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Eagle syndrome is defined as an elongated styloid process (ESP) that compresses nearby vasculo-nervous structures. The vascular variant of Eagle syndrome can lead to neurological symptoms including syncope, transient ischemic attack, or stroke; however, it has also been associated with other atypical presentations, making its diagnosis challenging. This review aimed to depict the characteristics of patients with the symptomatic vascular variant of Eagle syndrome. The literature search identified 56 reported cases of vascular variants of Eagle syndrome, with a mean age at onset of 51 years (range: 15-85 years), and the male-to-female ratio was 2:4. The ESP was bilateral in 63% of the cases, and the mean length was 48 mm (range: 31-77 mm). Vascular complications were mostly represented by internal jugular vein (IVJ) stenosis ( n  = 28), followed by internal carotid artery (ICA) dissection ( n  = 15). Additionally, eight cases of ICA thrombosis and two cases of severe chronic stenosis of the ICA > 90% were reported. Vascular complications may lead to cerebral ischemia due to either a thromboembolic mechanism or, less frequently, reduced blood flow. Laminar cortical necrosis, as a cerebral complication of ICA compression, was exceptionally described in one case, and such an atypical clinical presentation may be regarded as a diagnostic pitfall., Competing Interests: YB reports personal fees from BMS, Pfizer, Medtronic, Amgen, Servier, NovoNordisk, Novartis, Boehringer-Ingelheim, outside the submitted work. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Tadjer and Béjot.)

Purpose: Post-stroke (PS) cognitive impairment (CI) is frequent and its devastating functional and vital consequences are well known. Despite recent guidelines, they are still largely neglected. A large number of recent studies have re-examined the epidemiology, diagnosis, imaging determinants and management of PSCI. The aim of this update is to determine whether these new data answer the questions that are essential to reducing PSCI, the unmet needs, and steps still to be taken., Methods: Literature review of stroke unit-era studies examining key steps in the management of PSCI: epidemiology and risk factors, diagnosis (cognitive profile and assessments), imaging determinants (quantitative measures, voxelwise localization, the disconnectome and associated Alzheimer's disease [AD]) and treatment (secondary prevention, symptomatic drugs, rehabilitation and noninvasive brain stimulation) of PSCI., Findings: (1) the prevalence of PSCI of approximately 50% is probably underestimated; (2) the sensitivity of screening tests should be improved to detect mild PSCI; (3) comprehensive assessment is now well-defined and should include apathy; (4) easily available factors can identify patients at high risk of PSCI; (5) key imaging determinants are the location and volume of the lesion and the resulting disconnection, associated AD and brain atrophy; WMH, ePVS, microhemorrhages, hemosiderosis, and cortical microinfarcts may contribute to cognitive impairment but are more likely to be markers of brain vulnerability or associated AD that reduce PS recovery; (6) remote and online assessment is a promising approach for selected patients; (7) secondary stroke prevention has not been proven to prevent PSCI; (8) symptomatic drugs are ineffective in treating PSCI and apathy; (9) in addition to cognitive rehabilitation, the benefits of training platforms and computerized training are yet to be documented; (10) the results and the magnitude of improvement of noninvasive brain stimulation, while very promising, need to be substantiated by large, high-quality, sham-controlled RCTs., Discussion and Conclusion: These major advances pave the way for the reduction of PSCI. They include (1) the development of more sensitive screening tests applicable to all patients and (2) online remote assessment; crossvalidation of (3) clinical and (4) imaging factors to (5) identify patients at risk, as well as (6) factors that prompt a search for associated AD; (7) the inclusion of cognitive outcome as a secondary endpoint in acute and secondary stroke prevention trials; and (8) the validation of the benefit of noninvasive brain stimulation through high-quality, randomized, sham-controlled trials. Many of these objectives can be rapidly and easily attained., 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: Olivier Godefroy: has served on scientific advisory boards (Novartis and Astra Zeneca), received funding for travel and meetings from Novartis, Lilly, Genzyme, Astrazeneca, Biogen, Teva, Pfizer, CSL-Behring, GSK, Boehringer-Ingelheim, Ipsen, Covidien, Bristol-Myers Squibb. Ardalan Aarabi: none related to this study. Yannick Béjot meeting speaker: BMS, Pfizer, Boehringher-Ingelheim, Servier, Medtronic, Amgen; Consulting: Medtronic, NovoNordisk, Novartis. Geert J Biessels: Consulting : Nestle HealthScience. Bertrand Glize: Consulting: IPSEN. Vincent MT Mok: none related to this study. Michel Thiebaut de Schotten: none related to this study. Igor Sibon: meeting speaker: BMS, Pfizer, Boehringher-Ingelheim, Servier, Medtronic, Novonordisk, Novartis, Sanofi, Astra-Zeneca; Consulting: Medtronic, NovoNordisk, Novartis, Sanofi, Astra-Zeneca. Hugues Chabriat: none related to this study. M Roussel: none related to this study.

Introduction: Current guidelines indicate prolonged cardiac rhythm monitoring for atrial fibrillation screening in patients with cryptogenic ischemic stroke (IS) or transient ischemic attack (TIA). This study aimed to assess the incidence of cryptogenic IS/TIA eligible for such investigation, and to estimate the number of patients potentially concerned in whole France annually., Methods: All cryptogenic acute IS/TIA cases ⩾35 years old were retrieved from the population-based Dijon Stroke Registry, France (2013-2020). Patients eligible for prolonged cardiac rhythm monitoring were defined after excluding those who died in-hospital or within the first 30 days, or with preexisting major impairment. Annual incidence rates of eligible cryptogenic IS/TIA were calculated by age groups and sex. The total number of eligible patients in France was estimated by standardization to age- and sex-specific incidence., Results: Among 2811 IS/TIA patients recorded in the Dijon Stroke Registry, 1239 had cryptogenic IS/TIA of whom 1045 were eligible for prolonged cardiac rhythm monitoring (517 IS and 528 TIA, mean age 73.6 ± 14.6 years old, 55.4% women). Crude incidence rates of eligible cryptogenic IS/TIA were 169/100,000 per year (95% CI: 159-179) in overall sexes, 83/100,000 per year (95% CI: 76-91) for IS, and 85/100,000 per year (95% CI: 78-93) for TIA. The total number of patients with cryptogenic IS/TIA eligible for prolonged cardiac rhythm monitoring in France was estimated to be 66,125 (95% CI: 65,622-66,630) for the calendar year 2022, including 32,764 (95% CI: 32,410-33,120) with IS and 33,361 (95% CI: 33,004-33,721) with TIA., Conclusions: This study demonstrated a high incidence of cryptogenic IS/TIA eligible for prolonged cardiac rhythm monitoring. Estimates at a national level pointed out the large number of patients who may require access to such atrial fibrillation screening, with attention to be paid on regarding organization of care networks and related costs., 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: Charles Guenancia reports personal fees from MicroPort CRM, Medtronic, Astra-Zeneca, BMS, Pfizer, Abbott, outside the submitted work. Yannick Béjot reports personal fees from BMS, Pfizer, Medtronic, Amgen, Servier, NovoNordisk, Novartis, outside the submitted work. Other authors: none.

First described in December 2019 in Wuhan (China), COVID-19 disease rapidly spread worldwide, constituting the biggest pandemic in the last 100 years. Even if SARS-CoV-2, the agent responsible for COVID-19, is mainly associated with pulmonary injury, evidence is growing that this virus can affect many organs, including the heart and vascular endothelial cells, and cause haemostasis, CNS, and kidney and gastrointestinal tract abnormalities that can impact in the disease course and prognosis. In fact, COVID-19 may affect almost all the organs. Hence, SARS-CoV-2 is essentially a systemic infection that can present a large number of clinical manifestations, and it is variable in distribution and severity, which means it is potentially life-threatening. The goal of this comprehensive review paper in the series is to give an overview of non-pulmonary involvement in COVID-19, with a special focus on underlying pathophysiological mechanisms and clinical presentation.

(1) Background: bridging revascularization therapy is now the standard of care in patients with ischemic stroke due to large vessel occlusion. This study aimed to determine the frequency of symptomatic intracranial hemorrhage (sICH) related to this treatment, and to assess contributing factors and patients' outcomes. (2) Methods: consecutive ischemic stroke patients treated with bridging therapy were prospectively enrolled. sICH (intracranial hemorrhage with an increase in NIHSS score of ≥4 points) was assessed on imaging at 24 h. The functional status of patients was measured at 6 months using the mRS score; (3) Results: 176 patients were included (mean age 68.7 ± 1.2 years, 52.3% women), among whom 15 (8.5%) had sICH. Patients with sICH had more frequent alcohol abuse (30.1% versus 9.7%, p = 0.023), prestroke use of dual antiplatelet therapy (14.3% versus 1.3%, p = 0.002), higher NIHSS scores at admission (median score 20.5 versus 15, p = 0.01), greater systolic blood pressure upon admission, more frequent vascular intracranial calcifications ( p = 0.004), leukoaraiosis ( p = 0.001), and intracranial atheroma ( p = 0.02), and higher neutrophil-to-lymphocyte ratios ( p = 0.02) and neutrophil-to-platelet ratios ( p = 0.04). At 6-month follow-up, 9 (60%) patients with sICH died, versus 18% of patients without sICH ( p < 0.001). Only 1 (7%) patient with sICH had a good functional outcome, defined as an mRS score of 0 to 2, versus 51% of patients without sICH. (4) Conclusions: one in twelve ischemic stroke patients treated with bridging therapy suffered sICH. Given the observed poor outcomes after sICH, further studies are required to better identify patients at risk to help clinicians in guiding therapeutic strategies.

