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Phenolic compounds, which are significant emissions from biomass burning (BB), undergo rapid photochemical reactions in both gas and aqueous phases to form secondary organic aerosol, namely, gasSOA and aqSOA, respectively. The formation of gasSOA and aqSOA involves different reaction mechanisms, leading to different product distributions. In this study, we investigate the gaseous and aqueous reactions of guaiacol-a representative BB phenol-to elucidate the compositional differences between phenolic aqSOA and gasSOA. Aqueous-phase reactions of guaiacol produce higher SOA yields than gas-phase reactions (e.g., roughly 60 vs 30% at one half-life of guaiacol). These aqueous reactions involve more complex reaction mechanisms and exhibit a more gradual SOA evolution than their gaseous counterparts. Initially, gasSOA forms with high oxidation levels (O/C > 0.82), while aqSOA starts with lower O/C (0.55-0.75). However, prolonged aqueous-phase reactions substantially increase the oxidation state of aqSOA, making its bulk chemical composition closer to that of gasSOA. Additionally, aqueous reactions form a greater abundance of oligomers and high-molecular-weight compounds, alongside a more sustained production of carboxylic acids. AMS spectral signatures representative of phenolic gasSOA have been identified, which, together with tracer ions of aqSOA, can aid in the interpretation of field observation data on aerosol aging within BB smoke. The notable chemical differences between phenolic gasSOA and aqSOA highlighted in this study also underscore the importance of accurately representing both pathways in atmospheric models to better predict the aerosol properties and their environmental impacts., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Infant vaccination coverage rates in Peru have declined in recent years, exacerbated by the COVID-19 pandemic. Introduction of the fully-liquid diphtheria, tetanus, and acellular pertussis (DTaP)-inactivated polio vaccine (IPV)-hepatitis B (HB)-Haemophilus influenzae type B (Hib) hexavalent vaccine (DTaP-IPV-HB-Hib) in Peru's infant National Immunization Program may help improve coverage. We evaluated costs and healthcare outcomes, including coverage, of switching from a pentavalent vaccine containing whole-cell pertussis component (DTwP-HB-Hib) plus IPV/oral polio vaccine (IPV/OPV) to the hexavalent vaccine for the primary vaccination scheme (2, 4 and 6 months)., Methods: The analysis was performed over a 5-year period on a cohort of children born in Peru in 2020 (N = 494,595). Four scenarios were considered: the pentavalent plus IPV/OPV scheme (S1); replacing the pentavalent plus IPV/OPV scheme with the hexavalent scheme (S2); expanded delivery of the pentavalent plus IPV/OPV scheme (S3); expanded delivery of the hexavalent scheme (S4). Vaccine coverage and incidence of adverse reactions (ARs) were estimated using Monte Carlo simulations and previous estimates from the literature. Cases of vaccine-preventable diseases were estimated using a Markov model. Logistical and healthcare costs associated with these outcomes were estimated. Impact of key variables (including coverage rates, incidence of ARs and vaccine prices) on costs was evaluated in sensitivity analyses., Results: The overall cost from a public health payer perspective associated with the pentavalent plus IPV/OPV vaccine scheme (S1) was estimated at $56,719,350, increasing to $61,324,263 (+ 8.1%), $59,121,545 (+ 4.2%) and $64,872,734 (+ 14.4%) in scenarios S2, S3 and S4, respectively. Compared with the status quo (S1), coverage rates were estimated to increase by 3.1% points with expanded delivery alone, and by 9.4 and 14.3% points, if the hexavalent vaccine is deployed (S2 and S4, respectively). In both scenarios with the hexavalent vaccine (S2 and S4), pertussis cases would also be 5.7% and 8.7% lower, and AR rates would decrease by 32%. The cost per protected child would be reduced when the hexavalent vaccine scheme. Incidence of ARs was an important driver of cost variability in the sensitivity analysis., Conclusions: Implementation of the hexavalent vaccine in Peru's National Immunization Program has a positive public health cost consequence., (© 2024. The Author(s).)

Background and Objectives: Dual antiplatelet therapy (DAPT) is necessary to minimize the risk of periprocedural thromboembolic complications associated with aneurysm embolization using pipeline embolization device (PED). We aimed to assess the impact of platelet function testing (PFT) on reducing periprocedural thromboembolic complications associated with PED flow diversion in patients receiving aspirin and clopidogrel., Methods: Patients with unruptured intracranial aneurysms requiring PED flow diversion were identified from 13 centers for retrospective evaluation. Clinical variables including the results of PFT before treatment, periprocedural DAPT regimen, and intracranial complications occurring within 72 h of embolization were identified. Complication rates were compared between PFT and non-PFT groups. Differences between groups were tested for statistical significance using the Wilcoxon rank sum, Fisher exact, or χ 2 tests. A P -value <.05 was statistically significant., Results: 580 patients underwent PED embolization with 262 patients dichotomized to the PFT group and 318 patients to the non-PFT group. 13.7% of PFT group patients were clopidogrel nonresponders requiring changes in their pre-embolization DAPT regimen. Five percentage of PFT group [2.8%, 8.5%] patients experienced thromboembolic complications vs 1.6% of patients in the non-PFT group [0.6%, 3.8%] ( P = .019). Two (15.4%) PFT group patients with thromboembolic complications experienced permanent neurological disability vs 4 (80%) non-PFT group patients. 3.7% of PFT group patients [1.5%, 8.2%] and 3.5% [1.8%, 6.3%] of non-PFT group patients experienced hemorrhagic intracranial complications ( P > .9)., Conclusion: Preprocedural PFT before PED treatment of intracranial aneurysms in patients premedicated with an aspirin and clopidogrel DAPT regimen may not be necessary to significantly reduce the risk of procedure-related intracranial complications., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Objectives: Type 2 diabetes mellitus (T2DM) represents an increasing public health problem in Peru. This study aims to estimate the national economic burden of this disease for the public funder, the social security, and private sector insurers., Methods: Direct healthcare costs were estimated for a cohort of 45-to-75-year-old adults diagnosed with T2DM in 2019, over a 20-year period. Disease progression was modeled using PROSIT Models and literature, including acute and chronic microvascular and macrovascular complications. Three scenarios of glycemic control were considered: current levels of 35.8% of the population controlled (HbA1c < 7%) (S1); 100% controlled (S2) and; 100% uncontrolled (S3). The impact of diabetes prevalence on overall costs was evaluated in sensitivity analysis., Results: Total national economic burden was estimated at $15,405,448,731; an annual average per patient of $2,158. Total costs would decrease to $12,853,113,596 (-16.6%) in S2 and increase to $16,828,713,495 (+9.2%) in S3. Treating patients with complications and risk factors could cost 6.5 times more, being stroke the complication with the highest impact. Up to a 67.6% increase in total costs was found when increasing T2DM prevalence., Conclusions: T2DM places a heavy burden on the Peruvian healthcare budget that will be even greater if poor glycemic control is maintained.

A single center had a collaborative, multidisciplinary review to determine how to best implement new acute ischemic stroke trials involving large vessel occlusions. A flow diagram process map was created for clinical decision support. Patients were divided into four groups based upon size of infarct and timing of presentation. The process map, available in the electronic health record (EHR) for clinicians to reference, guides the selection of patients for endovascular therapy with neuroimaging. In addition, the process map offers guidance for discussions with families and patients experiencing large vessel occlusions with both small and large core infarcts. This manuscript describes the process of creating the process map through a multidisciplinary review and discussion, with points of controversy and how these were addressed., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Blister aneurysms are high-risk intracranial vascular lesions. Definitive treatment of these lesions has been challenging. Severe disability or mortality rates are as high as 55% when these lesions are treated with open surgery. Recent data show that flow diversion is a safe and effective alternative treatment for blister aneurysms. Rerupture of the functionally unsecured lesion remains a concern as flow diversion does not immediately exclude the aneurysm from the circulation., Methods: A retrospective review was performed of any patients with ruptured blister aneurysms treated with a pipeline embolization device between 2010 and 2020 at the University of Colorado., Results: In this paper, we present the results of the intensive care management of ruptured intracranial blister aneurysms after flow-diverting stent placement., Conclusion: Despite the need for dual antiplatelet therapy and the delayed occlusion of blister aneurysms treated with flow diversion, we did not find an increase in periprocedural complications., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Surgical Neurology International.)

