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Background : Pretreatment CTA-based Cortical Vein Opacification Score (COVES) has been shown to predict good functional outcomes at 90 days in patients with acute ischemic stroke secondary to large vessel occlusion (AIS-LVO). This is thought to be related to its ability to measure collateral status (CS). However, its association with the reference standard test, the DSA-based American Society of Interventional and Therapeutic Neuroradiology (ASITN) collateral score, has yet to be established. Therefore, this study assesses the relationship between COVES and ASITN CS. Methods : In this prospectively collected, retrospectively reviewed analysis, patients with anterior circulation LVO from September 1, 2017, to October 1, 2023, were included. The COVES grading, which ranges from 0 to 6, was independently assessed by two board-certified neuroradiologists. The ASITN CS was independently assessed by a board-certified neuroradiologist and the performing neurointerventionalist. Any discrepancies were resolved through consensus review. Spearman's rank correlation, univariable logistic regression, multivariable logistic regression, and receiver operating characteristic curve analysis were performed. A p-value of ≤0.05 was considered significant. Results : In total, 311 consecutive patients (median, IQR=68 years [59-78 years]; 55.9% female) met our inclusion criteria. There was significant positive correlation between COVES and ASITN CS (ρ=0.41,p<0.001), and higher COVES was significantly and independently associated with good ASITN CS (unadjusted-OR=1.74,p<0.001) and adjusted-OR=1.73, p<0.001). ROC analysis showed AUC of 0.71, p<0.001). Conclusion : In conclusion, by demonstrating the independent association of COVES with the reference standard test for collateral status assessment, the ASITN CS, we further validate the role of COVES in estimating collateral status.ABBREVIATIONS: AIS: Acute ischemic stroke; ASITN: American Society of Interventional and Therapeutic Neuroradiology; CS: Collateral status; COVES: Cortical Vein Opacification Score; HIR: Hypoperfusion Intensity Ratio; IVT: Intravenous thrombolysis; LVO: Large vessel occlusion; mRS: modified Rankin score; MT: mechanical thrombectomy; OR: odds ratio; aOR: adjusted odds ratio; ua: unadjusted odds ratio; rCBF: relative cerebral blood flow; Tmax: Time-to-Maximum., (© 2024 by American Journal of Neuroradiology.)

Background: Intracranial aneurysms (IAs) are the major cause of subarachnoid hemorrhage. Stent-assisted coiling, especially with the Neuroform Atlas stent (NAS), has proven more effective than coiling alone for treating these aneurysms., Purpose: To perform a systematic review and meta-analysis to investigate the efficacy and safety of NAS in treating IAs., Data Sources: A comprehensive literature search was conducted on PubMed, Embase, Cochrane CENTRAL library, and clinicaltrials.gov from inception till June 2024., Study Selection: We included studies on ruptured and unruptured IAs treated with the NAS, covering experimental, observational, and case series across all age groups. The aneurysm occlusion rate was assessed using the Raymond-Roy classification (RROC). The modified Rankin Scale (mRS) and adverse events related to stent use were also recorded., Data Analysis: The statistical analysis was conducted on R version 4.3.2 using the packages "meta" and "metasens". We reported our results as proportions with their corresponding confidence intervals (CIs). Meta-regression, leave-one-out and sensitivity analyses were conducted to confirm the robustness of our results., Data Synthesis: A total of 42 studies including 2434 participants with a mean age of 51 to 73 years were included. Among angiographic outcomes, the final RROC 1/RROC 2 was achieved in 95% of the patients, final RROC 1 in 82%, RROC 2 in 12%, and RROC 3 in 5% of the patients. Additionally, 93% of the patients showed mRS grade 0, 5% showed mRS grade 1, 3% showed mRS grade 2, 2% showed mRS grade 3, 0% showed mRS grade 4, 0% showed mRS grade 5, and 1% showed mRS grade 6. All adverse events had a ≤ 5% rate., Limitations: Due to limited cause-specific data, we were unable to analyse mortality specific to the stent placement and complications. Despite the large number of studies included, comparative studies were still observed to be scarce., Conclusions: Although the generalizability of our findings is limited, this study demonstrates that NAS is highly effective for treating IAs, with high occlusion rates and a low incidence of adverse events. The stent's performance, supported by comprehensive analysis, highlights its safety and efficacy in managing both ruptured and unruptured aneurysms., Abbreviations: NAS = Neuroform Atlas stent; IA = Intracranial aneurysm; SAC = stent-assisted coiling., Competing Interests: The authors declare no conflicts of interest related to the content of this article., (© 2024 by American Journal of Neuroradiology.)

