Are we ready to cure post-stroke cognitive impairment? Many key prerequisites can be achieved quickly and easily.

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.

Incidence and nationwide estimates of cryptogenic ischemic stroke or TIA eligible for prolonged cardiac rhythm monitoring.

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.

Proximal and distant expression of growth differentiation factor 15 (GDF15) correlate with neurological deficit following experimental ischemic stroke.

BACKGROUND AND PURPOSE: Growth differentiation factor 15 (GDF15) has emerged as a promising biomarker in cerebro-cardiovascular disease, particularly in acute and chronic inflammatory stress situations. However, understanding the origins, targets and functions of GDF15 in clinical situations, such as ischemic stroke, remains a complex challenge. This study aims to assess the sources of GDF15 production following an experimental ischemic stroke. METHODS: Adult male Wistar rats underwent cerebral embolization through microspheres injection into the left or right internal carotid artery. Two hours post-surgery, GDF15 expression was analyzed in the brain, blood, lungs, liver and heart using quantitative RT-PCR and Western blotting. RESULTS: Stroke model induced large cerebral infarcts accompanied by severe neurological deficits. GDF15 gene expression exhibited a substantial increase in the ipsilateral cortex and cerebellum, with a lesser extent in the contralateral cortex. Regarding GDF15 protein expression, proGDF15 levels were elevated in the 3 aforementioned organs mentioned and the heart. However, the mature form of GDF15 was exclusively present and increased in the heart. Finally, the expression of GDF15 expression was correlated with the neurological deficit score. CONCLUSIONS: Our findings suggest that both the GDF15 gene and pro-protein are expressed in the ischemic brain after a stroke, while only its mature form is expressed remotely in in the heart. The impact of increased GDF15 in the heart following a stroke remains to be established. This is particularly relevant in understanding its relationships with poor neurological outcomes, determining whether it may contribute to stroke-induced cardiac dysfunction.

Growth/differentiation factor 15 (GDF15) expression in the heart after myocardial infarction and cardioprotective effect of pre-ischemic rGDF15 administration.

Growth/differentiation factor-15 (GDF15) is considered an unfavourable prognostic biomarker for cardiovascular disease in clinical data, while experimental studies suggest it has cardioprotective potential. This study focuses on the direct cardiac effects of GDF15 during ischemia-reperfusion injury in Wistar male rats, employing concentrations relevant to patients at high cardiovascular risk. Initially, we examined circulating levels and heart tissue expression of GDF15 in rats subjected to ischemia-reperfusion and sham operations in vivo. We then evaluated the cardiac effects of GDF15 both in vivo and ex vivo, administering recombinant GDF15 either before 30 min of ischemia (preconditioning) or at the onset of reperfusion (postconditioning). We compared infarct size and cardiac contractile recovery between control and rGDF15-treated rats. Contrary to our expectations, ischemia-reperfusion did not increase GDF15 plasma levels compared to sham-operated rats. However, cardiac protein and mRNA expression increased in the infarcted zone of the ischemic heart after 24 h of reperfusion. Notably, preconditioning with rGDF15 had a cardioprotective effect, reducing infarct size both in vivo (65 ± 5% in control vs. 42 ± 6% in rGDF15 groups) and ex vivo (60 ± 4% in control vs. 45 ± 4% in rGDF15 groups), while enhancing cardiac contractile recovery ex vivo. However, postconditioning with rGDF15 did not alter infarct size or the recovery of contractile parameters in vivo or ex vivo. These novel findings reveal that the short-term exogenous administration of rGDF15 before ischemia, at physiologically relevant levels, protects the heart against ischemia-reperfusion injury in both in vivo and ex vivo settings. The ex vivo results indicate that rGDF15 operates independently of the inflammatory, endocrine and nervous systems, suggesting direct and potent cardioprotective properties against ischemia-reperfusion injury.

Trial of Thrombectomy for Stroke with a Large Infarct of Unrestricted Size.

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.).

Atrial fibrillation and preexisting cognitive impairment in ischemic stroke patients: Dijon Stroke Registry.

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.

Is COVID-19 Infection a Multiorganic Disease? Focus on Extrapulmonary Involvement of SARS-CoV-2.

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.

Prevalence and Characteristics of Known versus Newly Detected Atrial Fibrillation in Ischemic Stroke: A Population-Based Study.

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 < 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 < 0.001), and preexisting dementia (OR = 0.36; 95% CI: 0.21-0.63, p < 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.

Prevalence of major embolic findings and incidental findings on early cardiac CT in patients with suspected ischemic stroke.

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.

Climate Change and Stroke: A Topical Narrative Review.

