus transfemoral access (TFA) for neuroendovascular procedures remains unclear., Methods: A systematic literature review and meta-analysis using a random effects model was conducted to investigate the pooled odds ratios (OR) of ASCs and NASCs. Randomized, case-control, and cohort studies comparing access-related complications were analyzed. An assessment of study heterogeneity and publication bias was also completed., Results: Seventeen comparative studies met the inclusion criteria for final analysis. Overall, there was a composite ASC rate of 1.8% (49/2767) versus 3.2% (168/5222) for TRA and TFA, respectively (P<0.001). TRA was associated with a lower odds of ASC compared with TFA (OR 0.42; 95% CI 0.25 to 0.68, P<0.001, I 2 =31%). There was significantly lower odds of complications within the intervention and diagnostic subgroups. For NASC, TRA had a lower composite incidence of complications than TFA at 1.2% (31/2586) versus 4.2% (207/4909), P<0.001). However, on meta-analysis, we found no significant difference overall between TRA and TFA for NASCs (OR 0.79; 95% CI 0.51 to 1.22, P=0.28, I 2 =0%), which was also the case on subgroup analysis., Conclusion: On meta-analysis, the current literature indicates that TRA is associated with a lower incidence of ASCs compared with TFA, but is not associated with a lower rate of NASCs., Competing Interests: Competing interests: JB: Consulting relationships with Asahi Intecc and AvantGarde Health for work on coronary guidewires., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Stent-assisted coiling of wide-necked intracranial aneurysms (IAs) using the Neuroform Atlas Stent System (Atlas) has shown promising results., Objective: To present the primary efficacy and safety results of the ATLAS Investigational Device Exemption (IDE) trial in a cohort of patients with posterior circulation IAs., Methods: The ATLAS trial is a prospective, multicenter, single-arm, open-label study of unruptured, wide-necked, IAs treated with the Atlas stent and adjunctive coiling. This study reports the results of patients with posterior circulation IAs. The primary efficacy endpoint was complete aneurysm occlusion (Raymond-Roy (RR) class I) on 12-month angiography, in the absence of re-treatment or parent artery stenosis >50%. The primary safety endpoint was any major ipsilateral stroke or neurological death within 12 months. Adjudication of the primary endpoints was performed by an imaging core laboratory and a Clinical Events Committee., Results: The ATLAS trial enrolled and treated 116 patients at 25 medical centers with unruptured, wide-necked, posterior circulation IAs (mean age 60.2±10.5 years, 81.0% (94/116) female). Stents were placed in all patients with 100% technical success rate. A total of 95/116 (81.9%) patients had complete angiographic follow-up at 12 months, of whom 81 (85.3%) had complete aneurysm occlusion (RR class I). The primary effectiveness outcome was achieved in 76.7% (95% CI 67.0% to 86.5%) of patients. Overall, major ipsilateral stroke and secondary persistent neurological deficit occurred in 4.3% (5/116) and 1.7% (2/116) of patients, respectively., Conclusions: In the ATLAS IDE posterior circulation cohort, the Neuroform Atlas Stent System with adjunctive coiling demonstrated high rates of technical and safety performance. Trial registration number https://clinicaltrials.gov/ct2/show/NCT02340585., Competing Interests: Competing interests: BTJ: consultant for Stryker and a consultant/proctor for Medtronic. OOZ: research grant from Stryker, Medtronic, Cerenovus, Penumbra, and Genentech; consultant and speaker for Cerenovus, Stryker, Penumbra, and Medtronic; has ownership interest in Galaxy Therapeutics LLC; and serves on the endovascular committee as co-chair for National Institutes of Health StrokeNet Consortium and has served as an expert witness. SWH: Core Laboratory Services for Stryker and MicroVention Terumo (money paid to UCSF, over $5k); consulting for Microvention Terumo (money paid to SWH, under $5k). APJ: reports no conflicts. BG: consultant for Medtronic and Microvention. TGJ: consultant at Cerenovus (steering committee/DSMB–modest), Stryker Neurovascular (PI DAWN (DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With Trevo)-unpaid); holds Stock at Anaconda, Blockade Medical, Route 92, Corindus, FreeOx Biotech, Viz.ai, Silk Road. JFF: equity - Fawkes Biotechnology, Cerelux, LLC; consultant: Medtronic, Penumbra, Stream Biomedical. RAH: research Grant: Medtronic, Stryker, Microvention, Cerenovus; consultant: Stryker, Medtronic, Cerenovus, Microvention; stockholder: Neurvana, Elum, EndoStream, Three Rivers Medical Inc, Rist, Cerebrotech, InNeuroCo; Scientific Advisor: MIVI, Elum, Three Rivers Medical Inc, Shape Medical. ES: reports a speakers’ agreement with Stryker. AA: reports no conflicts. DF: consultant/speakers bureau for Stryker; consultant/speakers bureau for Siemens, Penumbra, Philips, Genentech, Viz.AI; Scientific Advisory Board for Shape Memory Medical. AMM: consulting fees/honoraria: Microvention-Terumo Inc., Stryker Inc; major stock shareholder/equity: Cerevasc LLC; ownership/founder: Cerevasc LLC; intellectual property rights: Cerevasc LLC, Tufts Medical Center. AT: SCENT data safety monitoring board, funds paid to the institution. GT: consultant to Dynamed, Medtronic, and Microvention. DKL: consultant for Stryker Neurovascular. MJA: consultant for Stryker Neurovascular. AHS: financial Interest/investor/stock options/ownership for Amnis Therapeutics, Boston Scientific (for acquisition of Claret Medical), Buffalo Technology Partners, Inc., Cognition Medical, Endostream Medical, Ltd, Imperative Care, International Medical Distribution Partners, Q’Apel Medical, Inc, Rebound Therapeutics Corp., Rist Neurovascular, Inc, Serenity Medical, Inc, Silk Road Medical, Spinnaker Medical, Inc, Synchron; consultant/advisory board for Amnis Therapeutics, Boston Scientific, Cerenovus, Endostream Medical, Ltd, Imperative Care, Integra LifeSciences Corp., Medtronic, MicroVention, Penumbra, Q’Apel Medical, Inc., Rapid Medical, Rebound Therapeutics Corp, Serenity Medical, Inc, Silk Road Medical, Stryker, W.L. Gore & Associates National PI/Steering Committees: Cerenovus LARGE Trial and ARISE II Trial, mal Medtronic SWIFT PRIME and SWIFT DIRECT Trials; MicroVention FRED Trial and CONFIDENCE Study; MUSC POSITIVE Trial; Penumbra 3D Separator Trial, COMPASS Trial, INVEST Trial. PK: consultant for Stryker and Cerenovus; stockholder of InNeuroCo. MTF: grant funding from NIH, Medtronic, Microvention, Stryker, and Genentech; consultant for Medtronic, Stryker, Balt USA, Viz.ai, Genentech, Cerenovus, Corindus, and EndoPhys. AMS: research support from Stryker, Medtronic, and Penumbra; consulting for Stryker, Terumo, Penumbra, and Siemens. ASA: consultant for Johnson and Johnson, Medtronic, Microvention, Penumbra, Scientia, Siemens, Stryker; research support from Balt, Cerenovus, Medtronic, Microvention, Penumbra, Siemens, and Stryker; shareholder in Bendit, Cerebrotech, Endostream, Magneto, Marblehead, Mentice, Neurogami, Serenity, Synchron, Triad Medical. RWC: proctor for Medtronic and Cerenovus. SRS: consultant for Balt, Cerenovus, Cordis, Medtronic, Microvention, Terumo, Stryker. GPC: consultant and proctor for Stryker, MicroVention, and Medtronic. JMC: reports no disclosures. AAA: reports no disclosures. JRC: reports no disclosures. AK: reports no disclosures. RCC: consulting for Stryker. EL: reports no disclosures. AST: reports no disclosures. DL: reports no disclosures. DK: reports no disclosures. DKH: reports no disclosures. ASP: reports no disclosures. No CEC/DSMB members are from participating sites of the study. UCSF is not a participating site. RB and RK delcare none., (© 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 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.)