Introduction: Aging population leads to changes in the profile of patients with acute ischemic stroke (IS), and older adults were largely excluded from randomized clinical trials of acute revascularization therapy. This study aimed to assess functional outcomes of treated IS patients > 80 years old according to prior disability and identify associated factors., Methods: Consecutively older patients with acute IS treated with either IV thrombolysis and/or mechanical thrombectomy were enrolled between 2016 and 2019. Pre-morbid disability was assessed using the modified Rankin Scale (mRS) score, and patients were classified as being independent (mRS score, 0-2) or having pre-existing disability (mRS score, 3-5). A multivariable logistic regression analysis was performed to assess factors associated with a poor functional outcome (mRS score > 3) at 3 and 12 months in each group of patients., Results: Among 300 included patients (mean age: 86.3 ± 4.6 years, 63% women, median NIHSS score: 14, IQR: 8-19), 100 had a pre-existing disability. In patients with a pre-morbid mRS score of 0-2, 51% had mRS >3 including 33% of deaths at 3 months. At 12 months, 50% had a poor outcome including 39% of deaths. In patients with a pre-morbid mRS score of 3-5, 71% had a poor outcome at 3 months including 43% of deaths, and at 12 months, 76% had mRS >3 including 52% of deaths. In multivariable models, the NIHSS score at 24 h was independently associated with poor outcomes at 3 and 12 months in both patients with (OR = 1.32; 95% CI: 1.16-1.51, p < 0.001 for 12 months outcome) or without (OR = 1.31; 95% CI: 1.19-1.44, p < 0.001 for 12 months outcome) pre-morbid disability., Conclusion: Although a large proportion of older patients with a pre-existing disability had a poor functional outcome, they did not differ from their non-impaired counterparts regarding prognostic factors. This means that there were no factors in our study that would help clinicians identify patients at risk of poor functional outcomes after revascularization therapy among those with prior disability. Further studies are needed to better understand the post-stroke trajectory of older IS patients with a pre-morbid disability., Competing Interests: YB received honoraria for lectures or consulting fees from BMS, Pfizer, Medtronic, Amgen, Servier, NovoNordisk and Boehringer-Ingelheim, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ruel, Baptiste, Duloquin and Béjot.)

Importance: Women with pregnancy-associated stroke might have different risks of stroke recurrence, including during subsequent pregnancies, and other cardiovascular events due to pregnancy-specific stroke risk factors, such as gestational hypertension, preeclampsia, or gestational diabetes., Objective: To estimate the rate of stroke recurrence, cardiovascular hospitalization, and death in women with pregnancy-associated stroke compared with women with non-pregnancy-associated stroke., Design, Setting, and Participants: This cohort study included all women aged 15 to 49 years in France who were affiliated with the general scheme of French health care insurance (94% of women) and had a first hospitalization for stroke between January 1, 2010, and December 31, 2018. Women were followed up until December 31, 2020, with the registration of stroke recurrence, hospitalization for cardiovascular conditions, and death. Data were from the French health care database Système National des Données de Santé. Statistical analyses were conducted between December 2021 and September 2022., Exposure: Pregnancy status at the time of stroke., Main Outcomes and Measures: Poisson regressions were used to estimate incidence rates of these events with 95% CIs. We used Cox proportional hazards regression models to estimate the hazard ratios (HRs) of each event during the follow-up for women with a pregnancy-associated stroke vs women with a non-pregnancy-associated stroke., Results: Among women aged between 15 and 49 years between 2010 and 2018 and living in France, 1204 had a pregnancy-associated stroke at a mean (SD) age of 31.5 (5.8) years, and 31 697 had a non-pregnancy-associated stroke at a mean age of 39.6 (8.2) years. Among the 1204 women with a pregnancy-associated stroke, the incidence rate was 11.4 (95% CI, 9.0-14.3) per 1000 person-years, with 2 recurrent events during a subsequent pregnancy. Compared with women with non-pregnancy-associated stroke, women with pregnancy-associated stroke had lower risks of ischemic stroke (adjusted HR, 0.53; 95% CI, 0.36-0.77), cardiovascular events (adjusted HR, 0.58; 95% CI, 0.49-0.69), and death (adjusted HR, 0.42; 95% CI, 0.22-0.79). In contrast, the risk of recurrent intracerebral hemorrhage and cerebral venous thrombosis did not differ significantly, whereas the risks of venous thromboembolism (HR, 2.02; 95% CI, 1.14-3.58) and acute coronary syndrome with ST-segment elevation (HR, 3.93; 95% CI, 1.10-14.0) were increased., Conclusions and Relevance: In this cohort study, although the risks of ischemic stroke, overall cardiovascular events, and mortality were lower after a pregnancy-associated stroke than after a non-pregnancy-associated stroke, the risks of venous thromboembolism and acute coronary syndrome with ST-segment elevation were higher. Recurrent stroke during a subsequent pregnancy remained rare.

Introduction: Intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) in women with ischemic stroke (IS) during pregnancy/post-partum is challenging, and recent guidelines claimed for additional information to better argue its effectiveness and safety. This observational national study aimed to describe characteristics, rates and outcomes of pregnant/post-partum women receiving acute revascularization therapy for IS compared to their non-pregnant counterparts, and pregnant women with IS not receiving such therapy., Patients and Methods: In this cross-sectional study, all women aged 15-49 years hospitalized in France for IS between 2012 and 2018 were retrieved from the French hospital discharge databases. Pregnant or post-partum (⩽6 weeks after delivery) women were identified. Data about patients' characteristics, risk factors, revascularization therapy, delivery, post-stroke survival, and recurrent vascular events during follow-up were recorded., Results: Over the study period, 382 women with pregnancy-related IS were registered. Among them, 7.3% ( n  = 28) received a revascularization therapy, including nine cases during pregnancy, one the same day as delivery, and 18 during the post-partum period, compared with 8.5% ( n  = 1285) in women with non-pregnancy-related IS ( n  = 15,084). Treated pregnant/post-partum women had more severe IS than not-treated pregnant/post-partum. Compared with treated not-pregnant women, they were younger, but did not differ regarding other characteristics including stroke severity. There were no differences in systemic or intracranial hemorrhages or in the length of hospital stay between pregnant/post-partum women compared with treated not-pregnant women. All women receiving revascularization during pregnancy had a live baby. After a mean follow-up of 4.3 years, all pregnant/post-partum women were alive, one had recurrent IS and none had other vascular events., Discussion and Conclusion: Only a few women with pregnancy-related IS were treated with acute revascularization therapy, but this was proportionately similar to their non-pregnant counterparts, from whom they did not differed regarding characteristics, survival, and risk of recurrent events. These findings suggest that stroke physicians applied treatment strategies of IS in a similar way regardless of pregnancy in France, and this attitude was an anticipation but consistent with the recently published guidelines on the topic.

Introduction: Data on the epidemiology of ischemic stroke (IS) with large vessel occlusion (LVO) are scarce although there is a need to better assess future demands for dedicated facilities in an aging population. This study aimed to estimate the number of expected cases of IS with LVO of the anterior circulation in the French population by 2050., Methods: IS were retrieved from the population-based registry of Dijon, France (2013-2017). Patients with LVO were identified and age-and sex-standardized incidence rates were calculated to estimate the number of expected cases in the whole French population by 2050 according three scenarios: stable incidence; a decrease in incidence rates of 0.5%/year in people >65 years old; a decrease in incidence rates of 0.5%/year in overall population., Results: 1,067 cases of IS with LVO were recorded in Dijon over the study period, corresponding to crude incidence rate of 22/100,000/year (95% CI: 18-25). By 2050, the number of cases is expected to increase by 51 to 81% according to the various scenarios, to reach between 22,457 cases (95% CI: 10,839 - 43,639) and 26,763 cases (95% CI: 12,918 - 52,008) annually. This increase will be mainly driven by patients >80  years old, with a rise of cases between +103% and +42% in this age group. The proportion of patients >80 years old among overall IS with LVO will increase from 43 to 57% approximately., Conclusion: The expected massive increase in IS with LVO highlights the need for a rapid action to cover stroke care requirements., Competing Interests: YB received honoraria for lectures or consulting fees from BMS, Pfizer, Medtronic, Amgen, Servier, and Novo-Nordisk, outside the submitted work. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Duloquin and Béjot.)

