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Background and purpose: Experimental studies suggest inflammation can contribute to blood barrier disruption and brain injury in cerebral venous thrombosis (CVT). We aimed to determine whether blood biomarkers of inflammation were associated with the evolution of brain lesions, persistent venous occlusion or functional outcome in patients with CVT. Methods: Pathophysiology of Venous Infarction—Prediction of Infarction and Recanalization in CVT (PRIORITy‐CVT) was a multicenter prospective cohort study of patients with newly diagnosed CVT. Evaluation of neutrophil‐to‐lymphocyte ratio (NLR) and C‐reactive protein (CRP) concentrations in peripheral blood samples was performed at admission in 62 patients. Additional quantification of interleukin (IL)‐6 was performed at day 1, 3 and 8 in 35 patients and 22 healthy controls. Standardized magnetic resonance imaging was performed at day 1, 8 and 90. Primary outcomes were early evolution of brain lesion, early recanalization and functional outcome at 90 days. Results: Interleukin‐6 levels were increased in patients with CVT with a peak at baseline. IL‐6, NLR and CRP levels were not related with brain lesion outcomes or early recanalization but had a significant association with unfavourable functional outcome at 90 days (IL‐6: OR = 1.28, 95% CI: 1.05–1.56, P = 0.046; NLR: OR = 1.39, 95% CI: 1.4–1.87, P = 0.014; CRP: OR = 1.756, 95% CI: 1.010–3.051, P = 0.029). Baseline IL‐6 had the best discriminative capacity, with an area under the receiver operating characteristic curve to predict unfavourable functional outcome of 0.74 (P = 0.031). Conclusions: Increased baseline levels of NLR, CRP and IL‐6 may serve as new predictive markers of worse functional prognosis at 90 days in patients with CVT. No association was found between inflammatory markers and early evolution of brain lesion or venous recanalization. [ABSTRACT FROM AUTHOR]

BACKGROUND The effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear. METHODS We performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days. RESULTS Of 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days. CONCLUSIONS In this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, NCT03148457.) [ABSTRACT FROM AUTHOR]

Introduction: Cerebral venous thrombosis (CVT) is a less common stroke subtype. While long term outcome factors have been extensively studied, short term deterioration remains poorly understood., Patients and Methods: We conducted a 10-years retrospective analysis at a high-volume tertiary center, including consecutive patients diagnosed with CVT. The primary outcome was early deterioration (ED), defined as decrease in Glasgow Coma Scale, de novo or worsening of focal deficit, death from neurological cause, new or enlarged parenchymal lesions or subarachnoid hemorrhage during hospitalization. Multivariable logistic regression analysis was performed to identify factors associated with ED., Results: We included 138 patients (81.2% female, median age 42.0 years (IQR 29.3-49.0)). Forty-five (32.6%) patients had ED, with 33 (23.9%) showing clinical deterioration and 35 of 104 (33.7%) imaging worsening. Variables selected from the multivariate model for association with ED were aphasia (OR 4.63, 95% CI 1.61-13.32), motor deficits (OR 2.34, 95% CI 0.97-5.61), and parenchymal lesion (OR 3.65, 95% CI 1.38-9.67). Twenty-seven patients underwent endovascular treatment after deterioration. Patients in the ED group had worse functional outcome at discharge, 6 and 12 months ( p  < 0.001)., Discussion: One third of patients in this cohort experienced ED. Patients with aphasia, motor deficit, or parenchymal brain lesion at baseline were at higher risk. These patients performed worse at long term follow-up., Conclusion: We identified predictors of ED in patients with CVT. These patients should be carefully monitored. These findings may inform the design of future clinical trials aimed at evaluating additional therapeutic interventions in the acute phase., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Promoting the highest quality, evidence-based research across Europe is a priority of the European Stroke Organisation (ESO). The ESO Guideline Board communicate and promote evidence-based recommendations for clinical practice through their Guidelines. However, there are many aspects of stroke care where robust scientific evidence may be unavailable or difficult to obtain. Thus, there is a need for practical, consensus guidance, produced following robust, consistent, and transparent methods, that is suitable for high-priority clinical scenarios where evidence is currently lacking. The ESO Guideline Board developed methods for producing practical clinical guidance based on expert consensus in response to this need. These ESO' White Papers' are intended to complement standard ESO Guidelines. Here, we outline the ESO White Papers' standard operating procedure (SOP). We will describe the motivation for creating White Papers, the preferred composition of writing groups and expert consensus panellists, the methods for achieving consensus, and how results will be communicated. To ensure that all voting members have an equal voice, our methods are based upon the Delphi process of repeated rounds of anonymous voting, feedback and review. We hope that the White Papers will add further value to the clinical practice guidance that is offered by ESO. We look forward to receiving suggestions for White Paper topics from the stroke community., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: TQ has received funding from NIHR for methodology work around guidelines and evidence synthesis. JCP has received consultation fees and travel expenses from Abbott, Akcea, Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer, outside the submitted work. SP received research support from BMS/Pfizer, Boehringer-Ingelheim, Daiichi Sankyo, DOASENSE, European Union, German Federal Joint Committee Innovation Fund, and German Federal Ministry of Education and Research, Helena Laboratories and Werfen as well as speakers’ honoraria/consulting fees from Alexion, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS/Pfizer, Daiichi Sankyo, Portola, and Werfen (all outside the submitted work). DS has received funding from: Advisory Board: Astra-Zeneca, Alexion, CSL Behring, Shionogi, BMS, Janssen. Unrestricted Research or Educational Grants: Boehringer-Ingelheim. DAdS reports grants from the Portuguese Foundation for Science and Technology, MSD and ESR, advisory board participation for Bayer, Johnson & Johnson and Daiichi-Sankyo, and speaker fees from Bial and Astrazeneca.