Aerosol vertical distribution plays a crucial role in cloud development and thus precipitation since both aerosol indirect and semi-direct effects significantly depend on the relative position of aerosol layer in reference to cloud, but its precise influence on cloud remains unclear. In this study, we integrated multi-year Raman Lidar measurements of aerosol vertical profiles from the U.S. Department of Energy Atmospheric Radiation Measurement (ARM) facility with available Value-Added Products of cloud features to characterize aerosol vertical distributions and their impacts on warm clouds over the continental and marine ARM atmospheric observatories, i.e., Southern Great Plains (SGP) and Eastern North Atlantic (ENA). A unimodal seasonal distribution of aerosol optical depths (AODs) with a peak in summer is found at upper boundary layer over SGP, while a bimodal distribution is observed at ENA for the AODs at lower levels with a major winter-spring maximum. The diurnal mean of upper-level AOD at SGP shows a maximum in the early evening. According to the relative positions of aerosol layers to clouds we further identify three primary types of aerosol vertical distribution, including Random, Decreasing, and Bottom. It is found that the impacts of aerosols on cloud may or may not vary with aerosol vertical distribution depending on environmental conditions, as reflected by the wide variations of the relations between AOD and cloud properties. For example, as AOD increases, the liquid water paths (LWPs) tend to be reduced at SGP but enhanced at ENA. The relations of cloud droplet effective radius with AOD largely depend on aerosol vertical distributions, particularly showing positive values in the Random type under low-LWP condition (<50 g m -2 ). The distinct features of aerosol-cloud interactions in relation to aerosol vertical distribution are likely attributed to the continental-marine contrast in thermodynamic environments and aerosol conditions between SGP and ENA., 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 © 2023 Elsevier B.V. All rights reserved.)

Objective: Endoluminal flow diversion reduces blood flow into intracranial aneurysms, promoting thrombosis. Postprocedural dual antiplatelet therapy (DAPT) is necessary for the prevention of thromboembolic complications. The purpose of this study is to therefore assess the impact that the type and duration of DAPT has on aneurysm occlusion rates and iatrogenic complications after flow diversion., Methods: A retrospective review of a multicenter aneurysm database was performed from 2012 to 2020 to identify unruptured intracranial aneurysms treated with single device flow diversion and ≥12-month follow-up. Clinical and radiologic data were analyzed with aneurysm occlusion as a function of DAPT duration serving as a primary outcome measure., Results: Two hundred five patients underwent flow diversion with a single pipeline embolization device with 12.7% of treated aneurysms remaining nonoccluded during the study period. There were no significant differences in aneurysm morphology or type of DAPT used between occluded and nonoccluded groups. Nonoccluded aneurysms received a longer mean duration of DAPT (9.4 vs 7.1 months, P = 0.016) with a significant effect of DAPT duration on the observed aneurysm occlusion rate (F(2, 202) = 4.2, P = 0.016). There was no significant difference in the rate of complications, including delayed ischemic strokes, observed between patients receiving short (≤6 months) and prolonged duration (>6 months) DAPT (7.9% vs 9.3%, P = 0.76)., Conclusions: After flow diversion, an abbreviated duration of DAPT lasting 6 months may be most appropriate before transitioning to low-dose aspirin monotherapy to promote timely aneurysm occlusion while minimizing thromboembolic complications., Competing Interests: J.R.M. has received consulting compensation for Stryker and Penumbra. A.B.P. has received consulting, proctoring, and lecturing compensation from Medtronic, Microvention, and Penumbra. J.S. has received consulting compensation from Medtronic. The remaining authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Ruptured blister, dissecting, and iatrogenic pseudoaneurysms are rare pathologies that pose significant challenges from a treatment standpoint. Endovascular treatment via flow diversion represents an increasingly popular option; however, drawbacks include the requirement for dual antiplatelet therapy and the potential for thromboembolic complications, particularly acute complications in the ruptured setting. The Pipeline Flex embolization device with Shield Technology (PED-Shield) offers reduced material thrombogenicity, which may aid in the treatment of ruptured internal carotid artery pseudoaneurysms., Methods: The authors conducted a multi-institution, retrospective case series to determine the safety and efficacy of PED-Shield for the treatment of ruptured blister, dissecting, and iatrogenic pseudoaneurysms of the internal carotid artery. Clinical, radiographic, treatment, and outcomes data were collected., Results: Thirty-three patients were included in the final analysis. Seventeen underwent placement of a single device, and 16 underwent placement of two devices. No thromboembolic complications occurred. Four patients were maintained on aspirin alone, and all others were treated with long-term dual antiplatelet therapy. Among patients with 3-month follow-up, 93.8% had a modified Rankin Scale score of 0-2. Complete occlusion at follow-up was observed in 82.6% of patients., Conclusions: PED-Shield represents a new option for the treatment of ruptured blister, dissecting, and iatrogenic pseudoaneurysms of the internal carotid artery. The reduced material thrombogenicity appeared to improve the safety of the PED-Shield device, as this series demonstrated no thromboembolic complications even among patients treated with only single antiplatelet therapy. The efficacy of PED-Shield reported in this series, particularly with placement of two devices, demonstrates its potential as a first-line treatment option for these pathologies.

Background: "Telescoping" multiple overlapping Pipeline Embolization Devices (PEDs; Medtronic) has increased their utility by allowing for more impermeable coverage and providing the ability to off-set landing zone sites and extend treatment constructs., Objective: To consider the technical nuances and challenges of telescoping PEDs for the treatment of intracranial aneurysms., Methods: Databases from 3 U.S. academic neurovascular centers were retrospectively queried to identify patients with intracranial aneurysms treated with multiple PED constructs. Data on patient and aneurysm characteristics, as well as outcomes including Raymond-Roy occlusion classification, modified Rankin Scale score, and complications, were gathered., Results: Forty-six patients had 48 intracranial aneurysms treated, including 16 (33%) in whom placement of telescoping PEDs was planned. Fourteen (30%) patients presented with a ruptured aneurysm. Twenty-one aneurysms (44%) were treated with proximal extension, 13 (27%) with distal extension, and 14 (29%) with PED placement inside one another. Thirty (70%) patients had complete aneurysm occlusion at follow-up. Two (4%) patients had to be retreated. Three patients with unruptured and 1 with ruptured aneurysm had a permanent intraprocedural complication. We present descriptive cases illustrating PEDs that were placed inside one another, proximally, distally, and to improve wall apposition because of vessel tortuosity., Conclusion: Our data indicate a higher than expected complication rate that is likely because of the technical complexity of these cases. The case illustrations presented demonstrate the indications and challenging aspects of telescoping PEDs., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Purpose: Flow diverting stents have revolutionized the treatment of intracranial aneurysms through endoluminal reconstruction of the parent vessel. Despite this, certain aneurysms require retreatment. The purpose of this study was to identify clinical and radiologic determinants of aneurysm retreatment following flow diversion., Methods: A multicenter flow diversion database was evaluated to identify patients presenting with an unruptured, previously untreated aneurysm with a minimum of 12 months' clinical and angiographic follow-up. Univariate and multivariate logistic regression modeling was performed to identify determinants of retreatment., Results: We identified 189 aneurysms treated in 189 patients with a single flow-diverting stent. Mean age was 54 years, and 89% were female. Complete occlusion was achieved in 70.3% and 83.6% of patients at six and 12 months, respectively. Aneurysm retreatment with additional flow-diverting stents occurred in 5.8% of cases. Univariate analysis revealed that dome diameter ≥ 10 mm ( p  = 0.012), pre-clinoid internal carotid artery location ( p  = 0.012), distal > proximal parent vessel diameter ( p  = 0.042), and later dual antiplatelet therapy (DAPT) discontinuation ( p  < 0.001) were predictive of retreatment. Multivariate analysis identified discontinuation of DAPT > 12 months ( p  = 0.003) as a strong determinant of retreatment with dome diameter ≥ 10 mm trending toward statistical significance ( p  = 0.064). Large aneurysm neck diameter, presence of aneurysm branch vessels, patient age, smoking history, and hypertension were not determinant of retreatment on multivariate analysis., Conclusions: Prolonged DAPT is the most important determinant of aneurysm retreatment following single-device flow diversion. Abbreviating DAPT duration to only six months should be a consideration in this population, especially for patients with a large aneurysm dome diameter.