Background and Purpose: This study aimed to investigate the effect of endovascular treatment (EVT, with or without intravenous thrombolysis [IVT]) versus IVT alone on outcomes in patients with acute ischemic stroke (AIS) and intracranial large vessel occlusion (LVO) attributable to cervical artery dissection (CeAD)., Methods: This multinational cohort study was conducted based on prospectively collected data from the EVA-TRISP (EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients) collaboration. Consecutive patients (2015-2019) with AIS-LVO attributable to CeAD treated with EVT and/or IVT were included. Primary outcome measures were (1) favorable 3-month outcome (modified Rankin Scale score 0-2) and (2) complete recanalization (thrombolysis in cerebral infarction scale 2b/3). Odds ratios with 95% confidence intervals (OR [95% CI]) from logistic regression models were calculated (unadjusted, adjusted). Secondary analyses were performed in the patients with LVO in the anterior circulation (LVOant) including propensity score matching., Results: Among 290 patients, 222 (76.6%) had EVT and 68 (23.4%) IVT alone. EVT-treated patients had more severe strokes (National Institutes of Health Stroke Scale score, median [interquartile range]: 14 [10-19] vs. 4 [2-7], P<0.001). The frequency of favorable 3-month outcome did not differ significantly between both groups (EVT: 64.0% vs. IVT: 86.8%; ORadjusted 0.56 [0.24-1.32]). EVT was associated with higher rates of recanalization (80.5% vs. 40.7%; ORadjusted 8.85 [4.28-18.29]) compared to IVT. All secondary analyses showed higher recanalization rates in the EVT-group, which however never translated into better functional outcome rates compared to the IVT-group., Conclusion: We observed no signal of superiority of EVT over IVT regarding functional outcome in CeAD-patients with AIS and LVO despite higher rates of complete recanalization with EVT. Whether pathophysiological CeAD-characteristics or their younger age might explain this observation deserves further research.

Introduction: The ongoing ageing population is associated with an increase in the number of patients suffering a stroke, transient ischaemic attack (TIA) or myocardial infarction (MI). In these patients, implementing secondary prevention is a critical challenge and new strategies need to be developed to close the gap between clinical practice and evidence-based recommendations. We describe the protocol of a randomised clinical trial that aims to evaluate the efficiency and effectiveness of an intensive multidisciplinary follow-up of patients compared with standard care., Methods and Analysis: The DiVa study is a randomised, prospective, controlled, multicentre trial including patients >18 years old with a first or recurrent stroke (ischaemic or haemorrhagic) or TIA, or a type I or II MI, managed in one of the participating hospitals of the study area, with a survival expectancy >12 months. Patients will be randomised with an allocation ratio of 1:1 in two parallel groups: one group assigned to a multidisciplinary, nurse-based and pharmacist-based 2-year follow-up in association with general practitioners, neurologists and cardiologists versus one group with usual follow-up. In each group for each disease (stroke/TIA or MI), 430 patients will be enrolled (total of 1720 patients) over 3 years. The primary outcome will be the incremental cost-utility ratio at 24 months between intensive and standard follow-up in a society perspective. Secondary outcomes will include the incremental cost-utility ratio at 6 and 12 months, the incremental cost-effectiveness ratio at 24 months, reduction at 6, 12 and 24 months of the rates of death, unscheduled rehospitalisation and iatrogenic complications, changes in quality of life, net budgetary impact at 5 years of the intensive follow-up on the national health insurance perspective and analysis of factors having positive or negative effects on the implementation of the project in the study area., Ethics and Dissemination: Ethical approval was obtained and all patients receive information about the study and give their consent to participate before randomisation. Results of the main trial and each of the secondary analyses will be submitted for publication in a peer-reviewed journal., Trial Registration Number: ClinicalTrials.gov Identifier: NCT04188457. Registered on 6 December 2019., Competing Interests: Competing interests: YB received honoraria for lectures or consulting fees from BMS, Pfizer, Medtronic, Amgen, Servier, Boehringer-Ingelheim and NovoNordisk, outside the submitted work. GL received honoraria for lectures or consulting fees from Abbott, Biotronik, Boston, Medtronic, MicroPort, Novo Nordisk, BMS and Pfizer, outside the submitted work. YC received honoraria for lectures or consulting fees from Bayer, BMS, Pfizer, Boehringer-Ingelheim, Novartis, Sanofi and Servier, outside the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Whether endovascular therapy (EVT) added on best medical management (BMM), as compared to BMM alone, is beneficial in acute ischemic stroke with isolated posterior cerebral artery occlusion is unknown., Methods: We conducted a multicenter international observational study of consecutive stroke patients admitted within 6 hours from symptoms onset in 26 stroke centers with isolated occlusion of the first (P1) or second (P2) segment of the posterior cerebral artery and treated either with BMM+EVT or BMM alone. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month good functional outcome (modified Rankin Scale [mRS] score 0-2 or return to baseline modified Rankin Scale). Secondary outcomes were 3-month excellent recovery (modified Rankin Scale score 0-1), symptomatic intracranial hemorrhage, and early neurological deterioration., Results: Overall, 752 patients were included (167 and 585 patients in the BMM+EVT and BMM alone groups, respectively). Median age was 74 (interquartile range, 63-82) years, 329 (44%) patients were female, median National Institutes of Health Stroke Scale was 6 (interquartile range 4-10), and occlusion site was P1 in 188 (25%) and P2 in 564 (75%) patients. Baseline clinical and radiological data were similar between the 2 groups following propensity score weighting. EVT was associated with a trend towards lower odds of good functional outcome (odds ratio, 0.81 [95% CI, 0.66-1.01]; P =0.06) and was not associated with excellent functional outcome (odds ratio, 1.17 [95% CI, 0.95-1.43]; P =0.15). EVT was associated with a higher risk of symptomatic intracranial hemorrhage (odds ratio, 2.51 [95% CI, 1.35-4.67]; P =0.004) and early neurological deterioration (odds ratio, 2.51 [95% CI, 1.64-3.84]; P <0.0001)., Conclusions: In this observational study of patients with proximal posterior cerebral artery occlusion, EVT was not associated with good or excellent functional outcome as compared to BMM alone. However, EVT was associated with higher rates of symptomatic intracranial hemorrhage and early neurological deterioration. EVT should not be routinely recommended in this population, but randomization into a clinical trial is highly warranted.

Introduction: Atrial fibrillation (AF) is one of the most common causes of ischemic stroke. It is essential to target patients at highest risk of AF detected after stroke (AFDAS), who should benefit from a prolonged rhythm screening strategy. Cardiac-CT angiography (CCTA) was added to the stroke protocol used in our institution in 2018. We sought to assess, for AFDAS, the predictive value of atrial cardiopathy markers by a CCTA performed on admission for acute ischemic stroke., Patients and Methods: From November 2018 to October 2019, consecutive stroke patients with no history of AF were included. Let atrial volume (LAV), epicardial adipose tissue (EAT) attenuation and volume, and LAA characteristics were measured on CCTA. The primary endpoint was the presence of AFDAS at follow-up, diagnosed by continuous electrocardiographic monitoring, long-term external Holter monitoring during hospital stay, or implantable cardiac monitor (ICM)., Results: Sixty of the 247 included patients developed AFDAS. Multivariable analysis shows independent predictors of AFDAS: age >80 years (HR 2.46; 95%CI (1.23-4.92), p  = 0.011), indexed LAV >45 mL/m 2 (HR 2.58; 95%CI (1.19-5.62), p  = 0.017), EAT attenuation > -85HU (HR 2.16; 95%CI (1.13-4.15), p  = 0.021) and LAA thrombus (HR 2.50; 95%CI (1.06-5.93), p  = 0.037). Added consecutively to AFDAS prediction AS5F score (combining age and NIHSS >5), these markers had an incrementally better predictive value compared with the global Chi 2 of the initial model ( p  = 0.001, 0.035, and 0.015 respectively)., Discussion and Conclusion: Adding CCTA to the acute stroke protocol to assess markers of atrial cardiopathy associated with AFDAS may help to better stratify the AF screening strategy, including the use of an ICM., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© European Stroke Organisation 2022.)

The COVID-19 pandemic modified the management of myocardial infarction (MI) and stroke. We aimed to evaluate the effect of the COVID-19 pandemic on the volume and spatial distribution of hospitalizations for MI and stroke, before, during and after the first nationwide lockdown in France in 2020, compared with 2019. Hospitalization data were extracted from the French National Discharge database. Patient's characteristics were compared according to COVID-19 status. Changes in hospitalization rates over time were measured using interrupted time series analysis. Possible spatial patterns of over or under-hospitalization rates were investigated using Moran's indices. We observed a rapid and significant drop in hospitalizations just before the beginning of the lockdown with a nadir at 36.5% for MI and 31.2% for stroke. Hospitalization volumes returned to those seen in 2019 four weeks after the end of the lockdown, except for MI, which rebounded excessively. Older age, male sex, elevated rate of hypertension, diabetes, obesity and mortality characterized COVID-19 patients. There was no evidence of a change in the spatial pattern of over- or under-hospitalization clusters over the three periods. After a steep drop, only MI showed a significant rebound after the first lockdown with no change in the spatial distribution of hospitalizations.

Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Recurrent stroke affects 9% to 15% of people within 1 year. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations on pharmacological management of blood pressure (BP), diabetes mellitus, lipid levels and antiplatelet therapy for the prevention of recurrent stroke and other important outcomes in people with ischaemic stroke or transient ischaemic attack (TIA). It does not cover interventions for specific causes of stroke, including anticoagulation for cardioembolic stroke, which are addressed in other guidelines. This guideline was developed through ESO standard operating procedures and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The working group identified clinical questions, selected outcomes, performed systematic reviews, with meta-analyses where appropriate, and made evidence-based recommendations, with expert consensus statements where evidence was insufficient to support a recommendation. To reduce the long-term risk of recurrent stroke or other important outcomes after ischaemic stroke or TIA, we recommend: BP lowering treatment to a target of <130/80 mmHg, except in subgroups at increased risk of harm; HMGCoA-reductase inhibitors (statins) and targeting a low density lipoprotein level of <1.8 mmol/l (70 mg/dl); avoidance of dual antiplatelet therapy with aspirin and clopidogrel after the first 90 days; to not give direct oral anticoagulant drugs (DOACs) for embolic stroke of undetermined source and to consider pioglitazone in people with diabetes or insulin resistance, after careful consideration of potential risks. In addition to the evidence-based recommendations, all or the majority of working group members supported: out-of-office BP monitoring; use of combination treatment for BP control; consideration of ezetimibe or PCSK9 inhibitors when lipid targets are not achieved; consideration of use of low-dose DOACs in addition to an antiplatelet in selected groups of people with coronary or peripheral artery disease and aiming for an HbA1c level of <53 mmol/mol (7%) in people with diabetes mellitus. These guidelines aim to standardise long-term pharmacological treatment to reduce the burden of recurrent stroke in Europe., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: All authors have completed a declaration of competing interests and details are available in Supplemental Table 1., (© European Stroke Organisation 2022.)

Background: Intensive screening for atrial fibrillation (AF) has led to a better recognition of this cause in stroke patients. However, it is currently debated whether AF Detected After Stroke (AFDAS) has the same pathophysiology and embolic risk as prior-to-stroke AF. We thus aimed to systematically approach AFDAS using a multimodal approach combining clinical, imaging, biological and electrocardiographic markers., Methods: Patients without previously known AF admitted to the Dijon University Hospital (France) stroke unit for acute ischemic stroke were prospectively enrolled. The primary endpoint was the presence of AFDAS at 6 months, diagnosed through admission ECG, continuous electrocardiographic monitoring, long-term external Holter during the hospital stay, or implantable cardiac monitor if clinically indicated after discharge., Results: Of the 240 included patients, 77 (32%) developed AFDAS. Compared with sinus rhythm patients, those developing AFDAS were older, more often women and less often active smokers. AFDAS patients had higher blood levels of NT-proBNP, osteoprotegerin, galectin-3, GDF-15 and ST2, as well as increased left atrial indexed volume and lower left ventricular ejection fraction. After multivariable analysis, galectin-3 ≧ 9 ng/ml [OR 3.10; 95% CI (1.03-9.254), p = 0.042], NT-proBNP ≧ 290 pg/ml [OR 3.950; 95% CI (1.754-8.892, p = 0.001], OPG ≥ 887 pg/ml [OR 2.338; 95% CI (1.015-5.620), p = 0.046) and LAVI ≥ 33.5 ml/m 2 [OR 2.982; 95% CI (1.342-6.625), p = 0.007] were independently associated with AFDAS., Conclusion: A multimodal approach combining imaging, electrocardiography and original biological markers resulted in good predictive models for AFDAS. These results also suggest that AFDAS is probably related to an underlying atrial cardiopathy., Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03570060]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Garnier, Duloquin, Meloux, Benali, Sagnard, Graber, Dogon, Didier, Pommier, Vergely, Béjot and Guenancia.)

(1) Background: we aimed to describe the disease-specific quality of life (QoL) of ischemic stroke patients treated with acute revascularization therapy, its evolution from 6 months to 12 months, and associated factors. (2) Methods: QoL was assessed with the SS-QoL in consecutive patients treated with either intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT). Variables associated with QoL scores and its evolution were studied using multivariate mixed models, and interaction with time. Analyses were performed in four domains of SS-QoL: self-care, mobility, mood, and social roles. (3) Results: Among the 501 included patients (mean (sd) age 68.9 (14.5), 49% women), lower post-stroke QoL was independently related to lower level of school education, prestroke mRS > 2, and 24 h NIHSS score > 4. Independent predictors of unfavorable evolution of QoL over time were age <75 years (Mobility p = 0.0194 and Mood p = 0.0015), NIHSS score ≤ 4, (Self-care p = 0.0053 and Mood p = 0.0048), and modified Rankin Scale score ≤ 2 (Social roles, p = 0.0006). Revascularization therapy had no significant effect on the QoL scores, but patients treated with MT (alone or as bridging therapy) had significantly greater improvement in mobility score between 6 and 12 months than patients treated with IVT alone (p = 0.0072). (4) Conclusion: QoL evolution over one year had only slight variation and was associated with the modalities of acute treatment, age, and stroke severity.

Background: The impact of the COVID-19 pandemic on hospitalization for cardiac infections is not well known. We aimed to evaluate the nationwide trends in hospital stays for myocarditis and endocarditis cases before, during and after the nationwide lockdown for the COVID-19 pandemic in France. We then aimed to describe the proportion of myocarditis and endocarditis patients with and without COVID-19 and their clinical characteristics., Methods: Hospitalized cases of cardiac infection were extracted from the French National Discharge database, which collects the medical records of all patients discharged from all public and private hospitals in France. Age, sex, and available cardiovascular risk factors were compared between stays with and without COVID-19 during the lockdown., Results: The number of myocarditis cases was 11% higher in 2020, compared to the average of the three prior years. In 2020, 439 of 3727 cases of myocarditis were associated with COVID-19. For endocarditis, there was an increase in cases by 7% in 2020 versus prior years. For endocarditis, 3% (240 of 8128 cases) of patients with endocarditis had COVID-19. For myocarditis, older age, hypertension, diabetes, obesity, and atrial fibrillation were more frequent in patients with COVID-19 than in those without. For endocarditis, only hypertension was more frequent in patients with COVID-19 than in those without., Conclusion: Our study reports an increase in hospitalizations for both myocarditis and endocarditis in 2020, possibly related to the COVID-19 pandemic. Interestingly, the trends differ according to the COVID-19 status. Knowledge of the factors associating myocarditis or endocarditis and COVID-19 may improve the quality and the type of monitoring for people with COVID-19, the identification of patients at risk of cardiac infections, and the treatment of COVID-19 patients.

Objective: To assess the efficiency and relevance of clinical exome sequencing (cES) as a first-tier or second-tier test for the diagnosis of progressive neurological disorders in the daily practice of Neurology and Genetic Departments., Methods: Sixty-seven probands with various progressive neurological disorders (cerebellar ataxias, neuromuscular disorders, spastic paraplegias, movement disorders and individuals with complex phenotypes labelled 'other') were recruited over a 4-year period regardless of their age, gender, familial history and clinical framework. Individuals could have had prior genetic tests as long as it was not cES. cES was performed in a proband-only (60/67) or trio (7/67) strategy depending on available samples and was analysed with an in-house pipeline including software for CNV and mitochondrial-DNA variant detection., Results: In 29/67 individuals, cES identified clearly pathogenic variants leading to a 43% positive yield. When performed as a first-tier test, cES identified pathogenic variants for 53% of individuals (10/19). Difficult cases were solved including double diagnoses within a kindred or identification of a neurodegeneration with brain iron accumulation in a patient with encephalopathy of suspected mitochondrial origin., Conclusion: This study shows that cES is a powerful tool for the daily practice of neurogenetics offering an efficient (43%) and appropriate approach for clinically and genetically complex and heterogeneous disorders., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Rates of patients hospitalized for stroke increased among people aged under 65 years in France, as has been found in other countries., Methods: To analyze time trends in the rates of patients hospitalized for ischemic stroke (IS) and intracerebral hemorrhage (ICH) in France between 2008 and 2019 and determine related short-term outcomes mainly, we selected all patients hospitalized for stroke using the French national hospital database., Results: The average annual percentage change in the rates of patients hospitalized for IS increased significantly in men and women aged 50-64 years (+2.0%) and in men aged 18-34 years (+1.5%) and 35-44 years (+2.2%). A decrease in the average annual percentage change was observed for IS among people aged over 75 years and among those over 50 years for ICH. After adjustment on confounding factors, women were less likely to die in hospital. Case fatality rates decreased overtime in all age groups for both sexes, with a more pronounced decrease for IS than ICH., Conclusions: The increasing trend of IS among adults under 65 years is ongoing, highlighting the urgent need for stroke prevention programs in that age. For the first time, we recorded a decrease in the rates of patients hospitalized for ICH among the population over 50 years.