The role of microsurgery and radiosurgery in the management of low-grade (Spetzler-Martin grade 1 and 2) arteriovenous malformations (AVMs) remains controversial. We aimed to compare outcomes of low-grade AVMs following microsurgery and radiosurgery using a database of AVM patients presenting between 1990 and 2017. Procedure-related complications, obliteration, and functional status at last follow-up were compared between groups. Hemorrhage-free survival was compared using Kaplan-Meier analysis with subgroup analyses by rupture status on presentation. The study involved 233 patients, of which 113 and 120 were treated with microsurgery and radiosurgery, respectively. The complication rates were statistically comparable between both treatment modalities. Mean follow-up time was 5.1 ± 5.2 years. In the complete cohort, there was no significant difference in hemorrhage-free survival between microsurgery and radiosurgery (log-rank p = 0.676, Breslow p = 0.493). When excluding procedure-related hemorrhage and partial resection, hemorrhage-free survival was significantly higher in the surgically treated cohort (log-rank = 0.094, Breslow p = 0.034). The obliteration rate was significantly higher in the surgical cohort (96% vs. 57%, p < 0.001), while functional status was similar. Microsurgery may offer superior hemorrhage-free survival in the early post-treatment period and demonstrates equivalent long-term hemorrhage control and functional outcome at 5 years compared to radiosurgery with nearly complete obliteration rates. Persistent neurologic deficits following microsurgery and symptomatic cerebral edema represent important treatment risks despite low SM grading. Appropriate patient selection even when dealing with low-grade AVMs is advised, as judicious patient selection and emphasis on technical success can minimize procedure-related hemorrhage and the incidence of subtotal resection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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.)

Deep-seated intracranial arteriovenous malformations (AVMs) represent a subset of AVMs characterized by variably reported outcomes regarding the risk of hemorrhage, microsurgical complications, and response to stereotactic radiosurgery (SRS). We aimed to compare outcomes of microsurgery, SRS, endovascular therapy, and conservative follow-up in deep-seated AVMs. A prospectively maintained database of AVM patients (1990-2017) was queried to identify patients with ruptured and unruptured deep-seated AVMs (extension into thalamus, basal ganglia, or brainstem). Comparisons of hemorrhage-free survival and poor functional outcome (modified Rankin scale [mRS] > 2) were performed between conservative management, microsurgery (±pre-procedural embolization), SRS (±pre-procedural embolization), and embolization utilizing multivariable Cox and logistic regression analyses controlling for univariable factors with p < 0.05. Of 789 AVM patients, 102 had deep-seated AVMs (conservative: 34; microsurgery: 6; SRS: 54; embolization: 8). Mean follow-up time was 6.1 years and did not differ significantly between management groups (p = 0.393). Complete obliteration was achieved in 49% of SRS patients. Upon multivariable analysis controlling for baseline rupture with conservative management as a reference group, embolization was associated with an increased hazard of hemorrhage (HR = 6.2, 95%CI [1.1-40.0], p = 0.037), while microsurgery (p = 0.118) and SRS (p = 0.167) provided no significant protection from hemorrhage. Controlling for baseline mRS, microsurgery was associated with an increased risk of poor outcome (OR = 9.2[1.2-68.3], p = 0.030), while SRS (p = 0.557) and embolization (p = 0.541) did not differ significantly from conservative management. Deep AVMs harbor a high risk of hemorrhage, but the benefit from intervention Remains uncertain. SRS may be a relatively more effective approach if interventional therapy is indicated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Pediatric intracranial aneurysms are rare. Most large series in the last 15 years reported on an average of only 39 patients. The authors sought to report their institutional experience with pediatric intracranial aneurysms from 1991 to 2021 and to compare pediatric patient and aneurysm characteristics with those of a contemporaneous adult cohort., Methods: Pediatric (≤ 18 years of age) and adult patients with one or more intracranial aneurysms were identified in a prospective database. Standard epidemiological features and outcomes of each pediatric patient were retrospectively recorded. These results were compared with those of adult aneurysm patients managed at a single institution over the same time period., Results: From a total of 4500 patients with 5150 intracranial aneurysms admitted over 30 years, there were 47 children with 53 aneurysms and 4453 adults with 5097 aneurysms; 53.2% of children and 36.4% of adults presented with a subarachnoid hemorrhage (SAH). Pediatric aneurysms were significantly more common in males, more likely giant (≥ 25 mm), and most frequently located in the middle cerebral artery. Overall, 85.1% of the pediatric patients had a modified Rankin Scale score ≤ 2 at the last follow-up (with a mean follow-up of 65.9 months), and the pediatric mortality rate was 10.6%; all 5 patients who died had an SAH. The recurrence rate of treated aneurysms was 6.7% (1/15) in the endovascular group but 0% (0/31) in the microsurgical group. No de novo aneurysms occurred in children (mean follow-up 5.5 years)., Conclusions: Pediatric intracranial aneurysms are significantly different from adult aneurysms in terms of sex, presentation, location, size, and outcomes. Future prospective studies will better characterize long-term aneurysm recurrence, rebleeds, and de novo aneurysm occurrences. The authors currently favor microsurgical over endovascular treatment for pediatric aneurysms.

