This boy in mid childhood presented with a sudden, excruciating occipital headache following a week of progressive gait unsteadiness and neck-accentuated meningeal pain. CT demonstrated tetraventricular haemorrhage with early obstructive hydrocephalus and perimesencephalic subarachnoid blood. CT angiography/magnetic resonance angiography (MRA) and digital subtraction angiography revealed a cervicomedullary perimedullary arteriovenous fistula (PMAVF) supplied by the anterior and posterior spinal arteries with a single venous pouch aneurysm at C3-4. Emergency external ventricular drain (EVD) placement was performed. Definitive endovascular cure was achieved 72 hours later using simultaneous bilateral micro-catheterisation of the venous pouch and 'parallel' coiling under multimodality neuromonitoring, completely occluding the shunt while preserving spinal arterial flow. The patient recovered without any neurological deficit, the EVD was gradually weaned over the first 5 postoperative days and removed without clinical or radiological difficulty, and the 12-week MRI/MRA confirmed complete occlusion; at that time, he had returned fully to school and sports including football. This case highlights the importance of cervicomedullary vascular imaging in atraumatic paediatric Subarachnoid Hemorrhage (SAH)/intraventricular haemorrhage and illustrates that complex type III/C PMAVFs can be safely cured in a single session using a dual-pedicle coiling strategy in select cases.

Despite advances in acute treatment, stroke remains the first cause of acquired disability. Today, there is no effective pharmacological therapy to improve recovery beyond the acute phase. Preclinical studies suggest that inhibition of the C-C chemokine Receptor 5 (CCR5) may promote recovery by enhancing plasticity in the peri-infarct cortex. However, the role of CCR5 to improve outcome after ischaemic stroke in humans is unknown.

MAraviroc for STrokE Recovery is a phase II, single-centre, randomised, double-blind, placebo-controlled trial. The aim is to assess the efficacy and safety of the CCR5 antagonist Maraviroc for improving motor recovery of the upper limb after ischaemic stroke. 80 ischaemic stroke patients with moderate but incomplete upper extremity motor impairment will be enrolled within 7 days of onset. Participants will be randomised (1:1) to receive either oral maraviroc (300 mg two times per day) or placebo for 90 days in addition to standard rehabilitation therapy. The primary outcome is upper limb motor function assessed using the Fugl-Meyer Assessment for the Upper Extremity at day 90. Secondary outcomes include motor learning skills and plasticity in the peri-infarct region assessed using MRI connectivity and spectroscopy at 90 days.

The study protocol has been reviewed and approved by the Geneva Competent Ethics Committee (Commission Cantonale d'Éthique, CEC; Reference Number: CCER 2024-02359) and Swissmedic (Swiss Agency for Therapeutic Products). Written informed consent will be obtained from all participants. Study results will be disseminated through peer-reviewed publications and scientific conferences.

2024-02359; NCT07080567.

To characterise post-stroke depression (PSD) diagnostic and treatment patterns in an outpatient primary care setting, including timing, screening methods, therapeutic interventions and associations with mortality.

A retrospective cohort study.

Maccabi Healthcare Services, the second largest Healthcare Maintenance Organisation in Israel, covering more than 2.7 million citizens between 2016 and 2022.

Participants were adult patients with a new stroke diagnosis between 2016 and 2022 and a subsequent diagnosis of depression according to International Classification of Diseases clinical criteria or antidepressant medication initiation. Patients with a diagnosis of depression or antidepressant treatment prior to stroke were excluded from the study.

Primary outcomes included PSD diagnosis rates, time to diagnosis and treatment, use of screening questionnaires, specialty of the physician making the diagnosis and all-cause mortality. Secondary outcomes included referral rates to mental health services, rehabilitation participation and its impact on mortality.

Among 11 499 patients, PSD occurred in 4620 (40.2%) patients. Primary care physicians diagnosed 53.1% of cases based on clinical assessment; only 4.5% of patients underwent Patient Health Questionnaire-2 screening. Most diagnoses occurred in the first year (53.4%). Antidepressants, predominantly selective serotonin reuptake inhibitors (58.3%), were initiated within 30 days in 65.1% of diagnosed patients. Patients with PSD demonstrated higher rehabilitation participation (69.5% vs 48.5%, p<0.001) and paradoxically lower mortality rates (22.1% vs 27.9%, p<0.001). Patients without PSD were older with a greater comorbidity burden. Cox regression identified physiotherapy visits (HR=0.625, p<0.001) and mental health consultations (HR=0.642, p<0.001) as protective factors.

In this cohort, in an outpatient primary care setting, primary care physicians diagnosed the majority of PSD cases, predominantly relying on clinical criteria, without using screening tools. The majority of PSD diagnoses occurred during the first year after stroke (53.1%), suggesting that repeated evaluation might be appropriate during this follow-up period. Early antidepressant treatment and enhanced rehabilitation engagement may positively influence mortality outcomes in patients with PSD. Low utilisation of standard screening tools and mental health referrals represents an area for potential improvement in PSD management.