Introduction: Strategy for the acute management of minor ischemic stroke (IS) with large vessel occlusion (LVO) is under debate, especially the benefits of mechanical thrombectomy. The frequency of minor IS with LVO among overall patients is not well established. This study aimed to assess the proportion of minor IS and to depict characteristics of patients according to the presence of LVO in a comprehensive population-based setting., Methods: Patients with acute IS were prospectively identified among residents of Dijon, France, using a population-based registry (2013-2017). All arterial imaging exams were reviewed to assess arterial occlusion. Minor stroke was defined as that with a National Institutes of Health Stroke Scale (NIHSS) score of <6. Proportion of patients with LVO was estimated in the minor IS population. The clinical presentation of patients was compared according to the presence of an LVO., Results: Nine hundred seventy-one patients were registered, including 582 (59.9%) patients with a minor IS. Of these patients, 23 (4.0%) had a LVO. Patients with minor IS and LVO had more severe presentation [median 3 (IQR 2-5) vs. 2 (IQR 1-3), p = 0.001] with decreased consciousness (13.0 vs. 1.6%, p <0.001) and cortical signs (56.5 vs. 30.8%, p = 0.009), especially aphasia (34.8 vs. 15.4%, p = 0.013) and altered item level of consciousness (LOC) questions (26.1 vs. 11.6%, p = 0.037). In multivariable analyses, only NIHSS score (OR = 1.45 per point; 95% CI: 1.11-1.91, p = 0.007) was associated with proximal LVO in patients with minor IS., Conclusion: Large vessel occlusion (LVO) in minor stroke is non-exceptional, and our findings highlight the need for emergency arterial imaging in any patients suspected of acute stroke, including those with minor symptoms because of the absence of obvious predictors of proximal LVO., Competing Interests: YB reports personal fees from BMS, Pfizer, Medtronic, Amgen, Servier, NovoNordisk, and Boehringer-Ingelheim, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Duloquin, Crespy, Jakubina, Giroud, Vergely and Béjot.)

(1) Background: The limited availability of thrombectomy-capable stroke centres raises questions about pre-hospital triage of patients with suspected stroke (IS) due to large vessel occlusion (LVO). Aims: This study aimed to evaluate the diagnostic accuracy of clinical stroke severity scales available for LVO detection. (2) Methods: Patients with IS were prospectively identified among residents of Dijon, France, using a population-based registry (2013-2017). Clinical signs and arterial imaging data were collected. LVO was defined as an occlusion site affecting the terminal intracranial internal carotid artery, the M1 segment of the middle cerebral artery (MCA), or the basilar artery (restricted definition). A wide definition of LVO also included the M2 segment of the MCA. For each of the 16 evaluated scales, a receiver operator characteristic (ROC) analysis was performed, and the c-statistic representing the area under the ROC curve was evaluated to assess discrimination for predicting LVO. (3) Results: 971 patients were registered, including 123 patients (12.7%) with an LVO according to the restricted definition. The c-statistic for LVO detection ranged between 0.66 and 0.80 according to the different scales, with a sensibility varying from 70% to 98% and a specificity from 33% to 86%. According to the wide definition of LVO (174 patients, 17.9%), the c-statistic was slightly lower, ranging between 0.64 and 0.79. The sensitivity was 59% to 93%, and the specificity was 34% to 89%. (4) Conclusion: The clinical scales failed to combine a high sensitivity and a high specificity to detect LVO. Further studies are needed to determine the best strategy for pre-hospital triage of IS patients.

Background Atrial fibrillation (AF) represents a major indication for oral anticoagulants (OAC) that contribute to spontaneous intracerebral hemorrhage (ICH). This study evaluated AF prevalence among patients with ICH, temporal trends, and early functional outcomes and death of patients. Methods and Results Patients with first-ever ICH were prospectively recorded in the population-based stroke registry of Dijon, France, (2006-2017). Association between AF and early outcome of patients with ICH (ordinal modified Rankin Scale score and death at discharge) were analyzed using ordinal and logistic regressions. Among 444 patients with ICH, 97 (21.9%) had AF, including 65 (14.6%) with previously known AF treated with OAC, and 13 (2.9%) with newly diagnosed AF. AF prevalence rose from 17.2% (2006-2011) to 25.8% (2012-2017) ( P -trend=0.05). An increase in the proportion of AF treated with OAC (11.3% to 17.5%, P -trend=0.09) and newly diagnosed AF (1.5% to 4.2%, P -trend=0.11) was observed. In multivariable analyses, after adjustment for premorbid OAC, AF was not significantly associated with ordinal modified Rankin Scale score (odds ratio [OR], 1.29; 95% CI, 0.69-2.42) or death (OR, 0.89; 95% CI, 0.40-1.96) in patients with ICH. Nevertheless, adjusted premorbid OAC use remained highly associated with a higher probability of death (OR, 2.53; 95% CI, 1.11-5.78). Conclusions AF prevalence and use of OAC among patients with ICH increased over time. Premorbid use of OAC was associated with poor outcome after ICH, thus suggesting a need to better identify ICH risk before initiating or pursuing OAC therapy in patients with AF, and to develop acute treatment and secondary prevention strategies after ICH in patients with AF.

Background and Purpose: Because of the aging population, an increase in the prevalence of atrial fibrillation (AF) is currently observed, thus leading to a rise in AF-related ischemic stroke (IS). We analyzed the current prevalence of AF among patients with IS, their characteristics, and temporal trends from 2006 to 2017 in the population-based Dijon Stroke Registry., Methods: We used data from the Dijon Stroke Registry, an ongoing population-based study that records all cases of acute stroke among residents of the city of Dijon. All patients with IS between 2006 and 2017 were included. Previous AF was defined if it was mentioned in the medical file before stroke and newly diagnosed AF if it was diagnosed during the diagnostic workup of patients with acute stroke., Results: During the period 2014 to 2017, among the 796 patients with IS recorded in the Dijon Stroke Registry, 239 (30.0%) had AF, of whom 79 (9.9% of total patients with IS) had newly diagnosed AF, and 98 (12.3%) had previous AF treated with oral anticoagulants. Patients with IS with AF had more disabilities and a higher initial severity according to the National Institutes of Health Stroke Scale compared with those without AF. The age-adjusted prevalence of AF in patients with IS increased between 2006 and 2017 (+9% per time period), with an important increase in men aged 65 to 74 years (+81%) and women aged ≥85 years (+24%), and a significant decrease in women aged 65 to 74 years (−39%). The use of oral anticoagulant treatment in previous AF patients increased between 2006 and 2009 and 2014 and 2017 (29.3% to 61.3%, P<0.0001). However, 37.5% of patients with previous AF and CHADS2 score ≥2 were not treated with OAC., Conclusions: The increase in AF prevalence in patients with IS could be related to a better diagnosis of this condition. The underuse of oral anticoagulation treatment was still observed.

Background: the ongoing growing and ageing population is associated with an increase in older patients suffering a stroke. We aimed to assess the current profile of these patients in a population-based setting., Methods: all patients with acute stroke were prospectively identified among residents of Dijon, France, between 2013 and 2017, using a population-based registry. Characteristics and early outcome of patients were compared according to age groups., Results: 1,288 stroke cases were recorded (median age: 81.1 years, interquartile range: 66.1-86.7, 54% women). Patients aged 75-85 years and those >85 years accounted for 27.6 and 33.9% of overall cases. Increasing age was associated with a greater prevalence of vascular risk factors, pre-existing cognitive impairment and handicap, higher initial severity, more frequent cardioembolic ischemic stroke, post-stroke pulmonary infection and delirium. Only 41% of patients aged 75-85 years and 18% of those aged >85 years had a good early recovery. Compared with patients aged <75 years, patients aged 75-85 years [adjusted odds ratio (OR) = 2.61; 95% confidence interval (CI): 1.74-3.93, P < 0.001] and those aged >85 years (adjusted OR = 7.18; 95% CI: 4.58-11.3, P < 0.001) had an increased risk of poor post-stroke functional outcome. Among survivors, the proportion of patients discharged to home was 60% in age group <75 years, compared with 49% in patients aged 75-85 years and 29% in those aged >85 years. Thirty per cent of patients >85 years old required a long-term care institution., Conclusion: the increasing burden of stroke in older people has major implications for future treatment strategies and need for dedicated care facilities., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Purpose: In France, the entire population was put under a total lockdown from March 17 to May 11, 2020 during the peak of the coronavirus disease 2019 (COVID-19) pandemic. Whether the lockdown had consequences on the management of medical emergencies such as stroke and transient ischemic attack (TIA) has yet to be fully evaluated. This article describes hospitalization rates for acute stroke in 2 French regions that experienced contrasting rates of COVID-19 infection, before, during, and after the nationwide lockdown (January to June 2020)., Methods: All patients admitted for acute stroke/TIA into all public and private hospitals of the 2 study regions were included. Data were retrieved from the National Hospitalization Database (PMSI). In the most affected region (Grand-Est), the hospitalization rates observed in April 2020 were compared with the rates in the same period in the least affected region (Occitanie) and in the 3 prior years (2017-2019)., Results: There was a significant decline in hospitalization rates for stroke/TIA within the region most affected by COVID-19 during the month of April 2020 compared with previous years, while no significant change was seen in the least affected region. After lockdown, we observed a fast rebound in the rate of hospitalization for stroke/TIA in the most affected region, contrasting with a slower rebound in the least affected region. In both regions, patients with COVID-19 stroke more frequently had ischemic stroke, a nonsignificant greater prevalence of diabetes, they were less frequently admitted to stroke units, and mortality was higher than in patients without COVID-19., Conclusions: Our results demonstrates a significant drop in stroke/TIA hospitalizations and a fast recovery after the end of the French lockdown in the most affected region, while the least affected region saw a nonsignificant drop in stroke/TIA hospitalizations and a slow recovery. These results and recommendations could be used by the health authorities to prepare for future challenges.