Spontaneous intracranial hypotension (SIH) is a disorder of CSF dynamics that causes a complex clinical syndrome and severe disability. SIH is challenging to diagnose because of the variability of its presenting clinical symptoms, the potential for subtle imaging findings to be easily overlooked, and the need for specialized diagnostic testing. Once SIH is suggested by clinical history and/or supported by initial neuroim-aging, many patients may undergo initial nontargeted epidural blood patching with variable and indefinite benefit. However, data suggest that precise localization of the CSF leak or CSF-venous fistula (CVF) can lead to more effective and durable treatment strategies. Leak localization can be achieved using a variety of advanced diagnostic imaging techniques, although these may not be widely performed at nontertiary medical centers, leaving many patients with the potential for inadequate workup or treatment. This review describes imaging techniques including dynamic fluoroscopic and CT myelography as well as delayed MR myelography and treatment options including percutaneous, endovascular, and surgical approaches for SIH. These are summarized by an algorithmic framework for radiologists to approach the workup and treatment of patients with suspected SIH. The importance of a multidisciplinary approach is emphasized.

Background and Purpose: Pediatric vertebral artery dissecting aneurysm is a subtype of vertebral artery dissection that can be challenging to diagnose and may be associated with stroke recurrence. This study examines the presenting features, clinical outcomes, and recurrence risk in a cohort of children with vertebral artery dissection, comparing those with aneurysms with those without., Materials and Methods: The medical records of children evaluated for vertebral artery dissection were retrospectively reviewed for neurologic presentation, treatment, stroke recurrence, and angiographic appearance of dissection. Cohort patients were categorized into 2 groups based on the presence or absence of a vertebral artery dissecting aneurysm and compared via the Fisher exact test, Student t test, and log-rank analyses. P < .05 was deemed statistically significant., Results: Thirty-two patients met the inclusion criteria, including 13 with vertebral artery dissecting aneurysms. Five cases of vertebral artery dissecting aneurysm were missed on the initial evaluation and diagnosed retrospectively. All patients received antiplatelet or anticoagulation therapy at the time of diagnosis. Children in the vertebral artery dissecting aneurysm group were more likely to present with stroke ( P = .059), present at a younger age ( P < .001), and have recurrent stroke ( P < .001) compared with the group of children with vertebral artery dissection without an aneurysm. After surgery, no patients with vertebral artery dissecting aneurysm experienced recurrent stroke ( P = .02)., Conclusions: Vertebral artery dissecting aneurysm is often missed on the initial diagnostic evaluation of children presenting with stroke. In children with vertebral artery dissection, the presence of an aneurysm is associated with stroke presentation at a younger age and stroke recurrence., (© 2022 by American Journal of Neuroradiology.)

Brain arteriovenous malformations (AVMs) often present treatment challenges. Patients with unruptured AVMs must consider not only whether they want to be treated, but what treatment modality they would prefer. Vascular neurosurgeons, neurointerventional surgeons, and stereotactic radiosurgeons must in turn guide their patients through the most appropriate treatment course considering the risk of AVM rupture, an individual AVM's characteristics, and patient preferences. In this review we will look at how the clinical trial "A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA)" has influenced the approach to unruptured brain AVMs and the treatment modalities available to clinicians to deal with these formidable lesions.

The diagnosis and treatment of cerebral cavernous malformations (CCMs), or cavernomas, continues to evolve as more data and treatment modalities become available. Intervention is necessary when a lesion causes symptomatic neurologic deficits, seizures, or has high risk of continued hemorrhage. Future medical treatment directions may specifically target the pathogenesis of these lesions. This review highlights the importance of individualized treatment plans based on specific CCM characteristics.

Background: This study aimed to estimate the economic impact of replacing the current Peruvian primary immunization scheme for infants under 1 year old with an alternative scheme with similar efficacy, based on a hexavalent vaccine., Methods: A cost-minimization analysis compared the costs associated with vaccine administration, adverse reactions medical treatment, logistical activities, and indirect social costs associated with time spent by parents in both schemes. A budgetary impact analysis assessed the financial impact of the alternative scheme on healthcare budget., Results: Incorporating the hexavalent vaccine would result in a 15.5% net increase in healthcare budget expenditure ($48,281,706 vs $55,744,653). Vaccination costs would increase by 54.1%, whereas logistical and adverse reaction costs would be reduced by 59.8% and 33.1%, respectively. When including indirect social costs in the analysis, the budgetary impact was reduced to 8.7%. Furthermore, the alternative scheme would enable the liberation of 17.5% of national vaccines storage capacity., Conclusions: Despite of the significant reduction of logistical and adverse reaction costs, including the hexavalent vaccine into the National Immunization Program of Peru in place of the current vaccination scheme for infants under 1 year of age would increase the public financial budget of the government as it would represent larger vaccine acquisition costs. Incorporating the indirect costs would reduce the budgetary impact demonstrating the social value of the alternative scheme. This merits consideration by government bodies, and future studies investigating such benefits would be informative., (© 2022. The Author(s).)

Background: Catheter retention and difficulty in retrieval have been observed during embolization of brain arteriovenous malformations (bAVMs) with the Onyx liquid embolic system (Onyx). The Apollo Onyx delivery microcatheter (Apollo) is a single lumen catheter designed for controlled delivery of Onyx into the neurovasculature, with a detachable distal tip to aid catheter retrieval. This study evaluates the safety of the Apollo for delivery of Onyx during embolization of bAVMs., Methods: This was a prospective, non-randomized, single-arm, multicenter, post-market study of patients with a bAVM who underwent Onyx embolization with the Apollo between May 2015 and February 2018. The primary endpoint was any catheter-related adverse event (AE) at 30 days, such as unintentional tip detachment or malfunction with clinical sequelae, or retained catheter. Procedure-related AEs (untoward medical occurrence, disease, injury, or clinical signs) and serious AEs (life threatening illness or injury, permanent physiological impairment, hospitalization, or requiring intervention) were also recorded., Results: A total of 112 patients were enrolled (mean age 44.1±17.6 years, 56.3% men), and 201 Apollo devices were used in 142 embolization procedures. The mean Spetzler-Martin grade was 2.38. The primary endpoint was not observed (0/112, 0%). The catheter tip detached during 83 (58.5%) procedures, of which 2 (2.4%) were unintentional and did not result in clinical sequelae. At 30 days, procedure related AEs occurred in 26 (23.2%) patients, and procedure-related serious AEs in 12 (10.7%). At 12 months, there were 3 (2.7%) mortalities, including 2 (1.8%) neurological deaths, none of which were device-related., Conclusion: This study demonstrates the safety of Apollo for Onyx embolization of bAVMs., Clinical Trial Registration: CNCT02378883., Competing Interests: Competing interests: JF reports grants and non-financial support from Stryker, grants and other funding from Penumbra, grants from Microvention, and equity in Cerebrotech and The Stroke Project. CAG serves on the speaker’s bureau and as a consultant and proctor for Medtronic and Stryker, and serves on the speaker’s bureau for Genentech. MM serves as a consultant for Toshiba/Canon Medical. PK serves as a consultant for Stryker Neurovascular, Medtronic, and Cerenovus. TY serves as a consultant and proctor for Medtronic. OD serves as a proctor for Microvention/Terumo. DF serves as a consultant for Balt, Marblehead Medical, Medtronic, Stryker, Microvention, Penumbra, and Cerenovus, receives research support from Cerenovus, Medtronic, Stryker, Siemens, Microvention, and Penumbra, receives royalties from Codman, and is a stockholder in Marblehead, Neurogami, and Vascular simulations outside the submitted work. RVC has received research funding from Microvention, Cerenovus, and Medtronic. AKW has received research grants from Philips Medical, serves as a consultant for Stryker and Phenox, is a stockholder in InNeuroCo, EpiEP, Neural Analytics, Rist, Analytics 4 Life, and ThrombX, and serves on the speaker’s bureau for SCENT trial presentations. ASP serves as a consultant for and has received research grants from Medtronic Neurovascular and Stryker Neurovascular. RAH serves as a consultant for Medtronic, Stryker, Codman, and Microvention, and is a stockholder in InNeuroCo. LFG holds stock in Culvert Therapeutics and NeuroCool, serves as a proctor for Medtronic Neurovascular, and participates in training other physicians in the use pipeline embolization device. MAA-S serves as a proctor for Medtronic Neurovascular, and participates in training other physicians in the use of the embolic agent Onyx and the pipeline embolization device., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

