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Purpose: The purpose of this study was to assess the type and prevalence of stroke and non-stroke-related findings diagnosed on early cardiac computed tomography (CT) in patients with suspected stroke. The secondary objective was to assess the clinical consequences on the management of patients with non-stroke-related conditions identified by early cardiac CT., Materials and Methods: This single-center, retrospective, observational study included 1111 consecutive patients with suspected ischemic stroke between November 2018 and March 2020 who underwent cardiac CT examination in addition to the usual brain CT protocol (i.e., non-enhanced brain CT, perfusion brain CT when needed, aortic arch and supra-aortic CT angiography, and post contrast brain CT). There were 562 women and 549 men with a median age of 74 years (range: 60-85 years). Of these, 415 (415/1111; 37.4%) patients had ischemic stroke and 692 (692/1111; 62.3%) had no stroke. Cardiac CT examinations were retrospectively reviewed for cardiac CT findings at high embolic risk and clinically significant extracardiac incidental findings., Results: Among 1111 included patients, 89 (89/1111; 8.0%) had a stroke-related condition identified on early cardiac CT. This was significantly more frequent in patients with ischemic stroke (66/415; 15.9%) by comparison with those without ischemic stroke (23/696; 3.3%) (P < 0.001), with 41 patients (41/415; 9.9%) diagnosed with left atrial thrombus. Cardiac CT revealed a clinically significant non-stroke-related finding in 173 patients (173/1111; 15.6%), including 17 pulmonary embolisms (1.5%), seven suspicious pulmonary lesions (0.6%), and three breast lesions suspected to be malignant (0.3%). Twenty out of 173 patients (20/173; 11.5%) with incidental findings on early cardiac CT had a change in their management., Conclusion: This study shows that adding early cardiac CT to brain CT during the acute phase of an ischemic stroke leads to a higher rate of etiological diagnoses and highlights the major interest of looking at the bigger picture., Competing Interests: Declaration of competing interest The authors declare no actual or potential conflict of interest related to this study., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: Although guidelines recommend screening patients for atrial fibrillation (AF) after stroke, the optimal timing and combination of screening tools remain unclear., Aims: We evaluated the suitability of a sequential combination of screening techniques for AF detected after stroke (AFDAS). We also compared patient characteristics according to the timing of AFDAS., Methods: Patients without previous AF admitted for acute ischaemic stroke were prospectively enrolled. After a stepwise screening approach for AFDAS based on electrocardiogram, telemetry monitoring and in-hospital long-term Holter, patients with cryptogenic stroke underwent implantation of an implantable cardiac monitor (ICM). Early AFDAS was defined as AF diagnosed during hospitalization and late AFDAS as AF diagnosed on an ICM., Results: Of the 240 patients included, 104 (43.3%) had a documented cause of stroke not related to AF. Among the 136 remaining patients, AFDAS was detected in 82 (60.3%) during the acute screening phase or during the 3-year follow-up by ICM. Early AFDAS was diagnosed by ECG, telemetry and in-hospital long-term Holter monitoring in 17 (20.7%), 25 (30.5%) and 18 (22.0%) patients, respectively. Among 76 patients who had an ICM implanted for cryptogenic stroke, AF was detected in 22 patients (28.9%). Except for age and stroke location, patients with early AFDAS did not differ from those with late AFDAS, particularly with regard to the prevalence of atrial cardiomyopathy markers., Conclusion: A stepwise approach to AFDAS screening allows early detection of AF in a considerable number of patients during their hospitalization. ICMs remain complementary to non-invasive screening tools for the detection of remote episodes of AF., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

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.