Background: Although recurrence and de novo formation of arteriovenous malformations (AVMs) have been reported following complete resection, the occurrence of hemorrhage in the same location of an AVM with no detectable lesion (lesion-negative hemorrhage) has not been described after microsurgery., Objective: To characterize the incidence and properties of lesion-negative hemorrhage following complete microsurgical resection., Methods: A prospectively maintained registry of AVM patients seen at our institution between 1990 and 2017 was used. Microsurgically treated patients were selected, and the incidence of a lesion-negative hemorrhage was calculated and described with a Kaplan-Meier curve. Baseline characteristics as well as functional outcome at last follow-up were compared between patients with and without a lesion-negative hemorrhage., Results: From a total of 789 AVM patients, 619 (79%) were treated, and 210 out of 619 patients (34%) underwent microsurgery with or without preoperative embolization or radiosurgery. The microsurgically treated cohort was followed up for a mean of 6.1 ± 3.0 yr after surgery with 5 (2.4%) patients experiencing postresection lesion-negative hemorrhage (3.9 per 1000 person-years) at an average of 8.6 ± 9.0 yr following surgery. Follow-up angiograms after hemorrhage (up to 2 mo posthemorrhage) confirmed the absence of a recurrent or de novo AVM in all cases. All patients with a lesion-negative hemorrhage initially presented with rupture before resection (Fisher P = .066; log-rank P = .057). The occurrence of a lesion-negative hemorrhage was significantly associated with worse modified Rankin scale scores at last follow-up (P = .031)., Conclusion: A lesion-negative hemorrhage can occur following complete microsurgical resection in up to 2.4% of patients. Exploration of possible underlying causes is warranted., (© Congress of Neurological Surgeons 2021.)

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.)

Background: Pipeline Embolization Device (PED; Medtronic) "twisting" manifests with the appearance of a "figure 8" in perpendicular planes on digital subtraction angiography. This phenomenon has received little attention in the literature, requires technical precision to remediate, and has potential to cause ischemic stroke if not properly remediated., Objective: To report incidence, risk factors, and sequelae of PED twisting and to discuss techniques to remediate a PED twist., Methods: Case images were reviewed for instances of twisting from a prospectively-maintained, Institutional Review Board-approved cohort of patients undergoing flow diversion for cerebral aneurysm., Results: From August 2011 to December 2017, 999 PED flow diverting stents were attempted in 782 cases for 653 patients. A total of 25 PED twists were observed while treating 20 patients (2.50%, 25/999). Multivariate analysis revealed predictors of twisting to be: Large and giant aneurysms (odds ratio (OR) = 9.66, P = .005; OR = 27.47, P < .001), increased PED length (OR = 1.14, P < .001), and advanced patient age (OR = 1.07, P = .002). Twisted PEDs were able to be remediated 75% of the time, and procedural success was achieved in 90% of cases. PED twisting was not found to be a significant cause of major or minor complications. However, at long-term follow-up, there was a trend towards poor occlusion outcomes for the cases that encountered twisting., Conclusion: Twisting is a rare event during PED deployment that was more likely to occur while treating large aneurysms with long devices in older patients. While twisting did not lead to major complications in this study, remediation can be challenging and may be associated with inferior occlusion outcomes., (Copyright © 2020 by the Congress of Neurological Surgeons.)

The current study, using a multi-factorial survey experiment with a sample of the general public ( N = 800), investigates if and how types of risk information on crime and public safety, such as maps, graphs, or tables, commonly used and communicated by law enforcement elicit dual-process (affective and cognitive) risk information processing in risk-based decision-making, and if such processing or decision-making differs depending on the risk level, context, or the type or format of risk information communicated. Participants responded to a vignette in which they were asked to choose a ride-share pick-up point within a certain geographic area with varying risk levels of being involved in a pedestrian-automobile crash. Results showed that risk information related to crime and public safety elicits dual-process risk information processing, and that both affective and cognitive processing significantly predicted risk-based decision-making, regardless of the risk level or type of risk information examined. Interestingly, risk information was used to create an almost "black and white" distinction for participants, in which their lowest-risk choice was treated as their comparison point, relative to all other higher levels of risk, in risk processing and decision-making. Further, the risk level or type of risk information examined did affect the nature and level of affective and cognitive processing elicited, suggesting that different types or characteristics of risk information can change modes of processing and their effects on risk-based decisions. Our findings provide first-of-its-kind data that show members of the general public, as consumers of risk information in relation to crime and public safety, process and make decisions surrounding such information using the dual-process approach. Implications for communicating risk information in relation to crime and public safety to both the general public and police, as well as how to extend the current inquiry to future areas of research on police, are discussed., (Copyright © 2020 Berryessa and Caplan.)