Purpose: The objectives were to analyse the determinants of stroke incidence and mortality as a competing event in AF patients newly treated with DOAC and to assess the impact of non-adherence to DOAC treatment., Methods: It is a population-based retrospective cohort study using the French national healthcare data system. AF patients aged >20 years were affiliated to the general health insurance scheme (66% of the French population) and newly treated with DOAC between 2012 and 2015 were included and followed for 2 years., Results: Overall 76,795 AF patients were newly treated with DOAC in 2015. Stroke incidence reached 10.1 (95% CI: 9.6-10.6) per 1000 person-year and death 39.7 (95% CI: 38.6-40.8) as a competitive risk. Female sex was associated with a lower risk of death but not of stroke. Non-adherence to DOAC treatment increased the risk of both stroke (42%) and death (38%). Acute coronary syndrome was associated with an increased risk of stroke alone, whereas heart failure decompensation, social deprivation, and haemorrhage were associated with an increased risk of death alone., Conclusion: Both stroke and death risks remain non-negligible in AF patients treated with DOAC. Non-adherence was associated with an increased risk of stroke and death., Competing Interests: Yannick Béjot received honoraria for lectures and consulting fees from AstraZeneca, Daiichi-Sankyo, BMS, Pfizer, Medtronic, Servier, MSD France, Amgen, and Boehringer-Ingelheim. The authors report no other conflicts of interest in this work., (© 2021 Gabet et al.)

Background and Purpose: Because of several methodological limitations, previous studies focusing on the prevalence of large vessel occlusion in ischemic stroke (IS) patients provided conflicting results. We evaluated the incidence of IS with a visible arterial occlusion using a comprehensive population-based registry., Methods: Patients with acute IS were prospectively identified among residents of Dijon, France, using a population-based registry (2013-2017). All arterial imaging exams were reviewed to assess arterial occlusion. Annual incidence rates of IS (first-ever and recurrent events) and IS with a visible occlusion were calculated., Results: One thousand sixty cases of IS were recorded (mean age: 76.0±15.8 years, 53.9% women). Information about arterial imaging was available in 971 (91.6%) of them, and only preexisting dementia was independently associated with having missing information (odds ratio=0.34 [95% CI, 0.18-0.65], P =0.001). Among these patients, 284 (29.2%) had a visible arterial occlusion. Occlusion site was the anterior circulation in 226 patients (23.3% of overall patients with available data) and the posterior circulation in 58 patients (6.0%). A proximal occlusion of the anterior circulation was observed in 167 patients (17.2%). The crude annual incidence rate of total IS per 100 000 was 138 (95% CI, 129-146). Corresponding standardized rates were 66 (95% CI, 50-82) to the World Health Organization and 141 (95% CI, 118-164) to the 2013 European populations. The crude annual incidence rate of IS with a visible arterial occlusion per 100 000 was 37 (95% CI, 33-41) and that of IS with a proximal occlusion of the anterior circulation was 22 (95% CI, 18-25). Corresponding standardized rates were 18 (95% CI, 10-26) and 10 (95% CI, 8-13) to the World Health Organization population, and 38 (95% CI, 26-50) and 23 (95% CI, 19-26) to the 2013 European population, respectively., Conclusions: These results will be helpful to plan the need for thrombectomy-capable stroke center resources.

Background and Purpose- The ongoing ageing population is associated with an increasing number of patients with stroke who have preexisting cognitive impairment. This study aimed to evaluate clinical severity in patients with ischemic stroke according to prestroke cognitive status. Methods- Patients with ischemic stroke were prospectively identified among residents of Dijon, France using a population-based registry (2013-2017). Prestroke cognitive status (no impairment, mild cognitive impairment [MCI], or dementia) was recorded, and severity at stroke onset was measured using the National Institutes of Health Stroke Scale (NIHSS) score. Association between prestroke cognitive status and severity was evaluated using ordinal regression analysis models in which the NIHSS score was considered as a categorical variable. Results- Among the 1048 patients (mean age, 76.3±15.2 years; 54.0% women), a greater severity was observed in those with MCI (n=132; median NIHSS: 6; interquartile range, 2-15), and those with dementia (n=164; median NIHSS: 7; interquartile range, 3-16), than in patients without cognitive impairment (n=752; median NIHSS: 3; interquartile range, 1-9). MCI (odds ratio [OR], 1.70 [95% CI, 1.21-2.38]; P =0.002) and dementia (OR, 2.24 [95% CI, 1.65-3.04]; P <0.001) were both associated with a greater severity at onset. The association was still observed after adjustment for clinical variables and proximal arterial occlusion (OR, 1.52 [95% CI, 1.02-2.28]; P =0.04 for MCI; OR, 2.16 [95% CI, 1.45-3.22]; P <0.001 dementia). Further adjustment for prestroke handicap slightly reduced the magnitude of the association (OR, 1.49 [95% CI, 0.98-2.25]; P =0.06 for MCI, and OR, 1.98 [95% CI, 1.26-3.12]; P =0.02 for dementia). The greater severity in patients with prestroke cognitive impairment was not specifically driven by a more severe impairment of either motor or language function. Conclusions- Patients with preexisting cognitive impairment suffered more severe ischemic stroke. This result could reflect a lower brain tolerance of acute ischemia. Further studies are needed to explore the underlying mechanisms that could be targeted from therapeutic perspectives focusing on neuroprotection.

Background: Multiple approaches have been proposed to measure low socio-economic status. In France the concept of precariousness, akin to social deprivation, was developed and is widely used. EPICES is a short questionnaire that was developed to measure this concept. This study aimed to evaluate Differential Item Functioning (DIF) in the EPICES questionnaire between contrasted areas: mainland France, French West Indies (FWI) and French Guiana (FG)., Methods: The population was taken from the INDIA study, which aimed to evaluate the impact of social inequalities on stroke characteristics and prognosis. Eligible people were patients referred to neurology or emergency departments for a suspicion of stroke. We assessed the DIF using hybrid ordinal logistic regression method, derived from item response theory., Results: We analysed 1 553 stroke patients, including 768 from FWI (49.5%), 289 from FG (18.6%) and 496 from mainland (31.9%). We identified five items with a moderate to large DIF in area comparisons: "meeting with a social worker", "complementary health insurance", "home-owning", "financial difficulties" and "sport activities". Correlation between EPICES score and the latent variable was strong (r = 0.84)., Conclusion: This is the first attempt to assess the DIF of the EPICES score between different French populations. We found several items with DIF, which can be explained by individual interpretation or local context. However, the DIFs did not lead to a large difference between the latent variable and the EPICES score, which indicates that it can be used to assess precariousness and social deprivation between contrasted areas., Competing Interests: We have read the journal’s policy, the authors of this manuscript have the following competing interests: Yannick Béjot received honoraria for participation to advisory boards or as a symposium speaker for AstraZeneca France, Daiichi-Sankyo, Pfizer-BMS, Bayer, Covidiem and MSD France. Other authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Fatigue is a frequent symptom after stroke. We aimed to determine the association between fatigue and cognitive performance in patients with ischemic stroke who received acute revascularization therapy (IV thrombolysis and/or mechanical thrombectomy). Methods: Seventy patients were prospectively included in the stroke unit of the University Hospital of Dijon, France. A follow-up was performed at 6 months with clinical examination, fatigue assessment by the Fatigue Severity Scale (FSS), and a comprehensive neuropsychological evaluation. Patients with fatigue (FSS score >4) were compared with patients without fatigue. Neuropsychological factors associated with fatigue at 6 months were analyzed using multivariable logistic regression models. Results: Fatigue was reported by 34.3% of patients. Patients with fatigue were older, had more frequent residual handicap, depressive symptoms, and impaired quality of life. They had more frequently low score (<26) on the MoCA scale (79.2 vs. 47.8%, OR = 4.15; 95% CI: 1.32-13, p = 0.015), memory impairment (60 vs. 30.6%, OR = 3.41; 95% CI: 1.09-10.7, p = 0.035), and executive dysfunction (65 vs. 30.8%, OR = 4.18; 95% CI: 1.33-13.1, p = 0.014). In multivariable logistic regression analysis, only memory impairment was independently associated with fatigue (OR = 5.70; 95% CI: 1.09-29.6, p = 0.039). Further analyses restricted to non-depressed patients ( n = 58, 84.1%) showed in multivariable models that a score < 26 on MoCA scale (OR 5.12; 95% CI: 1.00-26.2, p = 0.05), and a memory impairment (OR = 6.17; 95% CI: 1.06-35.9, p = 0.043) were associated with fatigue. There was also a non-significant trend toward an association between divided attention deficit and fatigue (OR = 6.79; 95% CI: 0.80-57.6, p = 0.079). Conclusion: The association between fatigue and subtle cognitive impairment including memory or attention deficits could be of interest in elaborating future interventional studies to evaluate the impact of therapeutic strategies, including cognitive rehabilitation, on fatigue.