While calpains have been implicated in neurogenesis for a long time, there is still little information regarding the specific contributions of various isoforms in this process. We took advantage of the availability of mutant mice with complete deletion of calpain-1 to analyze its contribution to neurogenesis. We first used the incorporation of BrdU in newly-generated cells in the subgranular zone of the dentate gyrus to determine the role of calpain-1 deletion in neuronal proliferation. Our results showed that the lack of calpain-1 decreased the rate of cell proliferation in adult hippocampus. As previously shown, it also decreased the long-term survival of newly-generated neurons. We also used data from previously reported RNA and miRNA sequencing analyses to identify differentially expressed genes in brain of calpain-1 knock-out mice related to cell division, cell migration, cell proliferation and cell survival. A number of differentially expressed genes were identified, which could play a significant role in the changes in neurogenesis in calpain-1 knock out mice. The results provide new information regarding the role of calpain-1 in neurogenesis and have implications for better understanding the pathologies associated with calpain-1 mutations in humans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Baudry, Su, Seinfeld, Sun and Bi.)

Objective: The repair of unruptured intracranial aneurysms has increased since 2000. In this study, we analyzed the Nationwide Readmission Database (NRD) to determine the rate of 90-day readmission. Our objective is to examine readmission trends after unruptured aneurysm repair., Methods: This study used the 2013 and 2014 NRD. Patient data included standard demographic, comorbidity, and payer information. We selected patients who had undergone microsurgical or endovascular repair for a nonruptured aneurysm. We excluded patients who were under 18 years of age, had a subarachnoid hemorrhage, or were discharged to home the same day. Readmission was calculated by counting the number of days between the end of the index visit and earliest readmission date., Results: A total of 2180 of 29,694 patients (7.34%) were readmitted within 90 days of their initial hospitalization. They were younger (mean, 52.6 years; 95% confidence interval [CI], 51.4-53.8) than patients not readmitted (mean, 57.4 years; 95% CI, 57.1-57.8; P < 0.0001). In total, endovascular repair was more frequent than microsurgery (79.8% vs. 20.2%, respectively). Mean days to readmission was 41.8 (95% CI, 39.7-43.9) and was higher for women (P < 0.0001). The odds ratio for readmission after an endovascular repair was 1.54 (95% CI, 1.27-1.86)., Conclusions: In this study of over 28,000 patients treated for an unruptured aneurysm, the 90-day readmission rate was 7.34%. Endovascular patients had higher odds of readmission than microsurgical patients. Patients with common medical comorbidities (hypertension, obesity, renal failure, and diabetes) were less likely to be readmitted than patients without those conditions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: The aim of this publication is to present a case of idiopathic spinal cord herniation (ISCH) associated with a transdural disk herniation, demonstrate an operative technique used to treat this condition and provide an updated review the literature., Background Context: ISCH is an infrequent condition that can cause progressive myelopathy leading to severe neurological dysfunction. This condition is characterized by ventral displacement of the spinal cord across a defect in the dura, either congenital or acquired, resulting in vascular compromise and adhesion that subsequently causes injury to the spinal cord. We present the management of such a patient, in addition to a review of the literature regarding management of ISCH., Methods: This patient underwent surgery using the dural graft sling technique for repair of the dural defect and restoration of normal spinal cord position within the thecal sac. A review of the literature revealed a total of 171 patients supplemented by our 1 patient, which were then analyzed., Results: The majority of patients, treated with a variety of surgical techniques, experienced improvements in symptomatology. Our patient experienced significant improvement in symptomatology., Conclusions: Although ISCH is a rare clinical condition that causes myelopathy, patients managed with surgery generally, though not universally, have a favorable neurological outcome. The associated surgical technique video demonstrates the dural sling technique for the treatment of this rare disorder.

During the Marine Aerosol Cloud and Wildfire Study (MACAWS) in June and July of 2018, aerosol composition and cloud condensation nuclei (CCN) properties were measured over the N.E. Pacific to characterize the influence of aerosol hygroscopicity on predictions of ambient CCN and stratocumulus cloud droplet number concentrations (CDNC). Three vertical regions were characterized, corresponding to the marine boundary layer (MBL), an above-cloud organic aerosol layer (AC-OAL), and the free troposphere (FT) above the AC-OAL. The aerosol hygroscopicity parameter ( κ ) was calculated from CCN measurements ( κ CCN ) and bulk aerosol mass spectrometer (AMS) measurements ( κ AMS ). Within the MBL, measured hygroscopicities varied between values typical of both continental environments (~0.2) and remote marine locations (~0.7). For most flights, CCN closure was achieved within 20% in the MBL. For five of the seven flights, assuming a constant aerosol size distribution produced similar or better CCN closure than assuming a constant "marine" hygroscopicity ( κ = 0.72). An aerosol-cloud parcel model was used to characterize the sensitivity of predicted stratocumulus CDNC to aerosol hygroscopicity, size distribution properties, and updraft velocity. Average CDNC sensitivity to accumulation mode aerosol hygroscopicity is 39% as large as the sensitivity to the geometric median diameter in this environment. Simulations suggest CDNC sensitivity to hygroscopicity is largest in marine stratocumulus with low updraft velocities (<0.2 m s -1 ), where accumulation mode particles are most relevant to CDNC, and in marine stratocumulus or cumulus with large updraft velocities (>0.6 m s -1 ), where hygroscopic properties of the Aitken mode dominate hygroscopicity sensitivity.

Idiopathic intracranial hypertension (IIH) is a disease process of abnormally increased intracranial pressure in the absence of a mass lesion. Medical management, optic nerve fenestration, and surgical shunting procedures have failed to produce consistently successful results. In an unknown percentage of cases, IIH is caused by dural venous sinus obstruction which can be cured by endovascular treatment with dural venous sinus stent placement. This helps prevent progressive vision loss and worsening papilledema caused by underlying increased intracranial pressure from venous outflow obstruction. Patients are required to have an established diagnosis of IIH, preferably made by a neuroophthalmologist, with clearly documented papilledema or at minimum visual disturbance along with lumbar puncture opening pressure greater than 25 cm H 2 O. Transverse to sigmoid sinus focal narrowing (intraluminal filling defect or extrinsic compression) must be seen during the venous phase of neuroangiography (NA) along with a pressure gradient of 10 mm Hg or greater across the focal narrowing during dural venous sinus pressure monitoring. A successful reduction is defined as a pressure gradient of less than 10 mm Hg after stent placement. Neuroophthalmologic follow-up occurs within 1 to 2 months to assess for changes in papilledema. If papilledema is unchanged or worsened, NA and hemodynamic evaluation is repeated for consideration of restenting. Appropriate patient selection criteria are required for IIH venous sinus stenting. The utilization of refined endovascular techniques along with postprocedure follow-up protocols can ultimately cure IIH for a select group of patients., Competing Interests: Conflict of Interest None declared., (© Thieme Medical Publishers.)

Neuroangiography (NA) is a minimally invasive procedure used to diagnose patients with neurovascular diseases. Noninvasive imaging has improved dramatically in recent years and is utilized more frequently; however, further evaluation with NA is still required in certain cases. NA indications include intracranial (cerebral aneurysms, arteriovenous malformations, dural arteriovenous fistula, cerebral vasculitis, cerebral vasospasm, ischemic stroke, nontraumatic subarachnoid hemorrhage, intracerebral hemorrhage, Moyamoya, vein of Galen malformation, intracranial tumors, and pseudotumor cerebri) and extracranial (internal and common carotid artery stenosis, vertebral artery stenosis, carotid artery blowout, vertebral artery blowout, epistaxis, oropharyngeal bleeding, and carotid body tumor) pathologies which can help with diagnosis and potential subsequent endovascular treatment. A thorough understanding of normal and variant cervical/cranial vascular anatomy is required. In addition, periprocedural management, catheter technique, equipment needed, and underlying disease pathology are paramount to successful and safe outcomes. This article will review basic neurovascular anatomy, periprocedural management, NA technique, and tips for safe and successful outcomes., Competing Interests: Conflict of Interest None declared., (© Thieme Medical Publishers.)