Background: Endovascular thrombectomy (EVT) has shown promise in randomized controlled trials (RCTs) for large ischemic core stroke patients, yet variability in core definition and onset-to-imaging time creates heterogeneity in outcomes. This study aims to clarify the prevalence and implications of core-perfusion mismatch (MM) versus no mismatch (No MM) in such patients, utilizing established imaging criteria., Methods: A retrospective cohort study was conducted including patients from 7/29/2019 to 1/29/2023, with data extracted from a continuously maintained database. Patients were eligible if they met criteria including multimodal CT imaging performed within 24 h from last known well (LKW), AIS-LVO diagnosis, and ischemic core size defined by specific rCBF thresholds. Mismatch was assessed based on different operational definitions from the EXTEND and DEFUSE 3 trials., Results: Fifty-two patients were included, with various time windows from LKW. Using EXTEND criteria, a significant portion of early window patients exhibited MM; however, fewer patients met MM criteria in the late window. Defining MM using DEFUSE 3 criteria yielded similar patterns, but with overall lower MM prevalence in the late window. When employing rCBF <38% as a surrogate for ischemic core, a higher percentage of patients were classified as MM across both time windows compared to rCBF <30%., Conclusion: The prevalence of MM in large ischemic core patients varies significantly depending on the imaging criteria and time from LKW. Notably, MM was more prevalent in the early time window across all criteria used. Additional RCTs are needed to determine if this definition of MM identifies patients who will benefit most from EVT., Competing Interests: Declarations Conflict of interest V. Yedavalli, H. Adel Salim, D.A. Lakhani, J. Mei, A. Balar, B. Musmar, N. Adeeb, M. Hoseinyazdi, L. Luna, F. Deng, N.Z. Hyson, A.A. Dmytriw, A. Guenego, H. Lu, V.C. Urrutia, K. Nael, E.B. Marsh, R. Llinas, A.E. Hillis, M. Wintermark, T.D. Faizy, J.J. Heit and G.W. Albers declare that they have no competing interests. Ethical standards This study was approved through the institutional review board (JHU-IRB00269637) and follows the STROBE checklist guidelines as an observational study., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background and Purpose: Acute ischemic strokes caused by distal medium vessel occlusions (DMVO) represent a significant proportion of all stroke cases, yet the predictors of excellent functional outcomes in these patients remain poorly understood. This study aims to identify pretreatment computed tomography perfusion (CTP) parameters associated with excellent functional outcomes, defined as a modified Rankin Scale (mRS) score of 0-1 at 90 days, in patients with anterior circulation DMVO., Materials and Methods: We conducted a retrospective multicenter study involving patients with anterior DMVO, from three stroke centers within the Johns Hopkins Medical Enterprise. Baseline demographic, clinical, and imaging data were collected, with CTP parameters analyzed using RAPIDAI software. Univariable and multivariable logistic regression models were used to identify predictors of excellent outcomes. Receiver operating characteristic (ROC) curves were constructed to assess the predictive accuracy of CTP parameters., Results: Among the 82 patients (median age, 71 years; 57% female), occlusions were located in the M2 segment in 89%, M3 in 8.5%, and A2 in 2.4%. IVT was administered to 37% of patients, and EVT was attempted in 59%. Excellent outcomes at 90 days were achieved in 45% of patients. In univariate analysis, white race (OR, 4.14; 95% CI, 1.66-10.9; P=0.003), higher CBV index (OR per 0.1-unit change, 1.45; 95% CI, 1.08-2.05; P=0.022), and lower relative cerebral blood flow (rCBF < 20%) volumes (OR, 0.91; 95% CI, 0.81-0.98; P=0.038) were significantly associated with excellent outcomes. In multivariate analysis adjusting for age, sex, race, IVT administration, EVT attempted, dyslipidemia, and premorbid mRS, higher CBV index remained a significant independent predictor (OR per 0.1-unit change, 1.72; 95% CI, 1.14-2.81; P=0.017), and lower rCBF < 20% volume was associated with better outcomes (OR, 0.91; 95% CI, 0.80-0.98; P=0.05). The multivariate model demonstrated good predictive performance (area under the ROC curve, 80%; 95% CI, 70%-90%; P < 0.001)., Conclusions: In patients with anterior circulation DMVO, a higher CBV index on pretreatment CTP is an independent predictor of excellent functional outcomes at 90 days. These findings suggest that CTP parameters, particularly the CBV index, may be useful in prognostic assessment for this stroke population. Further studies are needed to validate these results and optimize therapeutic approaches., Abbreviations: ABC＝ definition; XYZ＝ definition., (© 2024 by American Journal of Neuroradiology.)