Purpose of Review: This review intends to systematize the diagnostic and treatment approach to cerebral venous thrombosis (CVT), highlighting key studies that have been recently published., Recent Findings: In light of the recent pandemic, new risk factors for CVT have emerged. Contrast-enhanced MRI and susceptibility-weighted imaging have been shown to offer increased sensitivity for detecting cortical vein thrombosis.Dabigatran seems to be as effective and well tolerated as warfarin for long-term anticoagulation. Partial venous recanalization often occurs in patients treated with anticoagulation only, as early as 8 days after treatment onset. For patients with CVT and impending brain herniation, two-thirds of those who undergo decompressive craniectomy survive, with one-third being functionally independent 6 months after diagnosis., Summary: CVT is an unusual type of cerebrovascular disease that mostly affects women of fertile age. Risk factors should be identified and addressed. Diagnosis relies on confirmation of venous sinus and/or vein thrombosis, usually by CT venography or MRI. Anticoagulation is the cornerstone of treatment. Despite the lack of high-quality evidence, endovascular treatment is often considered in severe cases. Special populations require tailored approaches. About 80% achieve mRS 0-1, but residual symptoms often affect quality of life and the ability to return to work., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: There is a longstanding clinical uncertainty regarding the optimal timing of initiating oral anticoagulants (OAC) for non-valvular atrial fibrillation following acute ischemic stroke. Current international recommendations are based on expert opinions, while significant diversity among clinicians is noted in everyday practice., Methods: We conducted an updated systematic review and meta-analysis including all available randomized-controlled clinical trials (RCTs) and observational cohort studies that investigated early versus later OAC-initiation for atrial fibrillation after acute ischemic stroke. The primary outcome was defined as the composite of ischemic and hemorrhagic events and mortality at follow-up. Secondary outcomes included the components of the composite outcome (ischemic stroke recurrence, intracranial hemorrhage, major bleeding, and all-cause mortality). Pooled estimates were calculated with random-effects model., Results: Nine studies (two RCTs and seven observational) were included comprising a total of 4946 patients with early OAC-initiation versus 4573 patients with later OAC-initiation following acute ischemic stroke. Early OAC-initiation was associated with reduced risk of the composite outcome (RR = 0.74; 95% CI:0.56-0.98; I 2  = 46%) and ischemic stroke recurrence (RR = 0.64; 95% CI:0.43-0.95; I 2  = 60%) compared to late OAC-initiation. Regarding safety outcomes, similar rates of intracranial hemorrhage (RR = 0.98; 95% CI:0.57-1.69; I 2  = 21%), major bleeding (RR = 0.78; 95% CI:0.40-1.51; I 2  = 0%), and mortality (RR = 0.94; 95% CI:0.61-1.45; I 2  = 0%) were observed. There were no subgroup differences, when RCTs and observational studies were separately evaluated., Conclusions: Early OAC-initiation in acute ischemic stroke patients with non-valvular atrial fibrillation appears to have better efficacy and a similar safety profile compared to later OAC-initiation., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Epileptic seizures occur frequently after stroke due to changes in brain function and structure, and up to around 10% of stroke patients experience stroke recurrence in the first year. We aimed to establish the risk of acute symptomatic seizures in patients with recurrent stroke., Methods: Retrospective cohort study including consecutive admissions to a Stroke Unit due to acute ischemic stroke, during a 5-year period. Additional inclusion of patients admitted to two centers in different countries to corroborate findings (confirmatory cohort). We aimed to compare acute symptomatic seizure incidence in patients with and without previous stroke. Patients with history of epilepsy were excluded. Logistic regression modeling was performed to identify predictors in middle cerebral artery (MCA) stroke., Results: We included 1473 patients (1085 with MCA stroke), of which 117 had a recurrent ischemic stroke (84 with MCA stroke). Patients with recurrent stroke had a seizure risk during hospital stay similar to that of patients with a first-ever stroke (5.1% vs. 4.5%, OR 1.15, 95% CI .48-2.71, p = .75). Risk of acute symptomatic seizures was also similar (5.0% vs. 4.1, OR 1.22, 95% CI .29-5.27, p = .78). Older age, female sex, and hemorrhagic transformation were predictors of seizures in patients with a first MCA ischemic stroke, but not in recurrent stroke patients. Electrographic characteristics were similar between the two groups in patients who had an electroencephalogram (46 with first stroke, 5 with recurrent stroke). The low rate of seizures (1.5%) in the confirmatory cohort (n = 198) precluded full comparison with the initial cohort. Nevertheless, the rate of seizures was not higher in stroke recurrence., Significance: History of previous stroke was not associated with an increased risk of acute symptomatic seizures during hospital stay. Larger, prospective studies, with prospective electrophysiological evaluation, are needed to explore the impact of stroke recurrence on seizure risk., (© 2024 International League Against Epilepsy.)