Decades of empirical work have confirmed that experiences with violence are associated with a variety of adverse behavioral and mental health as well as academic outcomes for children and adolescents. Yet this research largely has relied on indirect measures of exposure. In this study, we apply geospatial analysis to examine the relation between neighborhood violent crime (via police reports) and academic performance (via school-level standardized test proficiency rates). Findings suggest that greater numbers of crimes proximal to school buildings relate to lower levels of academic performance. These results persisted even when controlling economic disadvantage in the student body. Implications for research and policy are discussed., (© 2020 Society for Community Research and Action.)

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.

Risk Terrain Modeling (RTM) is a spatial analysis technique used to diagnose environmental conditions that lead to hazardous outcomes. Originally developed for applications to violent crime analysis, RTM is utilized here to analyze Dr. John Snow's data from the 1854 cholera outbreak in London to demonstrate its potential value to contemporary epidemiological investigations. Dr. Snow saved countless lives when he traced the source of the cholera outbreak to a specific water pump through inductive reasoning, which he communicated through maps and spatial evidence. His methods have since inspired several fields of scientific inquiry. Informed by the extant research on RTM, we speculated that it could have helped test Dr. Snow's hypothesis about cholera and empirically identified the sole source of contaminated well water. We learned that it could and, although it was not available to Dr. Snow in the 1800s, we discuss RTM's implications for present-day research and practice as it relates to the analysis, prevention and treatment of cholera and other public health threats around the world., Competing Interests: The authors have read the journal's policy and have the following conflicts: Leslie Kennedy and Joel Caplan are co-founders of Simsi Inc., a Rutgers University start-up. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Background: Spontaneous obliteration (SpO) of untreated arteriovenous malformations (AVMs) is rare with fewer than 100 cases reported. The incidence and predisposing factors of SpO remain unclear, impeding our understanding of lesion progression in untreated patients., Objective: To determine the incidence rate and predisposing factors of SpO in a North American cohort., Methods: AVMs were retrospectively evaluated at our institution for over 25 yr. Untreated AVMs were divided into 2 groups: SpO-AVMs and non-SpO-AVMs. All statistical results were based on univariate analyses. Incidence was generated from counts of SpO over the untreated interval in patient years from birth until obliteration, treatment, or last follow-up., Results: One hundred fifty-four patients had untreated AVMs; SpO was observed in 4. Average ages were 49.0 ± 23.6 and 48.7 ± 20.4 yr in the SpO-AVM and non-SpO-AVM group, respectively (P = .98). Average AVM sizes were 2.0 ± 1.8 cm (SpO-AVMs) and 3.7 ± 2.6 cm (non-SpO-AVMs, P = .25). All SpO-AVMs and 40 (27.0%) non-SpO-AVMs had a ruptured presentation (P = .006). A single draining vein was observed in all SpO-AVMs and 39 (32.8%) non-SpO-AVMs (P = .01). Deep venous drainage was not observed in any SpO-AVMs, but in 81 (57.9%) non-SpO-AVMs (P = .04). Mean follow-up time was 37.0 ± 42.6 and 75.6 ± 161.7 mo in SpO-AVM and non-SpO-AVMs patients, respectively. Of the 2 SpO-AVM patients with postobliteration follow-up, 1 experienced recanalization. From a 672-patient cohort, the incidence of SpO over 28 961 patient years was 0.014%., Conclusion: SpO-AVMs have an annual incidence rate of approximately 0.014% and tend to present with rupture, a single draining vein, and superficial venous drainage. Expectation of SpO for untreated AVMs is not justified, and patients should anticipate life-long hemorrhagic risk for untreated AVMs., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Background: Dual antiplatelet therapy (DAT), most commonly with aspirin and Clopidogrel, is the standard of care for intracranial stenting, including flow diversion. Clopidogrel response varies by individual., Objective: To investigate the real-world precision of VerifyNow P2Y12 assessment (Accumetrics, San Diego, California) of Clopidogrel response., Methods: Using a prospectively-collected, IRB-approved cerebral aneurysm database 643 patients were identified who were treated with the Pipeline embolization device from 2011 to 2017. Patients with multiple P2Y12 assays drawn within a 24-h window were identified. A single patient could contribute multiple, independent sets. Levels drawn before a 5-d course of DAT and patients who received alternative antiplatelet agents were excluded. Therapeutic range was defined as platelet reaction units (PRU) 60-200., Results: A total of 1586 P2Y12 measurements were recorded; 293 (46%) patients had more than one assay. One hundred forty (22%) patients had multiple P2Y12 measurements within 24 h. These patients accounted for 230 independent 24-h sets. The average P2Y12 fluctuation across all sets was 35 points; the 25th, 50th, and 75th percentiles were 12, 26, and 48 points, respectively. Of the 230 24-h sets of P2Y12 assays, 76% remained within their original therapeutic category: 100 (43%) all therapeutic, 54 (23%) all hypo-responsive, and 21 (9%) all hyper-responsive. Twenty-four percent of patients fluctuated between therapeutic categories when multiple P2Y12 assessments were drawn within a 24-h period: 29 (13%) between hypo-response and therapeutic, 23 (10%) between hyper-response and therapeutic, and 3 (1%) between hypo-response and hyper-response., Conclusion: Our experience suggests P2Y12 is an often-imprecise measure, and this should be considered when utilizing P2Y12 levels for clinical decisions., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Background: Previous reports indicated an association between hemorrhagic presentation and flow-related aneurysms in arteriovenous malformation (AVM) patients. However, it remains unclear whether these flow-related aneurysms result in the hemorrhage of AVM., Objective: To characterize this hemorrhage risk using our institutional experience over 25 yr., Methods: We retrospectively reviewed records of patients at our institution diagnosed with AVM from 1990 to 2015. Patients without associated aneurysms (AVM only) and those with flow-related aneurysms (AVM-FA) were compared. Those with intranidal or unrelated aneurysms were excluded. Annual risk of AVM-related hemorrhage was calculated using the birth-to-treatment approach and compared using Poisson rate ratio test., Results: Among 526 patients, there were 457 AVM only patients and 69 with flow-related aneurysms. AVM-FA patients were older (P = .005). AVMs with flow-related aneurysms were more likely located in the cerebellar vermis and hemispheres (P = .023 and .001, respectively). Presence of flow-related aneurysms increased the risk of presentation with subarachnoid hemorrhage (P < .001). Interestingly, no significant differences in presenting hemorrhage due to AVM rupture were found (P > .356). The majority of aneurysms were untreated (69.5%), and only 8 (9.8%) had ruptured presentation. At follow-up (mean = 5.3 yr), patients with flow-related aneurysms were less likely to develop seizures (P = .004). The annual risk of AVM hemorrhage was 1.33% and 1.05% for AVM only patients and AVM-FA patients, respectively (P = .248)., Conclusion: Despite increased risk of subarachnoid hemorrhage at presentation, there was no increased likelihood of rupture in AVMs with flow-related aneurysms. More studies are warranted, as clarifying the competing risks of AVM vs aneurysm rupture may be critical in determining optimal treatment strategy., (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.