Background and Aims: Growth differentiation factor-15 (GDF-15) has been identified as a robust marker of developing cardiovascular disease, however, little is currently known about its prognostic value in stroke patients. In a context of growing interest to discover new biomarkers in stroke, we aimed to assess the association between circulating GDF-15 levels and three-month mortality in ischemic stroke patients treated with acute revascularization therapy. Methods: 173 patients hospitalized for acute ischemic stroke and treated with either intravenous thrombolysis ( n = 99, 57.2%), mechanical thrombectomy ( n = 41, 23.4%) or combined therapy ( n = 33, 19.1%) were prospectively included. Baseline clinical and biological characteristics were recorded. Plasma GDF-15 levels were measured at admission (D0), and at 24 h, 3 and 7 days. Clinical severity was assessed with the National Institutes of Health Stroke Scale (NIHSS) score, and vital status was obtained 3 months after the stroke. Results: At 3 months post-stroke, 32 patients (18.5%) had died. The deceased patients had higher D0 plasma GDF-15 levels (median [IQR]: 2,777 [1,769-5,446] vs. 1,460 [965-2,079] pg/mL, P < 0.001). In multivariable logistic regression analysis, D0 GDF-15 levels in the third tertile of the distribution were independently associated with mortality at 3 months (OR = 3.71; 95% CI: 1.09-12.6, P = 0.036), even after adjustment for confounding variables including clinical severity. Conclusions: Our data show for the first time that GDF-15 plasma concentration at admission is independently associated with 3-month mortality in ischemic stroke patients treated with acute revascularization therapy. The pathophysiological mechanisms that could explain this association warrant further study.

Background and Purpose- The aims of this study were to (1) describe early and late case fatality rates after stroke in France, (2) evaluate whether their determinants differed, and (3) analyze time trends between 2010 and 2015. Methods- Data were extracted from the Système National des données de santé database. Patients hospitalized for stroke each year from 2010 to 2015, aged ≥18 years, and affiliated to the general insurance scheme were selected. Cox regressions were used to separately analyze determinants of 30-day and 31- to 365-day case fatality rates for each stroke type (ischemic, intracerebral hemorrhage, and subarachnoid hemorrhage). Results- In 2015, of the 73 124 persons hospitalized for stroke, 26.8% died in the following year, with the majority of deaths occurring within the first 30 days (56.9%). Nonadmission to a stroke unit, older age, and having comorbidities were all associated with a poorer 30-day and 31- to 365-day prognosis. Female sex was associated with a lower 31- to 365-day case fatality rate for all patients with stroke. Living in an area with a high deprivation index was associated with both higher 30-day and 31- to 365-day case fatality rates for all stroke types. Between 2010 and 2015, significant decreases in both 30-day and 31- to 365-day case fatality rates for ischemic patients were observed. Conclusions- Case fatality rates after stroke remained high in 2015 in France, despite major improvements in stroke care and organization. Improvement in stroke awareness and preparedness, particularly in the most deprived areas, together with better follow-up after the acute phase are urgently needed.

Objectives: We aimed to study trends in stroke unit (SU) admission during a period of their deployment in France and to assess whether this led to better and more equitable access to this specialised care., Design: Analysis of records from the national hospital database., Setting: All acute care hospitals in metropolitan France for the period 2009-2014., Participants: Over 600 000 patients admitted in acute care with a main diagnosis of stroke., Main Outcome Measures: Admission to a SU., Results: Between 2009 and 2014, the number of stroke admissions rose from 93 728 to 109 456, and the proportion of SU admission from 23% to 44%. Overall, characteristics associated with higher probability of SU admission were: male gender, younger age, ischaemic stroke type, medium level of comorbidity and larger size of town of residence. Although likelihood of SU admission increased in all patients' categories during the study period, we identified steeper positive temporal trends among older patients, those with more comorbidities and those residing in medium or small towns (all p values <0.001), suggesting a 'catching up' phenomena. Temporal trends of men and women did not differ however., Conclusions: Admission to SU nearly doubled in France between 2009 and 2014. Faster trends observed for patients with lower admission to SU suggest that equity in access has improved over the period., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Non-vitamin K antagonist oral anticoagulants (NOACs) - dabigatran, rivaroxaban, apixaban and edoxaban - are well established in terms of preventing stroke or systemic embolism in patients with non-valvular atrial fibrillation and high thromboembolism risk. When prescribed incorrectly, NOACs are associated with an increased risk of ischaemic events and bleeding. Current NOAC labels explicitly address dose adjustments according to age, body weight, renal function and concomitant treatment with P-glycoprotein inhibitors. The required dose adjustments vary significantly from molecule to molecule, thereby creating a complex dose adjustment environment. Furthermore, recommendations support assessment of individual risk using thromboembolic and bleeding risk scores. Evidence-based medicine also provides data about specific patient profiles. In particular, some patients who are at higher risk of bleeding, such as patients on polymedication, are often at higher risk of stroke. More and more patients are being treated with NOACs. The question of appropriate dosing has become important, as studies are starting to show that reduced doses are being prescribed at very high rates. Although these data have not been evaluated in light of individual risk assessments, in everyday practice, physicians are often more concerned about drug-related bleeding than about the spontaneous evolution of the disease (stroke/systemic embolism), leading to high rates of prescription of inadequately low doses. Recent results have shown that only certain risk criteria justify dose reduction. Thus, the right dose needs to be prescribed for the right patient in order to obtain, in real-life practice, the benefits of NOACs that have been demonstrated in randomized clinical trials., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Uncertainties remain about the current risk of myocardial infarction (MI) after ischemic stroke or transient ischemic attack., Methods and Results: We undertook a systematic review to estimate the long-term risk of MI, compared to recurrent stroke, with temporal trends in ischemic stroke/transient ischemic attack patients. Annual risks and 95% confidence intervals (95% CI) of MI and recurrent stroke were estimated using random-effect meta-analyses. We calculated incidence ratios of MI/recurrent stroke, for fatal and nonfatal events, using similar analyses. Rate ratios for MI in patients with potential risk factors compared to those without were calculated using Poisson regression.A total of 58 studies (131 299 patients) with a mean (range) follow-up of 3.5 (1.0-10.0) years were included. The risk of MI was 1.67%/y (95% CI 1.36-1.98, P het =0.021); 96% of the heterogeneity between studies was explained by study design, study period, follow-up duration, mean age, proportion of patients on antithrombotic therapy, and incident versus combined ischemic stroke/transient ischemic attack. The risk of recurrent stroke was 4.26%/y (95% CI 3.43-5.09, P int =0.021); 96% of the heterogeneity between studies was explained by study design, study period, follow-up duration, mean age, proportion of patients on antithrombotic therapy, and incident versus combined ischemic stroke/transient ischemic attack. The risk of recurrent stroke was 4.26%/y (95% CI 3.43-5.09, P het <0.001), with no change over time ( P int =0.63). The risk of fatal MI was half the risk of recurrent strokes ending in fatality (incidence ratio=0.51, 95% CI 0.14-0.89, P het =0.58). The risk of nonfatal MI was 75% smaller than the risk of recurrent nonfatal stroke (incidence ratio=0.25, 95%CI 0.02-0.50, P het =0.68). Male sex, hypertension, coronary and peripheral artery diseases were associated with a doubled risk of MI., Conclusions: After ischemic stroke/transient ischemic attack, the risk of MI is currently <2%/y, and recurrent stroke is a more common cause of death than MI., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background and Purpose: Selective serotonin-reuptake inhibitors (SSRIs) impair platelet function and have been linked to a higher risk of spontaneous intracerebral hemorrhage-an association that may be augmented by oral anticoagulants (OAC). We aimed to assess whether preadmission treatment with SSRIs in patients with acute ischemic stroke is associated with post-thrombolysis symptomatic intracerebral hemorrhage (sICH) and functional outcome., Methods: A multicenter retrospective analysis was conducted in prospective registries of patients treated by thrombolysis within 4.5 hours of stroke onset. The association between preadmission treatment with SSRIs and sICH (ECASS II definition [European Cooperative Acute Stroke Study]) or unfavorable 3-month outcome (modified Rankin Scale >2) was assessed by logistic regression, taking into account potential interaction with concomitant use of antithrombotics., Results: Six thousand two hundred forty-two patients were included (mean age, 70.1±14.0 years; median National Institutes of Health Stroke Scale, 9 [5-16]). Preadmission treatment with SSRIs was present in 4.3% (n=266) of patients. Overall, SICH rate was 3.9% (95% confidence interval [CI], 3.5%-4.4%; n=244), and SSRI use was not significantly associated with sICH in unadjusted (odds ratio [OR], 1.28; 95% CI, 0.72-2.27) or adjusted (OR, 1.30; 95% CI, 0.71-2.40) analysis. However, there was a significant interaction of concomitant use of OACs (international normalized ratio <1.7) and SSRI for occurrence of sICH ( P =0.01). SICH was significantly more frequent in patients taking both OAC and SSRI (23.1%; 95% CI, 8.2%-50.3%) than in patients taking OAC but not SSRI (adjusted OR, 9.04; 95% CI, 1.95-41.89). Preadmission use of SSRI was associated with unfavorable 3-month outcome (unadjusted OR, 1.90; 95% CI, 1.48-2.46; adjusted OR, 1.59; 95% CI, 1.15-2.19)., Conclusions: Preadmission treatment with SSRIs was not significantly associated with an increased risk of post-thrombolysis sICH in this cohort study. However, subgroup analysis suggested an increased risk of sICH in patients taking both SSRI and OAC. Preadmission treatment with SSRIs was associated with unfavorable outcome, which may reflect the prognostic significance of prestroke depression., (© 2017 American Heart Association, Inc.)