Introduction: Mounting evidence suggests that glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) attenuate cardiovascular-risk in type-2 diabetes (T2DM). Tirzepatide is the first-in-class, dual glucose-dependent-insulinotropic-polypeptide GIP/GLP-1 RA approved for T2DM., Patients and Methods: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate: (i) the incidence of major adverse cardiovascular events (MACE); and (ii) incidence of stroke, fatal, and nonfatal stroke in T2DM-patients treated with GLP-1 or GIP/GLP-1 RAs (vs placebo)., Results: Thirteen RCTs (9 and 4 on GLP-1 RAs and tirzepatide, respectively) comprising 65,878 T2DM patients were included. Compared to placebo, GLP-1RAs or GIP/GLP-1 RAs reduced MACE (OR: 0.87; 95% CI: 0.81-0.94; p  < 0.01; I 2  = 37%), all-cause mortality (OR: 0.88; 95% CI: 0.82-0.96; p  < 0.01; I 2  = 21%) and cardiovascular-mortality (OR: 0.88; 95% CI: 0.80-0.96; p  < 0.01; I 2  = 14%), without differences between GLP-1 versus GIP/GLP-1 RAs. Additionally, GLP-1 RAs reduced the odds of stroke (OR: 0.84; 95% CI: 0.76-0.93; p  < 0.01; I 2  = 0%) and nonfatal stroke (OR: 0.85; 95% CI: 0.76-0.94; p  < 0.01; I 2  = 0%), whereas no association between fatal stroke and GLP-1RAs was uncovered (OR: 0.80; 95% CI: 0.61-1.05; p  = 0.105; I 2  = 0%). In secondary analyses, GLP-1 RAs prevented ischemic stroke (OR: 0.74; 95% CI: 0.61-0.91; p  < 0.01; I 2  = 0%) and MACE-recurrence, but not hemorrhagic stroke (OR: 0.92; 95% CI: 0.51-1.66; p  = 0.792; I 2  = 0%). There was no association between GLP-1RAs or GIP/GLP-1 RAs and fatal or nonfatal myocardial infarction., Discussion and Conclusion: GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and mortality in T2DM. While there is solid evidence that GLP-1 RAs significantly attenuate the risk of ischemic stroke in T2DM, dedicated RCTs are needed to evaluate the efficacy of novel GIP/GLP-1 RAs for primary and secondary stroke prevention., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Previous reports and meta-analyses derived from small case series reported a mortality rate of up to 40% in patients with coronavirus disease 2019 associated cerebral venous thrombosis (COVID-CVT). We assessed the clinical characteristics and outcomes in an international cohort of patients with COVID-CVT., Patients and Methods: This was a registry study of consecutive COVID-CVT patients diagnosed between March 2020 and March 2023. Data collected by the International Cerebral Venous Thrombosis Consortium from patients with CVT diagnosed between 2017 and 2018 served as a comparison. Outcome analyses were adjusted for age and sex., Results: We included 70 patients with COVID-CVT from 23 hospitals in 15 countries and 206 controls from 14 hospitals in 13 countries. The proportion of women was smaller in the COVID-CVT group (50% vs 68%, p  < 0.01). A higher proportion of COVID-CVT patients presented with altered mental state (44% vs 25%, p  < 0.01), the median thrombus load was higher in COVID-CVT patients (3 [IQR 2-4] vs 2 [1-3], p  < 0.01) and the length of hospital stay was longer compared to controls (11 days [IQR 7-20] vs 8 [4-15], p  = 0.02). In-hospital mortality did not differ (5/67 [7%, 95% CI 3-16] vs 7/206 [3%, 2-7], aOR 2.6 [95% CI 0.7-9]), nor did the frequency of functional independence after 6 months (modified Rankin Scale 0-2; 45/58 [78%, 95% CI 65-86] vs 161/185 [87%, 81-91], aOR 0.5 [95% CI 0.2-1.02])., Conclusion: In contrast to previous studies, the in-hospital mortality rate and functional outcomes during follow-up did not differ between COVID-CVT patients and the pre-COVID-19 controls., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AS reports a grant from the Swiss Heart Foundation. MRH reports grants from SITEM Research Support Funds and Swiss National Science Foundation, Swiss Heart Foundation, not directly related to this manuscript. MA reports personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Covidien, Daiichi Sankyo, Medtronic, Novartis, Pfizer, and Amgen. JMC has received grants paid to his institution from Boehringer Ingelheim and Bayer, and payments paid to his institution for data safety monitoring board participation by Bayer. JMF has received personal fees from Boehringer Ingelheim, Bayer, and Daiichi Sankyo as well as grants from Bayer. DAS reports travel support from Boehringer Ingelheim, speaker fees from Bayer, and Advisory Board participation for AstraZeneca. TT has received personal fees from Argenx, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Inventiva, and Portola Pharma. NR received consultant fees from Novartis. KJ has received academic grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement (ALFGBG 965417) for research on CVT. SP received research support from BMS/Pfizer, Boehringer-Ingelheim, Daiichi Sankyo, European Union, German Federal Joint Committee Innovation Fund, and German Federal Ministry of Education and Research, Helena Laboratories and Werfen as well as speakers’ honoraria/consulting fees from Alexion, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS/Pfizer, Daiichi Sankyo, Portola, and Werfen (all outside the submitted work). TNN reports advisory board Idorsia, Brainomix. KA reports a grant from Swiss National Science Foundation and Medtronic advisory board participation in 2022, not related to this manuscript. EL has received academic grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement (ALFGBG 942851), Swedish Neurologic Society, Elsa and Gustav Lindh’s Foundation, Wennerströms’ Foundation, P-O Ahl’s Foundation and Rune and Ulla Amlöv’s Foundation for research on CVT. All other co-authors report no disclosures.

Background: The superiority of endovascular thrombectomy (EVT) over medical management was not established in two early basilar artery occlusion (BAO) randomized controlled trials. Despite this, many clinicians recommended EVT for acute BAO under certain circumstances. This paper aims to compare physicians' diagnostic and management strategies of BAO according to gender., Methods: From January to March 2022 an international survey was conducted regarding management strategies in acute BAO. We compared responses between clinicians by identifying gender. Questions were designed to examine clinical and imaging parameters influencing management of patients with BAO., Results: Among the 1245 respondents from 73 countries, 311 (25.0%) identified as female. This figure was 13.6% amongst interventionists. Geographically, female respondents were lowest in Asia (14.5%) and North America (23.9%). The proportion of respondents identifying as female was consistent regardless of their years of experience. Female respondents were more likely to choose time of onset as time of first estimated stroke like symptom (48.0% vs. 38.5%, p  < .01), were less likely to favor thrombectomy in the V4 segment of vertebrobasilar artery occlusions (31.5% vs. 43.3%, p  < .01), and were less likely to find it acceptable to enroll all patients who met trial criteria in the standard medical treatment arm of a clinical trial (41.2% vs. 47.0%, p  = .01). Male respondents were more likely to agree that thrombolysis would not alter their decision on proceeding with EVT (93.7% vs. 88.3%, p  < .01)., Conclusions: Female clinicians appear to be significantly underrepresented in stroke medicine. This is most pronounced amongst interventionists and in Asia. Although male and female opinions were closely aligned on many aspects of BAO management, differences in opinion were observed in a number of significant areas which influence decision making.