Background and Aim: Recent studies have shown that the CT Perfusion (CTP) parameter of rCBV < 42 % lesion volume can predict 90-day functional outcomes in stroke patients. However, its correlation with discharge outcomes, including functional dependence, has not been investigated. Our study aims to evaluate the relationship between rCBV < 42 % and poor functional outcomes at discharge, defined as a modified Rankin score (mRS) of 3 or higher., Materials and Methods: This retrospective study analyzed patients with confirmed occlusion on CT angiography, who also received CT perfusion between 9/1/2017 and 10/01/2023. Statistical tests (Student's T, Mann-Whitney U, and Chi-Square) were used to assess differences. Univariable and multivariable logistic regression analyses were performed to evaluate the associations of rCBV < 42 % with discharge mRS. A p-value ≤ 0.05 was considered significant., Results: A total of 268 patients [median age: 68 years (IQR: 59-77), 56.3 % female] met the inclusion criteria. Among them, 85 patients (31.7 %) received intravenous thrombolysis (IVT), and 221 patients (82.5 %) underwent mechanical thrombectomy (MT). After adjusting for various variables, logistic regression analysis indicated that rCBV < 42 % lesion volume was associated with poor functional outcomes at discharge (aOR = 0.97, p < 0.05). T., Conclusion: The rCBV < 42 % could be a valuable tool in prognosticating AIS-LVO patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Drs. Dhairya Lakhani, Greg Albers, Jeremy Heit, and Vivek Yedavalli are consultants for Rapid (iSchemaView, Menlo Park, CA)., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Venous outflow (VO) impairment predicts unfavorable outcomes in patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO). Prolonged venous transit (PVT), a visual qualitative VO marker on CT perfusion (CTP) time to maximum (Tmax) maps, has been associated with unfavorable 90-day functional outcomes despite successful reperfusion. This study investigates the association between PVT and percent change on the National Institutes of Health Stroke Scale (NIHSS) among AIS-LVO patients who have undergone successful reperfusion., Methods: We performed a retrospective analysis of prospectively collected data from consecutive adult AIS-LVO patients with successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b/2c/3). PVT+ was defined as Tmax ≥10 s in the superior sagittal sinus, torcula, or both. The primary outcome was continuous NIHSS percent change and dichotomous NIHSS percent change ≥70%. Regression analyses were performed to assess the effect of PVT on NIHSS percent change., Results: In 119 patients of median (IQR) age 71 (63-81) years, the admission and discharge NIHSS scores were significantly higher in PVT+ patients compared to PVT- patients (17 [14-23.5] vs. 13 [9.5-19], p = 0.011, and 7.5 [4-12] vs. 3 [1-7], p < 0.001, respectively). After adjusting for age, sex, hypertension, diabetes, atrial fibrillation, administration of intravenous thrombolysis (IVT), Alberta Stroke Program Early CT Scores (ASPECTS), mTICI 2c and/or 3, Tmax >6 s volume, and hemorrhagic transformation, PVT+ was significantly associated with lower NIHSS percent change (B = -0.163, 95%CI -0.326 to -0.001, p = 0.049) and was less likely to achieve higher than 70% NIHSS improvement (OR = 0.331, 95% CI 0.127-0.863, p = 0.024)., Interpretation: PVT+ was significantly associated with reduced neurological improvement despite successful reperfusion in AIS-LVO patients, highlighting the critical role of VO impairment in short-term functional outcomes. These findings further validate PVT as a valuable adjunct imaging biomarker derived from CTP for assessing VO profiles in AIS-LVO., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background and Purpose: Ischemic strokes due to isolated posterior cerebral artery (PCA) occlusions represent 5% of all strokes but have significant impacts on patients' quality of life, primarily due to visual deficits and thalamic involvement. Current guidelines for acute PCA occlusion management are sparse, and the prognostic value of perfusion imaging parameters remains underexplored., Methods: We conducted a retrospective analysis of 32 patients with isolated PCA occlusions treated at Johns Hopkins Medical Institutions between January 2017 and March 2023. Patients underwent pretreatment perfusion imaging, with perfusion parameters analyzed using RAPID software. The primary outcome was short-term clinical outcome as measured by the National Institutes of Health Stroke Scale (NIHSS) at discharge., Results: The median age of the cohort was 70 years, with 34% female and 66% male. Significant correlations were found between NIHSS at discharge and various perfusion parameters, including time-to-maximum (Tmax) >6 seconds (ρ = .55, p = .004), Tmax >8 seconds (ρ = .59, p = .002), Tmax >10 seconds (ρ = .6, p = .001), mismatch volume (ρ = .51, p = .008), and cerebral blood volume (CBV) < 34% (ρ = .59, p = .002)., Conclusions: Tmax and CBV volumes significantly correlated with discharge NIHSS with marginal superiority of Tmax >10 seconds and CBV <42% volumes. These findings suggest that CT and MR perfusion imaging can play a crucial role in the acute management of PCA strokes, though larger, standardized studies are needed to validate these results and refine imaging thresholds specific to posterior circulation infarcts., (© 2024 American Society of Neuroimaging.)