Background and Importance: Dural arteriovenous fistulas (DAVFs) may present unique challenges for treatment depending on the anatomy and pattern of venous drainage. If endovascular techniques are to be employed, the DAVF must be amenable to transvenous or transarterial therapy. When access of peripheral vasculature does not provide a straightforward path, less conventional options may be available. This case highlights a novel, technically simple, and effective approach for the treatment of a subset of DAVFs, with venous drainage through calvarial diploic veins, that would make endovascular treatment otherwise challenging or impossible., Clinical Presentation: We present a case of a 66-yr-old female patient who was diagnosed with a symptomatic DAVF located along the sphenoid ridge with a large intraosseous channel containing the draining vein of the fistula. This lesion was successfully treated with transcranial endovascular embolization via direct intraosseous cannulation of the calvarial diploic vein. This novel approach obviated the need for a full-thickness craniotomy, afforded only minimal bone loss, and preserved the integrity of the dura. A 3-mo follow-up angiogram confirmed complete cure of the DAVF with no residual arteriovenous shunt. At 20 mo postembolization, the patient was symptom free, with no reported neurologic deficits. Complete diagnostic work-up, treatment planning in a multidisciplinary environment, and a novel approach for endovascular embolization utilizing a hybrid operating suite played key roles in the successful implementation of this technique., Conclusion: This is the first report of direct intraosseous cannulation of a calvarial diploic vein for successful transcranial endovascular embolization of a symptomatic DAVF., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Objective: The second-generation pipeline embolization device (PED), flex, has improved opening and resheathing ability compared to the first-generation classic PED device. A previously reported single-institutional study suggests that the PED flex devices are associated with lower rates of complications. However, there was limited discussion regarding the complication rate with respect to microcatheter choice for PED delivery and deployment. The present study aims to evaluate outcomes of aneurysm treatment with PED flex versus classic along with the Phenom microcatheter versus Marksman microcatheter., Methods: A retrospective, IRB-approved database of all patients who received a PED classic or PED flex device between January 2012 and July 2018 was analyzed. Microcatheter choice, patient demographics, medical comorbidities, aneurysm characteristics, treatment information, and outcome data were analyzed using univariate analyses., Results: A total of 75 PED procedures were analyzed. There was no significant difference in major complications between the PED classic and PED flex. However, those treated using the Marksman microcatheter were more likely to have a major complication (periprocedural hemorrhage or ischemic event; 16.6% vs. 0%, p = 0.0248) than those treated with the Phenom microcatheter. Within the PED flex cohort, all major complications were associated with the Marksman microcatheter ( p = 0.0289)., Conclusions: The present study does not replicate significantly fewer complications with PED flex but demonstrates a significant reduction in complications with the Phenom microcatheter. Ultimately, this suggests multiple factors are involved in achieving positive outcomes and low complication rates in PED treated unruptured cerebral aneurysms., (All Rights Reserved by JVIN. Unauthorized reproduction of this article is prohibited.)

Background: Wide-necked intracranial aneurysms present unique treatment challenges in the setting of subarachnoid hemorrhage. New generations of endoluminal devices (stents) have expanded our ability to treat complex aneurysms. The PulseRider Aneurysm Neck Reconstruction Device (PulseRider [Cerenovus, Irvine, California, USA]) is new to the U.S. market after receiving Food and Drug Administration approval in June 2017. Official recommendation for use of the PulseRider is with dual antiplatelet therapy (DAPT). Its design has been hypothesized to carry a lower risk of thromboembolic complications in the circumstance that DAPT needs to be discontinued., Methods: Between March and June 2018, we treated 4 cases of ruptured wide-necked basilar tip aneurysms at the University of Colorado Hospital, Aurora, Colorado, with PulseRider-assisted coil embolization. Imaging and chart reviews were performed retrospectively on each of these patients., Results: All 4 aneurysms were successfully treated with PulseRider-assisted coil embolization. There were no periprocedural hemorrhages and no postprocedural reruptures. Two patients developed nonocclusive thrombi in the posterior cerebral arteries at the time of coiling, which was resolved with intra-arterial glycoprotein IIb/IIIa receptor antagonists. Two patients developed external ventricular drain-associated hemorrhages, only one of which developed after the administration of DAPT. All patients were eventually discharged to home., Conclusions: The PulseRider device represents a novel design for stent-assisted coil embolization. We report a small but promising series of its successful use in the acute treatment of wide-necked, ruptured basilar artery aneurysms. Additional experience is needed to determine if this device has a place in our armamentarium for treatment of ruptured aneurysms., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This case report describes a 48-year old female who presented with altered mental status, lower extremity weakness, low back pain and a recent history of subjective fevers and night sweats found to have posterior parieto-occipital and spinal subarachnoid hemorrhage on imaging. Further work-up revealed vasculitic changes in the intracranial vasculature and the external carotid artery on angiography. She also demonstrated positivity for perinuclear anti-neutrophil cytoplasmic (p-ANCA) antibodies overall consistent with ANCA associated central nervous system vasculitis (AAV). The present case describes a rare and new presentation of AAV that caused both a cerebral and spinal subarachnoid hemorrhage. There has been no documentation of spinal subarachnoid hemorrhage associated with primary or secondary vasculitis in the literature. Ultimately, this case demonstrates the important finding that AAV can have spinal cord manifestations and cervical vasculature involvement along with the more classic intra-cranial vasculitis findings., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: Head and neck arteriovenous malformation (AVM) and fistulae treatment without reflux and with nidal penetration are challenging. We describe a case series including adult and pediatric patients utilizing a specific two-microcatheter technique using Onyx with strategic embolization of small feeding branches prior to dominant branch embolization. We aim to demonstrate the safety and efficacy of this technique., Patient Selection: Head and neck vascular malformation cases were reviewed from 2010 to 2017. 11 patients between 2010 and 2017 were treated with serial embolization along with Onyx embolization utilizing a two-microcatheter technique. Five patients had cerebral AVMs, three had dural arteriovenous fistulae, two had mandibular AVMs, and one had a posterior neck AVM. Vascular anatomy, location, and procedural details were recorded., Technique: During procedures 1-4, smaller arterial feeders were embolized first to maximally decrease the intranidal pressure at the time of the embolization of the major residual feeder. The dominant residual feeder was then embolized using two catheters. Coils followed by Onyx were initially deployed through the proximal catheter to form a dense plug. The plug was allowed to solidify for 30 min. Aggressive embolization of the nidus was then performed through the distal catheter., Results: All 11 patients had excellent treatment results with complete (6) or near-complete (5) obliteration of the vascular malformation nidus. No procedural complications were noted, specifically no strokes, hemorrhages, or unintentionally retained catheter fragments occurred., Conclusion: AVMs and fistulae are challenging to treat. A two-microcatheter technique for Onyx embolization with prior embolization of smaller arterial feeders is a safe and efficacious treatment option. This technique allows for maximal nidus penetration while minimizing the risk of nontarget embolization/reflux. In all cases, we achieved excellent results with complete or near-complete obliteration of the vascular malformation nidus.