Background and Purpose: Coma is an independent predictor of poor clinical outcomes in cerebral venous thrombosis (CVT). We aimed to describe the association of age, sex, and radiological characteristics of adult coma patients with CVT., Methods: We used data from the international, multicentre prospective observational BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) study. Only positively associated variables with coma with <10% missing data in univariate analysis were considered for the multivariate logistic regression model., Results: Of the 596 adult patients with CVT (75.7% women), 53 (8.9%) patients suffered coma. Despite being a female-predominant disease, the prevalence of coma was higher among men than women (13.1% vs. 7.5%, p = 0.04). Transverse sinus thrombosis was least likely to be associated with coma (23.9% vs. 73.3%, p < 0.001). The prevalence of superior sagittal sinus thrombosis was higher among men than women in the coma sample (73.6% vs. 37.5%, p = 0.01). Men were significantly older than women, with a median (interquartile range) age of 51 (38.5-60) versus 40 (33-47) years in the coma (p = 0.04) and 44.5 (34-58) versus 37 (29-48) years in the non-coma sample (p < 0.001), respectively. Furthermore, an age- and superior sagittal sinus-adjusted multivariate logistic regression model found male sex (odds ratio = 1.8, 95% confidence interval [CI] = 1.0-3.4, p = 0.04) to be an independent predictor of coma in CVT, with an area under the receiver operating characteristic curve of 0.61 (95% CI = 0.52-0.68, p = 0.01)., Conclusions: Although CVT is a female-predominant disease, men were older and nearly twice as likely to suffer from coma than women., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Competing Interests: Dr Aguiar de Sousa reported personal fees for AstraZeneca, Organon, Johnson & Johnson, and Daiichi-Sankyo advisory board participation, data safety monitoring board participation for the SECRET trial (University of British Columbia), and speaking fees from Bayer, Astrazeneca and Bial, outside the submitted work. The other author reports no conflicts

Background: Due to the rarity of cerebral venous thrombosis (CVT), performing high-quality scientific research in this field is challenging. Providing answers to unresolved research questions will improve prevention, diagnosis, and treatment, and ultimately translate to a better outcome of patients with CVT. We present an international research agenda, in which the most important research questions in the field of CVT are prioritized., Aims: This research agenda has three distinct goals: (1) to provide inspiration and focus to research on CVT for the coming years, (2) to reinforce international collaboration, and (3) to facilitate the acquisition of research funding., Summary of Review: This international research agenda is the result of a research summit organized by the International Cerebral Venous Thrombosis Consortium in Amsterdam, the Netherlands, in June 2023. The summit brought together 45 participants from 15 countries including clinical researchers from various disciplines, patients who previously suffered from CVT, and delegates from industry and non-profit funding organizations. The research agenda is categorized into six pre-specified themes: (1) epidemiology and clinical features, (2) life after CVT, (3) neuroimaging and diagnosis, (4) pathophysiology, (5) medical treatment, and (6) endovascular treatment. For each theme, we present two to four research questions, followed by a brief substantiation per question. The research questions were prioritized by the participants of the summit through consensus discussion., Conclusions: This international research agenda provides an overview of the most burning research questions on CVT. Answering these questions will advance our understanding and management of CVT, which will ultimately lead to improved outcomes for CVT patients worldwide., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.M.C. has received research support paid to his institution from Boehringer Ingelheim, Bayer, and Astra Zeneca. J.M.C. is co-founder and shareholder of TrianecT; D.A.d.S. reported personal fees for Astra Zeneca, Organon, Daiichi Sankyo and Johnson & Johnson advisory board participation, DSMB participation for the SECRET trial (University of British Columbia), and speaking fees from Bayer and Bial; S.P. has received research support from BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, European Union, German Federal Joint Committee Innovation Fund, German Federal Ministry of Education and Research, Helena Laboratories, and Werfen as well as speakers’ honoraria/consulting fees from Alexion, Astra Zeneca, Bayer, Boehringer Ingelheim, BMS/Pfizer, Daiichi Sankyo, Portola, and Werfen; A.A. has received research support paid to his Institution from Astra Zeneca; M.S.v.K. has received research support from the Amstol foundation; R.v.d.B. has received research support paid to his institution from CERENOVUS; T.S.F. has received in-kind study medication from Bayer Canada and has received personal fees from Bayer Canada and Roche for advosiry board participation; M.R.H. has received grants from the Swiss National Science Foundation, the SITEM Research Funds, and the Swiss Heart Foundation, all outside the submitted work; M.H.-P. has received compensation for scientific research by AptaTargets; F.A.K. has received research support from Bayer, BMS, BSCI, Astra Zeneca, MSD, Leo Pharma, Actelion, Farm-X, The Netherlands Organization for Health Research and Development, The Dutch Thrombosis Foundation, The Dutch Heart Foundation, and the Horizon Europe Program; R.R.L. has received speaker honoraria from IscemaView, Boehringer Ingelheim, Pfizer, Jansen, Biogen, Medtronic, and Abott and advisory board honoraria from Jansen, Bayer, and Filterlex; T.N.N. has disclosed advisory board for Idorsia and Brainomix; G.S. has received a stipend as the Editor-in-Chief of the World Stroke Academy for the World Stroke Organization; V.T. has received speaker honoraria from Boehringer Ingelheim and Bayer & Astra Zeneca and is on the steering committee of the Librexia Stroke trial, sponsored by Johnson & Johnson; D.J.W. has received grant funding from the Stroke Association and British Heart Foundation, speaking honoraria from Bayer, speaking and chairing honoraria from Alexion and NovoNordisk, and consultancy fees from Alnylam, Bayer, and NovoNordisk; T.T. has served/serves on scientific advisory boards for Astra Zeneca, Argenx, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Inventiva, and Portola Pharm and has received academic funding from University of Gothenburg, Sahlgrenska University Hospital, European Union, Sigrid Juselius Foundation, and Wennerström’s Foundation. The other authors have nothing to disclose.

