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 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.

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 (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 versus AFDAS). Regression logistic models were used to assess factors associated with AFDAS (compared to KAF). RESULTS: Among 1756 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.

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.

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.

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.

Comparison of Stroke Recurrence, Cardiovascular Events, and Death Among Patients With Pregnancy-Associated vs Non-Pregnancy-Associated Stroke.

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.

Recanalization Therapies for Large Vessel Occlusion Due to Cervical Artery Dissection: A Cohort Study of the EVA-TRISP Collaboration.

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.

Nationwide projections of ischemic stroke with large vessel occlusion of the anterior circulation by 2050: Dijon Stroke Registry.

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.