Heart failure occasionally develops after transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS), despite procedural success. Most cases present with mildly reduced or preserved left ventricular ejection fraction (LVEF), underscoring the role of diastolic dysfunction. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown benefits across the heart failure spectrum, independent of LVEF. The purpose of this randomised controlled trial is to determine whether adding a SGLT2 inhibitor to conventional medications improves LV diastolic function in patients with preserved LVEF after TAVI.

This study is a prospective, single-centre, open-label, randomised, parallel-group, two-arm trial enrolling patients with mildly reduced or preserved LVEF (≥40%) undergoing TAVI for severe AS. Participants will be randomised in a 1:1 ratio to receive either conventional medications plus empagliflozin or conventional medications alone. In the empagliflozin group, participants will receive conventional medical therapy plus empagliflozin 10 mg orally once daily, initiated 4 weeks after TAVI. Empagliflozin treatment will continue throughout the study period. Participants in the control group will receive conventional medications without empagliflozin. The primary endpoint is the change in E/e', assessed by echocardiography from treatment initiation at 4 weeks post TAVI (day 1) to day 168 (week 24). Each group will include 50 patients, totalling 100 patients.

Ethical approval for this study has been obtained from the Chiba University Hospital Certified Clinical Research Review Board (CRB0111-25).

jRCT1031250190.

Overweight and obesity are major global public health challenges and increase the risk of type 2 diabetes, dyslipidaemia, hypertension and cardiovascular disease. Exercise is a safe and cost-effective non-pharmacological strategy to improve cardiometabolic health, yet the optimal combinations of exercise modality and dose for key cardiometabolic outcomes remain uncertain. This protocol aims to synthesise evidence on the joint effects of exercise modality and dose in adults with overweight or obesity and to identify modality-dose combinations associated with the most favourable cardiometabolic profiles.

We will search PubMed, Embase, Web of Science, the Cochrane Library, Scopus, SPORTDiscus and China National Knowledge Infrastructure (CNKI) from inception to June 2026 for randomised controlled trials of exercise interventions in adults (≥18 years) with overweight or obesity. Risk of bias will be assessed using the Cochrane Risk of Bias 2 tool. We will conduct a Bayesian model-based dose-response network meta-analysis to estimate modality-specific dose-response relationships across cardiometabolic outcomes, with exercise dose standardised as metabolic equivalent of task minutes per week. Non-linear dose-response curves will be fitted to estimate minimum effective doses and optimal dose ranges. Meta-classification and regression tree analyses will be used to explore potential effect modifiers.

Ethical approval is not required because no primary data will be collected. Findings will be submitted to a peer-reviewed journal.

CRD420251229131.

Surgical and endovascular procedures are established treatments for extracranial stenoses of the internal carotid artery (ICA) according to current guidelines. Revascularization is generally recommended for symptomatic ICA stenoses between 50% and 99%. For asymptomatic stenoses, optimal medical therapy is the primary focus; revascularization should be considered for stenoses between 60% and 99%, depending on the individual risk. The choice between endarterectomy (CEA) and carotid artery stent implantation (CAS) is made by an interdisciplinary team, considering patient- and anatomy-specific factors. Interventional therapy is well-established; however, studies show an increased incidence of minor strokes and transient ischemic attacks (TIAs), which is why patient selection and embolic protection are becoming increasingly important in the field of endovascular revascularization. Technological advancements, such as innovative double-layer stents for improved plaque coverage, increase the safety of the procedure, and reduce the peri-procedural stroke rate. Anatomical features are essential for successful treatment when selecting devices and planning procedures.

Invasive treatment of carotid stenosis is directed towards the prevention of ischemic stroke. Contemporary guidelines, based on the best available evidence, recommend carotid endarterectomy for symptomatic carotid stenosis of 50-99%. Revascularization should ideally be performed within 48 hours to 14 days following the index ischemic event. In asymptomatic patients, intervention is indicated in the presence of clinical or morphological markers associated with an increased risk of carotid stenosis-related stroke. Carotid artery stenting represents a complementary alternative to endarterectomy, particularly in patients at high surgical risk. Given that several recommendations are based on expert opinion rather than high-level evidence, interdisciplinary decision-making plays a crucial role. Patients with limited life expectancy should not undergo invasive treatment; all patients with carotid artery disease should receive optimal medical therapy.