Objective: Aneurysmal subarachnoid hemorrhage (aSAH) has devastating consequences. The association between higher institutional volumes and improved outcomes for aSAH patients has been studied extensively. However, the literature exploring patterns of transfer in this context is sparse. Expansion of the endovascular workforce has raised concerns about the decentralization of care, reduced institutional volumes, and worsened patient outcomes. In this paper, the authors explored various patient and hospital factors associated with the transfer of aSAH patients by using a nationally representative database., Methods: The 2013 and 2014 years of the National Inpatient Sample (NIS) were used to define an observational cohort of patients with ruptured brain aneurysms. The initial search identified patients with SAH (ICD-9-CM 430). Those with concomitant codes suggesting trauma or other intracranial vascular abnormalities were excluded. Finally, the patients who had not undergone a subsequent procedure to repair an intracranial aneurysm were excluded. These criteria yielded a cohort of 4373 patients, 1379 of whom had undergone microsurgical clip ligation and 2994 of whom had undergone endovascular repair. The outcome of interest was transfer status, and the NIS data element TRAN&#95;IN was used to define this state. Multiple explanatory variables were identified, including age, sex, primary payer, median household income by zip code, race, hospital size, hospital control, hospital teaching status, and hospital location. These variables were evaluated using descriptive statistics, bivariate correlation analysis, and multivariable logistic regression modeling to determine their relationship with transfer status., Results: Patients with aSAH who were treated in an urban teaching hospital had higher odds of being a transfer (OR 2.15, 95% CI 1.71-2.72) than the patients in urban nonteaching hospitals. White patients were more likely to be transfer patients than were any of the other racial groups (p < 0.0001). Moreover, patients who lived in the highest-income zip codes were less likely to be transferred than the patients in the lowest income quartile (OR 0.78, 95% CI 0.64-0.95). Repair type (clip vs coil) and primary payer were not associated with transfer status., Conclusions: A relatively high percentage of patients with aSAH are transferred between acute care hospitals. Race and income were associated with transfer status. White patients are more likely to be transferred than other races. Patients from zip codes with the highest income transferred at lower rates than those from the lowest income quartile. Transfer patients were preferentially sent to urban teaching hospitals. The modality of aneurysm treatment was not associated with transfer status.

Objective: To evaluate patterns, predictors, and outcomes of postprocedure delayed hemorrhage (PPDH) following flow diversion therapy for intracranial aneurysm treatment., Methods: From 2012 to 2016, 50 patients with 52 aneurysms were treated with the Pipeline embolization device. Device placement was performed as a standalone therapy or with adjunctive coil embolization. Patients underwent dual antiplatelet therapy for 6 months after treatment. Medical comorbidities; aneurysm traits; and treatment factors, including platelet function testing, were studied. Statistical analysis was performed using cross-tabulation., Results: Six PPDHs (12%) occurred 2-16 days (mean 6.8 days) after Pipeline placement, manifesting as 1 of 2 distinct patterns: convexity subarachnoid hemorrhage (cSAH) (n = 4) or lobar intraparenchymal hemorrhage (IPH) (n = 2). All PPDHs occurred ipsilateral to the device; 1 IPH occurred ipsilateral but in a different arterial territory. PPDH occurred in both treated anterior communicating artery aneurysms. Cases of PPDH demonstrated on average lower P2Y12 reaction unit values at the time of treatment. Platelet function testing at the time of hemorrhage was consistently hypertherapeutic. Patients with cSAH had only minimal worsening of modified Rankin Scale score at the time of discharge, whereas the 2 patients with IPH experienced significant deterioration., Conclusions: PPDH is a poorly understood complication following flow diversion therapy that can result in significant morbidity. In our experience, nonaneurysmal cSAH does not result in poor clinical outcomes, whereas IPH leads to long-term deficits or death. As previously suggested, there appears to be a correlation between low P2Y12 reaction unit values and PPDH., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Stereotactic radiosurgery (SRS) is a treatment option for cerebral arteriovenous malformations (AVMs) to prevent intracranial hemorrhage. The decision to proceed with SRS is usually based on calculated nidal volume. Physicians commonly use the ABC/2 formula, based on digital subtraction angiography (DSA), when counseling patients for SRS., Objective: To determine whether AVM volume calculated using the ABC/2 method on DSA is accurate when compared to the exact volume calculated from thin-cut axial sections used for SRS planning., Methods: Retrospective search of neurovascular database to identify AVMs treated with SRS from 1995 to 2015. Maximum nidal diameters in orthogonal planes on DSA images were recorded to determine volume using ABC/2 formula. Nidal target volume was extracted from operative reports of SRS. Volumes were then compared using descriptive statistics and paired t-tests., Results: Ninety intracranial AVMs were identified. Median volume was 4.96 cm3 [interquartile range (IQR) 1.79-8.85] with SRS planning methods and 6.07 cm3 (IQR 1.3-13.6) with ABC/2 methodology. Moderate correlation was seen between SRS and ABC/2 (r = 0.662; P < .001). Paired sample t-tests revealed significant differences between SRS volume and ABC/2 (t = -3.2; P = .002). When AVMs were dichotomized based on ABC/2 volume, significant differences remained (t = 3.1, P = .003 for ABC/2 volume < 7 cm3; t = -4.4, P < .001 for ABC/2 volume > 7 cm3)., Conclusion: The ABC/2 method overestimates cerebral AVM volume when compared to volumetric analysis from SRS planning software. For AVMs > 7 cm3, the overestimation is even greater. SRS planning techniques were also significantly different than values derived from equations for cones and cylinders., (Copyright © 2017 by the Congress of Neurological Surgeons)

Aneurysm rebleeding following initial endovascular management is uncommon, and the factors associated with its occurrence are poorly defined. We retrospectively analyzed a consecutive series of patients presenting with aneurysmal subarachnoid hemorrhage who underwent endovascular management to determine factors associated with rebleeding. Rebleeding occurred in 7/183 (3.8%) patients, 6 of which had an adjacent hematoma on initial neuroimaging. Aneurysms were located on the ACoA (n=5), PCoA (n=1), and MCA (n=1). Sizes ranged from 3.5 to 13.0mm (mean 8.0), with neck sizes ranging from 1.8 to 4.6mm (mean 3.2). Time-to-rerupture ranged from hours to years, with 3/7 cases rebleeding within 30days and 4/7 cases rebleeding later than 30days. Initial incomplete angiographic occlusion occurred in 2/3 cases of early rebleeding. The presence of adjacent intracerebral hematoma (ɸ=0.354, p<0.005), increasing Fisher Grade (t(9.4)=7.72, p<0.005), and aneurysmal outpouching (ɸ=0.265, p<0.005) were found to be the only factors associated with rerupture status. Recurrent hemorrhage following endovascular management of ruptured intracranial aneurysms is an uncommon but important source of morbidity, particularly in the early post-embolization period. The presence of high-risk features, such as an adjacent intracerebral hematoma or aneurysm outpouching, warrant early and frequent angiographic follow up to document stability and mitigate rupture risk., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Dural venous sinus thrombosis (DVST) is a cause of infarction and intracranial hemorrhage (ICH) that can lead to significant morbidity. Endovascular therapy has emerged as an adjunctive therapy in select cases but has been associated with increased hemorrhagic complications. We present our experience with a large single-center cohort of DVST cases treated with current-generation thrombectomy devices., Materials and Methods: In this retrospective cohort study, a chart review was performed to compare presentations and outcomes of patients treated with anticoagulation alone with those treated with additional interventional therapy, using the modified Rankin Scale (mRS) score at discharge and at 90 days' follow-up., Results: A total of 66 patients were included; 37 were treated with anticoagulation alone, and 29 underwent additional interventional therapy. Patients presenting with ICH or infarction had a significantly greater likelihood of disability at the time of discharge (odds ratio [OR] of 64.5 and 45.8, respectively; P < .0001) and at 90 days (OR of 28.4 and 22.8, respectively; P < .0001). Patients presenting with ICH or infarction were more likely to be selected for endovascular therapy (P < .05). Endovascular therapy was typically performed within 24 hours of admission; 9 patients (31%) had post-treatment hemorrhage, with 2 being (6.9%) symptomatic. There were fewer patients with slight disability (mRS score ≤1) in the endovascular group compared with the anticoagulation group at discharge (P = .05), but outcomes were not significantly different at 90 days (P = .19)., Conclusions: Despite a higher rate of ICH or infarction at presentation in the endovascular group and an increased risk of postprocedural ICH, both treatment groups had similarly good functional outcomes at 90 days., (Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Some patients undergoing dural sinus stenting for idiopathic intracranial hypertension (IIH) develop clinical and hemodynamic failure (recurrence of the pressure gradient) owing to stent-adjacent stenosis., Objective: To characterize factors associated with hemodynamic failure, and to describe outcomes of patients after repeat stenting., Materials and Methods: We reviewed the initial and follow-up clinical, venographic, and hemodynamic data in 39 patients with IIH treated over 17 years with stenting. Thirty-two had follow-up angiographic and hemodynamic data at 1-99 months (mean 27.6, median 19.5 months). Eight patients were treated with 12 repeat stenting procedures, including extended stenting into the superior sagittal sinus (SSS)., Results: All patients had an initial successful hemodynamic result with the pressure gradient reduced from 10-43 to 0-7 mm Hg. 10/32 patients (31.3%), all women, developed new stenoses in the transverse sinus or posterior SSS above the stent with a recurrent pressure gradient. 7/9 patients with pure extrinsic stenosis of the transverse-sigmoid junction pre-stenting developed new stenoses and hemodynamic failure. All patients with hemodynamic failure who were restented had early and mid-term documented hemodynamic success at 1.7-50 months. They were free from papilledema at 3.8-50 months after the last restenting, and 11.5-99.5 months after initial stent placement (mean 45.3, median 38.5 months)., Conclusions: Pure extrinsic compression of the transverse-sigmoid junction and female gender were strongly associated with hemodynamic failure. Eight patients with hemodynamic failure who were restented had successful control of papilledema, including 4/4 who had extended stenting into the SSS., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Recent studies indicate that calpain-1 is required for the induction of long-term potentiation (LTP) elicited by theta-burst stimulation in field CA1 of hippocampus. Here we determined the contribution of calpain-1 in another type of synaptic plasticity, the long-term depression (LTD) elicited by activation of type-I metabotropic glutamate receptors (mGluR-LTD). mGluR-LTD was associated with calpain-1 activation following T-type calcium channel opening, and resulted in the truncation of a regulatory subunit of PP2A, B56α. This signaling pathway was required for both the early and late phase of Arc translation during mGluR-LTD, through a mechanism involving mTOR and ribosomal protein S6 activation. In contrast, in hippocampal slices from calpain-1 knock-out (KO) mice, application of the mGluR agonist, DHPG, did not result in B56α truncation, increased Arc synthesis and reduced levels of membrane GluA1-containing AMPA receptors. Consistently, mGluR-LTD was impaired in calpain-1 KO mice, and the impairment could be rescued by phosphatase inhibitors, which also restored Arc translation in response to DHPG. Furthermore, calpain-1 KO mice exhibited impairment in fear memory extinction to tone presentation. These results indicate that calpain-1 plays a critical role in mGluR-LTD and is involved in many forms of synaptic plasticity and learning and memory.