Importance: Whether infarct size modifies the treatment effect of early vs late direct oral anticoagulant (DOAC) initiation in people with ischemic stroke and atrial fibrillation is unknown., Objective: To assess whether infarct size modifies the safety and efficacy of early vs late DOAC initiation., Design, Setting, and Participants: Post hoc analysis of participants from the multinational (>100 sites in 15 countries) randomized clinical Early Versus Later Anticoagulation for Stroke With Atrial Fibrillation (ELAN) trial who had (1) acute ischemic stroke, (2) atrial fibrillation, and (3) brain imaging available before randomization. The ELAN trial was conducted between October 2017 and December 2022. Data were analyzed from October to December 2023 for this post hoc analysis., Intervention: Early vs late DOAC initiation after ischemic stroke. Early DOAC initiation was within 48 hours for minor or moderate stroke or on days 6 to 7 for major stroke; late DOAC initiation was on days 3 to 4 for minor stroke, days 6 to 7 for moderate stroke, and days 12 to 14 for major stroke., Main Outcomes and Measures: The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, extracranial bleeding, systemic embolism, or vascular death within 30 days. The outcome was assessed according to infarct size (minor, moderate, or major) using odds ratios and risk differences between treatment arms. Interrater reliability for infarct size between the core laboratory and local raters was assessed, and whether this modified the estimated treatment effects was also examined., Results: A total of 1962 of the original 2013 participants (909 [46.3%] female; median [IQR] age, 77 [70-84] years) were included. The primary outcome occurred in 10 of 371 participants (2.7%) with early DOAC initiation vs 11 of 364 (3.0%) with late DOAC initiation among those with minor stroke (odds ratio [OR], 0.89; 95% CI, 0.38-2.10); in 11 of 388 (2.8%) with early DOAC initiation vs 14 of 392 (3.6%) with late DOAC initiation among those with moderate stroke (OR, 0.80; 95% CI, 0.35-1.74); and in 8 of 219 (3.7%) with early DOAC initiation vs 16 of 228 (7.0%) with late DOAC initiation among those with major stroke (OR, 0.52; 95% CI, 0.21-1.18). The 95% CI for the estimated risk difference of the primary outcome in early anticoagulation was -2.78% to 2.12% for minor stroke, -3.23% to 1.76% for moderate stroke, and -7.49% to 0.81% for major stroke. There was no significant treatment interaction for the primary outcome. For infarct size, interrater reliability was moderate (κ = 0.675; 95% CI, 0.647-0.702) for local vs core laboratory raters and strong (κ = 0.875; 95% CI, 0.855-0.894) between core laboratory raters., Conclusions and Relevance: The treatment effect of early DOAC initiation did not differ in people with minor, moderate, or major stroke assessed by brain imaging. Early treatment was not associated with a higher rate of adverse events, especially symptomatic intracranial hemorrhage, for any infarct size, including major stroke., Trial Registration: ClinicalTrials.gov Identifier: NCT03148457.

Objectives: Prognostication for cerebral venous thrombosis (CVT) remains difficult. We sought to validate the SI 2 NCAL 2 C score in an international cohort., Materials and Methods: The SI 2 NCAL 2 C score was originally developed to predict poor outcome (modified Rankin Scale (mRS) 3-6) at 6 months, and mortality at 30 days and 1 year using data from the International CVT Consortium. The SI 2 NCAL 2 C score uses 9 variables: the absence of any female-sex-specific risk factors, intracerebral hemorrhage, central nervous system infection, focal neurological deficits, coma, age, lower level of hemoglobin, higher level of glucose, and cancer. The ACTION-CVT study was an international retrospective study that enrolled consecutive patients across 27 centers. The poor outcome score was validated using 90-day mRS due to lack of follow-up at the 6-month time-point in the ACTION-CVT cohort. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Missing data were imputed using the additive regression and predictive mean matching methods. Bootstrapping was performed with 1000 iterations., Results: Mortality data were available for 950 patients and poor outcome data were available for 587 of 1,025 patients enrolled in ACTION-CVT. Compared to the International CVT Consortium, the ACTION-CVT cohort was older, less often female, and with milder clinical presentation. Mortality was 2.5% by 30 days and 6.0% by one year. At 90-days, 16.7% had a poor outcome. The SI 2 NCAL 2 C score had an AUC of 0.74 [95% CI 0.69-0.79] for 90-day poor outcome, 0.72 [0.60-0.82] for mortality by 30 days, and 0.82 [0.76-0.88] for mortality by one year., Conclusions: The SI 2 NCAL 2 C score had acceptable to good performance in an international external validation cohort. The SI 2 NCAL 2 C score warrants additional validation studies in diverse populations and clinical implementation studies., Competing Interests: Declaration of competing interest Thanh Nguyen reports research support from Medtronic and the Society of Vascular and Interventional Neurology; advisory board with Brainomix, Aruna Bio; Associate Editor of Stroke. Erik Lindgren reports research support from the Swedish state, ALF agreement (ALFGBG 942851), the Swedish Neurological Society, Elsa and Gustav Lindh's Foundation, Wennerström's Foundation, P-O Ahl's Foundation, and the Rune and Ulla Amlöv's Foundation. Katarina Jood reports research support from the Swedish state ALF agreement (ALFGBG-965417). Mirjam R. Heldner reports grants from SITEM Research Support Funds and Swiss National Science Foundation, Swiss Heart Foundation, not directly related to this manuscript. Thalia S Field reports honoraria for advisory board work for HLS Therapeutics, Roche Canada, AstraZeneca, in-kind study medication from Bayer Canada, is on the board of DESTINE Health, and is supported by a Heart and Stroke/Sauder Family Professorship of Stroke Research at the University of British Columbia. Christoph Stretz reports departmental funding (funds managed by Rhode Island Hospital) for his site's participation in the Neuro AFib study from Massachusetts General Hospital/BSC. Nils Henninger was supported by NINDS R21NS131756 during the conduct of this study (unrelated). Turgut Tatlisumak serves or has served on advisory boards for Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Inventiva, and Portola Pharma and received research funding from European Union, Sahlgrenska University Hospital, University of Gothenburg, and Wennerström's Foundation. Diana Aguiar de Sousa reports advisory board participation for Astrazenica, Organon, and Johnson & Johnson, speaker fees from Bial, Bayer, and Astrazeneca, and DSMB participation for the SECRET trial (all unrelated)., (Copyright © 2024. Published by Elsevier Inc.)