Background: Atrial Fibrillation (AF) is a common cause of ischemic stroke (IS), and is associated with cognitive impairment in the general population. We aimed to compare the prevalence of preexisting cognitive impairment between IS patients with and without AF, and to assess whether prior brain damage could contribute to the observed differences., Methods: Patients with acute IS were prospectively identified from the population-based Dijon Stroke Registry, France. Patients who had a CT-scan as brain imaging modality were included in this analysis to assess the presence of preexisting leukoaraiosis, old vascular brain lesions, and cerebral atrophy. Characteristics of patients including prior-to-stroke cognitive status (normal cognition, mild cognitive impairment (MCI), or dementia) were compared between those with and without AF., Results: Among 916 IS patients, 288 (31.4 %) had AF, of whom 88 had newly diagnosed AF. AF patients had more frequent prior MCI (17.8 % versus 10.2 %) or dementia (22.4 % versus 13.1 %) (p = 0.001), vascular risk factors, and preexisting brain damage. In unadjusted model, preexisting cognitive impairment was associated with AF (OR=2.24; 95 % CI: 1.49-3.37, p < 0.001 for MCI; OR=2.20; 95 % CI: 1.52-3.18, p < 0.001 for dementia). After adjustment for clinical and imaging variables, preexisting mild cognitive impairment (OR=1.87; 95 % CI: 1.06-3.32, p = 0.032) and dementia (OR=1.98; 95 % CI: 1.15-3.40, p = 0.013) were independently associated with AF., Conclusion: AF is a common condition in IS patients and is associated with preexisting cognitive impairment. Brain lesions visible on imaging did not seem to fully account for this association that may involve other mechanisms yet to be elucidated., Competing Interests: Declaration of competing interest 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, Boehringer-Ingelheim, Medtronic, Amgen, Servier, NovoNordisk, Novartis, outside the submitted work. Other authors: none, (Copyright © 2024. Published by Elsevier B.V.)

Background: The use of thrombectomy in patients with acute stroke and a large infarct of unrestricted size has not been well studied., Methods: We assigned, in a 1:1 ratio, patients with proximal cerebral vessel occlusion in the anterior circulation and a large infarct (as defined by an Alberta Stroke Program Early Computed Tomographic Score of ≤5; values range from 0 to 10) detected on magnetic resonance imaging or computed tomography within 6.5 hours after symptom onset to undergo endovascular thrombectomy and receive medical care (thrombectomy group) or to receive medical care alone (control group). The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). The primary safety outcome was death from any cause at 90 days, and an ancillary safety outcome was symptomatic intracerebral hemorrhage., Results: A total of 333 patients were assigned to either the thrombectomy group (166 patients) or the control group (167 patients); 9 were excluded from the analysis because of consent withdrawal or legal reasons. The trial was stopped early because results of similar trials favored thrombectomy. Approximately 35% of the patients received thrombolysis therapy. The median modified Rankin scale score at 90 days was 4 in the thrombectomy group and 6 in the control group (generalized odds ratio, 1.63; 95% confidence interval [CI], 1.29 to 2.06; P<0.001). Death from any cause at 90 days occurred in 36.1% of the patients in the thrombectomy group and in 55.5% of those in the control group (adjusted relative risk, 0.65; 95% CI, 0.50 to 0.84), and the percentage of patients with symptomatic intracerebral hemorrhage was 9.6% and 5.7%, respectively (adjusted relative risk, 1.73; 95% CI, 0.78 to 4.68). Eleven procedure-related complications occurred in the thrombectomy group., Conclusions: In patients with acute stroke and a large infarct of unrestricted size, thrombectomy plus medical care resulted in better functional outcomes and lower mortality than medical care alone but led to a higher incidence of symptomatic intracerebral hemorrhage. (Funded by Montpellier University Hospital; LASTE ClinicalTrials.gov number, NCT03811769.)., (Copyright © 2024 Massachusetts Medical Society.)

