European Stroke Journal最新文献

Up to 20% of patients with cryptogenic ischemic stroke have an occult malignancy at the time of stroke presentation, providing an opportunity for early cancer detection. Despite this significant association, there is currently no consensus in international guidelines on how to systematically screen for malignancy in ischemic stroke patients. This review aims to summarize recent evidence on clinical features and scores, and predictive laboratory tests, that can guide malignancy screening in ischemic stroke patients. Our systemic search included PubMed, MEDLINE and Cochrane databases and yielded a total of 12 studies meeting the inclusion criteria for review. Elevated D-dimer levels and multiple infarcts in different cerebral circulations emerged as key markers. Based on the summarized data, we propose a flowchart for clinical decision-making regarding malignancy screening in patients with ischemic stroke. As the initial steps, we recommend using D-dimers cut-offs and stroke pattern on brain imaging to classify patients according to their risk profile. Based on the identified risk, we recommend a subsequent diagnostic workup addressing the most prevalent cancer types, including gastrointestinal tract, lung adenocarcinoma and gender-related cancer. The clinical implications of early malignancy screening and the need for evidence-based guidelines in cryptogenic stroke are discussed.

Introduction: Dual antiplatelet therapy (DAPT) is superior to single antiplatelet therapy (SAPT) for secondary prevention after minor, non-cardioembolic stroke. We aimed to assess whether DAPT efficacy is modified by large artery atherosclerotic (LAA) etiology, and DAPT safety by stroke size on MRI.

Patients and methods: Post hoc analysis of the Phase 2 PACIFIC-STROKE randomized clinical trial, which enrolled patients with non-cardioembolic stroke, all with baseline MRI and compared the Factor XIa inhibitor asundexian with placebo on a background of DAPT or SAPT. We compared patients treated with DAPT versus SAPT. The efficacy endpoint was the rate of recurrent ischemic stroke, the safety endpoint was major or clinically relevant non-major bleeding during follow-up.

Results: 1590 patients were included, median NIHSS was 2 (interquartile range [IQR] 1-4), 40% received DAPT. Median follow-up was 11.5 months. The efficacy endpoint occurred in 4.4% and 4.8% in the DAPT group and SAPT group, respectively, with the strongest numerical benefit of DAPT over SAPT among patients with NIHSS ⩽ 3 not treated by intravenous thrombolysis. LAA index stroke etiology did not modify DAPT treatment effect. The safety endpoint occurred more often in the DAPT than in the SAPT group (4.6% vs 2.7%), with the numerically lowest risk among patients with NIHSS ⩽ 3 not treated by intravenous thrombolysis. Stroke size did not modify the effect of DAPT on the safety endpoint.

Discussion and conclusion: We found no evidence of major treatment effect heterogeneity with DAPT compared with SAPT in patients with and without LAA or by stroke size on MR-DWI.

Introduction: The modified Rankin Scale (mRS) is the most frequently used primary outcome measure in acute stroke research despite significant interobserver variability in assigning grades. We assessed the use of central blinded adjudication of the mRS based on a video recording of an interview in the PRECIOUS trial.

Patients and methods: PRECIOUS was an international, randomized, open-label, clinical trial with blinded outcome assessment of preventive treatment with metoclopramide, paracetamol, and ceftriaxone in elderly patients with acute stroke. Trained local investigators interviewed patients or their representatives and graded functional outcome at 90 days after stroke with the mRS. In each participating country, a video recording of the interview was assessed by three blinded, independent adjudicators. The primary outcome of the present substudy was interobserver agreement between the local mRS score and the median score of the three central adjudicators for patients alive at 90 days, assessed with Cohen's kappa and quadratic weighted kappa statistics. The difference between treatment effect estimates based on local and central adjudication was a secondary outcome.

Results: Of 1493 patients enrolled in PRECIOUS, 1471 were included in this analysis. At 90 days, 1117 patients (75.9%) were alive and had both a central and local assessment; 28 participants did not have a central mRS score. Interobserver agreement was seen in 829 (74.2%) patients and was substantial (kappa of 0.68; 95% CI 0.65-0.71). Disagreement occurred more often in patients with a central mRS score of 0-2 (OR 2.24; 95% CI 1.14-4.24). Treatment effects were neutral for all three study drugs and did not differ between central and local adjudication.