Background: Flow diversion is increasingly used for off-label treatments of distal circulation aneurysms. Reports of use in sub-2.0-mm vessels are scant., Methods: A prospectively collected, institutional review board-approved cerebral aneurysm database was reviewed to identify patients who underwent flow diversion with a 2.5-mm diameter Pipeline embolization device., Results: Sixty-seven aneurysms were treated in 67 procedures (66 [99%] successful, 64 [96%] single device, 2 [3%] with 2 devices) in 57 patients. Average age was 56 years and 60% were female. Aneurysm location was 51 (76%) anterior cerebral artery, 14 (21%) middle cerebral artery, and 2 (3%) posterior cerebral artery. Aneurysm size was 4.1 ± 3.0 mm (1-20 mm). Safety outcomes included 3 major strokes (4.5%) resulting in permanent neurologic deficit (modified Rankin Scale score 6,4,4), including 1 mortality (1.5%). Acute stent thrombosis was observed intraprocedurally or within 24 hours of each stroke. There were 2 small-volume (<10 cm 3 , 40 cm 3 ) dependent intracerebral hemorrhage (3.0%) that resolved without permanent neurologic deficit. For effectiveness, 71% of patients underwent follow-up angiography. Complete occlusion was achieved by 88% at 6 months, 86% at 12 months, and 89% at last follow-up. A slight vessel diameter reduction was apparent on average 6.9 months after the procedure, which was statistically significant at the proximal (P = 0.001) but not distal (P = 0.317) device end. Preoperative average parent vessel diameter was 1.9 mm proximally (range, 1.1-2.6 mm) and 1.7 mm distally (range, 1.0-2.3 mm) of the Pipeline embolization device. Follow-up average vessel diameter was 1.7 mm proximally (range, 0.7-2.4 mm) and 1.6 mm distally (range, 0.6-2.1 mm). Flow delay associated with vessel diameter reduction occurred once. There were no cases of asymptomatic vessel occlusion., Conclusions: Flow diversion can be safe and effective for aneurysms originating from vessels <2.0 mm in diameter. Heightened vigilance for the prevention and management of acute stent and vessel thrombosis is warranted in these cases., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The risk of hemorrhage remains after radiosurgery for patients with arteriovenous malformations (AVMs), especially during the latency period. The effect of venous outflow stenosis on postradiosurgery AVM hemorrhage has been understudied. The present study sought to clarify the effect of venous stenosis on postradiation hemorrhage., Methods: We retrospectively reviewed the records of patients with AVM seen at our institution from 1990 to 2015. Patients who had undergone radiosurgery were included, and those without sufficient data were excluded. We performed multivariable Cox regression to evaluate the predictors of postradiosurgery hemorrhage, with specific emphasis on venous stenosis. Patients were censored from the first radiosurgery to hemorrhage or the last follow-up visit. The baseline and angiographic characteristics were compared between those with venous stenosis and those without to address potential confounders., Results: The present study included 240 patients, of whom 29 (12.1%) had venous stenosis. The venous stenosis cohort included more patients with venous varices (P = 0.009) and fewer with deep venous drainage (P = 0.048) compared with those without venous stenosis. Most patients had grade III or higher AVMs (63.2%), with an obliteration rate of 32.9%. In an all-inclusive multivariable Cox regression, hemorrhage risk was associated with venous stenosis (hazard ratio [HR], 3.70; P = 0.034), age (HR, 1.05; P = 0.002), AVM volume (HR, 1.04; P = 0.004), and hemorrhage before treatment (HR, 4.11; P = 0.014). Male gender was protective (HR, 0.31; P = 0.036) against hemorrhage., Conclusions: We identified statistically significant risk factors for postradiosurgery AVM hemorrhage, which included advanced age, female gender, the presence of venous stenosis, a larger AVM volume, and previous hemorrhage. We recommend cautious selection of patients for radiosurgery with close follow-up after treatment, especially for patients with these risk factors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Posterior circulation cerebral aneurysms are at higher risk of rupture and are more symptomatic than those in the anterior circulation. Existing treatments carry significant morbidity. Early reports of flow diversion for posterior circulation aneurysms have suggested high complication and low occlusion rates., Objective: To report safety and efficacy of flow diversion with the pipeline embolization device (ev3, Medtronic Inc, Dublin, Ireland) for aneurysms located throughout the posterior circulation., Methods: A prospective, institutional review board-approved database was analyzed for all patients with posterior circulation aneurysms treated by flow diversion at our institution., Results: Fifty-nine embolization procedures were performed on 55 patients. Average aneurysm size was 9.4 mm. Morphology was saccular (45%), fusiform (29%), or dissecting/pseudo-aneurysms (25%). Sixty-two percent of aneurysms arose along the vertebral artery. There were 7 mid-basilar (13%) and 7 basilar apex (13%) aneurysms. Procedural success was 98%; 1 Pipeline embolization device was placed in 85%; and coiling was performed in 17% of cases. There were 5 major complications (8%), all strokes. Patients with major stroke had modified Rankin Scale score at last follow-up of 1, 3, 4, 6, and 6 (2 mortalities). There were zero intracerebral or subarachnoid hemorrhages. No variable predicted complications on univariate or multivariate analysis. Follow-up digital subtraction angiography was performed for 43 patients (78%). Complete occlusion was 68% at 6 mo and 78% at 12 mo. Average follow-up was 11.8 mo. Fusiform or dissecting morphology and large or giant aneurysm size were predictors of aneurysm persistence at 6 mo on multivariate logistic regression., Conclusion: This is a large single-institution series of Pipeline (Medtronic Inc) for posterior circulation aneurysms and demonstrates acceptable safety and effectiveness in these challenging cases.

