Neurovascular Adverse Effects of Sars-Cov-2 Vaccination.

The global deployment of SARS-CoV-2 vaccines has been pivotal in curbing the COVID-19 pandemic, reducing morbidity and mortality associated with the virus. While most of these vaccines have demonstrated high efficacy and overall safety, emerging reports have highlighted potential neurovascular adverse effects, albeit uncommon, associated with these vaccinations. This review aims to assess and summarize the current knowledge on the neurovascular complications arising post-SARS-CoV-2 vaccination. We conducted an extensive literature review, focusing on clinical studies and case reports to identify reported neurovascular events, such as ischemic stroke, cerebral sinus venous thrombosis, intracerebral hemorrhage, pituitary apoplexy and primary CNS angiitis Despite the relative rarity of these events, their impact on affected individuals underscores the importance of ongoing surveillance, early detection, and management strategies. We aim to provide healthcare professionals with the latest evidence on neurovascular adverse effects, facilitating informed decision-making in the context of SARS-CoV-2 vaccination programs. Furthermore, we highlight areas requiring further research to understand the pathophysiology of these adverse events better and to develop targeted prevention and treatment strategies

Circle of Willis variants and their association with outcome in patients with middle cerebral artery-M1-occlusion stroke

BACKGROUND: An incomplete circle of Willis (CoW) has been associated with a higher risk of stroke and might affect collateral flow in large vessel occlusion (LVO) stroke. We aimed to investigate the distribution of CoW variants in a LVO stroke and transient ischemic attack (TIA) cohort and analyze their impact on 3-month functional outcome. METHODS: CoW anatomy was assessed with time-of-flight magnetic resonance angiography (TOF-MRA) in 193 stroke patients with acute middle cerebral artery (MCA)-M1-occlusion receiving endovascular treatment (EVT) and 73 TIA patients without LVO. The main CoW variants were categorized into four vascular models of presumed collateral flow via the CoW. RESULTS: 82.4% (n = 159) of stroke and 72.6% (n = 53) of TIA patients had an incomplete CoW. Most variants affected the posterior circulation (stroke: 77.2%, n = 149; TIA: 58.9%, n = 43; p = 0.004). Initial stroke severity defined by the National Institutes of Health Stroke Scale (NIHSS) on admission was similar for patients with and without CoW variants. CoW integrity did not differ between groups with favorable (modified Rankin Scale [mRS]): 0-2) and unfavorable (mRS: 3-6) 3-month outcome. However, we found trends towards a higher mortality in patients with any type of CoW variant (p = 0.08) and a higher frequency of incomplete CoW among patients dying within 3 months after stroke onset (p = 0.119). In a logistic regression analysis adjusted for the potential confounders age, sex and atrial fibrillation, neither the vascular models nor anterior or posterior variants were independently associated with outcome. CONCLUSION: Our data provide no evidence for an association of CoW variants with clinical outcome in LVO stroke patients receiving EVT

Circle of Willis variants and their association with outcome in patients with middle cerebral artery-M1-occlusion stroke.

BACKGROUND An incomplete circle of Willis (CoW) has been associated with a higher risk of stroke and might affect collateral flow in large vessel occlusion (LVO) stroke. We aimed to investigate the distribution of CoW variants in a LVO stroke and transient ischemic attack (TIA) cohort and analyze their impact on 3-month functional outcome. METHODS CoW anatomy was assessed with time-of-flight magnetic resonance angiography (TOF-MRA) in 193 stroke patients with acute middle cerebral artery (MCA)-M1-occlusion receiving endovascular treatment (EVT) and 73 TIA patients without LVO. The main CoW variants were categorized into four vascular models of presumed collateral flow via the CoW. RESULTS 82.4% (n = 159) of stroke and 72.6% (n = 53) of TIA patients had an incomplete CoW. Most variants affected the posterior circulation (stroke: 77.2%, n = 149; TIA: 58.9%, n = 43; p = 0.004). Initial stroke severity defined by the National Institutes of Health Stroke Scale (NIHSS) on admission was similar for patients with and without CoW variants. CoW integrity did not differ between groups with favorable (modified Rankin Scale [mRS]): 0-2) and unfavorable (mRS: 3-6) 3-month outcome. However, we found trends towards a higher mortality in patients with any type of CoW variant (p = 0.08) and a higher frequency of incomplete CoW among patients dying within 3 months after stroke onset (p = 0.119). In a logistic regression analysis adjusted for the potential confounders age, sex and atrial fibrillation, neither the vascular models nor anterior or posterior variants were independently associated with outcome. CONCLUSION Our data provide no evidence for an association of CoW variants with clinical outcome in LVO stroke patients receiving EVT

Clinical associations and prognostic value of MRI-visible perivascular spaces in patients with ischemic stroke or TIA: a pooled analysis