Background: Decompressive neurosurgery is recommended for patients with cerebral venous thrombosis (CVT) who have large parenchymal lesions and impending brain herniation. This recommendation is based on limited evidence. We report long-term outcomes of patients with CVT treated by decompressive neurosurgery in an international cohort., Methods: DECOMPRESS2 (Decompressive Surgery for Patients With Cerebral Venous Thrombosis, Part 2) was a prospective, international cohort study. Consecutive patients with CVT treated by decompressive neurosurgery were evaluated at admission, discharge, 6 months, and 12 months. The primary outcome was death or severe disability (modified Rankin Scale scores, 5-6) at 12 months. The secondary outcomes included patient and caregiver opinions on the benefits of surgery. The association between baseline variables before surgery and the primary outcome was assessed by multivariable logistic regression., Results: A total of 118 patients (80 women; median age, 38 years) were included from 15 centers in 10 countries from December 2011 to December 2019. Surgery (115 craniectomies and 37 hematoma evacuations) was performed within a median of 1 day after diagnosis. At last assessment before surgery, 68 (57.6%) patients were comatose, fixed dilated pupils were found unilaterally in 27 (22.9%) and bilaterally in 9 (7.6%). Twelve-month follow-up data were available for 113 (95.8%) patients. Forty-six (39%) patients were dead or severely disabled (modified Rankin Scale scores, 5-6), of whom 40 (33.9%) patients had died. Forty-two (35.6%) patients were independent (modified Rankin Scale scores, 0-2). Coma (odds ratio, 2.39 [95% CI, 1.03-5.56]) and fixed dilated pupil (odds ratio, 2.22 [95% CI, 0.90-4.92]) were predictors of death or severe disability. Of the survivors, 56 (78.9%) patients and 61 (87.1%) caregivers expressed a positive opinion on surgery., Conclusions: Two-thirds of patients with severe CVT were alive and more than one-third were independent 1 year after decompressive surgery. Among survivors, surgery was judged as worthwhile by 4 out of 5 patients and caregivers. These results support the recommendation to perform decompressive neurosurgery in patients with CVT with impending brain herniation., Competing Interests: Disclosures Dr Coutinho reports grants paid to his institution from Boehringer Ingelheim and Bayer. Dr Uyttenboogaart reports grants from Hartstichting and ZonMw. Dr Werring reports grant funding from the Stroke Association and British Heart Foundation, speaking honoraria from Bayer, speaking and chairing honoraria from Alexion and NovoNordisk, and consultancy fees from Alnylam, Bayer, and NovoNordisk. Dr Aguiar de Sousa reports personal fees for AstraZeneca, Organon, and Johnson & Johnson advisory board participation, travel support from Boehringer Ingelheim, DSMB participation for the SECRET trial (University of British Columbia), and speaking fees from Bayer and Bial. Dr Ferro reports personal fees from Bayer. The other authors report no conflicts.