Introduction: Internal carotid artery termination (ICAT) and proximal A1 aneurysms can be challenging for open surgical clipping or endovascular coiling. Treatment with flow diversion covering the middle cerebral artery (MCA), an end vessel supplying a terminal circulation, has not been reported., Methods: A prospective, Institutional Review Board-approved database was analysed for patients with pipeline embolisation device (PED) placement from the anterior cerebral artery (ACA) to the ICA during cerebral aneurysm treatment., Results: Nine cases were identified, including five proximal A1, three posterior communicating artery and one ICAT aneurysm locations. Average aneurysm size was 8.3 mm (range 3-17), with 67% saccular and 78% right-sided. Primary indication for treatment was significant dome irregularity (44%), recurrence or enlargement (33%), underlying collagen vascular disorder (11%) and traumatic pseudoaneurysm (11%). Preservation of the ipsilateral ACA (with PED placed in A1) was performed when the anterior communicating artery (67%) or contralateral A1 (33%) were absent on angiography. Adjunctive coiling was done in four cases (44%). There was one major stroke leading to mortality (11%) and one minor stroke (11%). Clinical follow-up was 27 months on average. Follow-up digital subtraction angiography (average interval 15 months) showed complete aneurysm obliteration (88%) or dome occlusion with entry remnant (12%). The jailed MCA showed minimal or mild delay (primarily anterograde flow) in 75% of cases and significant delay (reliance primarily on ACA and external carotid artery collaterals) in 25%., Conclusions: Covering the MCA with a flow diverting stent should be reserved for select rare cases. Strict attention to blood pressure augmentation during the periprocedural period is necessary to minimise potential ischaemic compromise., Competing Interests: Competing interests: ALC is a consultant for InNeuroCo, a consultant and proctor for Medtronic Neurovascular, MicroVention-Terumo and Stryker Neurovascular. L-ML is a proctor for Medtronic Neurovascular, consultant for Stryker Neurovascular and Cerenovus. GPC is a consultant for Stryker Neurovascular. The other authors have no conflict of interest., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

OBJECTIVEThe second-generation Pipeline embolization device (PED), Flex, has several design upgrades, including improved opening and the ability to be resheathed, in comparison with the original device (PED classic). The authors hypothesized that Flex is associated with a lower rate of major complications.METHODSA prospective, IRB-approved, single-institution database was analyzed for all patients with anterior circulation aneurysms treated by flow diversion. The PED classic was used from August 2011 to January 2015, and the Pipeline Flex has been used since February 2015.RESULTSA total of 568 PED procedures (252 classic and 316 Flex) were performed for anterior circulation aneurysms. The average aneurysm size was 6.8 mm. Patients undergoing treatment with the Flex device had smaller aneurysms (p = 0.006) and were more likely to have undergone previous treatments (p = 0.001). Most aneurysms originated along the internal carotid artery (89% classic and 75% Flex) but there were more anterior cerebral artery (18%) and middle cerebral artery (7%) deployments with Flex (p = 0.001). Procedural success was achieved in 96% of classic and 98% of Flex cases (p = 0.078). Major morbidity or death occurred in 3.5% of cases overall: 5.6% of classic cases, and 1.9% of Flex cases (p = 0.019). On multivariate logistic regression, predictors of major complications were in situ thrombosis (OR 4.3, p = 0.006), classic as opposed to Flex device (OR 3.7, p = 0.008), and device deployment in the anterior cerebral artery or middle cerebral artery as opposed to the internal carotid artery (OR 3.5, p = 0.034).CONCLUSIONSFlow diversion of anterior circulation cerebral aneurysms is associated with an overall low rate of major complications. The complication rate is significantly lower since the introduction of the second-generation PED (Flex).