BACKGROUND AND OBJECTIVES: Visible perivascular spaces are an MRI marker of cerebral small vessel disease and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large collaborative multicenter analysis. METHODS: We pooled individual patient data from a consortium of prospective cohort studies. Participants had recent ischemic stroke or transient ischemic attack (TIA), underwent baseline MRI, and were followed up for ischemic stroke and symptomatic intracranial hemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and perivascular spaces in the centrum semiovale (CSOPVS) were rated locally using a validated visual scale. We investigated clinical and radiologic associations cross-sectionally using multinomial logistic regression and prospective associations with ischemic stroke and ICH using Cox regression. RESULTS: We included 7,778 participants (mean age 70.6 years; 42.7% female) from 16 studies, followed up for a median of 1.44 years. Eighty ICH and 424 ischemic strokes occurred. BGPVS were associated with increasing age, hypertension, previous ischemic stroke, previous ICH, lacunes, cerebral microbleeds, and white matter hyperintensities. CSOPVS showed consistently weaker associations. Prospectively, after adjusting for potential confounders including cerebral microbleeds, increasing BGPVS burden was independently associated with future ischemic stroke (versus 0-10 BGPVS, 11-20 BGPVS: HR 1.19, 95% CI 0.93-1.53; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; = 0.040). Higher BGPVS burden was associated with increased ICH risk in univariable analysis, but not in adjusted analyses. CSOPVS were not significantly associated with either outcome. DISCUSSION: In patients with ischemic stroke or TIA, increasing BGPVS burden is associated with more severe cerebral small vessel disease and higher ischemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH

Increased risk of recurrent stroke in patients with impaired kidney function: results of a pooled analysis of individual patient data from the MICON international collaboration

BACKGROUND: Patients with chronic kidney disease are at increased risk of stroke and frequently have cerebral microbleeds. Whether such patients also encounter an increased risk of recurrent stroke has not been firmly established. We aimed to determine whether impaired kidney function is associated with the risk of recurrent stroke, and microbleed presence, distribution and severity. METHODS: We used pooled data from the Microbleeds International Collaborate Network to investigate associations of impaired kidney function, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Our primary outcome was a composite of recurrent ischaemic stroke (IS) and intracranial haemorrhage (ICrH). Secondary outcomes included: (1) individual components of the primary outcome; (2) modification of the primary outcome by microbleed presence or anticoagulant use and (3) microbleed presence, distribution and severity. RESULTS: 11 175 patients (mean age 70.7±12.6, 42% female) were included, of which 2815 (25.2%) had impaired kidney function. Compared with eGFR ≥60, eGFR <60 was associated with a higher risk of the primary outcome (adjusted HR, aHR 1.33 (95% CI 1.14 to 1.56), p<0.001) and higher rates of the recurrent IS (aHR 1.33 (95% CI 1.12 to 1.58)). Reduced eGFR was not associated with ICrH risk (aHR 1.07 (95% CI 0.70 to 1.60)). eGFR was also associated with microbleed presence (adjusted OR, aOR 1.14 (95% CI 1.03 to 1.26)) and severity (aOR 1.17 (95% CI 1.06 to 1.29)). Compared with having no microbleeds, eGFR was lower in those with strictly lobar microbleeds (adjusted mean difference (aMD) -2.10 mL/min/1.73 cm2 (95% CI -3.39 to -0.81)) and mixed microbleeds (aMD -2.42 (95% CI -3.70 to -1.15)), but not strictly deep microbleeds (aMD -0.67 (95% CI -1.85 to 0.51)). CONCLUSIONS: In patients with IS or transient ischaemic attack, impaired kidney function was associated with a higher risk of recurrent stroke and higher microbleeds burden, compared with those with normal kidney function. Further research is needed to investigate potential additional measures for secondary prevention in this high-risk group

Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation

OBJECTIVES: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with Vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet) METHODS: We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. RESULTS: A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (aHR 2.74, 95% confidence interval 1.76 - 4.26) and ischemic stroke (aHR 1.29, 95% confidence interval 1.04 - 1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleeds burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2-4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥11 microbleeds (94 vs 48 per 1,000 patient-years). INTERPRETATION: Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high-risk group. This article is protected by copyright. All rights reserved

Global, Regional, and National Burden of Nontraumatic Subarachnoid Hemorrhage

Importance: Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective: To estimate the worldwide burden of SAH. Design, setting, and participants: Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures: SAH and 14 modifiable risk factors. Main outcomes and measures: Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor-specific population attributable fractions (PAFs). Results: In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and relevance: Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions

Observation of γγ → ττ in proton-proton collisions and limits on the anomalous electromagnetic moments of the τ lepton

The production of a pair of τ leptons via photon–photon fusion, γγ → ττ, is observed for the f irst time in proton–proton collisions, with a significance of 5.3 standard deviations. This observation is based on a data set recorded with the CMS detector at the LHC at a center-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 138 fb−1. Events with a pair of τ leptons produced via photon–photon fusion are selected by requiring them to be back-to-back in the azimuthal direction and to have a minimum number of charged hadrons associated with their production vertex. The τ leptons are reconstructed in their leptonic and hadronic decay modes. The measured fiducial cross section of γγ → ττ is σfid obs = 12.4+3.8 −3.1 fb. Constraints are set on the contributions to the anomalous magnetic moment (aτ) and electric dipole moments (dτ) of the τ lepton originating from potential effects of new physics on the γττ vertex: aτ = 0.0009+0.0032 −0.0031 and |dτ| &lt; 2.9×10−17ecm (95% confidence level), consistent with the standard model