Purpose: To assess the likely pathogenic/pathogenic (LP/P) variants rates in Mendelian dementia genes and the moderate-to-strong risk factors rates in patients with Alzheimer disease (AD)., Methods: We included 700 patients in a prospective study and performed exome sequencing. A panel of 28 Mendelian and 6 risk-factor genes was interpreted and returned to patients. We built a framework for risk variant interpretation and risk gradation and assessed the detection rates among early-onset AD (EOAD, age of onset (AOO) ≤65 years, n = 608) depending on AOO and pedigree structure and late-onset AD (66 < AOO < 75, n = 92)., Results: Twenty-one patients carried a LP/P variant in a Mendelian gene (all with EOAD, 3.4%), 20 of 21 affected APP, PSEN1, or PSEN2. LP/P variant detection rates in EOAD ranged from 1.7% to 11.6% based on AOO and pedigree structure. Risk factors were found in 69.5% of the remaining 679 patients, including 83 (12.2%) being heterozygotes for rare risk variants, in decreasing order of frequency, in TREM2, ABCA7, ATP8B4, SORL1, and ABCA1, including 5 heterozygotes for multiple rare risk variants, suggesting non-monogenic inheritance, even in some autosomal-dominant-like pedigrees., Conclusion: We suggest that genetic screening should be proposed to all EOAD patients and should no longer be prioritized based on pedigree structure., Competing Interests: Conflict of Interest The authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The impacts of accumulating atmospheric greenhouse gases on the earth's climate are now well established. As a result, there have been increases in ambient temperatures and resultant higher frequency and duration of temperature extremes and other extreme weather events, which have been linked to a wide range of adverse health outcomes. This topical narrative review provides a summary of published evidence on the links between climate change and stroke. There is consistent evidence of associations between stroke incidence and mortality and increasing ambient temperature and air pollution. Associations have also been shown for changes in barometric pressure, wildfires, and desert dust and sandstorms, but current evidence is limited. Flooding and other extreme weather events appear to primarily cause service disruption, but more direct links to stroke may emerge. Synergies between dietary changes that reduce stroke risk and may also reduce carbon footprint are being explored. We also discuss the impact on vulnerable populations, proposed pathophysiologic mechanisms, mitigation strategies, and current research priorities. In conclusion, climate change increasingly impacts the stroke community, warranting elevated attention., Competing Interests: Disclosures Dr Ranta discloses employment at Capital Coast District Health Board and University of Otago Wellington, consultancy for Ministry of Health, and research funding from the Ministry of Health and Health Research Council of New Zealand. Dr Douwes discloses research funding from Health Research Council of New Zealand and Marsden Fund. The other authors report no conflicts.

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.

Background: Persistent foramen ovale (PFO) contributes to cryptogenic stroke and is associated with stroke recurrence, although the exact mechanism of ischemic events is not fully understood. Several biomarkers have been developed for the prediction of atrial fibrillation after stroke, but there are currently only limited data on their potential value for the diagnosis of PFO-related stroke., Methods: This study was a prospective single-center study that included all patients hospitalized between March 31, 2018, and January 18, 2020, in the stroke department of the Dijon University Hospital for ischemic stroke without obvious cause and without a history of atrial fibrillation. PFO was systematically screened by transthoracic echocardiography and images were reviewed by an independent cardiologist blinded from clinical data. PFO was defined according to the CLOSE trial criteria: PFO associated with interatrial septal aneurysm or significant interatrial shunt (> 30 microbubbles in the left atrium within three cardiac cycles after right atrial opacification). The potential association of PFO-related stroke with biomarkers of cardiac fibrosis and inflammation such as galectin-3, GDF-15, ST-2, osteoprotegerin and NT-proBNP was tested using multivariate backward stepwise logistic regression., Results: Of the 240 patients included in the SAFAS study, 229 had complete echocardiographic data, and 23 (10%) had PFO-related stroke. Patients with PFO-related stroke were significantly younger (58±14 vs. 69±14, P<0.001), had less frequent previous arterial hypertension (30 vs. 60%, P=0.008), and more frequent cerebellar territory involvement (26 vs. 9%, P=0.014) compared to the other patients. In addition, they had less frequently left atrial dilatation (left atrial index volume>34mL/m 2 [9 vs. 35%, P=0.009]). After ROC curve analysis for definition of thresholds, PFO-related stroke patients more often had galectin-3<9.5ng/mL (59 vs. 27%, P=0.002), ST2<13380pg/ml (23 vs. 50%, P=0.007), GDF-15<1200ng/mL (59 vs. 27%, P=0.002), osteoprotegerin<1133pg/mL (82 vs. 58%, P=0.033) and NT-proBNP<300pg/mL (88 vs. 55%, P=0.009). After multivariate analysis, only galectin-3<9.5ng/mL (OR [95% CI] 3.4 [1.18; 9.8], P=0.024) and osteoprotegerin<1133pg/L (OR [95% CI] 5.0 [1.1; 22.9], P=0.038) were independently associated with PFO-related stroke., Conclusion: Patients in whom cryptogenic stroke is attributed to a significant PFO have a specific clinical and biological phenotype. Low levels of galectin-3 and osteoprotegerin may help identify patients with PFO-related strokes., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Atrial fibrillation (AF) is frequently diagnosed during the acute stage of ischemic stroke (IS), and it may reflect undiagnosed AF before stroke, thus representing a missed opportunity for stroke prevention. This population-based study aimed to assess the prevalence of known AF (KAF) and AF diagnosed early after IS (AFDAS) and to compare clinical and brain/arterial imaging characteristics between patients., Methods: Among patients with acute IS recorded in the population-based Dijon Stroke Registry, France (2013-2020), we identified those with KAF or AFDAS. AFDAS was considered when AF was diagnosed during the initial work-up based on electrocardiograms, in-hospital continuous electrocardiographic and/or Holter monitoring. Clinical and imaging characteristics on brain CT scan or angio-CT scan when available including old parenchymal lesions, arterial territory of the index IS, and aortic arch, cervical and intracranial arteries atheroma were compared between groups (KAF vs. AFDAS). Regression logistic models were used to assess factors associated with AFDAS (compared to KAF)., Results: Among 1,756 IS patients, 550 (31.3%) had AF (mean age: 83.6 ± 10.3 years old, 60.5% women), of whom 367 (66.7%) presented with KAF and 183 (33.3%) had AFDAS. In multivariable model, hypertension (OR = 0.37; 95% CI: 0.21-0.64, p &lt; 0.001), chronic heart failure (OR = 0.34; 95% CI: 0.18-0.67, p = 0.002), previous stroke (OR = 0.42; 95% CI: 0.26-0.67, p &lt; 0.001), and preexisting dementia (OR = 0.36; 95% CI: 0.21-0.63, p &lt; 0.001) were inversely associated with AFDAS, whereas NIHSS score was associated with AFDAS (OR = 1.02; 95% CI: 1.00-1.05, p = 0.012)., Conclusions: Our findings indicate a more advanced stage of the atrial cardiomyopathy in KAF as compared with AFDAS patients and may thus contribute to the fact that in these latter patients AF had not been diagnosed prior to stroke. This group of patients undeniably represents a missed opportunity for stroke prevention., (© 2024 S. Karger AG, Basel.)