Introduction: This study assessed the safety and effectiveness of the Pipeline embolization device (PED) for persistent and recurrent aneurysms previously treated with either a vascular reconstruction device (VRD) or a flow diverter (FD)., Methods: A prospective, IRB-approved database was analyzed for patients treated with PED for aneurysms previously treated with a stent., Results: Twenty procedures were performed on 18 patients, 11 with prior FD, 7 with VRD, and 2 previously treated with both. Overall, 15 aneurysms were saccular (75%), and size was 13.5 ± 7.6 mm. Location was internal carotid artery (ICA) in 14 cases (70%) and posterior circulation in 6 cases (30%). Average prior treatments were 1.7. Previously FD cases were re-treated at an average of 18.1 months from most recent treatment. Each case used 1 device, 82% with distal coverage and 82% with proximal coverage of prior stent. Balloon remodeling was performed in 3 cases (27%) and no in-stent thrombosis was observed. Previously VRD stent-coiled cases were re-treated at an average of 87.5 months. These cases used on average 1.9 devices, 89% with distal and 100% proximal coverage. Adjunctive coiling was performed in 1 case (11%), balloon remodeling in 5 cases (56%), and 2 cases (28%) developed thrombosis that resolved with abciximab. Re-VRD cases were longer (59.1 vs. 33.7 min, p = 0.02) than re-FD. Angiographic follow-up was available for 16 cases (80%). In re-FD, occlusion was complete in 56% and partial progressive in 33% at 17.1 months digital subtraction angiography. In re-VRD, occlusion was complete in 57% and partial progressive in 27% at 8.1 months. Two complications occurred (10%), including one asymptomatic cervical ICA occlusion and one stent occlusion with associated mortality (5%). Clinical follow-up was 17.8 months on average (range 0.5-51.9)., Conclusions: Salvage flow diversion for previously stented aneurysms is technically challenging but offers good prospects of aneurysm obliteration with acceptable complication rates.

Background: Adjunctive coiling may improve occlusion outcomes when combined in a single stage with cerebral aneurysm flow diversion. This technique has not been well described., Objective: To present a series of aneurysm patients treated by single-stage flow diversion with adjunctive coiling, describing technical considerations and outcomes., Methods: This was a retrospective cohort study using an IRB-approved database of procedures performed at a single institution. Treatment selection was based on large aneurysm size, morphological irregularity, branch vessel location, and wide neck., Results: A total of 72 Pipeline with adjunctive coiling (PAC) procedures were performed on 69 patients. Average aneurysm size was 11.0 mm and 86% were wide-necked. Three progressively complex techniques were performed approximately equally: 27 sequential (38%), 23 jailed single-intermediate (32%), and 22 bifemoral jailed microcatheter (31%) cases. Aneurysm dome (P=0.0223) and neck size (P=0.001) increased with procedural complexity and there was a trend toward increased procedure length, radiation exposure, and stent thrombosis. A 'light' coil pack was used with an average packing density of 14% that did not vary by technique. Of the three major complications (4.2%), none were observed with the sequential approach (0%), one with the jailed single-intermediate (4.3%), and two with bifemoral cases (9.1%) (P=0.116). Complete occlusion was achieved in 85% of PAC cases at 6 months and 96% at 12-month follow-up angiography., Conclusions: There are multiple approaches to flow diversion with adjunctive coiling, each with technical challenges, suitable to different types of aneurysms. Flow diversion with coiling can expedite and improve occlusion outcomes without a significant increase in morbidity., Competing Interests: Competing interests: ALC is a consultant and proctor for Medtronic, Stryker, and Microvention. GPC is a consultant for Medtronic and Microvention. L-ML is a proctor for Medtronic., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Embolization has been discussed as a feasible single modality treatment for intracranial arteriovenous malformations (AVMs)., Objective: To compare hemorrhagic risk between embolization and conservative management in a multivariate survival analysis., Methods: We retrospectively reviewed records of patients with intracranial AVMs evaluated at our institution from 1990 to 2013. We included patients recommended to undergo embolization without other treatment modalities and patients managed conservatively. Multivariate Cox regression analysis of hemorrhage-free survival was performed, with the survival interval right-censored to date of either last follow-up or salvage treatment., Results: We identified 205 patients matching our inclusion criteria, with 160 patients in the noninterventional group and 45 in the embolization group. The average age of all patients was 40.2 ± 19.5 yr, with younger patients undergoing embolization more often (P = .026). Fifty-one (31.9%) conservatively managed patients and 13 (28.9%) patients treated by embolization (P = .703) presented with hemorrhage. Other baseline characteristics were similar between the 2 management groups. During an average follow-up period of 7.7 yr, 30 patients (14.6%) experienced hemorrhage recurrence. Multivariate Cox regression revealed older age (P = .031) and hemorrhagic presentation (P < .001) to be statistically associated with follow-up hemorrhage. In a subset analysis of unruptured AVMs, embolization was associated with a 4-fold hazard ratio of hemorrhage compared to conservative management (P = .044)., Conclusion: Older age and initial presentation with hemorrhage were associated with increased risk of hemorrhage during follow-up. Treatment of AVMs with embolization as the sole modality may increase hemorrhagic risk compared with conservative management, especially in unruptured AVMs.

Background: Posterior fossa arteriovenous malformations (AVMs) are associated with increased risk of rupture and severe consequences from such rupture. The hemorrhagic risk of prenidal aneurysms (anr) on the posterior inferior cerebellar artery (PICA) may exceed that of the AVM in posterior fossa AVMs fed by PICA (PICA-AVM)., Objective: To characterize the relative risks of aneurysm and AVM hemorrhage in patients with posterior fossa AVMs., Methods: We retrospectively reviewed patients diagnosed with AVM. Patients with posterior fossa AVMs were divided into 3 groups: PICA-AVM with prenidal aneurysm (PICA-AVM-anr group), PICA-AVM without prenidal aneurysm (PICA-AVM group), and AVMs without PICA feeder with/without aneurysm (AVM-only group). Patient and lesion characteristics and treatment outcomes were compared. ANOVA and chi squared tests were used for statistical analyses., Results: Our cohort included 85 patients. Mean age was 45.3 ± 18.1 yr, with 43(50.6%) female patients. Fifty-one patients (60.0%) had hemorrhagic presentation, and 27 (31.8%) experienced acute hydrocephalus. Patients in the PICA-AVM-anr group (n = 11) were more likely to present with aneurysmal subarachnoid hemorrhage (SAH; P = .005) and less likely to have AVM rupture (P < .001). Ten (90.9%) patients presented with hemorrhage, 6 (60.0%) of which resulted from aneurysm rupture. Of these 6, 5 (83.3%) had acute hydrocephalus. No patients with AVM rupture had hydrocephalus. Eight (72.7%) received aneurysm treatment prior to AVM treatment. There were no significant differences in post-treatment outcomes dependent on treatment order., Conclusion: In addition to relatively higher risk of AVM rupture from infratentorial location and prenidal aneurysm, a higher risk of aneurysm rupture rather than AVM rupture was observed in patients with PICA-AVM-anr complex.