Background: Recent advances have highlighted the efficacy of endovascular thrombectomy (EVT) in patients with large ischemic core stroke, yet a significant portion still experience very poor outcomes, defined as a 90-day modified Rankin Score (mRS) of 5-6. This study aims to investigate the hypoperfusion intensity ratio (HIR) as a prognostic imaging parameter for these outcomes., Methods: In a multicenter retrospective cohort study, data from consecutive patients undergoing EVT for acute ischemic stroke with large vessel occlusion (AIS-LVO) at two comprehensive stroke centers were analyzed. The study included patients with an Alberta Stroke Program Early CT Score (ASPECTS) of 5 or less and utilized pretreatment perfusion imaging to calculate HIR. The primary outcome was very poor outcomes (90 days mRS 5-6)., Results: Among 102 patients included, 59 (57.8%) had very poor outcome (90 days mRS 5-6). Multivariable logistic regression analysis adjusting for multiple covariates including admission National Institutes of Health Stroke Scale (NIHSS) and EVT revealed that higher admission NIHSS (adjusted odds ratio [aOR] 1.224, 95% CI 1.089-1.374, p = 0.001) and HIR (aOR per 0.1 incremental change, 1.34, 95% CI 1.02-1.82, P = 0.042) were independently associated with very poor outcomes., Conclusion: This study demonstrates that admission NIHSS and HIR are independently associated with very poor outcome (90 days mRS 5-6) in patients with large ischemic core strokes. These findings highlight the importance of collateral status and perfusion imaging in predicting outcomes in this patient population, suggesting a potential role for HIR in the triage and management of large core stroke patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Mechanical thrombectomy (MT) is the treatment standard in eligible patients with acute ischemic stroke (AIS) secondary to large vessel occlusions (LVO). Studies have shown that good collateral status is a strong predictor of MT efficacy, thus making collateral status important to quickly assess. The Los Angeles Motor Scale is a clinically validated tool for identifying LVO in the field. The aim of this study is to investigate whether admission LAMS score is also associated with the American Society of Interventional and Therapeutic Neuroradiology (ASITN) collateral score on digital subtraction angiography (DSA)., Methods: We conducted a retrospective multicenter cohort study of consecutive patients presenting with AIS caused by LVO from 9/1/2017 to 10/1/2023 with diagnostically adequate DSA imaging. Demographic, clinical, and imaging data was collected through manual chart review. Both univariate and multivariate analysis were applied to assess associations. A p -value <0.05 was considered significant., Results: A total of 308 patients (median age: 68, IQR: 57.5-77) were included in the study. On multivariate logistic regression analysis, we found that lower admission LAMS score (adjusted OR: 0.82, 95% CI: 0.68-0.98, p  < 0.05) and higher ASPECTS score (adjusted OR: 1.21, 95% CI: 1.02-1.42, p  < 0.05) were independently associated with good DSA ASITN collateral score of 3-4., Conclusions: Admission LAMS and ASPECTS score are both independently associated with DSA ASITN collateral score. This demonstrates the capability of LAMS to act as a surrogate marker of CS in the field.