Objective: The characteristics, diagnosis, and preferred management strategies for distal posterior inferior cerebellar artery (PICA) aneurysms associated with cerebellar arteriovenous malformation (AVMs) are poorly understood. We present a case series with attention to aneurysm angioarchitecture, diagnostic imaging, treatment approaches, and a thorough review of the literature. With this information, we demonstrate a specific anatomical pattern for these aneurysms, an underreported need for conventional digital subtraction angiography (DSA) during evaluation, along with the utility of endovascular treatment with liquid embolic agents., Methods: Neurosurgical patients from 2005 to 2016 were reviewed to identify PICA aneurysms along with distal PICA aneurysms. Details of their presentation, imaging studies, associated AVMs and treatment were recorded. A thorough literature search of previous case series and case reports of distal PICA aneurysms with and without associated small cerebellar AVMs was performed with PubMed and Google Scholar., Results: Thirty-four patients with PICA aneurysms were identified at our institution, 12 of which were in a distal segment. All 12 of these patients underwent DSA as a part of their evaluation. Of the 12 patients with distal PICA aneurysms, 9 presented with subarachnoid hemorrhage and intraventricular hemorrhage. Five of these patients had a small occult cerebellar AVM. All nine patients presenting with a ruptured distal PICA aneurysm had a Fischer grade 4 subarachnoid hemorrhage. Of the five patients with a small occult cerebellar AVM, the AVM nidus was missed on computed tomography angiogram (CTA) interpretation but easily visualized with DSA. CTA followed by DSA with concurrent endovascular treatment was performed in 9 of the 12 patients with distal PICA aneurysms. Two of the 12 patients were treated with microsurgical clip ligation, and one mycotic aneurysm was identified and treated with antibiotics. Parent vessel sacrifice was used distal to the aneurysm in all 5 associated AVM cases with liquid embolic agents as well as AVM embolization in 3 of the 5 cases. Fifty-one well-described case reports of distal PICA aneurysms associated with small cerebellar AVMs have been reported in the literature. A total of 12 well-described case series of distal PICA aneurysms that comment on associated AVMs describe an associated small cerebellar AVM incidence of 4%-50%. In our case series, the incidence of an associated small cerebellar AVM with a distal PICA aneurysm was 42%., Conclusions: In cases of distal PICA aneurysms, there is a frequent association of a small cerebellar AVM. In our series, CTA was an inadequate diagnostic study to identify the associated AVM, and DSA was necessary to definitely visualize the AVM nidus. Endovascular treatment of the aneurysm and AVM with the use of liquid embolic agents was a feasible and useful management strategy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Systemic injection of kainate produces repetitive seizure activity in both rats and mice. It also results in short-term synaptic modifications as well as delayed neurodegeneration. The signaling cascades involved in both short-term and delayed responses are not clearly defined. The calcium-dependent protease calpain is activated in various brain structures following systemic kainate injection, although the precise involvement of the two major brain calpain isoforms, calpain-1 and calpain-2, remains to be defined. It has recently been reported that calpain-1 and calpain-2 play opposite roles in NMDA receptor-mediated neuroprotection or neurodegeneration, with calpain-1 being neuroprotective and calpain-2 being neurodegenerative. In the present study, we determined the activation pattern of calpain-1 and calpain-2 by analyzing changes in levels of different calpain substrates, including spectrin, drebrin, and PTEN (phosphatase and tensin homolog; a specific calpain-2 substrate) in both rats, and wild-type and calpain-1 knock-out mice. The results indicate that, while calpain-2 is rapidly activated in pyramidal cells throughout CA1 and CA3, rapid calpain-1 activation is restricted to parvalbumin-positive and to a lesser extent CCK-positive, but not somatostatin-positive, interneurons. In addition, calpain-1 knock-out mice exhibit increased long-term neurodegeneration in CA1, reinforcing the notion that calpain-1 activation is neuroprotective.

A CAPN1 missense mutation in Parson Russell Terrier dogs is associated with spinocerebellar ataxia. We now report that homozygous or heterozygous CAPN1-null mutations in humans result in cerebellar ataxia and limb spasticity in four independent pedigrees. Calpain-1 knockout (KO) mice also exhibit a mild form of ataxia due to abnormal cerebellar development, including enhanced neuronal apoptosis, decreased number of cerebellar granule cells, and altered synaptic transmission. Enhanced apoptosis is due to absence of calpain-1-mediated cleavage of PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1), which results in inhibition of the Akt pro-survival pathway in developing granule cells. Injection of neonatal mice with the indirect Akt activator, bisperoxovanadium, or crossing calpain-1 KO mice with PHLPP1 KO mice prevented increased postnatal cerebellar granule cell apoptosis and restored granule cell density and motor coordination in adult mice. Thus, mutations in CAPN1 are an additional cause of ataxia in mammals, including humans., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Present a case report of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) associated with stroke along with the serologic findings, diagnostic findings, and treatment in addition to presenting a review of other case reports to date in literature. With this information, we are attempting to identify key diagnostic features and appropriate treatment options for patients with this disease., Methods: Presentation of case report, background on APMPPE, review of the literature and previous case reports, and discussion of diagnostic workup and treatment options for these patients., Results: There are 28 well-described case reports in the literature to date, not including our case report; 23 had documented radiographic findings consistent with parenchymal injury, ischemic stroke, hemorrhagic stroke, or cerebral venous thrombosis. We report a 23-year-old right-handed man with left hemiparesis, ischemic strokes, and angiographic findings characteristic of cerebral vasculitis 4 months after he was diagnosed with APMPPE., Conclusions: Based on our present case and previously documented cases to date, corticosteroid therapy with potential escalation of care to immunomodulatory treatment appears to benefit clinical outcomes., (Published by Elsevier Inc.)