Objectives: Up to 20 % of ischemic strokes are associated with overt atrial fibrillation (AF). Furthermore, silent AF was detected by an implantable cardiac monitor (ICM) in 1 in 3 cryptogenic strokes in the CRYSTAL AF study. An ESC position paper has suggested a HAVOC score ≥ 4 or a Brown ESUS-AF score ≥ 2 as criteria for ICM implantation after cryptogenic stroke, but neither of these criteria has been developed or validated in ICM populations. We assessed the performance of HAVOC and Brown ESUS-AF scores in a cohort of ICM patients implanted after embolic stroke of undetermined source (ESUS)., Methods: All patients implanted with an ICM for ESUS between February 2016 and February 2022 at two French University Hospitals were retrospectively included. Demographic data, cardiovascular risk factors, and clinical and biological data were collected after a review of electronic medical records. HAVOC and Brown ESUS-AF scores were calculated for all patients., Findings: Among the 384 patients included, 106 (27 %) developed AF during a mean follow-up of 33 months. The scores performances for predicting AF during follow-up were: HAVOC= AUC: 68.5 %, C-Index: 0.662, and Brown ESUS-AF=AUC: 72.9 %, C-index 0.712. Compared with the CHA 2 DS 2 -VASc score, only the Brown ESUS-AF score showed significant improvement in NRI/IDI. Furthermore, classifying patients according to the suggested HAVOC and Brown ESUS-AF thresholds, only 24 % and 31 % of the cohort, respectively, would have received an ICM, and 58 (55 %) and 47 (44 %) of the AF patients, respectively, would not have been implanted with an ICM., Conclusion: HAVOC and Brown ESUS-AF scores showed close and moderate performance in predicting AF on ICM after cryptogenic stroke, with a significant lack of sensitivity. Specific risk scores should be developed and validated in large ICM cohorts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Stroke is a leading cause of death and adult disability globally. In addition to traditional risk factors, environmental risk factors have emerged over the recent past and are becoming increasingly important. The disproportionate rise of stroke incidence in low- and middle-income countries has been attributed, at least in part, to environmental factors. This narrative review provides details on the interplay between the environment and health generally and stroke specifically, covering topics including air pollution, atmospheric brown clouds, desert dust storms, giant wildfires, chemical contamination, biological aggressors, urbanization, and climate change. It also covers some beneficial environmental effects such as can be harnessed from the exposure to green spaces. It concludes with a summary of pragmatic actions that can be taken to help address some of these challenges at individual, community, and political advocacy levels., Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest relevant to this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Objectives: IV thrombolysis (IVT) for suspected ischemic stroke in patients with intracranial neoplasms is off-label. However, data on risks of intracranial hemorrhage (ICH) are scarce., Methods: In a multicenter registry-based analysis within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration, we assessed frequencies of symptomatic and fatal ICH after IVT for suspected ischemic stroke in patients with intracranial tumors by descriptive statistics and analyzed associations with clinical and imaging characteristics by binary logistic regression. Definition of symptomatic ICH was based on the clinical criteria of the European Cooperative Acute Stroke-II trial including hemorrhage at any site in cranial imaging and concurrent clinical deterioration., Results: Screening data of 21,289 patients from 14 centers, we identified 105 patients receiving IVT; among them were 29 patients (28%) with additional endovascular treatment, with suspected, that is, imaging-based, or histologically confirmed diagnosis of intracranial tumors. Among 104 patients with CT or MRI after IVT available, symptomatic and fatal ICH were observed in 9 and 4 patients (9% and 4%, respectively). Among 82 patients with suspected or confirmed meningioma, symptomatic and fatal ICH occurred in 6 and 3 patients (7% and 4%), respectively. In 18 patients with intra-axial suspected or confirmed primary or secondary brain tumors, there was 1 symptomatic nonfatal ICH (6%). Of 4 patients with tumors of the pituitary region, 2 patients (50%) had symptomatic ICH including 1 fatal ICH (25%). Tumor size was not associated with the occurrence of symptomatic ICH (odds ratio 2.8, 95% CI 0.3-24.8, p = 0.34)., Discussion: In our dataset from routine clinical care, we provide insights on the safety of IVT for suspected ischemic stroke in patients with intracranial tumors, a population that is commonly withheld thrombolysis in clinical practice and prospective trials. Except for a potential high risk of symptomatic ICH after IVT in patients with tumors of the pituitary region, frequencies of symptomatic ICH in patients with intracranial tumors in our cohort seem to be in the upper range of rates observed in previous studies within the TRISP cooperation. These results may guide individual treatment decisions in patients with acute stroke and intracranial tumors with potential benefit of IVT., (© 2023 American Academy of Neurology.)