Discussion and conclusion: Central adjudication of the mRS based on a video recording is feasible in a large international, randomized stroke trial. This ensures blinding of the outcome assessment. In this neutral trial, the impact of central adjudication on the precision of effect size estimates could not be assessed.

Introduction: Infective endocarditis (IE) is a life-threatening condition and a rare cause of ischemic stroke (IS). This study aimed to evaluate the utility of analyzing cerebral thrombi, obtained through endovascular thrombectomy in IS, for the pathological diagnosis of IE.

Patients and methods: Cerebral thrombi from three groups of IS patients were compared: definite IE (n = 10), cardioembolic stroke without and with concomitant infection (CE-I^-: n = 30, CE-I⁺: n = 10). We performed histological examination, molecular biology, and microbiological tests on cerebral thrombi, to detect microorganisms and assess their composition.

Results: Median age of included patients was 73 years and 50% were females. Hematoxylin & Eosin and Grocott-Gomori Methenamine Silver stains detected microorganisms in all IE cerebral thrombi, and none in the control groups. Thrombus PCR detected relevant microorganism in n = 2/7 IE. Compared to control groups, IE thrombi were characterized by significant lower content of red blood cells (median [IQR]: IE = 7.4 [4.2-26.7], CE-I^- = 49.3 [17-62.6], CE-I⁺ = 57.5 [40.7-60.8], % over thrombus section area [%TSA], p = 0.001), increased von Willebrand Factor (IE = 23.9 [19.1-32], CE-I^- = 11.2 [8.2-12.8], CE-I⁺ = 12.9 [10.7-18.3], %TSA, p = 0.001), cell-dominant pattern of Neutrophil Extracellular Traps (IE = 100%, CE-I^- = 69%, CE-I⁺ = 70%, p ⩽ 0.001), and more frequent sub-acute or chronic thrombus age classification (p ⩽ 0.001). These latter thrombus features displayed good discriminative ability between IE and controls, with AUC values between 0.84 and 0.95.

Discussion: Multimodal analysis of cerebral thrombi in IS with suspected IE supports early and definite pathological diagnosis by detecting pathogens and assessing changes in thrombus composition.

Background: The optimal acute management of patients with acute ischemic stroke and a tandem lesion, defined as intracranial large vessel occlusion (LVO) with concomitant carotid artery stenosis or occlusion, remains unclear. Our aim is to assess the efficacy and safety of immediate carotid artery stenting (CAS) compared to delayed management in patients undergoing endovascular treatment (EVT) for acute ischemic stroke due to tandem lesions.

Study design: CASES is a phase 3 multicenter prospective randomized open-label blinded endpoint (PROBE) non-inferiority clinical trial. Patients with a computed tomography angiography proven intracranial LVO in the anterior circulation and ipsilateral proximal carotid artery stenosis (⩾50%) or occlusion of presumed atherosclerotic origin will be randomized to either immediate CAS during EVT or to EVT followed by a deferred strategy, which may include carotid endarterectomy (CEA), CAS, or medical management. CASES will be conducted in 27 EVT centers in Belgium and the Netherlands. A total of 600 patients will be included.

Study outcomes: The primary outcome is the score on the modified Rankin Scale (mRS) at 90 days. Secondary outcomes include excellent (mRS 0-1) and good (mRS 0-2) functional outcome at 90 days, stroke severity measured with the National Institutes of Health Stroke Scale (NIHSS) at 24 h and 5-7 days, recanalization, infarct volume at 24 h, ischemic stroke recurrence, carotid artery re-occlusion, symptomatic intracranial hemorrhage, and mortality.

Summary: This study will provide high-quality randomized data on the efficacy and safety of immediate CAS in patients undergoing EVT for acute ischemic stroke due to a tandem lesion.

Trial registration: ClinicalTrials.gov NCT06511089; ISRCTN 14956654.

Introduction: While adiposity is an established risk factor for incident ischemic stroke, its influence on functional recovery after stroke is uncertain. We leveraged Mendelian randomization (MR) to examine the causal effects of body mass index (BMI) and waist-to-hip ratio (WHR) on post-stroke motor, cognitive, and global recovery.