Competing Interests: Competing interests: Dr Chen reports being a consultant for Medtronic, Penumbra, Stryker and Genentech Dr Fraser is an equity interest holder for Fawkes Biotechnology, LLC, and a consultant for Stream Biomedical. Dr Hetts reports being a consultant for Medina and Neuravi, as well as research contracts with Stryker Neurovascular, Siemens, Micro Vention Terumo. Dr. Klucznik reports being a proctor and speaker for Medtronic. Dr Mocco reports the following: Consultant: Rebound Therapeutics, TSP Inc., Cerebrotech, Lazarus Effect, Pulsar, Medina. investor: Blockade Medical, TSP Inc., Lazarus effect, Medina PI/CO-PI for the following trials: THERAPY (PI), FEAT (PI), INVEST (Co-PI), COMPASS (Co-PI), LARGE (Co-PI), COAST (Co-PI), POSITIVE (Co-PI). Steering committee for the MAPS trial. Dr Prestigiacomo reports the following: Consultant, Codman Neurovascular (serving on DSMB) Dr Pride reports the following: Consultant, Sequent Medical (DSMB for Web-IT study) Dr Sunenshine reports protctoring for Medtronic, and is an investigator in STRATIS (Medtronic) and CARE (Penumbra) studies. All other authors report no relevant conflicts of interest.

Despite concern of hemorrhagic risk, patients with occipital AVMs are at significant risk for visual disturbances after treatment. We aim to characterize the hemorrhage risk and visual disturbance in occipital AVMs patients from our experience and literature review. We performed retrospective review of occipital AVM patients seen at our institution from 1990 to 2015. Patient characteristics were compared using multivariable logistic regression with follow-up visual disturbance as the outcome. We also systematically reviewed the PubMed database for English literature describing occipital AVMs (with exclusion of case reports). Ninety-seven patients satisfied inclusion criteria for our study. Mean age was 34.9 ± 16.4 years, with 50.5% male. Thirty-one (32.0%) presented with hemorrhage, and 32 (33.0%) presented with visual disturbance. Average AVM size was 4.0 ± 2.5 cm. Twenty-five (25.8%) were conservatively managed, 13 (13.4%) underwent surgery, and the rest were managed by radiosurgery (52.6%) or embolization (8.2%), with an obliteration rate of 38.9% in treated patients. During average follow-up of 5.4 years, 6 patients (6.7%) hemorrhaged yielding an annual hemorrhage rate of 1.2% for all patients, and 0.0% for surgically-treated patients. Thirty-seven (38.3%) patients experienced visual disturbance in some capacity, nineteen (21.1%) had de novo visual disturbance, fourteen of which were surgically treated patients (19.4%). Multivariable analysis reveals visual disturbance at presentation (p = .012) and microsurgery (p = .047) are significantly predictors of follow-up visual disturbance. While hemorrhage control remains the primary goal of AVM treatment, visual preservation in occipital AVMs is also a major concern. Recommending patients for microsurgery should be weighed carefully and individualized as it bears the highest risk of visual field disturbance despite most optimal hemorrhage control., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Few reports have compared surgical intervention with conservative treatment for moyamoya disease (MMD) in non-Asian cohorts. This study describes the effectiveness of follow-up stroke prevention by indirect revascularization relative to conservative management in a Northeast United States study population., Method: We retrospectively reviewed records of patients with MMD at our institution from 1990 to 2014. Baseline characteristics and follow-up results including subsequent ipsilateral strokes were collected, and compared between an indirect revascularization group and a conservatively treated group on a per-hemisphere basis., Results: A total of 94 patients with 184 hemispheres were included. The average age was 23.9 ± 18.1 years, with 76.6% (n = 141) being female. Racial distribution comprised white (n = 75, 40.8%), African-American (n = 57, 31.0%), Asian (n = 30, 16.3%), and other (n = 22, 12.0%). Eighty-three hemispheres (45.1%) presented with ipsilateral stroke and 54 (29.3%) with ipsilateral TIA. Management strategies included either conservative management (51.1%) or indirect bypass (48.9%). Patients who were male (P < 0.001), on baseline antiplatelets (P = 0.043), or with speech disturbance (P = 0.002) were more likely to receive indirect revascularization. Patients with headache history were more likely to be treated conservatively (P = 0.046). History of ipsilateral stroke was borderline associated with indirect bypass (P = 0.058). During a follow-up period of 6.37 ± 5.81 years, the annual risk of stroke for indirect revascularization group was 0.93% and 2.70% for the conservative group. Multivariate analysis found that increasing age (P = 0.029), posterior cerebral artery involvement (P = 0.040), and conservative treatment (P = 0.048) were associated with follow-up stroke., Conclusion: Our results suggests that indirect revascularization provides symptom relief and lower risk of stroke during follow-up compared with conservative management. Indirect revascularization should be considered for symptomatic MMD patients with a low surgical risk profile in a similar patient population., (Copyright © 2017 Elsevier Inc. All rights reserved.)