(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: Identifying biological markers of ischemic stroke (IS) is an important research approach to develop innovative therapeutic strategies. This study aimed to assess the association between plasma Growth Differentiation Factor-8 (GDF-8)/Myostatin levels and outcome of IS patients., Methods: Consecutive patients with acute IS treated with either intravenous thrombolysis and/or mechanical thrombectomy at Dijon University Hospital, France were prospectively included. Clinical variables were recorded, and plasma GDF-8 was collected just after the revascularization procedure. Primary endpoint was functional outcome at 3 months assessed by the modified Rankin Scale (mRS) score. Secondary endpoints included mRS scores at 6 and 12 months, and overall mortality over 1-year of follow-up., Results: Among the 173 included patients (median age: 76 years, Interquartile range (IQR): 66-85; 49% women), median plasma GDF-8 levels at admission were significantly lower in those with a poor outcome at 3 months defined as a mRS score > 2 (2073 (IQR: 1564-2757) pg/mL versus 1471 (1192-2241) pg/mL, p < 0.001). Lower GDF-8 levels at admission were associated with higher 3-months mRS score in multivariable ordinal logistic regression analysis (OR = 0.9995; 95% CI: 0.9991-0.9999, p = 0.011). The association was also observed with 6- and 12-month mRS scores. Although mortality was higher in patients with lower GDF-8 levels, the association was not significant in multivariable Cox analysis., Conclusion: Lower plasma GDF-8 levels were associated with a poorer functional outcome in IS patients treated with acute revascularization therapy. Underlying pathophysiological mechanisms involving GDF-8 in post-stroke outcome remain to be elucidated., Competing Interests: Declaration of Competing Interest Yannick Béjot received honoraria for lectures or consulting fees from BMS, Pfizer, Medtronic, Amgen, Servier, and NovoNordisk, outside the submitted work. Other authors: none., (Copyright © 2023. Published by Elsevier B.V.)

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.