Carotid artery stenosis is a major cause of ischemic stroke, with prevalence increasing with age and vascular risk factors. Targeted diagnosis in patients with acute cerebrovascular disease and high-risk populations, combined with consistent conservative management, is essential to significantly reduce stroke risk. This article reviews current diagnostic strategies, including duplex ultrasound as the cornerstone of non-invasive assessment, and discusses pharmacological and non-pharmacological treatment approaches. Medical therapy-including antiplatelet therapy, statins, and vascular risk factor control-is crucial across all stenosis stages and may suffice even in some cases traditionally considered for revascularization. Current research focuses on individualized therapy guided by risk stratification to identify patients for whom conservative management alone provides optimal stroke prevention. Interdisciplinary decision-making is essential to tailor treatment strategies.

Ischemic stroke (IS) accounts for 87% of all strokes and is a leading cause of disability worldwide. Women face higher lifetime IS risk and worse functional outcomes, yet predictive biomarkers remain limited. Moreover, inflammation is increasingly recognized as a contributor to IS pathogenesis, with inflammatory markers such as C-reactive protein (CRP) positively associated with IS. Yet, the metabolic pathways linking chronic inflammation to IS risk are poorly understood. We aimed to identify a metabolomic signature reflecting systemic inflammation and evaluate its association with incident IS in women.

This study used nested case-control designs within the Nurses' Health Study (NHS), a prospective cohort of US female registered nurses aged 30-55 at enrollment. Using elastic net regression in a derivation cohort with inflammatory biomarker (high-sensitive CRP, interleukin 6, tumor necrosis factor receptor 2, adiponectin) and metabolomic data, we developed a metabolomic signature index of inflammation (i-MSI). The i-MSI's association with incident IS was examined in an independent NHS nested case-control study using conditional logistic regression, adjusting for cardiovascular risk factors. Generalizability to atherosclerotic disease was evaluated in a coronary heart disease (CHD) nested case-control study from the Women's Health Initiative (WHI).

The derivation cohort included 1,699 women (mean age 58 years, 94% White). The i-MSI comprised 102 metabolites, with lysophosphatidylcholine species-promoters of endothelial activation, vascular inflammation, and plaque instability-contributing most significantly. In the independent IS case-control study (454 cases, 454 controls; mean age 66 years), women in the highest compared with lowest i-MSI quartile had a multivariable-adjusted odds ratio (OR) of 1.76 (95% CI 1.02-3.03) for IS, whereas each 1-SD increase in the i-MSI was associated with an OR of 1.35 (95% CI 1.09-1.67). In the WHI study (793 cases, 795 controls; mean age 67 years), each SD increase in the i-MSI was associated with an OR of 1.20 (95% CI 1.05-1.37) for CHD.

An inflammatory metabolomic signature was associated with higher IS risk, independent of traditional cardiovascular disease risk factors, with consistent findings for CHD. Future studies should replicate these findings in other populations and evaluate whether these metabolites can improve risk stratification and serve as biomarkers for atherosclerotic cardiovascular diseases.

The frequency and cognitive trajectory of cerebral amyloid angiopathy (CAA) in patients from memory clinics is uncertain. We aimed to determine whether patients with CAA have an increased risk of dementia in nondemented individuals presenting with a cognitive complaint.

We retrospectively analyzed data of the MEMENTO prospective cohort that enrolled outpatients from 26 centers in France presenting with a cognitive complaint and a Clinical Dementia Rating (CDR) scale score ≤0.5. Participants aged >50 years who had interpretable baseline brain MRI were eligible for this study and followed every 6 months for 5 years with systematic assessment of dementia. Based on MRI analysis, participants were classified into 4 categories using the Boston criteria V2.0 and V1.5: probable CAA, possible CAA, deep/mixed small vessel disease (SVD), or controls (without imaging markers of SVD). The primary outcome was the progression to dementia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Revision criteria) evaluated by an expert committee. Cox proportional hazards models were used to determine hazard ratios (HRs) and CIs for the primary outcome.

Of 2,323 MEMENTO participants, 2,136 (92%) were included in this study. The mean age (SD) at baseline was 71.3 (7.9) years and 1,320 (62%) were women. Probable CAA was diagnosed in 413 (19.3%) patients using the Boston criteria V2.0, and 144 (7.0%) using the Boston criteria V1.5. During a median follow-up of 5.0 years (interquartile range 3.1-5.1), 307 participants developed dementia. Compared with controls, patients with probable CAA according to the Boston criteria V2.0 (HR 1.73, 95% CI 1.23-2.42) and V1.5 (HR 2.23, 95% CI 1.56-3.20) had increased risk of dementia. After adjusting for age, sex, baseline Mini-Mental State Examination score and hippocampal volume, patients with probable CAA per Boston criteria V1.5 but not V2.0 had an increased risk of dementia compared with controls. This association was not significant when further adjusting with APOE ε4.

CAA is a common condition in outpatients with mild cognitive symptoms. Patients with probable CAA according to the Boston criteria V1.5 but not V2.0 have increased risk of dementia. Further studies are required to externally validate these findings and evaluate potential mediation effect of APOE genotype.