Background: Recent large core trials have highlighted the effectiveness of mechanical thrombectomy (MT) in acute ischemic stroke with large vessel occlusion. Variable perfusion-imaging thresholds and poor Alberta Stroke Program Early Computed Tomography Score reliability underline the need for more standardized, quantitative ischemia measures for MT patient selection. We aimed to identify the computed tomography perfusion parameter most strongly associated with poor outcomes in patients with acute ischemic stroke-large vessel occlusion with significant ischemic cores., Methods: In this study from 2 comprehensive stroke centers from 2 comprehensive stroke centers within the Johns Hopkins Medical Enterprise (Johns Hopkins Hospita-East Baltimore and Bayview Medical Campus) from July 29, 2019 to January 29, 2023 in a continuously maintained database, we included patients with acute ischemic stroke-large vessel occlusion with ischemic core volumes defined as relative cerebral blood flow <30% and ≥50 mL on computed tomography perfusion or Alberta Stroke Program Early Computed Tomography Score <6. We used receiver operating characteristics to find the optimal cutoff for parameters like cerebral blood volume (CBV) <34%, 38%, 42%, and relative cerebral blood flow >20%, 30%, 34%, 38%, and time-to-maximum >4, 6, 8, and 10 seconds. The primary outcome was unfavorable outcomes (90-day modified Rankin Scale score 4-6). Multivariable models were adjusted for age, sex, diabetes, baseline National Institutes of Health Stroke Scale, intravenous thrombolysis, and MT., Results: We identified 59 patients with large ischemic cores. A receiver operating characteristic curve analysis showed that CBV<42% ≥68 mL is associated with unfavorable outcomes (90-day modified Rankin Scale score 4-6) with an area under the curve of 0.90 (95% CI, 0.82-0.99) in the total and MT-only cohorts. Dichotomizing at this CBV threshold, patients in the ≥68 mL group exhibited significantly higher relative cerebral blood flow, time-to-maximum >8 and 10 seconds volumes, higher CBV volumes, higher HIR, and lower CBV index. The multivariable model incorporating CBV<42% ≥68 mL predicted poor outcomes robustly in both cohorts (area under the curve for MT-only subgroup was 0.87 [95% CI, 0.75-1.00])., Conclusions: CBV<42% ≥68 mL most effectively forecasts poor outcomes in patients with large-core stroke, confirming its value alongside other parameters like time-to-maximum in managing acute ischemic stroke-large vessel occlusion., Competing Interests: Dr Yedavalli reports compensation from IschemaView (RAPID AI) for consultant services and compensation from MRIOnline for consultant services. Dr Guenego reports compensation from Acandis for consultant services; compensation from Rapid Medical Ltd for consultant services; and compensation from phenox, Inc, for consultant services. Dr Heit reports compensation from iSchemaView for consultant services; compensation from Medtronic for consultant services; and compensation from MicroVention Inc for consultant services. Dr Albers reports compensation from iSchemaView for consultant services; compensation from Genentech for consultant services; and stock holdings in iSchemaView. Dr Urrutia reports grants from Genentech and employment by Johns Hopkins University School of Medicine. Dr Nael reports compensation from BRAINOMIX LIMITED for consultant services and compensation from Olea Medical for consultant services. Dr Hillis reports compensation from American Heart Association for other services; compensation from Elsevier Publishing for other services; employment by Johns Hopkins University School of Medicine; compensation from National Institute on Deafness and Other Communication Disorders for other services; and grants from National Institute on Deafness and Other Communication Disorders. The other authors report no conflicts.

Background and Purpose: Distal medium vessel occlusions (DMVOs) are a significant contributor to acute ischemic stroke (AIS), with collateral status (CS) playing a pivotal role in modulating ischemic damage progression. We aimed to explore baseline characteristics associated with CS in AIS-DMVO., Methods: This retrospective analysis of a prospectively collected database enrolled 130 AIS-DMVO patients from two comprehensive stroke centers. Baseline characteristics, including patient demographics, admission National Institutes of Health Stroke Scale (NIHSS) score, admission Los Angeles Motor Scale (LAMS) score, and co-morbidities, including hypertension, hyperlipidemia, diabetes, coronary artery disease, atrial fibrillation, and history of transient ischemic attack or stroke, were collected. The analysis was dichotomized to good CS, reflected by hypoperfusion index ratio (HIR) <.3, versus poor CS, reflected by HIR ≥.3., Results: Good CS was observed in 34% of the patients. As to the occluded location, 43.8% occurred in proximal M2, 16.9% in mid M2, 35.4% in more distal middle cerebral artery, and 3.8% in distal anterior cerebral artery. In multivariate logistic analysis, a lower NIHSS score and a lower LAMS score were both independently associated with a good CS (odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.82-0.95, p < .001 and OR: 0.77, 95% CI: 0.62-0.96, p = .018, respectively). Patients with poor CS were more likely to manifest as moderate to severe stroke (29.1% vs. 4.5%, p < .001), while patients with good CS had a significantly higher chance of having a minor stroke clinically (40.9% vs. 12.8%, p < .001)., Conclusions: CS remains an important determinant in the severity of AIS-DMVO. Collateral enhancement strategies may be a worthwhile pursuit in AIS-DMVO patients with more severe initial stroke presentation, which can be swiftly identified by the concise LAMS and serves as a proxy for underlying poor CS., (© 2024 American Society of Neuroimaging.)