Materials and methods: Genetic proxies for BMI and WHR were obtained from a genome-wide association study (GWAS) meta-analysis of the GIANT consortium and the UK Biobank (n = 806,834). The primary outcomes were longitudinal trajectories of three National Institutes of Health Stroke Scale (NIHSS) measures assessed over a 2-year period: motor function subscores, cognitive performance subscores, and total NIHSS scores (as a measure of global recovery). Genetic associations with these stroke recovery outcomes were obtained from a GWAS conducted within the VISP trial of mild ischemic stroke (n = 1270). MR effects were estimated using the inverse-variance weighted method.

Results: A 1-standard deviation (SD) increase (~4.8 kg/m²) in genetically predicted BMI associated with lower odds of post-stroke motor improvement (OR = 0.37, 95% CI = 0.19-0.72; p = 0.003). Similarly, a genetically predicted increase in BMI was associated with worse cognitive (β = -0.12, 95% CI = -0.21, -0.03; p = 0.009) and global recovery (β = -0.36, 95% CI = -0.59, -0.13; p = 0.002). Associations between genetically predicted WHR and post-stroke recovery were directionally concordant but were not statistically significant (p > 0.05).

Discussions and conclusions: Human genetic evidence suggests that elevated adiposity negatively impacts multiple post-stroke outcomes, including motor function, cognition, and overall recovery. The biological pathways underlying these associations warrant further investigation.

Introduction: Contemporary estimates of the impact of type 2 diabetes (T2D) on stroke outcomes are important for care planning and resource allocation. This retrospective cohort study compared the incidence of stroke and subsequent clinical and economic outcomes following stroke among people with and without T2D.

Patients and methods: Data were extracted from a subset of the French Système National des Données de Santé database. Stroke incidence as well as post-stroke clinical outcomes, healthcare resource utilization (HCRU), use of stroke preventative treatments, and costs were compared among people with and without T2D.

Results: The study included 10,906 patients hospitalized for stroke including 2141 (19.6%) people with T2D. Age-standardized stroke incidence rates were 3.3 (95% confidence interval [CI] 3.1; 3.6) per 1000 person-years and 2.2 (2.1; 2.3) in people with and without T2D, respectively. Patients with T2D had significantly higher risk of stroke recurrence (adjusted hazard ratio [HR] 1.14, 95% CI: 1.01; 1.30) and mortality (HR 1.16, 95% CI: 1.08; 1.25) than patients without T2D. The proportion of patients with T2D treated with statins decreased from 27.3% pre-stroke to 20.6% post-stroke but remained relatively stable among patients without T2D (from 13.4% to 13.1%). The mean healthcare costs in the 12 months following stroke were higher among patients with T2D than those without (€22,635 vs €18,629).

Discussion and conclusion: The incidence and clinical and economic burden of stroke is considerably higher among people with T2D. Further efforts are needed to reduce this disparity.

Introduction: The degree of culprit artery stenosis affects the risk of early neurological deterioration (END) after acute ischemic stroke (AIS). The TREND trial demonstrated the efficacy of tirofiban in preventing END in patients with AIS. We aimed to investigate whether the degree of intracranial artery stenosis affects the efficacy of tirofiban in preventing END in patients with AIS.

Patients and methods: We conducted a post hoc analysis of the TREND trial, which enrolled patients within 24 h of onset and randomly allocated to receive intravenous tirofiban or oral aspirin. We stratified the stenosis degrees into three subgroups: no stenosis, mild-to-moderate stenosis (stenosis <70%), and severe stenosis or occlusion (stenosis ⩾70%). The primary endpoint is END₄ defined as an increase of the NIHSS ⩾4 within 72 h after randomization. Secondary outcomes include END₂ (defined as an increase of NIHSS ⩾2) within 72 h after randomization, the proportion of mRS 0-1 and 0-2 at 90 days.

Results: A total of 296 patients were analyzed. In patients with severe stenosis or occlusion, tirofiban significantly reduced the incidence of END₄ (5.7% vs 30.8%, adjusted OR 0.156, 95% CI 0.028-0.873, adjusted p = 0.034), whereas its effects in preventing END₄ were similar to those of aspirin in patients with no stenosis (2.4% vs 4.6%, adjusted OR 0.193, 95% CI 0.018-2.083, adjusted p = 0.175) or mild-to-moderate stenosis (2.9% vs 10.0%, adjusted OR 0.171, 95% CI 0.015-1.943, adjusted p = 0.155). The p value for interaction between stenosis subgroups and treatment was 0.513. Furthermore, tirofiban significantly reduced the incidence of END₂ in patients with mild-to-moderate stenosis (5.9% vs 22.5%, OR 0.146, 95% CI 0.022-0.951, adjusted p = 0.044) and severe stenosis or occlusion (11.4% vs 43.6%, adjusted OR 0.140, 95% CI 0.036-0.540, adjusted p = 0.004). A significant improvement in favorable outcomes with a 90-day mRS of 0-1 was observed only in patients with mild-to-moderate stenosis (85.3% vs 70.0%, adjusted OR 4.617, 95% CI 1.077-19.798, adjusted p = 0.039).