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.

Assessment of Mendelian and risk-factor genes in Alzheimer disease: A prospective nationwide clinical utility study and recommendations for genetic screening.

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.

Value of HAVOC and Brown ESUS-AF scores for atrial fibrillation on implantable cardiac monitors after embolic stroke of undetermined source.

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 CHA2DS2-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.

Environmental factors and stroke: Risk and prevention.

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.

Changes in Taste Perception in Patients with Minor and Major Cognitive Impairment Linked to Alzheimer's Disease Recorded by Gustatory Evoked Potentials.

BACKGROUND: The need for early diagnosis biomarkers in Alzheimer's disease (AD) is growing. Only few studies have reported gustatory dysfunctions in AD using subjective taste tests. OBJECTIVE: The main purpose of the study was to explore gustatory functions using subjective taste tests and recordings of gustatory evoked potentials (GEPs) for sucrose solution in patients with minor or major cognitive impairment (CI) linked to AD, and to compare them with healthy controls. The secondary objective was to evaluate the relationships between GEPs and the results of cognitive assessments and fasting blood samples. METHODS: A total of 45 subjects (15 healthy subjects, 15 minor CI patients, 15 major CI patients) were included to compare their gustatory functions and brain activity by recording GEPs in response to a sucrose stimulation. CI groups were combined in second analyses in order to keep a high power in the study. Correlations were made with cognitive scores and hormone levels (ghrelin, leptin, insulin, serotonin). RESULTS: Increased P1 latencies and reduced N1 amplitudes were observed in minor or major patients compared to controls. GEPs were undetectable in 6 major and 4 minor CI patients. Thresholds for sucrose detection were significantly higher in the major CI group than in controls or the minor CI group. No correlation was found with hormone levels. CONCLUSIONS: The cortical processing of sensory taste information seems to be altered in patients with minor or major CI linked to AD. This disturbance was identifiable with subjective taste tests only later, at the major CI stage.

Long-Term Survival of Ischemic Stroke Patients according to Prior Cognitive Status: Dijon Stroke Registry.

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 < 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 < 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 < 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.

Functional outcomes of ischemic stroke patients aged over 80 years treated with acute revascularization therapy according to pre-morbid disability: a PARADISE study.

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.

IV Thrombolysis With or Without Endovascular Treatment for Suspected Ischemic Stroke in Patients With Intracranial Tumors.

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.

Symptomatic Intracranial Hemorrhage after Ischemic Stroke Treated with Bridging Revascularization Therapy.

(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.

Distribution of atrial cardiomyopathy markers and association with atrial fibrillation detected after ischaemic stroke in the SAFAS study.

BACKGROUND: Atrial cardiomyopathy (AC) is an emerging concept explaining the pathophysiology of cardioembolic strokes in absence of atrial fibrillation (AF). A definition based on the presence of electrical abnormality (P-wave terminal force in lead V1 (PTFV1) >5000 µV×ms), N-Terminal pro-B-type natriuretic peptide (NT pro BNP) >250 pg/mL and/or indexed left atrial diameter (LADI) >3 cm/m² is currently tested in the ARCADIA (AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke) trial. We set out to estimate the prevalence of AC as defined in the ARCADIA trial, its determinants and its association with AF detected after stroke (AFDAS). METHODS: Stepwise screening for silent Atrial Fibrillation After Stroke (SAFAS) study prospectively included 240 ischaemic stroke patients. AC markers were complete for 192 of them and 9 were not included in this analysis because AF had been diagnosed on admission. RESULTS: A total of 183 patients were analysed, of whom 57% (104 patients) met the AC criteria (79 NT-proBNP, 47 PTFV1, 4 LADI). In the multivariate logistic regression, C reactive protein >3 mg/L (OR (95% CI) 2.60 (1.30 to 5.21), p=0.007) and age (OR (95% CI) 1.07 (1.04 to 1.10), p<0.001) were found to be independently associated with AC. After 6 months of follow-up, AFDAS was detected in 33% of AC patients and in 14% of the remaining ones (p=0.003). However, AC was not independently associated with AFDAS, contrary to left atrial volume index (>34 mL/m2, OR 2.35 (CI 1.09 to 5.06) p=0029). CONCLUSION: AC as defined in ARCADIA is mostly based on NT pro BNP elevation (76% of patients) and is associated with age and inflammation. Moreover, AC was not independently associated with AFDAS at follow-up. The ARCADIA trial, which compares aspirin to apixaban in patients with embolic strokes of undetermined source with AC markers and must, therefore be analysed in the light of these limitations. TRIAL REGISTRATION NUMBER: NCT03570060.