Background: Distal medium vessel occlusions (DMVOs) contribute substantially to the incidence of acute ischemic strokes (AIS) and pose distinct challenges in clinical management and prognosis. Neuroimaging techniques, such as Fluid Attenuation Inversion Recovery (FLAIR) imaging and cerebral blood volume (CBV) index derived from perfusion imaging, have significantly improved our ability to assess the impact of strokes and predict their outcomes. The primary objective of this study was to investigate relationship between follow-up infarct volume (FIV) as assessed by FLAIR imaging in patients with DMVOs., Methods: This prospectively collected, retrospective reviewed cohort study included patients from two comprehensive stroke centers within the Johns Hopkins Medical Enterprise, spanning August 2018-October 2022. The cohort consisted of adults with AIS attributable to DMVO. Detailed imaging analyses were conducted, encompassing non-contrast CT, CT angiography (CTA), CT perfusion (CTP), and FLAIR imaging. Univariable and multivariable linear regression models were employed to assess the association between different factors and FIV., Results: The study included 79 patients with DMVO stroke with a median age of 69 years (IQR, 62-77 years), and 57% (n = 45) were female. There was a negative correlation between the CBV index and FIV in a univariable linear regression analysis (Beta =  - 16; 95% CI,  - 23 to  - 8.3; p < 0.001) and a multivariable linear regression model (Beta =  - 9.1 per 0.1 change; 95% CI,  - 15 to  - 2.7; p = 0.006). Diabetes was independently associated with larger FIV (Beta = 46; 95% CI, 16 to 75; p = 0.003). Additionally, a higher baseline ASPECTS was associated with lower FIV (Beta =  - 30; 95% CI,  - 41 to  - 20; p < 0.001)., Conclusion: Our findings underscore the CBV index as an independent association with FIV in DMVOs, which highlights the critical role of collateral circulation in determining stroke outcomes in this patient population. In addition, our study confirms a negative association of ASPECTS with FLAIR FIV and identifies diabetes as independent factor associated with larger FIV. These insights pave the way for further large-scale, prospective studies to corroborate these findings, thereby refining the strategies for stroke prognostication and management., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: The pretreatment CT perfusion (CTP) marker the relative cerebral blood volume (rCBV) < 42% lesion volume has recently been shown to predict 90-day functional outcomes; however, studies assessing correlations of the rCBV < 42% lesion volume with other outcomes remain sparse. Here, we aim to assess the relationship between the rCBV < 42% lesion volume and the reference standard digital subtraction angiography (DSA)-derived American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN) collateral score, hereby referred as the DSA CS. Methods: In this retrospective evaluation of our prospectively collected database, we included acute stroke patients triaged by multimodal CT imaging, including CT angiography and perfusion imaging, with confirmed anterior circulation large vessel occlusion between 1 September 2017 and 1 October 2023. Group differences were assessed using the Student's t test, Mann-Whitney U test and Chi-Square test. Spearman's rank correlation and logistic regression analyses were used to assess associations between rCBV < 42% and DSA CS. Results: In total, 222 patients (median age: 69 years, 56.3% female) met our inclusion criteria. In the multivariable logistic regression analysis, taking into account age, sex, race, hypertension, hyperlipidemia, diabetes, atrial fibrillation, prior stroke or transient ischemic attack, the admission National Institute of Health stroke scale, the premorbid modified Rankin score, the Alberta stroke program early CT score (ASPECTS), and segment occlusion, the rCBV < 42% lesion volume (adjusted OR: 0.98, p < 0.05) was independently associated with the DSA CS. Conclusion: The rCBV < 42% lesion volume is independently associated with the DSA CS.