Objective: Present a case report of an anomalous origin of the right vertebral artery originating from the aortic arch distal to the left subclavian along with a review of cases reported to date in the literature., Methods: Provide background information on this rare anomaly, present the case report, review the literature using PubMed, summarize previously reported cases to date, and discuss the underlying embryologic development of this anomaly along with its significance., Results: We report a 54-year-old man presenting with a subarachnoid hemorrhage referred for diagnostic cerebral arteriography who was found to have an anomalous origin of the right vertebral artery originating from the aortic arch distal to the left subclavian artery in conjunction with a bovine arch. We also report 13 previously reported cases along with their other associated variant anatomy., Conclusions: Based upon our present case and previously documented cases to date, this anomaly is a rare finding. An understanding of aberrant anatomy and its embryologic basis is paramount to avoiding inadvertent vascular injury during diagnostic cerebral angiography. Therefore, this abnormality must be considered if selective vertebral artery catheterization is difficult or unsuccessful.

Background: Intracoronary delivery of cardiosphere-derived cells (CDCs) has been demonstrated to be safe and effective in porcine and human chronic myocardial infarction. However, intracoronary delivery of CDCs after reperfusion in acute myocardial infarction has never been assessed in a clinically-relevant large animal model. We tested CDCs as adjunctive therapy to reperfusion in a porcine model of myocardial infarction., Methods and Results: First, escalating doses (5, 7.5, and 10 million cells) of allogeneic CDCs were administered intracoronary 30 minutes after reperfusion. Forty-eight hours later, left ventriculography was performed and animals euthanized to measure area at risk, infarct size (IS), and microvascular obstruction. Second, identical end points were measured in a pivotal study of minipigs (n=14) that received 8.5 to 9 million allogeneic CDCs, placebo solution, or sham. Multiple indicators of cardioprotection were observed with 7.5 and 10 million allogeneic CDCs, but not 5 million CDCs, relative to control. In the pivotal study, IS, microvascular obstruction, cardiomyocyte apoptosis, and adverse left ventricular remodeling were all smaller in the CDC group than in sham or placebo groups. In addition, serum troponin I level at 24 hours was lower after CDC infusion than that in the placebo or sham groups, consistent with the histologically-demonstrated reduction in IS., Conclusions: Intracoronary delivery of allogeneic CDCs is safe, feasible, and effective in cardioprotection, reducing IS, preventing microvascular obstruction, and attenuating adverse acute remodeling. This novel cardioprotective effect, which we call cellular postconditioning, differs from previous strategies to reduce IS in that it works even when initiated with significant delay after reflow., (© 2015 American Heart Association, Inc.)

Background: Epicardial injection of heart-derived cell products is safe and effective post-myocardial infarction (MI), but clinically-translatable transendocardial injection has never been evaluated. We sought to assess the feasibility, safety and efficacy of percutaneous transendocardial injection of heart-derived cells in porcine chronic ischemic cardiomyopathy., Methods and Results: We studied a total of 89 minipigs; 63 completed the specified protocols. After NOGA-guided transendocardial injection, we quantified engraftment of escalating doses of allogeneic cardiospheres or cardiosphere-derived cells in minipigs (n = 22) post-MI. Next, a dose-ranging, blinded, randomized, placebo-controlled ("dose optimization") study of transendocardial injection of the better-engrafting product was performed in infarcted minipigs (n = 16). Finally, the superior product and dose (150 million cardiospheres) were tested in a blinded, randomized, placebo-controlled ("pivotal") study (n = 22). Contrast-enhanced cardiac MRI revealed that all cardiosphere doses preserved systolic function and attenuated remodeling. The maximum feasible dose (150 million cells) was most effective in reducing scar size, increasing viable myocardium and improving ejection fraction. In the pivotal study, eight weeks post-injection, histopathology demonstrated no excess inflammation, and no myocyte hypertrophy, in treated minipigs versus controls. No alloreactive donor-specific antibodies developed over time. MRI showed reduced scar size, increased viable mass, and attenuation of cardiac dilatation with no effect on ejection fraction in the treated group compared to placebo., Conclusions: Dose-optimized injection of allogeneic cardiospheres is safe, decreases scar size, increases viable myocardium, and attenuates cardiac dilatation in porcine chronic ischemic cardiomyopathy. The decreases in scar size, mirrored by increases in viable myocardium, are consistent with therapeutic regeneration.

Controversy surrounds the identity, origin, and physiologic role of endogenous cardiomyocyte progenitors in adult mammals. Using an inducible genetic labeling approach to identify small non-myocyte cells expressing cardiac markers, we find that activated endogenous cardioblasts are rarely evident in the normal adult mouse heart. However, myocardial infarction results in significant cardioblast activation at the site of injury. Genetically labeled isolated cardioblasts express cardiac transcription factors and sarcomeric proteins, exhibit spontaneous contractions, and form mature cardiomyocytes in vivo after injection into unlabeled recipient hearts. The activated cardioblasts do not arise from hematogenous seeding, cardiomyocyte dedifferentiation, or mere expansion of a preformed progenitor pool. Cell therapy with cardiosphere-derived cells amplifies innate cardioblast-mediated tissue regeneration, in part through the secretion of stromal cell-derived factor 1 by transplanted cells. Thus, stimulation of endogenous cardioblasts by exogenous cells mediates therapeutic regeneration of injured myocardium., (© 2014 The Authors. Published under the terms of the CC BY 4.0 license.)

Background: Magnetic resonance imaging (MRI) in the CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction (CADUCEUS) trial revealed that cardiosphere-derived cells (CDCs) decrease scar size and increase viable myocardium after myocardial infarction (MI), but MRI has not been validated as an index of regeneration after cell therapy. We tested the validity of contrast-enhanced MRI in quantifying scarred and viable myocardium after cell therapy in a porcine model of convalescent MI., Methods and Results: Yucatan minipigs underwent induction of MI and 2-3 weeks later were randomized to receive intracoronary infusion of 12.5×10(6) mismatched allogeneic CDCs or vehicle. Allogeneic CDCs induced mild local mononuclear infiltration but no systemic immunogenicity. MRI revealed that allogeneic CDCs attenuated remodeling, improved global and regional function, decreased scar size, and increased viable myocardium compared with placebo 2 months post-treatment. Extensive histological analysis validated quantitatively the MRI measurements of scar size, scar mass, and viable mass. CDCs neither altered gadolinium contrast myocardial kinetics nor induced changes in vascular density or architecture in viable and scarred myocardium. Histology demonstrated that CDCs lead to cardiomyocyte hyperplasia in the border zone, consistent with the observed stimulation of endogenous regenerative mechanisms (cardiomyocyte cycling, upregulation of endogenous progenitors, angiogenesis)., Conclusions: Contrast-enhanced MRI accurately measures scarred and viable myocardium after cell therapy in a porcine model of convalescent MI. MRI represents a useful tool for assessing dynamic changes in the infarct and monitoring regenerative efficacy.

The reactive uptake and aqueous oxidation of glycolaldehyde were examined in a photochemical flow reactor using hydrated ammonium sulfate (AS) seed aerosols at RH = 80%. The glycolaldehyde that partitioned into the aerosol liquid water was oxidized via two mechanisms that may produce aqueous OH: hydrogen peroxide photolysis (H2O2 + hν) and the photo-Fenton reaction (Fe (II) + H2O2 + hν). The uptake of 80 (±10) ppb glycolaldehyde produced 2-4 wt % organic aerosol mass in the dark (kH* = (2.09-4.17) × 10(6) M atm(-1)), and the presence of an OH source increased the aqueous uptake by a factor of 4. Although the uptake was similar in both OH-aging mechanisms, photo-Fenton significantly increased the degree of oxidation (O/C = 0.9) of the aerosols compared to H2O2 photolysis (O/C = 0.5). Aerosol organics oxidized by photo-Fenton and H2O2 photolysis resemble ambient "aged" and "fresh" OA, respectively, after the equivalent of 2 h atmospheric aging. No uptake or changes in particle composition occurred on dry seed aerosol. This work illustrates that photo-Fenton chemistry efficiently forms highly oxidized organic mass in aerosol liquid water, providing a possible mechanism to bridge the gap between bulk-phase experiments and ambient particles.