Importance: International guidelines recommend avoiding intravenous thrombolysis (IVT) in patients with ischemic stroke who have a recent intake of a direct oral anticoagulant (DOAC)., Objective: To determine the risk of symptomatic intracranial hemorrhage (sICH) associated with use of IVT in patients with recent DOAC ingestion., Design, Setting, and Participants: This international, multicenter, retrospective cohort study included 64 primary and comprehensive stroke centers across Europe, Asia, Australia, and New Zealand. Consecutive adult patients with ischemic stroke who received IVT (both with and without thrombectomy) were included. Patients whose last known DOAC ingestion was more than 48 hours before stroke onset were excluded. A total of 832 patients with recent DOAC use were compared with 32 375 controls without recent DOAC use. Data were collected from January 2008 to December 2021., Exposures: Prior DOAC therapy (confirmed last ingestion within 48 hours prior to IVT) compared with no prior oral anticoagulation., Main Outcomes and Measures: The main outcome was sICH within 36 hours after IVT, defined as worsening of at least 4 points on the National Institutes of Health Stroke Scale and attributed to radiologically evident intracranial hemorrhage. Outcomes were compared according to different selection strategies (DOAC-level measurements, DOAC reversal treatment, IVT with neither DOAC-level measurement nor idarucizumab). The association of sICH with DOAC plasma levels and very recent ingestions was explored in sensitivity analyses., Results: Of 33 207 included patients, 14 458 (43.5%) were female, and the median (IQR) age was 73 (62-80) years. The median (IQR) National Institutes of Health Stroke Scale score was 9 (5-16). Of the 832 patients taking DOAC, 252 (30.3%) received DOAC reversal before IVT (all idarucizumab), 225 (27.0%) had DOAC-level measurements, and 355 (42.7%) received IVT without measuring DOAC plasma levels or reversal treatment. The unadjusted rate of sICH was 2.5% (95% CI, 1.6-3.8) in patients taking DOACs compared with 4.1% (95% CI, 3.9-4.4) in control patients using no anticoagulants. Recent DOAC ingestion was associated with lower odds of sICH after IVT compared with no anticoagulation (adjusted odds ratio, 0.57; 95% CI, 0.36-0.92). This finding was consistent among the different selection strategies and in sensitivity analyses of patients with detectable plasma levels or very recent ingestion., Conclusions and Relevance: In this study, there was insufficient evidence of excess harm associated with off-label IVT in selected patients after ischemic stroke with recent DOAC ingestion.

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.)

Background: We evaluated whether pre-existing brain damage may explain greater severity in cognitively-impaired patients with ischemic stroke (IS)., Methods: IS patients were retrieved from the population-based registry of Dijon, France. Pre-existing damage (leukoaraiosis, old vascular brain lesions, cortical and central brain atrophy) was assessed on initial CT-scan. Association between prestroke cognitive status defined as no impairment, mild cognitive impairment (MCI), or dementia, and clinical severity at IS onset assessed with the NIHSS score was evaluated using ordinal regression analysis. Mediation analysis was performed to assess pre-existing brain lesions as mediators of the relationship between cognitive status and severity., Results: Among the 916 included patients (mean age 76.8 ± 15.0 years, 54.3% women), those with pre-existing MCI (n = 115, median NIHSS [IQR]: 6 [2-15]) or dementia (n = 147, median NIHSS: 6 [3-15]) had a greater severity than patients without (n = 654, median NIHSS: 3 [1-9]) in univariate analysis (OR=1.69; 95% CI: 1.18-2.42, p = 0.004, and OR=2.06; 95% CI: 1.49-2.84, p < 0.001, respectively). Old cortical lesion (OR=1.53, p = 0.002), central atrophy (OR=1.41, p = 0.005), cortical atrophy (OR=1.90, p < 0.001) and moderate (OR=1.41, p = 0.005) or severe (OR=1.84, p = 0.002) leukoaraiosis were also associated with greater severity. After adjustments, pre-existing MCI (OR=1.52; 95% CI: 1.03-2.26, p = 0.037) or dementia (OR=1.94; 95% CI: 1.32-2.86, p = 0.001) remained associated with higher severity at IS onset, independently of confounding factors including imaging variables. Association between cognitive impairment and severity was not mediated by pre-existing visible brain damages., Conclusion: Impaired brain ischemic tolerance in IS patients with prior cognitive impairment could involve other mechanisms than pre-existing visible brain damage., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: The ongoing aging population in high-income countries is responsible for a dramatic rise in the number of elderly stroke patients in whom many questions remain regarding the use of acute revascularization therapy. This review aimed to compare stroke patients from population-based studies to those included in RCTs in terms of age., Summary: Population-based incidence studies conducted in high income that complied with the defined quality criteria were reviewed (period 1985-2020). RCTs of acute ischemic stroke therapy including intravenous thrombolysis (IVT) with either alteplase or tenecteplase and mechanical thrombectomy (MT) were retrieved from systematic reviews performed in recent guidelines from the European Stroke Organisation. When available, information on either mean and/or median age was extracted from each selected article. As a result, 36 population-based registries were included, 34 of which recorded patients with first-ever stroke over 63 distinct time periods with a total of 38,188 patients. Twenty-nine RCTs enrolling 11,666 patients were identified including 13 RCTs related to IVT with alteplase, 11 RCTs about MT, and 5 RCTs on IVT with tenecteplase. A gap in age between stroke patients in the RCTs and those in population-based studies was observed. With few exceptions, mean age of patients in the RCTs was about 4 years younger than in population-based studies, while the median age was approximately 7 years younger. Thirty-five (83%) population-based incidence studies and 8 RCTs (32%) reported a mean age of patients >70 years old. Mean age ≥75 years was observed in 9 (21%) population-based studies and in only 1 (4%) RCT. All population-based studies and half of the RCTs reported a median age >70 years., Key Messages: The gap in age between patients enrolled in acute stroke therapy RCTs and those from population-based studies highlights an under-representation of elderly stroke patients in RCTs. With the current aging of the population, this trend is likely to increase in the coming years, and there is a need to promote the inclusion of older patients, particularly those with disabilities, in future trials to reflect the true population of stroke patients and to help clinicians have evidence-based data to guide their decision-making., (© 2023 S. Karger AG, Basel.)