Ischemic strokes in young adults are increasing in incidence and have emerged as a public health issue. The radiological features are not only diagnostic in identifying ischemic infarctions but also provide important clues in the investigation of the underlying causes or in the identification of risk factors. According to the different imaging patterns associated with ischemic stroke in young adults, the causes can be classified into 5 categories: cardioembolism, large vessel vasculopathy, small vessel vasculopathy, toxic-metabolic, and hypercoagulable disorders. The radiological features of each category and cause are described and summarized in this review., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Carotid artery webs are shelf-like protrusions of intimal fibrous tissue arising from the posterior wall of the carotid bulb, found to have a 2.3% prevalence in the United States. Previous studies have demonstrated its association with ipsilateral anterior circulation stroke. The aim of this study is to assess the prevalence of carotid webs in the largest US epidemiologic study to date, and to further characterize the clinical features of carotid web patients. We assembled a cohort of 1467 adult patients with CT angiogram neck from January 1, 2011 to January 1, 2017. CT angiograms were reviewed for diagnosis of carotid web. Demographic and clinical details of web patients were obtained. Differences in demographics and CT angiogram indication between patients with and without carotid web were assessed using appropriate statistical tests. Twenty-four (24/1467 = 1.6%) carotid web patients were identified (mean age: 63 years; 62.5% female; 50% African American). Twelve (12/24 = 50%) had ipsilateral anterior circulation stroke. Of them, 8 were deemed cryptogenic. Four (4/24 = 16.7%) web patients had at least one recurrent stroke in the ipsilateral anterior circulation. One case was reported on the radiology report at the time the study was initially performed. This study confirms a prevalence of 1.6% in our urban, North American cohort. Among carotid web patients, there was a high incidence of ipsilateral anterior circulation stroke, the majority of which were classified as cryptogenic. This study affirms the importance of the diagnosis of carotid web, especially in cryptogenic stroke patients, as a potential unrecognized stroke risk factor., (© 2021 American Association of Clinical Anatomists.)

Introduction: The standard protocol for exsanguinating trauma patients involves initial evaluation and resuscitation in the emergency department which then sets the stage for subsequent definitive care and disposition. This involves major coordination and mobilisation of resources which may cause a delay in intervention especially when most of these cases present after office hours. Our centre has employed a second-tier activation system (CHOP protocol) that immediately mobilises all respective trauma specialists including interventional radiologists and allows rapid access to the operating room., Objective: We hypothesised that exsanguinating patients managed by CHOP protocol have better overall outcome and survival., Methods: We identified trauma patients that fulfilled CHOP criteria from 2016 to 2019 and divided them into two groups: preCHOP (standard protocol) and CHOP. Data was extracted from a prospectively maintained trauma registry. Demographics, injury pattern and in-hospital data were analysed. The key outcome studied was the impact of CHOP protocol on the mortality rate. Success and failure of the two groups were analysed using CUSUM methodology., Results: Thirty-seven patients were managed by CHOP protocol since its introduction in March 2018 compared to 36 patients who underwent standard protocol. Majority of the cases were blunt trauma (89% CHOP vs 92% preCHOP). The mean Injury Severity Score was 37 for CHOP group and 39 for preCHOP group. We observed a significant improvement in time to intervention in CHOP patients (78 min vs 113 min), both during and after office hours. CHOP patients had lower mortality compared to preCHOP group (11% vs 31%) and the effectiveness of the protocol was seen in achieving significantly lower mortality compared to the predicted model. CHOP protocol was able to produce a consistent trend of desired outcomes leading to the CUSUM curve exhibiting a sustained downward slope., Conclusion: The CHOP protocol, a relatively novel system in the local context, was able to achieve sustained improved outcomes compared to standard protocol. The CUSUM analysis concurred that implementation of CHOP protocol has helped to achieve consistent desired outcomes. It also suggested that the uptake and use of this protocol has integrated well into the existing workflow., Competing Interests: Declaration of Competing Interest None declared for all authors., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Mitochondrial disease is a family of genetic disorders characterized by defects in the generation and regulation of energy. Epilepsy is a common symptom of mitochondrial disease, and in the vast majority of cases, refractory to commonly used antiepileptic drugs. Ferroptosis is a recently-described form of iron- and lipid-dependent regulated cell death associated with glutathione depletion and production of lipid peroxides by lipoxygenase enzymes. Activation of the ferroptosis pathway has been implicated in a growing number of disorders, including epilepsy. Given that ferroptosis is regulated by balancing the activities of glutathione peroxidase-4 (GPX4) and 15-lipoxygenase (15-LO), targeting these enzymes may provide a rational therapeutic strategy to modulate seizure. The clinical-stage