Discussion and conclusion: Tirofiban may significantly reduce the incidence of END in patients with severe arterial stenosis or occlusion. Further studies are required to confirm the effects of intracranial artery stenosis on the benefits of intravenous tirofiban.

Trial registration: ClinicalTrials.gov; identifier: NCT04491695.

Introduction: Sex differences in stroke incidence, vascular risk factors (VRFs), and etiologies among young adults remain underexplored, particularly regarding age-related patterns.

Patients and methods: We retrospectively analyzed young adults (18-55 years) with first-ever ischemic stroke treated at certified acute stroke units/centers between 2014 and 2022, using Swiss Stroke Registry data. Stroke rates (per 100,000 person-years), VRFs, and etiologies were assessed by age and sex.

Results: Among 3,995 stroke patients, stroke rates were similar between sexes until age 35, after which men showed a more pronounced exponential increase. This rise was particularly notable in patients with elevated BMI and ⩾2 VRFs. The proportion of patients with ⩾2 VRFs rose with age (18-35: 22%; 36-50: 48%; 51-55: 63%). While no statistically significant differences in VRF profiles were observed between men and women aged 18-35, men accumulated VRFs about five years earlier than women, leading to a higher prevalence of multiple VRFs in men aged 36-50, with the gap narrowing in the 51-55 group. Stroke etiologies shifted with age: patent foramen ovale and cervical artery dissection predominated in younger patients, while large artery atherosclerosis, small vessel disease, and strokes of undetermined etiology increased with age, with notable sex differences.

Discussion and conclusions: This study highlights sex and age differences in ischemic stroke rates, VRFs, and etiologies among adults under 55 years. After 35, stroke rates rose more sharply in men, paralleling their higher VRF burden. These findings emphasize the importance of early management of VRFs-including overweight-to mitigate stroke risk.

Introduction: Cervical artery dissection is a major cause of stroke in the young. The optimal choice and duration of antithrombotic treatment for stroke prevention are debated, particularly beyond 3 months after symptom onset.

Patients and methods: TREAT-CAD (TREATment of Cervical Artery Dissection) was a randomized controlled trial with blinded outcome assessment comparing non-inferiority of aspirin to anticoagulation (Vitamin-K-antagonists) in participants with symptomatic, Magnetic-Resonance-(MR)-imaging-verified cervical artery dissection. TREAT-CAD could not establish non-inferiority of aspirin to anticoagulation at 3 months. Thereafter participants could continue antithrombotic medication and obtained a standardized assessment of clinical and MR-Imaging outcomes between 3 and 6 months. As crossover to the other treatment arm was possible, we performed an as-treated analysis as main analysis. The main outcomes were new clinical (ischemic stroke, intracranial/major extracranial bleeding, or death) and new MR-Imaging outcomes (ischemic or hemorrhagic brain lesions).

Results: Among the 122 participants in the as-treated analysis, 3/93 (3.2%) aspirin-treated participants had new clinical (n = 1) and MRI-outcomes (n = 2) between 3 and 6 months while 1/29 (3.4%) anticoagulated participants had an MRI-outcome (n = 1). All outcome events were hemorrhagic while ischemic events were absent. No deaths occurred. This yields an absolute difference of 0.2% (95% CI -8.0% to 7.5%, p = 1.0).

Discussion and conclusion: During the extended follow-up period of a controlled randomized trial comparing aspirin to anticoagulation in cervical artery dissection, outcomes between 3 and 6 months after randomization occurred rarely, similarly often in both groups and were exclusively hemorrhagic events. Thus, studies balancing benefits versus harms of antithrombotic treatment beyond 3 months are warranted. Registration: ClinicalTrials.gov: NCT02046460. https://clinicaltrials.gov/ct2/show/NCT02046460.