Background: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation., Methods: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments., Results: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P =0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P =0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P =0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P =0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; P interaction =0.009)., Conclusions: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings., Competing Interests: Disclosures Disclosures provided by Dr Nguyen in compliance with American Heart Association annual Journal Editor Disclosure Questionnaire are available at https://www.ahajournals.org/editor-coi-disclosures. Dr Arnold reports compensation from Boehringer Ingelheim, AstraZeneca, Bayer, Bristol-Myers Squibb, Covidien, Daiichi Sankyo, Novartis, Sanofi, Pfizer, Medtronic, Novo Nordisk, and Amgen for consultant services. Dr Lester reports a provisional patent for Methods and compositions for disrupting tau aggregates. Dr Touze reports compensation from Elsevier for other services and employment by Caen. J.E. Kaufman reports grants from Goldschmidt Jacobson-Stiftung. Dr Traenka reports travel support from Bayer Healthcare. Dr Aguiar de Sousa reports compensation from Daiichi Sankyo, Bayer, AstraZeneca, Johnson & Johnson, and Fundação Bial for other services; compensation from the University of British Columbia for data and safety monitoring services; compensation from Organon & Co for consultant services. Dr Rosa reports grants from Merck Sharp & Dohme Corporation. Dr Field reports compensation from HLS Therapeutics, AstraZeneca Canada, and Roche for consultant services; service as a board member for Destine Health; and compensation from the Canadian Medical Protective Association for expert witness services; and grants from Bayer. Dr Leker reports compensation from Medtronic, Ischemaview, Bayer, Abbott Diabetes Care, Biogen, Janssen Biotech, and Boehringer Ingelheim for other services. Dr Nolte reports compensation from Daiichi Sankyo Europe GmbH, Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, and Alexion Pharmaceuticals for consultant services; and compensation from AstraZeneca, Abbott Canada, Deutsches Zentrum für Neurodegenerative Erkrankungen, Novartis, Portola Pharmaceuticals, Deutsches Zentrum für Herz-Kreislaufforschung, and Novartis for other services. Dr Poppe reports grants from Foundation Brain Canada, Heart and Stroke Foundation of Canada, and Stryker; and compensation from Roche for other services. Dr Liebeskind reports compensation from Medtronic, Genentech, Cerenovus, Stryker, and Rapid Medical Ltd, for consultant services. B. Mac Grory reports grants from the National Institutes of Health; employment by Duke University Medical Center; compensation from Bayer for other services; grants from the American Heart Association, Duke Bass Connections, and the Duke Office of Physician Scientist Development. Dr Al Kasab reports compensation from Stryker for other services and employment by Medical University of South Carolina. Dr Kicielinski reports compensation from Stryker, Penumbra Inc, Medtronic, and MicroVention Inc, for other services; travel support from MicroVention Inc; and employment by Medical University of South Carolina and Elsevier. Dr de Havenon reports stock options in TitinKM and Certus; grants from the National Institutes of Health; and compensation from Novo Nordisk for consultant services. Dr Siegler reports grants from Philips and employment by the University of Chicago. Dr Willey reports compensation from Edwards Lifesciences Corporation and Abbott Fund for end point review committee services; compensation from Uptodate for other services; and compensation from the Abbott Laboratories for consultant services. Dr Sharma reports a provisional patent for a stroke etiology classifier algorithm and grants from the National Institutes of Health Clinical Center. Dr Martins reports compensation from Pfizer, Medtronic, Servier Affaires Medicales, Daiichi Sankyo, Bayer, Novo Nordisk, Novartis, Penumbra Inc, and Boehringer Ingelheim for other services. Dr Simpkins reports grants from the National Institutes of Health. Dr Stretz reports grants from Massachusetts General Hospital. Dr Furie reports compensation from Janssen Biotech for consultant services. The other authors report no conflicts

Introduction: There is little data on the role of endovascular treatment (EVT) of cerebral venous sinus thrombosis (CVST) due to vaccine-induced immune thrombotic thrombocytopenia (VITT). Here, we describe clinical characteristics and outcomes of CVST-VITT patients who were treated with EVT., Patients and Methods: We report data from an international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 6 March 2023. VITT was defined according to the Pavord criteria., Results: EVT was performed in 18/136 (13%) patients with CVST-VITT (92% aspiration and/or stent retrieval, 8% local thrombolysis). Most common indications were extensive thrombosis and clinical or radiological deterioration. Compared to non-EVT patients, those receiving EVT had a higher median thrombus load (4.5 vs 3). Following EVT, local blood flow was improved in 83% (10/12, 95% confidence interval [CI] 54-96). One (6%) asymptomatic sinus perforation occurred. Eight (44%) patients treated with EVT also underwent decompressive surgery. Mortality was 50% (9/18, 95% CI 29-71) and 88% (8/9, 95% CI 25-66) of surviving EVT patients achieved functional independence with a modified Rankin Scale score of 0-2 at follow-up. In multivariable analysis, EVT was not associated with increased mortality (adjusted odds ratio, 0.66, 95% CI 0.16-2.58)., Discussion and Conclusion: We describe the largest cohort of CVST-VITT patients receiving EVT. Half of the patients receiving EVT died during hospital admission, but most survivors achieved functional independence., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AA serves as an advisory board member for Bayer and Bristol Myers Squibb and consulting fees for Boheringer Ingelheim. ABC received consulting fees from Boehringer Ingelheim. SM reports grants from Bayer, Pfizer, Boehringer Ingelheim and Daiichi Sankyo paid to her institution, and personal fees from Bayer, BMS/Pfizer, Boehringer Ingelheim, Abbvie, Portola/Alexion and Daiichi Sankyo paid to her institution. AG received speaker’s honoraria from Boehringer Ingelheim, Daichii Sankyo, Pfizer, Occlutech, Merz, and Ipsen. CGE received funding to attend a conference from Boehringer Ingelheim and Bayer and speaker honoraria from the AAN. AS has received a grant from Swiss Heart Foundation. CC received speaker honoraria from Boehringer Ingelheim, personal fees for advisory board participation from AstraZeneca and Biogen, and personal fees from Biogen and Bristol Myers Squibb. CGE received travel funding from Boehringer Ingelheim and Bayer and speaker honoraria from the AAN. DAS reports travel support from Boehringer Ingelheim, DSMB participation for the SECRET trial, advisory board participation for AstraZeneca and membership on the ESO Executive Committee. EL received grants from the Swedish State, Swedish Neurologic Society, Elsa and Gustav Lindh’s Foundation, P-O Ahl’s Foundation and Rune and Ulla Amlöv’s Foundation. FD is a consultant/proctor for Cerenovus/Johnson&Johnson, Balt, Cerus Endovascular and Phenox and received speaker’s honoraria from Acandis, Stryker, Cerenovus/Johnson&Johnson, Asahi and research support from Cerenovus/Johnson&Johnson. JMC received grants paid to his institution from Boehringer Ingelheim and Bayer for DSMB participation by Bayer. JMF reports fees and DSMB or Advisory Board participation for Boehringer Ingelheim and consulting fees from Bayer. JPa received personal fees from Boehringer Ingelheim, Bayer, Herantis Pharma and Abbott and stock ownership in Vital Signum. MA reports compensation from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Covidien, Daiichi Sankyo, Novartis, Sanofi, Pfizer, Medtronic and research grants from the Swiss National Science Foundation and the Swiss Heart Foundation. MP received personal fees for advisory board participation from Alexion. MRH reports grants from the Swiss Heart Foundation, the Bangerter Foundation, Swiss National Science Foundation, and SITEM Research Funds, and Advisory Board participation for Amgen. NR received research grants from Fulbright, Harvard University and Philippe Foundation. RL reports fees paid to his institution by Boehringer Ingelheim, Genentech, Ischemaview, Medtronic, and Medpass. SN has received consulting fees from Brainomix and lecture fees from Boehringer Ingelheim and BMS-Pfizer. SP received research support from BMS/Pfizer, Boehringer-Ingelheim, Daiichi Sankyo, European Union, German Federal Joint Committee Innovation Fund, and German Federal Ministry of Education and Research, Helena Laboratories and Werfen and speakers’ honoraria/consulting fees from Alexion, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS/Pfizer, Daiichi Sankyo, Portola, and Werfen. TK received personal fees from Boehringer Ingelheim. TSF received study medication from Bayer Canada and personal fees from HLS Therapeutics. TT has received personal fees from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Inventiva, and Portola Pharma. All other authors declare that there is no conflict of interest.