therapeutic vatiquinone (EPI-743, α-tocotrienol quinone) was reported to reduce seizure frequency and associated morbidity in children with the mitochondrial disorder pontocerebellar hypoplasia type 6. We sought to elucidate the molecular mechanism of EPI-743 and explore the potential of targeting 15-LO to treat additional mitochondrial disease-associated epilepsies., Methods: Primary fibroblasts and B-lymphocytes derived from patients with mitochondrial disease-associated epilepsy were cultured under standardized conditions. Ferroptosis was induced by treatment with the irreversible GPX4 inhibitor RSL3 or a combination of pharmacological glutathione depletion and excess iron. EPI-743 was co-administered and endpoints, including cell viability and 15-LO-dependent lipid oxidation, were measured., Results: EPI-743 potently prevented ferroptosis in patient cells representing five distinct pediatric disease syndromes with associated epilepsy. Cytoprotection was preceded by a dose-dependent decrease in general lipid oxidation and the specific 15-LO product 15-hydroxyeicosatetraenoic acid (15-HETE)., Conclusions: These findings support the continued clinical evaluation of EPI-743 as a therapeutic agent for PCH6 and other mitochondrial diseases with associated epilepsy., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: The following authors declare financial competing interests as paid current or former employees and/or equity holders of BioElectron Technology Corporation, Inc.: AA, JJB, AH, KGH, CRH, AHKK, VK, MBK, YK, JCL, CIM, SAM, JJM, WDS, SS, JKT, LWang. EPI-743 is a commercial product in development by BioElectron Technology Corporation, Inc., from which employees may benefit. The following authors declare patent applications (pending or actual) belonging to BioElectron Technology Corporation, from which they may benefit: JJB, AH, CRH, AHKK, JCL, SAM, WDS, JKT. The following authors declare grant support from BioElectron Technology Corporation pertaining to the work under consideration forpublication: GME, CD-V, DM. WG declares a cooperative research agreement between NHGRI and BioElectron pertaining to the scope of the work under consideration, as well as to activities outside the submitted work. RPS is a site principal investigator for two studies sponsored by BioElectron Technology Corporation. GME is a site principal investigator for an emergency protocol sponsored by BioElectron Technology Corporation. Outside the scope of the submitted work, EAA declares he is a Co-Founder of Personalis Inc., and DeepCell, Inc. CD-V declares grant support from Actelion and Sanofi Genzyme, as well as personal fees from Actelion, CureVac, Moderna Therapeutics, Logic- Biotherapeutics, Nutricia, Orphan Europe, Medifood, Promethera, Sanofi Genzyme, and SOBI. GME declares grant support and serving as site principal investigator for a clinical trial sponsored by Stealth Therapeutics. DM declares personal fees from SOBI. Thefollowing authors declared no competing interests: EB, RC, KAC, SCJ, MTW, LWolfe. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Ferroptosis is a form of programmed cell death associated with inflammation, neurodegeneration, and ischemia. Vitamin E (alpha-tocopherol) has been reported to prevent ferroptosis, but the mechanism by which this occurs is controversial. To elucidate the biochemical mechanism of vitamin E activity, we systematically investigated the effects of its major vitamers and metabolites on lipid oxidation and ferroptosis in a striatal cell model. We found that a specific endogenous metabolite of vitamin E, alpha-tocopherol hydroquinone, was a dramatically more potent inhibitor of ferroptosis than its parent compound, and inhibits 15-lipoxygenase via reduction of the enzyme's non-heme iron from its active Fe3+ state to an inactive Fe2+ state. Furthermore, a non-metabolizable isosteric analog of vitamin E which retains antioxidant activity neither inhibited 15-lipoxygenase nor prevented ferroptosis. These results call into question the prevailing model that vitamin E acts predominantly as a non-specific lipophilic antioxidant. We propose that, similar to the other lipophilic vitamins A, D and K, vitamin E is instead a pro-vitamin, with its quinone/hydroquinone metabolites responsible for its anti-ferroptotic cytoprotective activity., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: All authors are employees of, and/or hold equity in BioElectron Technology Corporation, Inc. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Background: Studies have been published showing both increased and decreased utilization of cancer screening services in cancer survivors compared with cancer-free counterparts. This study synthesizes existing evidence in a meta-analysis., Methods: A systematic literature review was conducted in August 2016. Studies were included if they compared the utilization of screening services for cervical, breast and colorectal cancer among adulthood cancer survivors to cancer-free controls. Random effects meta-analyses were conducted to pool estimates., Results: Of 3538 studies, 19 fulfilled the inclusion criteria. Cancer survivors were more likely to utilize screening services for breast cancer (odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.13-1.42, P < 0.001), colorectal cancer (OR = 1.25, 95% CI: 1.15-1.37, P < 0.001) and cervical cancer (OR = 1.38, 95% CI: 1.08-1.75, P < 0.001) than cancer-free controls., Conclusions: Overall, cancer survivors were more likely to utilize cancer screening services when compared with cancer-free controls. Future studies should evaluate, whether the utilization of screening services translates into prolonged survival.