Background and Purpose: Stroke is the leading cause of death in women and the third leading cause in men in France. In young adults (ie, <65 years old), an increase in the incidence of ischemic stroke was observed at a local scale between 1985 and 2011. After the implementation of the 2010 to 2014 National Stroke Action Plan, this study investigates national trends in patients hospitalized by stroke subtypes, in-hospital mortality, and stroke mortality between 2008 and 2014., Methods: Hospitalization data were extracted from the French national hospital discharge databases and mortality data from the French national medical causes of death database. Time trends were tested using a Poisson regression model., Results: From 2008 to 2014, the age-standardized rates of patients hospitalized for ischemic stroke increased by 14.3% in patients <65 years old and decreased by 1.5% in those aged ≥65 years. The rate of patients hospitalized for hemorrhagic stroke was stable (+2.0%), irrespective of age and sex. The proportion of patients hospitalized in stroke units substantially increased. In-hospital mortality decreased by 17.1% in patients with ischemic stroke. From 2008 to 2013, stroke mortality decreased, except for women between 45 and 64 years old and for people aged ≥85 years., Conclusions: An increase in cardiovascular risk factors and improved stroke management may explain the increase in the rates of patients hospitalized for ischemic stroke. The decrease observed for in-hospital stroke mortality may be because of recent improvements in acute-phase management., (© 2017 American Heart Association, Inc.)

Air pollution is composed of particulate matter (PM) and gaseous pollutants, such as nitrogen dioxide and ozone. PM is classified according to size into coarse particles (PM 10 ), fine particles (PM 2.5 ) and ultrafine particles. We aim to provide an original review of the scientific evidence from epidemiological and experimental studies examining the cardiovascular effects of outdoor air pollution. Pooled epidemiological studies reported that a 10μg/m 3 increase in long-term exposure to PM 2.5 was associated with an 11% increase in cardiovascular mortality. Increased cardiovascular mortality was also related to long-term and short-term exposure to nitrogen dioxide. Exposure to air pollution and road traffic was associated with an increased risk of arteriosclerosis, as shown by premature aortic and coronary calcification. Short-term increases in air pollution were associated with an increased risk of myocardial infarction, stroke and acute heart failure. The risk was increased even when pollutant concentrations were below European standards. Reinforcing the evidence from epidemiological studies, numerous experimental studies demonstrated that air pollution promotes a systemic vascular oxidative stress reaction. Radical oxygen species induce endothelial dysfunction, monocyte activation and some proatherogenic changes in lipoproteins, which initiate plaque formation. Furthermore, air pollution favours thrombus formation, because of an increase in coagulation factors and platelet activation. Experimental studies also indicate that some pollutants have more harmful cardiovascular effects, such as combustion-derived PM 2.5 and ultrafine particles. Air pollution is a major contributor to cardiovascular diseases. Promotion of safer air quality appears to be a new challenge in cardiovascular disease prevention., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background and Purpose: Pregnancy is associated with increased risk of venous thrombotic events, including cerebral venous thrombosis. We aimed to study the complications and outcome of subsequent pregnancies in women with previous cerebral venous thrombosis., Methods: Follow-up study of women with acute cerebral venous thrombosis at childbearing age included in a previously described cohort (International Study of Cerebral Vein and Dural Sinus Thrombosis). Patients were interviewed by local neurologists to assess rate of venous thrombotic events, pregnancy outcomes, and antithrombotic prophylaxis during subsequent pregnancies., Results: A total of 119 women were included, with a median follow-up of 14 years. Eighty-two new pregnancies occurred in 47 women. In 83% (68 of 82), some form of antithrombotic prophylaxis was given during at least 1 trimester of pregnancy or puerperium. Venous thrombotic events occurred in 3 pregnancies, including 1 recurrent cerebral venous thrombosis. Two of the 3 women were on prophylactic low-molecular-weight heparin at the time of the event. Outcomes of pregnancies were 51 full-term newborns, 9 preterm births, 2 stillbirths, and 20 abortions (14 spontaneous)., Conclusions: In women with prior cerebral venous thrombosis, recurrent venous thrombotic events during subsequent pregnancies are infrequent., (© 2017 American Heart Association, Inc.)

Introduction: Stroke is a leading cause of adult disability and death worldwide. The neurological impairments associated with stroke prevent patients from performing basic daily activities and have enormous impact on families and caregivers. Practical and accurate tools to assist in predicting outcome after stroke at patient level can provide significant aid for patient management. Furthermore, prediction models of this kind can be useful for clinical research, health economics, policymaking and clinical decision support., Methods: 2869 patients with first-ever stroke from South London Stroke Register (SLSR) (1995-2004) will be included in the development cohort. We will use information captured after baseline to construct multilevel models and a Cox proportional hazard model to predict cognitive impairment, functional outcome and mortality up to 5 years after stroke. Repeated random subsampling validation (Monte Carlo cross-validation) will be evaluated in model development. Data from participants recruited to the stroke register (2005-2014) will be used for temporal validation of the models. Data from participants recruited to the Dijon Stroke Register (1985-2015) will be used for external validation. Discrimination, calibration and clinical utility of the models will be presented., Ethics: Patients, or for patients who cannot consent their relatives, gave written informed consent to participate in stroke-related studies within the SLSR. The SLSR design was approved by the ethics committees of Guy's and St Thomas' NHS Foundation Trust, Kings College Hospital, Queens Square and Westminster Hospitals (London). The Dijon Stroke Registry was approved by the Comité National des Registres and the InVS and has authorisation of the Commission Nationale de l'Informatique et des Libertés., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background and Purpose: We evaluated temporal trends in stroke incidence between men and women to determine whether changes in the distribution of vascular risk factors have influenced sex differences in stroke epidemiology., Methods: Patients with first-ever stroke including ischemic stroke, spontaneous intracerebral hemorrhage, subarachnoid hemorrhage, and undetermined stroke between 1987 and 2012 were identified through the population-based registry of Dijon, France. Incidence rates were calculated for age groups, sex, and stroke subtypes. Sex differences and temporal trends (according to 5-year time periods) were evaluated by calculating incidence rate ratios (IRRs) with Poisson regression., Results: Four thousand six hundred and fourteen patients with a first-ever stroke (53.1% women) were recorded. Incidence was lower in women than in men (112 versus 166 per 100 000/y; IRR, 0.68; P <0.001), especially in age group 45 to 84 years, and for both ischemic stroke and intracerebral hemorrhage. From 1987 to 2012, the lower incidence of overall stroke in women was stable (IRR ranging between 0.63 and 0.72 according to study periods). When considering stroke subtype, a slight increase in the incidence of ischemic stroke was observed in both men (IRR, 1.011; 95% confidence interval, 1.005-1.016; P =0.001) and women (IRR, 1.013; 95% confidence interval, 1.007-1.018; P =0.001). The sex gap in incidence remained unchanged in ischemic stroke and intracerebral hemorrhage. Conversely, the lower subarachnoid hemorrhage incidence in women vanished with time because of an increasing incidence., Conclusions: The sex gap in stroke incidence did not change with time except for subarachnoid hemorrhage. Despite lower rates, more women than men experience an incident stroke each year because of a longer life expectancy., (© 2017 American Heart Association, Inc.)