Early-onset forms of Alzheimer disease (AD) have been associated with pathogenic variants in the APP , PSEN1 , and PSEN2 genes. Mutations in presenilin-1 ( PSEN1 ) account for the majority of cases of autosomal dominant AD. Numerous phenotypes have been associated with PSEN1 -pathogenic variants, including cerebellar ataxia and spastic paraplegia. Here, we describe a patient with early-onset AD presenting with extrapyramidal symptoms and supranuclear gaze palsy, mimicking progressive supranuclear palsy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Understanding the influence of preexisting cognitive impairment on the poststroke outcome is a critical challenge in the context of current aging and growing population. This study aimed to assess long-term survival of patients with acute ischemic stroke (IS) according to their premorbid cognitive status and to identify contributing factors of death., Methods: Patients with IS were prospectively identified among residents of Dijon, France, using a population-based registry (2013-2017). The association between case fatality at 5 years and prestroke cognitive status was assessed by multivariable Cox models adjusted for other clinical characteristics and preexisting brain damage on the initial CT scan including leukoaraiosis, old vascular brain lesions, and cortical and central brain atrophy, as well as major arterial occlusion., Results: 1,049 patients were included (mean age ± SD: 76.3 ± 15.2 years old, 54% women). Case fatality rates at 5 years were 38.1% in patients without cognitive impairment, 65.9% in patients with prior mild cognitive impairment (MCI, n = 132, 12.6%), and 86.6% in patients with dementia (n = 164, 15.6%) (p &lt; 0.001). MCI (HR = 1.39; 95% CI: 1.06-1.81, p = 0.016) and dementia (HR = 1.89; 95% CI: 1.45-2.46, p &lt; 0.001) were both independently associated with higher case fatality after adjustment for clinical variables. The association remained significant after further adjustment for preexisting brain damage and major arterial occlusion (HR = 1.47; 95% CI: 1.10-1.98, p = 0.009, for MCI and HR = 1.90; 95% CI: 1.43-2.53, p &lt; 0.001, for dementia) among patients with available data on the CT scan (n = 916). Factors associated with death were roughly similar across groups., Conclusion: This study highlighted a poor long-term survival of IS patients with preexisting cognitive impairment, independently of other contributing factors of death. It is critical to better understand the trajectory of IS patients with preexisting cognitive impairment and to identify prognostic markers to guide clinicians in their management strategies., (© 2023 S. Karger AG, Basel.)