Background: The periprocedural antithrombotic regimen might affect the risk-benefit profile of emergent carotid artery stenting (eCAS) in patients with acute ischemic stroke (AIS) due to tandem lesions, especially after intravenous thrombolysis. We conducted a systematic review and meta-analysis to evaluate the safety and efficacy of antithrombotics following eCAS., Methods: We followed PRISMA guidelines and searched MEDLINE, Embase, and Scopus from January 1, 2004 to November 30, 2022 for studies evaluating eCAS in tandem occlusion. The primary endpoint was 90-day good functional outcome. Secondary outcomes were symptomatic intracerebral hemorrhage, in-stent thrombosis, delayed stent thrombosis, and successful recanalization. Meta-analysis of proportions and meta-analysis of odds ratios were implemented., Results: 34 studies with 1658 patients were included. We found that the use of no antiplatelets (noAPT), single antiplatelet (SAPT), dual antiplatelets (DAPT), or glycoprotein IIb/IIIa inhibitors (GPI) yielded similar rates of good functional outcomes, with a marginal benefit of GPI over SAPT (OR 1.88, 95% CI 1.05 to 3.35, P heterogeneity =0.31). Sensitivity analysis and meta-regression excluded a significant impact of intravenous thrombolysis and Alberta Stroke Program Early CT Score (ASPECTS). We observed no increase in symptomatic intracerebral hemorrhage (sICH) with DAPT or GPI compared with noAPT or SAPT. We also found similar rates of delayed stent thrombosis across groups, with acute in-stent thrombosis showing marginal, non-significant benefits from GPI and DAPT over SAPT and noAPT., Conclusions: In AIS due to tandem occlusion, the periprocedural antithrombotic regimen of eCAS seems to have a marginal effect on good functional outcome. Overall, high intensity antithrombotic therapy may provide a marginal benefit on good functional outcome and carotid stent patency without a significant increase in risk of sICH., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To review the optimal diagnostic cut-off of ultrasonographic optic nerve sheath diameter (ONSD) in the diagnosis of increased intracranial pressure (IICP)., Methods: A systematic search was conducted of available studies assessing the use of ONSD ultrasonography in patients with suspected IICP. Meta-analysis of diagnostic accuracy of ultrasonographic ONSD was performed using a bivariate model of random effects to summarize pooled sensitivity and specificity. A summary receiver operating characteristics (SROC) curve was plotted. Accuracy measures associated with ONSD cut-off and predefined covariates were investigated with meta-regression., Results: We included 38 studies, comprising a total of 2824 patients. A total of 21 studies used invasive techniques as a reference standard estimation of IICP and meta-analysis revealed a pooled sensitivity of 0.90 (95% CI 0.85-0.93) and specificity of 0.87 (95% CI 0.80-0.91). Optimal ONSD cut-off values ranged between 4.1 mm and 7.2 mm. Meta-regression analysis showed that ONSD cut-off values of 5.6 to 6.3 mm were associated with higher pooled specificity compared to cut-off values of 4.9 to 5.5 mm (0.93, 95% CI 0.85-0.97 vs. 0.78, 95% CI 0.65-0.87; p = 0.036)., Conclusions: Ultrasonography of ONSD shows a high diagnostic accuracy for IICP, with high pooled sensitivity and specificity. Additionally, larger cut-off values seem to significantly increase specificity without compromising sensitivity, which support their use as optimal ONSD cut-off. The overall high sensitivity of ultrasonographic ONSD suggests its usefulness as a screening tool for IIC, which may provide an estimate of when invasive methods are warranted., Clinical Relevance: ONSD ultrasonography is a fast and cost-effective method with a high diagnostic accuracy to detect IICP. The optimum ONSD cut-off hasn't been established before, but we suggest the 5.6 to 6.3 mm range as the best for the diagnosis of IICP., Competing Interests: Declaration of Competing Interest DB has received support for scientific meetings and courses, including travel grants, from Roche and Sanofi, and research grants from the Sumaira Foundation. DAS has received personal fees for AstraZeneca and Organon advisory board participation, travel support from Boehringer Ingelheim, DSMB participation for the SECRET trial (University of British Columbia) and speaking fees from Bayer and Bial outside the submitted work., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)